School of Chinese Medicine

SCHOOL OF CHINESE MEDICINE

Researcher : Chen J

Project Title:	Investigation of the Mechanisms and Effects of Phytoestrogen from Dang-gui (Angellica sinensis) on Breast Cancer Cells
Investigator(s):	Chen J, Loo TY
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009

Abstract:

Epidemic results demonstrated that the frequent intake of phytoestrogen would decrease breast cancer incidences [1-2]. The mechanism of reducing breast cancer incidences by phytoestrogen, however, is still unclear. At present, the experimental data in vitro has become a controversial issue that whether phytoestrogen is an estrogen agonist or antagonist, as well [3-4]. Since phytoestrogen exists in daily dietary and in many traditional Chinese medicines, it is worth exploring and determining the relation between phytoestrogen and breast cancer for its prognosis and treatment. Dang-gui is a kind of traditional Chinese medicine for female diseases with a thousand years application history, which has been fine efficiency for mammary hyperplasia, and also a frequent component in compound recipe against breast cancer. However, recent studies indicated that Dang-gui positively affected on breast cancer cell proliferation because of its high concentration phytoestrogen[5]. It is important to identify Dang-gui’s effects on breast cancer, which would enhance or inhibit breast cancer proliferation. to explore mechanism of phytoestrogen derived from Dang-gui, and to verify specific genes that phytoestrogen targets on. 1.To identify effective phytoestrogen components in Dang-gui and to find out responsive dose of Dang-gui that affects the proliferation and morphology of estrogen-positive and estrogen-negative breast cancer cell line. 2.To explore the influences of Dang-gui acting on breast cancer cell signal transduction pathway, to test for the Dang-gui regulator expression in SRC-1, SMRT, NcoR factors. 3.To analyze the effects of Dang-gui in status of estrogen receptor in cancer cells. Reference 1.Joanne T, Michelle C, Beatrice AB, Nancy K, Lilian UT. Adolescent dietary phytoestrogen intake and breast cancer risk. Cancer Causes Control, 2006, 17:1253-1261. 2.Marie L, Elisabete W. Epidemiologic evidence suggests that dietary phytoestrogen intake is associated with reduced risk of breast, endometrial, and prostate cancers. Nutrition Research, 2006, 26:609-619. 3.Daniela G, Cristiano F, Manuela F, Silvia P, Giovanni S. Lack of stimulatory activity of a phytoestrogencontaining soy extract on the growth of breast cancer tumors in mice. Carcinogenesis, 2006, 27(7):1404-1409. 4.Hsu JT, Hung HC, Chen CJ, Hsu WL, Ying C. Effects of the dietary phytoestrogen biochanin A on cell growth in the mammary carcinoma cell line MCF-7. Journal of Nutrition Biochemistry, 1999, 10:510-517. 5.Christine D, Kimberly P, Ann Partridge. Implication of phytoestrogen intake for breast cancer. CA cancer Journal of Clinicians, 2007,57:260-277.

Project Title:	Effects and Mechanisms of Litchi seed Extracts against Lung Specific Metastasis of Breast Cancer
Investigator(s):	Chen J, Guan XY
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009

Abstract:

Metastasis is frequently a final and fatal step in the progression of solid malignancies. Tumor cell intravasation, survival in circulation, extravasation into a distant organ, angiogenesis and uninhibited growth constitute the metastatic process [1-2]. However, it has long been noted that the process is not random. For example, liver, lungs, lymph nodes, brain and bone marrow are common sites of metastasis; whereas heart and muscle are seldom infected. This characteristic is called organ specific metastasis or organ-tropism [3-4]. Mechanisms account for this phenomenon remains unknown, but it is of great value to clarify the detailed mechanisms to control metastasis and improve prognosis. The identity and time of onset of the changes that endow tumor cells with organ specific metastasis function is critical in the process. It is believed that genomic instability generates large-scale cellular heterogeneity within tumor populations, from which the cell populations with metastatic abilities evolve [5-6]. The theory is supported by a lot of experimental work that reinjection of metastatic cell populations can lead to enrichment in the metastatic phenotype. However, the view is challenged by another opinion that considers the organ specific metastasis ability was existed early in the primary tumor population [7-8]. It needs further exploration to clarify the truth. Lung is the frequent site of breast cancer metastasis and also the common cause for breast cancer related death. To prolong the survival duration, reduce mortality and improve life quality, it’s important to elucidate the genes or proteins which induce lung metastasis. Meanwhile, it is necessary to develop the new anti-metastasis drugs from natural resources. Epidemiological studies suggested that antioxidant supplements might reduce the risk of breast cancer recurrence or metastasis [9-10], and consuming vegetables and foods rich in catechins, flavones or saponins is associated with a lower incidence of cancers [11-12]. Litchi seed is frequently used in breast cancer patients’ CM therapy for many years because of its good clinical efficiency [13]. Pharmaceutical studies showed that the litchi seed contains significant amounts of flavones and saponins, which exhibited powerful anti-oxidative activity in vitro [14]. Recent researches also indicated that litchi seed extracts could inhibit cancer cell proliferation, induce apoptosis and suppress tumor growth in vivo [15-17]. However, the effects of litchi seed extracts on inhibiting metastasis are still unclear. Nevertheless, many studies indicated that the saponins or flavones extracted from certain foods could suppress cancer invasion and metastasis by inhibiting angiogenesis or key gene expression sun as VEGF, MMP-9 or NF-kB, etc[18-20]. Based on the main components of litchi seed extracts and their antioxidant properties, we hypothesized that litchi seed extracts may prevent or inhibit lung metastasis of breast cancer. The aim is to determine litchi seed’s effects on inhibiting lung metastasis and to explain the mechanisms. Meanwhile, we hope to identify the genes or proteins which may participate in regulating cancer cell metastasis to the lung. References: 1.Steeg PS, Theodorescu D. Metastasis: a therapeutic target for cancer. Nature Clinical Private Oncology, 2008, 5(4): 206-219. 2.Duffy MJ, McGowan PM, Gallagher WM. Cancer invasion and metastasis: changing views. Journal of Pathology, 2008, 214(3): 283-293. 3.Ben-Baruch A. Organ selectivity in metastasis: regulation by chemokines and their receptors. Clinical & Experimental Metastasis, 2008, 25(4): 345-356. 4.Sone S. Critical determinants of organ specific lung cancer metastasis for therapy. Clinical & Experimental Metastasis, 2007, 24(4):213-213. 5.Gassmann P, Hemping-Bovenkerk A, Enns A, Haier J. Modelling early steps of organ specific metastasis formation. Clinical & Experimental Metastasis, 2007, 24(4): 230-230. 6.Lee H, Lin ECK, Liu LM, Smith JW. Gene expression profiling of tumor xenografts: In vivo analysis of organ-specific metastasis. International Journal of Cancer, 2003, 107(4): 528-534. 7.Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nature Genet, 2003, 33: 49-54. 8.Vant Veer LJ, Dai HY, Van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature, 2002, 415(6871):530-536. 9.Fleischauer AT, Simonsen N, Arab L. Antioxidant supplements and risk of breast cancer recurrence and breast cacner-related mortality among postmenopausal women. Nutrition and cancer –an international journal, 2003, 46(1): 15-22. 10.Hirvonen T, Mennen Li, De Bree A, et al. Consumption of antioxidant-rich beverages and risk for breast cancer in French women. Annals of epideminology, 2006, 16(7): 503-508. 11.Uraiwan K, Pornchai O, Kannika J, et al. The anticancer effects of Thai medical plants containing antioxidant phenolics on breast cancer cells. Acta pharmacologica sinica, 2006, 27: 319-320. 12.Kim J, Jayaprakasha GK, Murthy KNC, et al. Lemon seed extracts: antioxidant capacity and inhibition of breast cancer cells. Hortscience, 2008, 43(3): 603-603. 13.Loo WT, Chen JP, Chow LW, Chou JW (2007). Effects of Shugansanjie Tang on matrix metalloproteinases 1, 3 and 9 and Telomerase reverse transcriptase expression in human breast cells in vitro, Biomed Pharmacother. 61(9):601-5. 14.Guo JW, Pan JQ. Chemical compositions, biological activites and pharmaceutical effects of litchi or litchi seeds. Chinese Journal of new drugs, 2006, 15(8): 585-588. 15.Wang XJ, Yuan SL, Wang J, et al. Anticancer activity of litchi fruit pericarp extract against human breast cancer in vitro and vivo. Toxicology and applied pharmacology, 2006, 215: 168-178. 16.Xiao LY, Pan JQ, Hong HJ, et al. Anti-tumor effects of semen litchi and its effect on telomerse activation of hepatoma tissue. China pharmacy, 2007, 18(18): 133-1368. 17.Wang XY, Xiao LY, Pan JQ, et al. Experimental studies of effects of antitumor of litchi seed ke li and the activity of in the tissue-end of EAC, S180 and hepatic carcinoma of rats. China Healthcare innovation, 2007, 2(12): 54-56. 18.Kang JH, Han IH, Sung MK, et al. Soybean saponin inhibits tumor cell metastasis by modulating expression of MMP-2, MMP-9 and TIMP-2. Cancer letters, 2008, 261(1): 84-92. 19.Sato K, Mochizuki M, Saiki I, et al. Inhibition of tumor angiogenesis and metastasis by a saponin of panax-ginseng, ginsenoside- RB2. Biological& Pharmaceutical bulletin, 1994, 17(5): 635-639. 20.Bracke Me, Bruyneel EA, Vermeulen SJ, et al. Citrus flavonoid effect on tumor invasion and metastasis. Food technology, 1994, 48(11):121-124.

Project Title:	*Molecular mechanisms of natural LDH-A inhibitors from Spatholobus suberectus* inducing mitochondrial pathway apoptosis**
Investigator(s):	Chen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Travel Grants for NSFC/RGC JRS
Start Date:	12/2009

Abstract:

Travel grants for NSFC/RGC JRS

Project Title:	The 6th World Congress of Chinese Mediicne CORRELATIONAL STUDY ON THE FIVE PERSONALITIES AND BREAST CANCER
Investigator(s):	Chen J
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	12/2009
Completion Date:	12/2009

Abstract:

N/A

Project Title:	Mechanism exploration of increased intracellular level of ROS in inhibiting breast caner growth and metastasis caused by Spatholobus suberectus
Investigator(s):	Chen J, Guan XY, Shen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Background & Introduction: Breast cancer is the first killer among female malignacy diseases. In Hong Kong, the rapid increase of breast cancer cases in recent years and the increasing trend of breast cancer affecting younger women have made it even more worrying. With breast cancer the most common cancer form women in Hong Kong face, there are more than 2,000 new breast cancer cases in Hong Kong annually [1] . Besides early detection, there is obviously a pressing need to develop therapeutic agents which can effectively treat breast cancer and prevent its metastasis. With Traditional Chinese Medicine (TCM)’s unique views on breast cancer occurrence and development, together with certain Chinese herbs which have been proved to have sound effects on fighting cancer and preventing metastasis, TCM offers itself as a clinically viable and effective option for breast cancer treatment. Spatholobus suberectus ( JIxietang,雞血藤 SSD) has been found to be an effective herb for treating breast cancer.SSD is a traditional Chinese medicinal herb which has the characterisitics of promoting blood circulation and removing blood stasis. It is widely used in clinical practice for treatment of rheumatoid, paralysis, irregular menstruation and so on. In our previous studies, we have found that spatholobus suberectus could induce cell apoptosis and arrest cell cycle in vitro. It can also significantly suppress tumor growth in vivo. Through preliminary mechanisms exploration, DNA damage has been demonstrated to be the main function responsible for its anti-tumor effects. However, it remains unknown how the DNA damage was induced by spatholobus suberectus. Our recent studies have demonstrated that spatholobus suberectus could significantly elevate the intracellular reactive oxygen species (ROS) level. We therefore hypothesize that a high level of ROS might be the direct cause of DNA damage and it participates in inducing cell apoptosis and cell cycle arrestion. ROS are constantly generate and eliminate oxygen-containing molecules which include superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (•OH) and nitric oxide (NO).. ROS exist in all biological systems, and play important roles in a variety of normal biochemical functions and abnormal pathological processes. It is widely accepted that an increase in ROS may contribute to carcinogenesis by oxidative DNA modification and that antioxidant is able to prevent humans from getting cancer. However, current studies have yet to find evidence to support this view. In contrast, many studies have demonstrated that an increased intracellular ROS level can induce apoptosis in human cancer cells[9]. These observations indicate that cancer cells may produce lower levels of ROS than normal ones and therefore elevating ROS might become a new strategy against cancer. However, the mechanisms of regulating the ROS level and the process of inducing apoptosis by the high level ROS still remain unclear. Further research is necessary to investigate the ROS signalling pathway in cancer cells. Central Hypothesis: Based on the characteristics of SSD and our preliminary data, we hypothesize that the cancer fighting and metastasis preventing effects of saptholobus suberectus might contribute to the changes of cancer microenvironment and constitute a key factor of such change in up-regualted intracellular ROS, which are related to mitochondrial dysfunction. Furthermore, the high ROS level might have influence on other critical signal molecules involved in hypoxic regualtion (HIF-1), angiogenesis (VEGF) and metastasis (MMPs, etc). Objectives: 1:. To address whether a high level of ROS induces DNA damage and apoptosis 2: To elucidate the mechanism of SSD in inducing a high level of ROS 3: To elucidate the role of a high level of ROS in HIF-1 expression and angiogenesis 4: To elucidate the potential effects of a high level of ROS on cancer metastasis Key References: 1.Fast stats for female breast cancer 2005. Hong Kong cancer registry hospital authority. http:// www3. ha.org.hk/cancereg/eng/breast.pdf 2.Zheng Y, Liu H, Ba YJ, Ma YM, Zhao YY, Five flavono ids from Spa tholobus suberectus. J Chinese Materia Medica 2008;33(2):152-154. 3. Cui YJ, Liu P, Chen RY， Studies on the chemical constituents of Spa tholobus suberectus Dunn.. J Yao Xue Xue Bao. 2002 ;37(10):784-7). 4.Su EY, Chen HS，Clinical Observation on Aplastic Anemia Treated by SSD Composita. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997;17(4):213-5 5.Wang XH, Liu ED, Xu SY，Study antithrombotic effects of Spa tholobus suberectus Academic Periodical of Changchun College of Traditional Chinese Medicine. 2005;21(4):41-43. 6.Tang Y, He W,Wang YZ, Zhang GL , Wang XM1 Studies on the Anti-tumor Activity of the Extract of Spatholobus suberctus Dunn.Chinese Journal of Experimental Traditional Medical Formulae . 2007;13(2) :51-54. 7.In - Cheol kang, Seung - Ae kim, Cyu Yong Song. Effects of the ethyl acetate fraction of Spatholobi caulis on tumour cell aggregation and migration [ J ]. Phytotherapy Research, 2003,17 (2) : 163 – 167. 8. Tang Y, Wang XM, He W, Wang YZ, Li CM,Ge YJ. Studies on the Anti-tumor Activity of the Extract of Spatholobus suberctus Dunn in vitro. Chinese Journal of Basic Medicine in Traditional Chinese Medicine. 20071;13(.4):306-308. 9.Lu F Reactive oxygen species in cancer, too much or too little? Med Hypotheses. 2007;69(6):1293-8.

Project Title:	Exploration of active components from Spatholobus suberectus for treating breast cancer and preventing its recurrence and metastasis
Investigator(s):	Chen J, Guan XY, Shen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	02/2010

Abstract:

Globally, breast cancer is the first killer among women malignancy diseases. In Hong Kong, the rapid increase of breast cancer cases in recent years and the increasing trend of breast cancer affecting younger women have made it an even more worrying issue. With breast cancer the most common cancer form women in Hong Kong face, there are about 2000 new breast cancer cases in Hong Kong annually. Metastasis and recurrence often constitute the final and fatal step in cancer development. It is the leading cause of breast cancer death. So far there has been no effective therapeutic treatment. Traditional Chinese Medicine (TCM) has offered an alternative view on cancer, especially on the residual cancer cells after surgery, radiation therapy or chemotherapy. Now, more and more patients with breast cancer tend to seek treatment from traditional Chinese medicine (TCM) as the core programme or as an adjuvant for healing or prevention of metastasis. Many studies have found TCM prescription compound or single herb can significantly help inhibit cancer invasiveness and metastasis [1-3]. . Jixueteng((雞血藤), Spatholobus suberectus Dunn (SSD) has been found to be an effective herb for treating breast cancer., SSD is a traditional Chinese medicinal herb which has the characteristic functions of promoting blood circulation and removing blood stasis. SSD has been widely used in cliniccal practice for the treatment of blood stasis related diseases such as rheumatoid, paralysis, irregular menstruation and so on. I have also been using SSD for many years in my clinical practice to treat breast cancer and prevent its metastasis. The herb has been proved effective without undesirable side effects observed during therapy cycles. [4-6, and preliminary data]. Through laboratory research, we have further discovered that the herb can help induce cancer cell apoptosis and arrest cell cycle at G1 phase. Moreover, our breast cancer animal model has demonstrated that SSD can inhibit cancer growth in vivo with an inhibitory ratio of 49.93%. However, the active compounds in the herb is still unclear. In order to further develop the new cancer fighting agents from SSD and clarify its potential mechanisms, this project has included three key areas of study: firstly, to identify the active fraction or compounds in the SSD herb; secondly, to identify the structure of the active compounds and the characteristics of the active fraction; and thirdly, to explore the mechanism of these active compounds. This study therefore has following specific aims: 1. To extract and isolate the chemical compounds and fraction from SSD and identify its active compounds or fraction by cell culture and transwell model. The chemical compounds or bioactive compound will be extracted and separated from SSD by using system separate methods; 2. To identify the structure of chemical components. The structure of active compounds will be analyzed by modern spectroscopic techniques; 3. To explore the relationship between these compound structures and SSD functions. We aim to explore the mechanism of these compounds, compare the different mechanisms or pathways of these compounds and SSD draft extraction. Key References: 1.Fleischauer AT, Simonsen N, Arab L. Antioxidant supplements and risk of breast cancer recurrence and breast cacner-related mortality among postmenopausal women. Nutrition and cancer –an international journal, 2003, 46(1): 15-22. 2.Hirvonen T, Mennen Li, De Bree A, et al. Consumption of antioxidant-rich beverages and risk for breast cancer in French women. Annals of epideminology, 2006, 16(7): 503-508. 3.Uraiwan K, Pornchai O, Kannika J, et al. The anticancer effects of Thai medical plants containing antioxidant phenolics on breast cancer cells. Acta pharmacologica sinica, 2006, 27: 319-320. 4.Wings T.Y. Loo, J.P. Chen,*, Louis W.C. Chow, Jeffrey W.K. Chou. Effects of Shugansanjie Tang on matrix metalloproteinases 1, 3 and 9 and Telomerase reverse transcriptase expression in human breast cells in vitro, Biomedicine et Pharmacotherapy, 2007; 61(9):601-5. 5..In - Cheol kang, Seung - Ae kim, Cyu Yong Song. Effects of the ethyl acetate fraction of Spatholobi caulis on tumour cell aggregation and migration [ J ]. Phytotherapy Research, 2003,17 (2) : 163 – 167. 6.Tang Y, Wang XM, He W, Wang YZ, Li CM,Ge YJ. Studies on the Anti-tumor Activity of the Extract of Spatholobus suberctus Dunn in vitro. Chinese Journal of Basic Medicine in Traditional Chinese Medicine. 20071;13(.4):306-308.

List of Research Outputs

Lin X., Sze C.W., Tong Y., Zhang Z., Feng Y., Chen J., Ng T.B., Lin X., Shaw P.C. and Zhang Y., Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren’s Syndrome, Journal of Complementary and Integrative Medicine . 2010, in press.

Lu J., Wang D., Maio A., yang D. and Chen J., HPLC-DAD-MS/MS analysis of purine alkaloids and tea polyphenols in Young leaves of Yinghong 1 Yinghong 9 and Qimen cultivars., Journal Scientiarum Naturalium Universitatis Sun Yatseni, Guangzhou, 2009, 72-75.

Mao W.W., Wang T.T., Zeng H.P., Wang Z., Chen J. and Shen J., Synthesis and evaluation of novel substituted 5-hydroxycoumarin and pyranocoumarin derivatives exhibiting significant antiproliferative activity against breast cancer cell lines , Bioorganic & Medicinal Chemistry Letters. 2009, 19: 4570-4573.

Wang Z., Guan X.Y. and Chen J., Anti-tumor effects and mechanisms of Spatholobus suberectus water extracts in vitro and in vivo., HK, 2009, 98.

Wang Z., Loo T.Y., Wang D., Cheng Y., Guan X.Y. and Chen J., Spatholobus suberectus, a potential Chinese herb for cancer treatment, In: OOTR the 6th Annual Conference, OOTR the 6th Annual Conference. Kyoto, Japan, 2010.

Yang X., Huang S., Chen J., Zhang Z., Deng G., Zheng H., Zhu X.Q. and Lu F., Evaluation of the adjuvant properties of Astragalus membranaceus and Scutellaria baicalensis GEORGI in the immune protection induced by UV-attenuated Toxoplasma gondii in mouse models, Vaccine. 2010, 28: 737-43.

li J., Guo Z., Jiang L., yang D., Chen J. and Wang D., 大孔吸附树脂纯化岩黄连总生物碱的研究, 中国医药工业杂志, GZ, 2009, 750-754.

Researcher : Chen RQ

List of Research Outputs

Chen R.Q., Validation of Chinese Medicine syndrome theory with a four-step approach, In: Academic Department of World Federation of Chinese Medicine Society, The 6th International Congress on Chinese Medicine, Melbourne, 2009.. 2009.

Chen R.Q., Davis S.R., Wong C.M. and Lam T.H., Validity and cultural equivalence of the standard Greene Climacteric Scale in Hong Kong, In: Isaac Schiff, MD Editor-in-Chief, Menopause Menopause - The Journal of The North American Menopause Society, Menopause - The Journal of The North American Menopause Society. Lippincott Williams & Wilkins, 2010, 17(3):630-635.

Chen R.Q., 中醫問診客觀化的探討及其在中醫教學中應用的展望, 第二屆海峽兩岸中醫藥教育與傳承與發展論壇 -- 中醫藥教育高峰論壇, 中國上海, 2010.

Chen R.Q., 從溫病學說探討中老年病症的中醫治療原則, 香港中醫師公會, 香港, 2010.

Chen R.Q., 中醫預防和治療中年男女常見的健康問題, 香港大學中醫藥學院中央圖書館健康講座, 2009.

Researcher : Chen X

List of Research Outputs

Feng Y., Chen X., Wang N. and Shen J., Current Progress on Medicinal Plants and their Biological Properties in Contemporary China, In: Govil J.N. , Recent Progress in Medicinal Plants Vol. 28: Ethnomedicine: Source & Mechanism-II. Houston, USA, Studium Press LLC, 2009, 28: 529-588.

Zheng G., Li Y., Gu Y., Chen X., Zhou Y., Zhao S. and Shen J., Beyond Water Channel: Aquaporin-4 in Adult Neurogenesis., Neurochemistry International. 2010, 56(5): 651-654.

Researcher : Chu OM

List of Research Outputs

Chu O.M., 中醫藥對鼻咽癌電療.化療後毒副反應的康復治療的探討, 全國中華醫學會耳鼻咽喉科分會論文集, 2009.

Chu O.M., <<中醫藥對鼻咽癌電療、化療後毒副反應康復治療的探討>>, 全國喉癌、下咽癌學術研討會, 2009.

Chu O.M., <<中醫藥對鼻咽癌電療、化療後毒副作用的康復治療探討>>, 全國中華醫學會鼻咽癌、下咽癌學術研討會, 2009.

Researcher : Chu SME

List of Research Outputs

Chu S.M.E., Sze C.W. and Tong Y., Modulation of MMP2 and VEGF expression by Chinese medicine decoction TXL in human colorectal cancer cells, International Conference on Traditional Medicine 2009 – Evaluation on the efficacy, safety and quality control of Traditional medicine, Guangzhou, China. 2009, pp96.

Sze C.W., Chu S.M.E., Wong K.L., Liu Q., Yow C.M.N., Liu W.K., Ng T.B. and Tong Y., Anti-Cancer Effect of Tian Xian Liquid, a Chinese Medicine Formula, in Human Colon Carcinoma HT29, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Tong Y., Yow C.M.N., Liu W.K., Ng T.B., Liu Q. and Chu S.M.E., Regulation of p21, MMP-1 and MDR-1 expression in Human colon carcinoma HT29 by Tian Xian Liquid, a Chinese Medicine Formula, in vitro and in vivo, The 7th Annual Congress of IDDST 2009, Shanghai, China. 2009.

Sze C.W., Wong K.L., Chu S.M.E., Zhong L. and Tong Y., Synergistic Effect of Six Estrogenic Compounds isolated from Erxian Decoction for Relieving Menopausal Syndrome, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Researcher : Deng R

List of Research Outputs

Deng R., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui Buxue Tang (DBT) and its major components on hematopoiesis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Researcher : Feng Y

Project Title:	Mechanism involved in inhibition of tumor cell invasion by berberine derived from Coptis
Investigator(s):	Feng Y, Ching YP, Sze CW, Tong Y, Tsao GSW
Department:	School of Chinese Medicine
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2008

Abstract:

(1) To examine if inhibition of RhoGTPase is involved in mediating inhibition of NF-kappaB signaling pathway and cyclin D1 by berberine; (2) To examine the effects of berberine to inhibit Rho-family GTPase and cell motility by live cell imaging; (3) To determine the effective dosages of berberine to inhibit above intracellular signaling and anti-invasion.

Project Title:	The effects of berberine and its mechanism on angiogenesis in hepatocellular carcinoma in vitro and in vivo systems
Investigator(s):	Feng Y, Tong Y, Tsao GSW
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009

Abstract:

We and others have demonstrated that Coptis (huanglian 黄连 in Chinese) and its major active compound, berberine, possess anti-inflammatory and anti-cancer properties. Previous studies, largely in in vitro cancer cell systems, showed that berberine has broad spectrum of anti-cancer activities and multiple cellular signaling pathways are involved. In our preliminary studies, berberine could also inhibit proliferation of hepatocellular carcinoma (HCC) cells in vitro. Downregulation of Id1 and EGFR expression by berberine was also observed. Our previous studies showed that Id1 induces cell proliferation and activate angiogenesis. Other studies have also showed that activation of EGFR signaling could induce VEGF expression which is a potent factor to stimulate angiogenesis. Angiogenesis activation is crucial for growth of cancer cells in vivo to combat hypoxia. Overexpression of Id-1 promotes angiogenesis in HCC in vivo and HIF1 activation is involved. HIF1 activation could up regulate VEGF expression to stimulate angiogenesis. Another study has showed that berberine could inhibit HIF1- activation by enhancing its proteolytic degradation. The ability of berberine to inhibit multiple pathways of angiogenesis has prompted us to investigate if berberine may inhibit the growth of HCC cells in vivo model. In a pilot study, we have examined the effect of berberine on the growth of HCC cells orthotropically implanted in the liver of athymic nude mice. Oral administration of berberine was able to inhibit the growth of HCC cells in vivo. This has prompted us to carry out a more comprehensive study to investigate the therapeutic potential of berberine in treatment of HCC. We therefore hypothesized that berberine could inhibit angiogenesis in HCC cell lines and animal model may down-regulate Id-1 through VEGF-dependent and/or EGFR-dependent pathway(s). In this study, we propose to examine expression of Id-1 on angiogenesis in HCC cell lines and animal model by berberine derived from Coptis. The relationship between VEGF-dependent and/or EGFR-dependent pathway(s) on angiogenesis in HCC cell lines will be examined. Above target genes treated by berberine in HCC cell lines and HCC cell lines bearing nude mice will also be examined using molecular biotechnologies. Specific objects are: 1. To examine if berberine may inhibit the growth of hepatcellular carcinoma via anti-angiogenesis in an in vivo orthotropic HCC animal model. 2. To investigate the involvement of VEGF, HIF-1alpha and Id-1 in the anti-angiogenesis effect of berberine on HCC cell lines under hypoxic condition.

Project Title:	8th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM) Inhibitory action of berberine on cell migration and motility in cancer cell lines may via the suppression of Rho GTPase signaling
Investigator(s):	Feng Y
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

Project Title:	The role of autophagy and mitochondrial apoptosis in berberine induced hepatocellular caricinoma cell death and its underlying mechanism
Investigator(s):	Feng Y, Tsao GSW
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	09/2009

Abstract:

We and others have demonstrated that Coptis (huanglian 黄连 in Chinese) and its major active compound, berberine, possess anti-inflammatory and anti-cancer properties. Previous studies, largely in in vitro cancer cell systems, showed that berberine has broad spectrum of anti-cancer activities and multiple cellular signaling pathways are involved. In our preliminary studies, berberine could also inhibit proliferation of hepatocellular carcinoma (HCC) cells in vitro.. This has prompted us to carry out a more comprehensive study to investigate the underlying mechanism of berberine-induced cancer cell death. Several types of cell death have been classified and defined by the Nomenclature Committee on Cell Death (NCCD), including apoptotic and autophagic cell death. These two types of cell death, also known as Type I and Type II Programmed Cell Death (PCD) respectively, differ in morphological features and signal transduction but share the same result on cell death. Apoptosis is considered as a conventional type of cell death whereas autophagic cell death is simply defined as cell death with autophagy, which process is also thought to be one of mechanisms for cell survival. Recently, extensive studies report apoptosis and autopahgy are both involved in chemotherapeutic agents-induced cancer cell death, suggesting that apoptosis and autophagy may be important for illustrating the underlying mechanism for novel therapeutic agents. In our pilot study, we have found that berberine can dose-dependently induce autophagy in hepatocellular carcinoma cells, HepG2 and MHCC-97L, and also we observed the berberine-induced apoptosis in HepG2 and MHCC-97L, which was characterized by annexin V generation in cell membrane. A rapid decrease in mitochondrial membrane potential in berberine treated HepG2 and MHCC-97L cells was observed in our previous study. We therefore hypothesized that berberine could suppress the hepatocellular carcinoma via inducing autopahgic cell death and mitochondrial apoptosis in hepatoma cells. In this study, we propose to examine several signal pathways which may involve in the berberine induced autophagy and apoptosis in hepatocellular carcinoma cells. To major signal pathways, the PI3K/Akt/mTOR and PI3KC3/Beclin-1, will be evaluated to elucidate their role in berberine induced autophagic cell death and the mitochondrial aopotosis related signal transduction, the Bcl/capspase scaffold, will be also studied. Specific objects are: 1. To examine the autophagic cell death and mitochondrial apoptosis induced berberine in various hepatocellular carcinoma cell lines with different reliable methods. 2. To examine the inhibiton of PI3KC1/Akt/mTOR pathway and activation of PI3KC3/Beclin-1 pahtway in berberine induced autphagy in hepatocellular carcinoma cells. 3. To determine the role of Bax/caspase signal activation and Cytochrome C release in berberien induced hepatic cancer cells’ apoptosis.

List of Research Outputs

Feng Y., Liu K.J., Wang J., Shen J., Zhang Y., Rong J., Tong Y., Chan K.S. and Wong B.W., Basic and clinical Toxicology of Chinese Medicines, 基礎和臨床中藥毒理學, Hong Kong, Commercial Press (HK) Ltd., 2009, p394.

Feng Y., Cheung K.F., Wang N., Liu P., Nagamatsu T. and Tong Y., Chinese medicines as a resource for liver fibrosis treatment , In: Hin Wing Yeung, Chinese Medicine . Macau, International association of Chinese Medicine, 2009, 4(1): 16.

Feng Y., Chen X., Wang N. and Shen J., Current Progress on Medicinal Plants and their Biological Properties in Contemporary China, In: Govil J.N. , Recent Progress in Medicinal Plants Vol. 28: Ethnomedicine: Source & Mechanism-II. Houston, USA, Studium Press LLC, 2009, 28: 529-588.

Feng Y., Editorial Board member from January 2010 to December 2011, In: Yeung Hin Win, Chinese Medicine. BioMed Central, 2010.

Feng Y., Hong Kong Chinese Medical Journal, In: 陈抗生, 邓春, 温桂荣, 赵中正, 冯奕斌, 吴俊来, 王如跃, 黄约爱,, Hong Kong Chinese Medical Journal. 香港中医杂志, Hong Kong, 香港中医杂志出版社, 2010.

Feng Y., Recent Patents on Recent Patents on Food, Nutrition & Agriculture , In: Yibin Feng , Journal editor. USA, BENTHAM SCIENCE PUBLISHERS LTD., 2009.

Feng Y., Toxicology of Chinese Medicines and its application in clinical practice. , Seminar for Hong Kong Registered Chinese Medicine Practitioner Association. Hong Kong. . 2010.

Feng Y., 熊膽替代品的研究進展, 中藥與資源保護及健康產業發展國際論壇. 北京., 2009.

Lin X., Sze C.W., Tong Y., Zhang Z., Feng Y., Chen J., Ng T.B., Lin X., Shaw P.C. and Zhang Y., Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren’s Syndrome, Journal of Complementary and Integrative Medicine . 2010, in press.

Tang J., Feng Y., Tsao G.S.W., Wang N., Curtain R.P. and Wang Y., Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations. , Journal of Ethnopharmacology. . 2009, 126: 5-17.

Tsang C.M., Lau P.W.E., Di K., Cheung P.P.Y., Hau P.M., Ching Y.P., Wong Y.C., Cheung A., Wan T.S.K., Tong Y., Tsao G.S.W. and Feng Y., Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells, International Journal of Molecular Medicine. 2009, 24: 131-138.

Zhang Y., Feng Y., Sze C.W., Tong Y., Mo F., Yiu Y.M., Xiao L., Wong JH Y., Ng T.B., Shaw P.C., Xiao Y. and Li Z.M., Dendrobium candidum Extract Increases the Expression of Aquaporin 5 in Labial Glands from Patients with Sjögren’s Syndrome. , In: Lin Xiao, Tzi Bun Ng, Yi-Bin Feng, Tong Yao, Jack Ho Wong, Ren-Min Yao, Lei Li, Fei-Zhi Mo, Yin Xiao, Pang-Chui Shaw, Ze-Min Li, Stephen Cho Wing Sze, Kalin Yanbo Zhang, Phytomedicine, Accepted. 2010.

Zhang Y., Sze C.W., Tong Y., Feng Y., Ng T.B., Shaw P.C., Xiao L. and Xiao K., Protective effect of Dendrobium officinale polysaccharides on experimental Sjögren’s Syndrome, In: Xiang Lin, Stephen Cho-Wing Sze, Yao Tong, Zhangjin Zhang, Yibin Feng, Jian ping Chen, Tzi Bun Ng, Xiao Lin, PC Shaw, and Kalin Yanbo Zhang., Journal of Complementary and Integrative Medicine. 2010, 17: 1-18.

Researcher : Gu Y

List of Research Outputs

Zheng G., Li Y., Gu Y., Chen X., Zhou Y., Zhao S. and Shen J., Beyond Water Channel: Aquaporin-4 in Adult Neurogenesis., Neurochemistry International. 2010, 56(5): 651-654.

Researcher : Hu KY

Project Title:	Quality Assessment of Chinese Medicine Formula, Erxian Decoction, by high-performance liquid chromatography coupled with diode array detector
Investigator(s):	Hu KY, Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	10/2008

Abstract:

Chinese medicine formulas are “holistic medicine”, which are tailor-made for specific conditions and exert multiple effects on human body, but this raises questions over exactly which chemical is doing what, and also brings problems with maintaining quality control over the drugs being used. Besides, most of Chinese Medicines are lack of quality standards and difficult to be evaluated [1, 2]. Due to the complexity of chemical constituents contained in Chinese medicine formula, it's very difficult to address the essence of them and so as a result, it is very difficult to properly introduce Chinese medicine to the world. However, it possesses high-reputational clinical efficacy, such as Erxian Decoction (EXD). Erxian Decoction, comprising six Chinese herbs, i.e. (1) Rhizome Curliginis: (2) Herba Epimedii: (3) Radix Morindae Officinalis: (4) Radix Anemarrhenae: (5) Cortex Phellodendri: (6) Radix Angelicae sinensis, which has been used to relive menopausal syndrome for 50 years. Experimental studies have revealed that EXD has multiple pharmacological actions on such multiple targets as hypothalamus-pituitary-target glad axis, immune function and free radical metabolism, etc. As EXD formula is composed six Chinese herbs, quality control is an important issue in the pharmacological study of the formula. To achieve this goal, we made the formula with restrict pharmaceutical procedures and will perform comprehensive chromatographic fingerprints with HPLC. Although the quality control data provided by this study and the previous study [3] cannot solve the problem over which chemical is doing what, we will develop relative analytic protocols and a standard chromatographic fingerprint to at least ensure that our latent pharmacological investigation of EXD will not be influenced by any unknown variability or instability found in the composition of the active constituents. A chromatographic fingerprint for the Chinese Medicine is an average chromatographic pattern of all the components rather than a chromatogram of an individual components [4~6]. Actually, fingerprint analysis has been widely used for the quality assessment of Chinese Medicine products. Some assessment has been conducted by studying the similarities between the chromatograms of the samples and their standard components or the batch to batch consistency of Chinese Medicine products [7]. Phytochemical investigations [8-22] demonstrated that the eight categories of bioactive compounds in these six composition herbs are phenols, phenolic acids, flavones, alkaloids, saponins, quinoids, pyrrones and polysaccharide etc. However, the special study of the whole profile constituents of EXD has not been reported yet. In our pilot study, 20 compounds have been identified from EXD based on their physic-chemical data and spectral analysis. In this study, a simple, rapid, reliable method for quality assessment of EXD and its standard chromatographic fingerprint will be developed. Objectives: 1. Optimization of EXD preparation and chromatographic conditions will be conducted. 2. The validation of method will be evaluated. 3. Standard fingerprint will be established and analyzed. References: 1. Y. H. Liu, Y. L. Sun. World Patent Inf. 26(2004) 91-96. 2. R. Yuan, Y. Lin. Pharmacol. Ther. 86 (2000) 191-198. 3. Chew T: Evaluation of the total flavonoid and saponins in er xian tang using uv/vis spectrophotometery. Medical Journal of National Defending Forces in Southwest China 2005;6 (7):189 - 190. 4. State Drug Administration of China. Chin Tradit. Pat. Med. 22 (2000) 671-675. 5. E. S. Ong. J. Sep. Scin. 25 (2002) 825-831. 6. P. S. Xie. China J. Chin. Mater Med. 10 (2001) 653-655. 7. Y. X. Zhou. Technology of TCM fingerprints, Chemical Industry Press, Beijing. (2002) 3-4. 8. R. S. Xu. Phytochemistry. 31 (1992) 2455. 9. R. S. Xu. Planta Med. 58 (1992) 208. 10. J. X. Zhang, Z. X. Su, S. J. Liu. Journal of Sichuan Teachers Colledge (Natural Science). 24 (2003) 160-166. (XLP) 11. X. J. Chen, H. Ji, Q. W. Zhang, P. F. Tu, Y. T. Wang, B. L. Guo, S. P. Li. Journal of Pharmaceutical and Biomedical Analysis. 46 (2008) 226-135. 12. Y. Zhao, S. H. Guo. Strait Pharmaceutical Journal (Haixia yaoxue). 19 (2007) 59-60. 13. H. L. Liao, W. X. Wang, F. S. Zhao, et al. Journal of Pharmaceutical Practice. 23 (2005) 12-14. 14. Yuji Ito, Fusayoshi Hirayama, Keiichi Suto, et al. Phytochemistry. 27 (1988) 911. 15. M. Mizuno, N. Sakakibara, S. Hanioka, et al. Phytochemistry. 27 (1988) 3641. 16. S. S. Kang, Y. J. Kang, M. W. Lee. J. Nat. Prod. 54 (1991) 542. 17. B. L. Guo, P. G. Xiao, The Research and Development of Natural Product. 8 (1996) 74. 18. X. S. Jia, J. Q. Wu. Chinese Traditional Patent Medicine. 23 (1998) 162, 737 19. X. S. Jia, J. Q. Wu, Q. Mao. Chinese Pharmaceutical Journal (Zhong guo yao xue zazhi). 34 (1999) 442. 20. C. X. Chen, W. Ni, W. L. Mei. Acta Botanic Yunnanica. 21 (1999) 521-524. 21. N. Li, Y. X. Zhao, A. Q. Jia, et al. Natural Product Research and Development. 15 (2003) 208-211. 22. V. Josep, R. Tristan, L. Fabienne, L. Veronique, et al. Fitoterapia. 77 (2006) 416-419.

Project Title:	The 6th World Congress of Chinese Medicine 2009 The International Spread Characteristics of Traditional Chinese Medicine
Investigator(s):	Hu KY
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	12/2009

Abstract:

N/A

List of Research Outputs

Hu K.Y., Wang Y.T., Sze S.C., Tsang K.W., Wong H.K., Liu Q., Zhong L. and Tong Y., Identification of the major chemical constituents and their metabolites in rat plasma and various organs after oral administration of effective Erxian Decoction (EXD) fraction by liquid chromatography-mass spectrometry., Biomed Chromatogr. 2010 May;24(5):. 2010, 479-89.

Researcher : Jiang J

List of Research Outputs

Tu T.Z., Shen J. and Jiang J., Studies on constituents from the roots of astrgalus membranaceus (Fisch.) Bge. Hisao., West China Journal of Pharmaceutical Sciences. 2009, 24(5): 27-29.

Researcher : Lam SS

List of Research Outputs

Lam S.S., Chinese Chiropractic Practitioner , 中國整脊師, China Association of Chinese Medicine . 中華中醫藥學會, 2010.

Lam S.S., Chinese Chiropractic Practitioner Teaching License, 中國整脊教師証, China Association of Chinese Medicine. 中華中醫學會, , 2010.

Lam S.S., How to keep body healthily in one day, 一天之中如何養生, Hong Kong Healthy Ambassador Association. 香港健康大使協會, 2009.

Lam S.S., Li L., Chu V.L.Y. and Wong V.C.N., Pilot project of integratin of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Wong V.C.N., Li L., Lam S.S., Wong C.L. and Chu V.L.Y., Pilot project of integration of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, 19th World Congress of Neurology, Bangkok, Thailand, 24-30 October 2009.

Researcher : Lau ASY

Project Title:	Cytokines, Signaling & Diseases 2003 The Role of Protein Kinase PKR in the Induction of Cytokine Expression by Bacillus Calmette Guerin Through NF-kappaB
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2003

Abstract:

N/A

Project Title:	Cytokine Dysregulation and Virus-Induced Cell Death in Avian Influenza Virus Infections
Investigator(s):	Lau ASY, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2005

Abstract:

Objectives: In this project, we will use H9N2 as prototypes to examine the cellular effects of TNF and IFN induction by avian influenza viruses. We will delineate whether there is differential induction of cytotoxicity by the avian viruses from the human ones. We will also examine the consequences of simultaneous induction of TNF and IFN on cell survival and expression of apoptotic genes. Our Specific Aims are 1) We will delineate whether there is a differential induction of cytotoxicity by the avian viruses (H9N2) compared to the human ones (H1N1 or H3N2). 2) We will examine the consequences of simultaneous induction of TNF and IFN on cell survival and expression of apoptotic genes. Background Influenza A virus infects a wide range of species, including poultry, swine, horses, seals and humans. Of the 15 hemagglutinins (HA) subtypes of influenza A, only H1, H2 and H3 had been known to cause significant morbidity and mortality in humans (1-3). The 1997 outbreak of avian influenza H5N1/97 in Hong Kong was the first documented cases of primary pneumonia rapidly progressing to adult respiratory distress syndrome and multiple organ dysfunctions in humans. In light of the high mortality of H5N1/97 infection, it would be desirable to understand the pathogenesis in order to enhance the development of novel therapy. Influenza A viruses are known to replicate in epithelial cells and leukocytes, resulting in induction of cytokines(4). During influenza virus infection, a multiple array of cytokines, including chemokines (Rantes, MIP-1), and interferons (IFN-α and –β), is induced (5,6). The biological actions of IFNs are mediated by multiple pathways resulting in mRNA degradation by ribonuclease L and inhibition of translation by a dsRNA-activated kinase, PKR. PKR is inducible by IFN, TNF-α, and dsRNA [viral RNA analogue] (7,8). We have previously shown that PKR mediates the cytotoxicity of TNF-α in cells of diverse tissue origins including fibroblasts and monocytes (9). It has been proposed that PKR serves as a common pattern-recognition molecule responsible for mediating these virus-induced antiviral effects (8-11). We previously demonstrated PKR serves multiple roles in the cell including the mediation of TNF-induced cytotoxicity, and induction of apoptotic gene p53 and IFN expression (9, 12-16). The signal transduction role of PKR is further confirmed by its effects on the induction of Fas and NF-kB, following TNF-α or endotoxin treatment. TNF-α is a potent, cytotoxic molecule induced in response to invasion by infectious pathogens or cancer cells. Elevated levels of TNF-α in the serum have been correlated to and predictive of morbidity and mortality in patients with meningococcemia. To unravel the pathogenesis of fulminant H5N1/97 disease in humans, we have developed a H5N1/97-blood macrophage (BMac) model to examine the interactions of H5N1/97-encoded genes and cellular factors which may result in immune dysregulation (17: Peiris as PI and Lau as co-I). Using our model, we have previously demonstrated that H5N1/97 induced dramatically higher levels of cytokine expression when compared to those elicited by “conventional” human H1N1 or H3N2 viruses (17). TNF-α protein levels in H5N1/97-infected macrophage culture supernatants were comparable to those induced by stimulation with E. coli endotoxin, and much higher than those in H1N1 or H3N2 infections (17). Recently, we further demonstrated that the TNF induction and its cytotoxicity are mediated, at least in part, by mitogen-activated protein (MAP) kinases including p38 and ERK (18: J Virol 2005, accepted May 2005, Lau as PI). Induction of proinflammatory cytokines is a major defense mechanism of the host to mobilize the immune system and to combat the invading pathogen. We hypothesize the high mortality associated with H5N1/97 infections may be due to an uncontrolled induction of IFN and TNF, consequent to virus interactions with cellular signaling pathways, leading to dysregulated immune response and differential effects on cell death.

Project Title:	HIV dysregulation of the toll-like receptor system - implications for pathogenesis
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2006

Abstract:

To investigate the effects of Tat on the expression of TLR2 in primary blood monocytes and identify whether there are other TLRs inducible by Tat; to identify the kinases and signaling pathways operative in Tat induction of TLR2 and its related receptors; to investigate whether the enhanced TLR plays a role in infection by HSV and the level of viral replication in monocytes; to examine the effects of Tat on astrocytic cells including TLR expression and infection by HSV.

Project Title:	HIV suppression of the interferon-gamma signaling pathway and autophagy: implications for mycobacterial pathogenesis
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2007

Abstract:

To confirm the mechanism of HIV suppression of the IFN-gamma induced signaling system; to examine whether SOCS genes play a role in HIV perturbation of Jak/STAT1 activation; to investigate whether HIV and its proteins suppress IFN-gamma-induced autophagy activities against mycobacteria; to identify potential IFN-gamma-induced autophagy genes that are suppressed by HIV.

Project Title:	Immunomodulatory effects of Panax ginseng on Human Monocytic Cells
Investigator(s):	Lau ASY, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2007

Abstract:

Objectives: In this project, we will perform microarray analysis to investigate the gene expression profile of human monocytic cells after Panax ginseng treatment and the mechanisms of immunomodulatory effects of Panax ginseng on inflammation. Our Specific Aims are: 1) We will investigate the gene expression profile of human monocytic cells with Panax ginseng treatment during inflammation. 2) We will delineate the mechanisms of the immunomodulatory effects of Panax ginseng on inflammation. Background Traditional Chinese Medicine (TCM) has long been recognized as a potential alternative remedy to treat chronic diseases and microbial infections by modulating the host’s immune system (1, 2). Panax ginseng, also known as Asian ginseng, is one of the most commonly used herbal medicines in China, Asia and Western countries (3). Ginseng contains multiple active components with potential beneficial effects on the central nervous system, neuroendocrine function, immune and cardiovascular systems in humans (3, 4). However, the precise actions of ginseng in humans remain to be investigated. Cytokines are potent pleiotropic polypeptides that play critical roles in inflammatory responses and are capable of orchestrating the complicated network of innate and adaptive immune responses following microbial infection. Production of cytokines in the host is tightly regulated by different mechanisms to maintain the immunologic homeostasis. Recent studies including ours have shown that an imbalanced production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF) and interleukin-6 (IL-6), and anti-inflammatory cytokines, including IL-10, is implicated in the pathogenesis of diseases (5, 6, 7, 8). TNF is a major mediator of apoptosis and inflammation and it has been shown to have a pivotal role in the pathogenesis of a wide variety of human diseases. TNF, upon binding to its cognate receptor (TNF receptor-1), recruits several intracellular adaptor proteins including TRADD, TRAF2, RIP, and FADD leading to activation of MAP kinase signaling cascades and their associated transcription factors NF-kB and AP-1(9, 10). Studies of the polysaccharide extracts of ginseng and ginsenosides have shown that ginseng modulates the inflammatory response by enhancing the phagocytic activity of macrophages and blocking the activation of specific transcriptions such as NF-kB and AP-1 (11, 12). The immunomodulatory and anti-inflammatory properties of ginseng have been attributed to its effects in regulating phagocytic activities and cytokine production of immune cells (13, 14, 15, 16). We hypothesize that ginseng modulates the inflammatory responses via regulation of specific signaling kinase activities that lead to cytokine expression in immune cells. In this project, we will confirm our pilot results that ginseng regulates the expression of several proinflammatory cytokines. Further, we will examine the gene expression profile of monocytic cells treated with ginseng and its component molecules, ginsenosides. Reference: 1. Fan TP et al. Trends Pharm Sci 2006; 27: 297-309 2. Tan BK and Vanitha J. Curr Med Chem 2004; 11: 1423-30 3. Gillis CN. Biochemical Pharmacology 1997; 54: 1-8 4. Attele AS et al. Biochemical Pharmacology 1999; 58: 1685-93 5. McInnes IB and Schett G. Nat Rev Immunol 2007; 7: 429-42 6. Lin WW and Karin M. J Clin Invest 2007; 117: 1175-83 7. Lee DCW, Lau AS et al. J Virol 2005; 79: 10147-54. 8. A) Li JCB, Lau AS et al. FEBS Lett 2005; 579: 3055-62. B) Cheung BKW, Lau AS et al. J Immunol. 2005;175:7218-25. 9. Chen G and Goeddel DV. Science. 2002; 296:1634-5 10. Dempsey PW et al. Cytokine Growth Factor Rev. 2003;14: 193-209 11. Ahn JY et al. Eur J Immunol. 2006; 36: 37-45 12. Park SA etal. Ann N Y Acad Sci. 2007; 1095: 545-53. 13. Nakaya TA et al. J Interferon Cytokine Res 2004; 24: 93-100 14. Shin JY et al. Immunopharmacol Immunotoxicol 2002; 24: 469-82 15. Mizuno M et al. Biochem Biophys Res Commun 1994; 200: 1672-8 16. Sonoda Y. Immunopharmacology 1998; 38: 287-94

Project Title:	Roles of Autophagy in Host Immune Response to Influenza Virus Infection
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2008

Abstract:

Following virus infection, host cells mount different antiviral responses to control the invasion, and in extreme cases, death of the infected cells. The cell death processes including apoptosis has been postulated to be one of the effective host defense mechanisms for virus invasion (1). Induction of apoptosis results in inhibition of virus replication, limitation of virus dissemination, and minimization of uncontrolled inflammatory responses. Autophagy is a conserved homeostatic process to serve as a cell survival mechanism during starvation (2). The antiviral role of autophagy is strengthened by the involvement of autophagic process in the induction of type I IFNs in virus infection (3). However, viruses such as coronavirus and poliovirus have evolved strategies to divert autophagy to promote their own replication and survival in the autophagic cells (2,4). It is possible that influenza viruses may evade host immunity via prevention of early cell death. To investigate the mechanisms underlying the diversion of cell death processes, we hypothesize that avian influenza viruses divert the cell death pathways from apoptosis, which ultimately involves whole cell death, to that of autophagy, which is a self-sustained process resulting in removal of unwanted subcellular structures, leading to prolonged survival of the avian virus-infected cells. With longer survival of H5N1-infected cells in autophagy instead of apoptosis, there are opportunities for the completion of virus replication and consequent immune dysregulation. Question I. Since we have documented a delayed apoptosis in primary blood macrophages with H5N1 infection, is there an activation of the autophagy process? What is the process of cell death in avian virus-infected cells, compared to human influenza viruses? Aim 1. To examine whether autophagy is activated in the avian and human influenza viruses infected cells, in addition to apoptosis. Question II. Once autophagy is documented, what are the mechansims utilized by the avian and human influenza viruses? What is/are the functional role(s) of autophagy in host’s immune responses? Aim 2. To investigate the mechanisms underlying the activation of autophagy and the role of autophagy involved in the induction of cytokines.

Project Title:	Factors affecting mycobacteria evasion of immunity: effects of HIV on cellular signaling and kinases
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	09/2009

Abstract:

To investigate what are the DUSPs inducible by MAC/BCG to deactivate MAPK activity and suppress cytokine expression; to determine whether HIV proteins are inducers of DUSPs and suppressors of BCG/MAC-induced TNF-alpha expression; to delineate whether HIV induction of DUSPs is associated with enhanced growth of MAC/BCG.

Project Title:	Cellular response to influenza virus infection: effect of autophagy versus apoptosis on virus replication
Investigator(s):	Lau ASY, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	10/2009

Abstract:

To investigate whether autophagy-specific genes are activated in the avian influenza virus-infected cells, in addition to apoptosis; the global gene expression profile related to apoptosis and autophagy in avian influenza virus-infected cells and the crosstalk between apoptosis and autophagy in delzyed onset of death in avian influenza virus-infected cells by using immunomodulators or pharmacological agents.

Project Title:	Mycobacteria Evasion of Immunity: a Potential Role for IL-10 and its consequent Suppression of MHC Antigen Expression
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2009

Abstract:

1) To investigate whether IL-10 induced by BCG or MAC is capable of suppressing IFN-gamma induction of MHC class II antigen expression; 2) To define whether the effects of IL-10 or BCG/MAC on HLA-DRA act through the Jak/Stat pathways; 3) To delineate the detailed mechanisms underlying IL-10 or mycobacteria perturbation of MHC class II antigen processing and expression including the role of cathepsin S and transcription factor CIITA; 4) To utilize IL-17 to reverse the suppressive effects of IL-10 and augment IFN-gamma-induced signal transduction; 5) Significance: Investigating the mechansisms underlying mycobacteria evasion of immunity, we expect to confirm our recent findings that mycobacteria induce the expression of IL-10, which in turn inhibits IFN-gamma signal transduction resulting in the suppression of MHC class II antigen expression and consequent development of cell-mediated immunity. We expect to delineate some of the key mechanisms underlying how mycobacteria and its induced IL-10 perturb IFN-gamma signaling events such as Jak/Stat pathways and processing of MHC-II antigens. Understanding these mechanisms would provide rationales for immunotherapy. For example, we expect to confirm that the regulatory cytokine IL-17 is capable of reversing the effects of IL-10 and augment IFN-gamma induced effects. Thus, defining the mechanisms underlying these microbe-immune cell interactions would provide rationales for designing specific therapeutics to block the activity of IL-10 and to treat MTB/MAC patients with a combination of key immunoregulatory cytokines or drugs.

Project Title:	Tri-Society Annual Conference 2009 MECHANISMS UNDERLYING HIV-1 SUPPRESSION OF IFN-g SIGNALING PATHWAYS: A ROLE FOR TRANSACTIVATOR TAT IN THE INDUCTION OF SOCS-2 IN PRIMARY HUMAN BLOOD MONOCYTES
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

List of Research Outputs

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N., Lai Y.M. and Ng T.B., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis., IEEE PUBLICATION: Biomedical Engineering and Informatics, BMEI 2009. 2009, 1: 47-49.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N. and LAI Y.M., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis, The 2nd International Conference on BioMedical Engineering and Informatics (BMEI'09). 2009.

Researcher : Lau PWE

List of Research Outputs

Tsang C.M., Lau P.W.E., Di K., Cheung P.P.Y., Hau P.M., Ching Y.P., Wong Y.C., Cheung A., Wan T.S.K., Tong Y., Tsao G.S.W. and Feng Y., Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells, International Journal of Molecular Medicine. 2009, 24: 131-138.

Researcher : Lee WS

List of Research Outputs

Shen J., Lee W.S., Li Y. and Fung M.L., INTERACTION OF CAVEOLIN-1, NITRIC OXIDE AND NITRIC OXIDE SYNTHASES IN HYPOXIC HUMAN SK-N-MC NEUROBLASTOMA CELLS AND RAT ISCHEMIC BRAINS, 6th World Congress for Brain Mapping and Image Guided Therapy. Harvard Medical School, Boston, USA, 2009.

Researcher : Li L

Project Title:	Effect of acupuncturing different acupoints at different time on the melatonin level of normal mice
Investigator(s):	Li L
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2008

Abstract:

Using melatonin level as an indicator, this research is to study the relationship between acupoint specificity and circadianl rhythm by observing the different effect of acupuncturing different acupoints on different time under physiological condition, and hence to further study the acupuncture functioning mechanism. Currently there have been extensive domestic and foreign researches done on acupoints. Such researches include studies on acupoints’morphology and structure, its electricity characteristic, its pathological reaction, its close relationship with clinical diagnosis, and also the multidimensional, multi-linkage, multilevel and multi-pathway regulation of the organs and systems of organisms by acupuncturing different acupoints. However, these researches substantiate only the objective existence of acupoints and that there exist regulating functions by acupuncturing these points on organisms. There has been no breakthrough on the fundamental issue of what the actual functioning mechanism is for acupuncturing the acupoints, meridians and collaterals. To deepen the research work has become the key issue of current acupuncture studies. We are of the opinion that changing the previous mentality and methodology of acupuncture researches, and gradually conducting thorough research on acupoints and meridians, are helpful in deepening and widening the studies of acupuncture functioning mechanism. In the research work of acupuncture, focus should be put on multi-factor analysis, impact of physiological rhythm and pathological rhythm on acupuncture effects, and observation of effects on various acupoints under identical experimental conditions. Possible breakthrough in the research of acupuncture functioning mechanism may be achieved via the study of the relative specificity of acupoints under physiological condition, via the study of the impact of physiological rhythm on acupuncture effects, and via the study of the relationship between acupoint specificity and physiological rhythm. OBJECTIVES OF THE RESEARCH: 1. The relative specificity of acupoints; 2. The impact of circadian rhythm on acupuncture effects; and 3. The relationship between acupoint’s relative specificity and time effect. KEY ISSUES INTENDED TO BE SOLVED: 1.Acupoints possess the characteristic of relative specificity; 2.Acupuncturing at different time gives different effects; 3.Time factor has impact on acupoints, causing them to express relative specificity; 4.Acupuncturing on different acupoints and at different time give different effects; and 5.Acupuncture can be used as a modulating factor for circadian rhythm regulating .

List of Research Outputs

Lam S.S., Li L., Chu V.L.Y. and Wong V.C.N., Pilot project of integratin of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Li L., 類風濕關節炎的中醫治療與康復, In: 香港大學中醫藥學院, 中醫防治常見都市病, 2009.

Li L., 釋“得氣”, In: 世界科學技術雜誌社編輯部, 世界科學技術——中醫藥現代化, 北京, 世界科學技術雜誌社, 2010, 12(1): 86~88.

Li L., “經絡系統”芻議, In: 針灸臨床雜誌編輯部, 針灸臨床雜誌, 哈爾濱, 針灸臨床雜誌編輯部, 2010, 26(3): 60~61.

Li L., 《〈難經‧七十五難〉新解》, In: 世界中醫藥學會聯合會，浙江中醫藥大學, 2009首屆中醫經典與臨床國際學術研討會, 杭州, 2009.

Li L., 釋“得氣” （優秀論文獎）, In: 中國科技部、衛生部、廣東省政府、世界衛生組織, 2009傳統醫藥國際科技大會暨博覽會, 廣州, 2009.

Li L. and 羅桂青 , 試論PBL中醫教案的要求及選材, In: 上海中醫藥大學和臺灣中國醫藥大學主辦, 第二屆海峽兩岸中醫藥傳承與發展論壇——中醫藥教育高峰論壇, 上海, 2010.

Li L., 痛症針法——類風濕性關節炎的針灸治療, 香港中國醫藥學會, 香港, 2009.

Li L., 子午流注與骨傷科疾病, 香港中醫骨傷學會, 香港, 2009.

Li L., 類風濕關節炎的中醫治療與康復, 香港大學職員協會, 香港, 2010.

Lin P...F. and Li L., 近10年來針灸治療功能失調性子宮出血的臨床研究綜述, In: 香港註冊中醫學會，中國中醫雜誌社, 香港中醫雜誌, 香港, 香港中醫雜誌出版部, 2009, 4(3): 77~80.

Wong V.C.N., Li L., Lam S.S., Wong C.L. and Chu V.L.Y., Pilot project of integration of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, 19th World Congress of Neurology, Bangkok, Thailand, 24-30 October 2009.

陳雲 , Li L. and 薛凱睿 , “胃腎相關”淺識, In: 香港註冊中醫學會，中國中醫雜誌社, 香港中醫雜誌, 香港, 香港中醫雜誌出版部, 2010, 5(3): 22~23.

霍潤深 and Li L., 不同頭皮針流派刺激區的定位與主治比較, In: 香港註冊中醫學會，中國中醫雜誌社, 香港中醫雜誌, 香港, 香港中醫雜誌出版部, 2009, 4(4): 87~90.

Researcher : Li Y

List of Research Outputs

Shen J. and Li Y., Elucidating Caveolin-1 as a Negative Regulating Protein for Proliferation and Neural Differentiation of Neural stem/progenitor Cells in Post-ischemic Brain with Fluorescent Imaging Technology, 7th Annual World Congress for Brain Mapping and Image Guided Therapy at UNIFORMED SERVICES UNIVERSITY HEALTH SCIENCES (MAY 24-27th 2010). 2010.

Shen J., Lee W.S., Li Y. and Fung M.L., INTERACTION OF CAVEOLIN-1, NITRIC OXIDE AND NITRIC OXIDE SYNTHASES IN HYPOXIC HUMAN SK-N-MC NEUROBLASTOMA CELLS AND RAT ISCHEMIC BRAINS, 6th World Congress for Brain Mapping and Image Guided Therapy. Harvard Medical School, Boston, USA, 2009.

Zheng G., Li Y., Gu Y., Chen X., Zhou Y., Zhao S. and Shen J., Beyond Water Channel: Aquaporin-4 in Adult Neurogenesis., Neurochemistry International. 2010, 56(5): 651-654.

Researcher : Lin X

List of Research Outputs

Jia H.S., Lin X., He Y., Che C.T., Ho Y.S. and Chang R.C.C., The neuroprotection effects of a cognitive-enhancing herb Alpinae Oxyphyllae and its component chrysin on glutamate-induced neurotoxicity, Society for Neuroscience 2009. Program No. 626.16: Poster No. H29.

Lin X., Sze C.W., Tong Y., Zhang Z., Feng Y., Chen J., Ng T.B., Lin X., Shaw P.C. and Zhang Y., Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren’s Syndrome, Journal of Complementary and Integrative Medicine . 2010, in press.

Shen F., Lin X., Zhang Y., Tong Y. and Sze C.W., 複方黃苦膏劑對濕疹外治消炎止癢作用的實驗研究, 江蘇中醫藥雜誌, 2010.

Song J., Lin X., Sze C.W., Tong Y., Wong N.S., Shaw P.C. and Zhang Y., Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells, In: Song JX, Lin X, Ricky NS Wong, Stephen CW Sze, Tong Y, Shaw PC, Zhang YB, Phytotherapy, accepted . 2010.

Researcher : Lin X

List of Research Outputs

Shen F., Lin X., Zhang Y., Tong Y. and Sze C.W., 複方黃苦膏劑對濕疹外治消炎止癢作用的實驗研究, 江蘇中醫藥雜誌, 2010.

Researcher : Liu C

Project Title:	6th Annual Rocky Mountain Bioinformatics Conference CADEG, a Set of Software Tools for High Resolution Identification of Potential Chromosomal Abnormalities
Investigator(s):	Liu C
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	12/2008

Abstract:

N/A

List of Research Outputs

Deng R., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui Buxue Tang (DBT) and its major components on hematopoiesis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Deng R.X., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui and its component Ferulic Acid on haematopoiesis and platelet production, Blood [Abstract in 2009 American Society of Hematology], 20 November 2009. 114.

Researcher : Liu KJ

List of Research Outputs

Shen J., Rosen C.M. and Liu K.J., Development of 3-actoxymethoxycarbonyl- 2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an Electron Paramagnetic Resonance Imaging Reagent for In Vivo Mapping Brain Oxygen Distribution in Ischemic Brain, 6th Annual World Congress for Brain Mapping and Image Guided Therapy, Boston, . 2009.

Shen J., Rosen G.M. and Liu K.J., Development of 3-actoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an Electron Paramagnetic Resonance Imaging Reagent for In Vivo Mapping Brain Oxygen Distribution in Ischemic Brain , 6th Annual World Congress for Brain Mapping and Image Guided Therapy. Harvard Medical School, Boston, USA, 2009.

Shen J., Sood R., Weaver J., Timmins G.S., Schnell A., Miyake M., Kao J.P., Rosen G.M. and Liu K.J., Direct visualization of mouse brain oxygen distribution by electron paramagnetic resonance imaging: Application to focal cerebral ischemia., Journal of Cerebral Blood Flow & Metabolism. Nature Group Publishing, 2009, 29: 1695-1703.

Researcher : Liu Q

List of Research Outputs

Hu K.Y., Wang Y.T., Sze S.C., Tsang K.W., Wong H.K., Liu Q., Zhong L. and Tong Y., Identification of the major chemical constituents and their metabolites in rat plasma and various organs after oral administration of effective Erxian Decoction (EXD) fraction by liquid chromatography-mass spectrometry., Biomed Chromatogr. 2010 May;24(5):. 2010, 479-89.

Hu Y.M., Wu J.J., Liu Q., Sze C.W., Zhong L. and Tong Y., Identification of the Multiple Chemical Constituents from a Chinese Medicinal Prescription- Erxian Decoction by LC-DAD-ESI-MS, International Conference on Traditional Medicine. Guangzhou, China, 2009.

Liu Q., Sze C.W. and Tong Y., Chinese Medicine Decoction (Tian-Xian Liquid) induces apoptosis in HT-29 Colon Cancer Cells via Mitochondrial Dysfunction, International Conference on Traditional Medicine. Guangzhou, China, 2009.

Sze C.W., Chu S.M.E., Wong K.L., Liu Q., Yow C.M.N., Liu W.K., Ng T.B. and Tong Y., Anti-Cancer Effect of Tian Xian Liquid, a Chinese Medicine Formula, in Human Colon Carcinoma HT29, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Tsang K.W., Wong H.K., Liu Q. and Zhong L., Identification Of The Major Chemical Constituents And Their Metabolites In Rat Plasma And Various Organs After Oral Administration Of Effective Exd Fraction By Liquid Chromatography-mass Spectrometry , In: Lim, Chang Kee , Biomedical Chromatography. 2009.

Sze C.W., Tong Y., Yow C.M.N., Liu W.K., Ng T.B., Liu Q. and Chu S.M.E., Regulation of p21, MMP-1 and MDR-1 expression in Human colon carcinoma HT29 by Tian Xian Liquid, a Chinese Medicine Formula, in vitro and in vivo, The 7th Annual Congress of IDDST 2009, Shanghai, China. 2009.

Researcher : Liu Q

List of Research Outputs

Researcher : Loo TY

List of Research Outputs

Wang Z., Loo T.Y., Wang D., Cheng Y., Guan X.Y. and Chen J., Spatholobus suberectus, a potential Chinese herb for cancer treatment, In: OOTR the 6th Annual Conference, OOTR the 6th Annual Conference. Kyoto, Japan, 2010.

Researcher : Mo F

List of Research Outputs

Mo F., Zhong L. and Yip W.K., Ju Ching Chu Secondary School (Yuen Long) Chinese Medicine Talk and Demonstration, 元朗裘錦秋中學座談分享及手法示範, In: Ju Ching Chu Secondary School (Yuen Long) , 2009.

Mo F., Mo Feizhi，Deng Tietao. Formation of the System of the Properties of the Five Organs. Proceedings of the International Conference on Traditional Medicine Session (3)—Research on the Basic Theory of Traditional Medicine. November 9-11, Guangzhou, China: 28-32 , 2009.

Mo F., 莫飛智.針刺治外感發熱.鄧鐵濤審定中醫簡便廉驗治法.北京：人民衛生出版社，2009年10月：6-7, 北京, 人民衛生出版社, 2009.

Mo F., 莫飛智.針刺或點穴治呃逆.鄧鐵濤審定中醫簡便廉驗治法. 北京：人民衛生出版社，2009年10月：74-75, beijing, 人民衛生出版社, 2009.

Mo F., 莫飛智.針刺治小兒遺尿症.鄧鐵濤審定中醫簡便廉驗治法.北京：人民衛生出版社，2009年10月：111-112, beijing, 人民衛生出版社, 2009.

Mo F., 莫飛智.針刺治壓力性尿失禁.鄧鐵濤審定中醫簡便廉驗治法. 北京：人民衛生出版社，2009年10月：112, Beijing, 人民衛生出版社, 2009.

Zhang Y., Feng Y., Sze C.W., Tong Y., Mo F., Yiu Y.M., Xiao L., Wong JH Y., Ng T.B., Shaw P.C., Xiao Y. and Li Z.M., Dendrobium candidum Extract Increases the Expression of Aquaporin 5 in Labial Glands from Patients with Sjögren’s Syndrome. , In: Lin Xiao, Tzi Bun Ng, Yi-Bin Feng, Tong Yao, Jack Ho Wong, Ren-Min Yao, Lei Li, Fei-Zhi Mo, Yin Xiao, Pang-Chui Shaw, Ze-Min Li, Stephen Cho Wing Sze, Kalin Yanbo Zhang, Phytomedicine, Accepted. 2010.

Researcher : Qi H

List of Research Outputs

Qi H., Wei L., Han Y., Zhang Q., Lau A.S.Y. and Rong J., Proteomic characterization of the cellular response to chemopreventive triterpenoid astragaloside IV in human hepatocellular carcinoma cell line HepG2, In: Professor DEMETRIOS A. SPANDIDOS, International Journal of Oncology. Athens, Greece, Spandidos Publications, 2010, 36: 725-735.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolide isomers H and I from Rhizoma Chuanxiong attenuate hydrogen peroxide-induced oxidative stress in human liver HepG2 cells via induction of heme oxygenase-1, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM). Nottingham, UK, 2009.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1, Chemico-Biological Interactions. 2010, 183(3): 380-389.

Qi H. and Rong J., Z-ligustilide protects neuronal PC12 cells from oxidative stress by inducing heme oxygenase-1 via the Nrf2 and PI3K/Akt mediated pathways, Gordon Research Conference: 2010 High Throughput Chemistry and Chemical Biology. 2010.

Researcher : Qi H

List of Research Outputs

Researcher : Rong J

Project Title:	The 7th International Conference on Systems Biology Genome-wide Biological Response Fingerprinting (BioReF) of Traditional Chinese Medicine Formula ISF-1 Reveals a Potential Role of Heme Oxygenase-1 Pathway in the Antioxidant Therapy
Investigator(s):	Rong J
Department:	Medical Faculty
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2006

Abstract:

N/A

Project Title:	Molecular characterization of the transcriptional regulatory elements involved in the synergistic induction of heme oxygenase-1 expression by traditional Chinese medicines
Investigator(s):	Rong J, Chen Y, Lau ASY, Tam PKH, Tong Y
Department:	Medical Faculty
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2007
Completion Date:	02/2010

Abstract:

To characterize the regulatory responsive elements contributing to the synergistic regulation of HO-1 expression; to isolate the active components responsible for the synergistic induction of HO-1 expression; to evaluate the biological importance of synergistic induction of HO-1 expression in animal model.

Project Title:	Synergistic induction of leukotriene B4 12-hydroxydehydrogenase (LTB4DH) by Chinese medicines Radix Astragali and Radix Paeoniae Rubrae: Identification of the active compounds and their intracellular targets
Investigator(s):	Rong J
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009
Completion Date:	08/2010

Abstract:

Stroke causes increasing incidence of severe disabilities and mortalities worldwide [1]. Stroke-induced brain damage is mainly resulted from uncontrolled immunological and inflammatory responses [2, 3]. Leukotriene B4 (LTB4) is a chemoattractant and proinflammatory lipid mediator generated from arachidonic acids by 5-lipoxygenase and leukotriene A hydrolase [4, 5]. The production of LTB4 is elevated in ischemic stroke [6-8]. LTB4 is a chemoattactant for neutrophiles, macrophages, mast cells, eosinophiles and T-cells. LTB4 stimulates granulocytes and macrophages to release lysosomal enzymes and to generate reactive oxygen species [9]. Thus, uncontrolled recruitment of immune cells often causes tissue damage in the inflammatory diseases. Although the role of LTB4 in ischemic stroke has not fully characterized yet, a previous study demonstrated that LTB4 induced reduction of voltage-dependent potassium outward currents resulted in the neuronal dysfunction in the inflammatory sites [10]. Inhibition of the production of various lipid mediators including LTB4 conferred the reduced neuronal death after transient focal cerebral ischaemia [11]. On the other hand, LTB4 12-hydroxydehydrogenase (LTB4DH) catalyzes the conversion of LTB4 to the less bioactive metabolite 12-keto-LTB4 in the presence of NADP+ and thus LTB4DH plays a critical role in activating LTB4 [12-14]. Similarly, LTB4DH also degrades the lipoxins (LX), the autacoids that dampen neutrophil recruitment and promote resolution within a local inflammatory milieu [15]. In fact, the activation of LTB4 catabolism via enhanced LTB4DH activity by several chemopreventive agents such as dithiolethione may suppress inflammatory processes implicated in tumorigenesis [16, 17]. Owing to its ability to reduce the alpha, beta-carbon=carbon double bond to a single bond in various exogenous and endogenous compounds, LTB4DH was suggested as the fourth class of detoxication enzyme [18]. LTB4DH activity determines the sensitivity of cancer cells to the chemotherapeutic alkylating agent irofulven [19]. These results stimulate us to question if pharmacological induction of LTB4DH expression could inhibit LTB4-mediated inflammatory responses in ischemic stroke. Several herbal medicines are known to inhibit the biosynthesis of LTB4 [20-22]. Little is known about the regulation of LTB4 metabolism by herbal compounds. As an example, Panax notoginseng Buck F.H. Chen. (Arialiaceae) root is widely used to treat haemorrhages and to promote health in traditional Chinese medicine. A recent study demonstrated that Panax notoginseng extract inhibited neutrophil functions such as degranulation, superoxide generation and leukotriene B4 production [23]. By investigating the cellular response to Chinese traditional medicines at the genome-wide scale, we found that a well-documented post-stroke rehabilitation formulation ISF-1 induced heme oxygenase-1 in a synergistic fashion, conferring the cytoprotection of neurons from oxidant-induced injuries in the post-stroke rehabilitation [24, 25]. In addition, the formulation ISF-1 also induced several anti-inflammatory genes such as LTB4DH [24]. These results suggest that LTB4DH may play a potential role in the post-stroke rehabilitation by degrading LTB4. Consequently, we further studied the regulation of LTB4DH expression by the herbal ingredients of the formulation ISF-1. It is intriguing that both Radix Astragali and Radix Paeoniae Rubrae are required to induce LTB4DH expression and none of the ingredients in the formulation ISF-1 alone showed any activity. Thus, we hypothesize that LTB4DH expression is synergistically regulated by two different signals that are triggered by Radix Astragali and Radix Paeoniae Rubrae, respectively. Due to the chemical complexity of herbal extracts, we will apply a bioactivity-guided fractionation strategy to isolate the active compounds from Radix Astragali and Radix Paeoniae Rubrae. When the active compounds are identified, we will subsequently elucidate the mechanisms by which Radix Astragali and Radix Paeoniae Rubrae induce LTB4DH expression. The long term objective of this project is to develop new chemically defined formulations for the treatment of ischemic stroke by inducing LTB4DH expression. Specific Aim 1: To isolate the active compounds from Chinese medicines Radix Astragali and Radix Paeoniae Rubrae. Radix Astragali and Radix Paeoniae Rubrae are widely used as anti-inflammatory, anti-oxidant, anti-cancer and immunomodulatory drugs in traditional Chinese medicine [26-28]. However, the underlying mechanisms remain largely unknown. We recently demonstrated that the post-stroke rehabilitation formulation ISF-1 containing both herbs significantly upregulated LTB4DH, known as an anti-oxidant and anti-inflammatory gene [24]. In our subsequent effort to identify the active ingredients from the formulation ISF-1, both Radix Astragali and Radix Paeoniae Rubrae were found to be essential for effective induction of LTB4DH expression, suggesting a synergistic mechanism. The objective of this study is to isolate the active compounds for inducing LTB4DH expression. We will adapt a bioactivity-guided fractionation strategy to isolate the compounds capable of inducing LTB4DH expression. Induction of LTB4DH expression will be assayed by RT-PCR technique using specific primers. The results will be verified by Western blot analysis using anti-human LTB4DH antibody. The active fractions will be subjected to further chemical identification by mass spectrometry and NMR technique. Specific Aim 2. To elucidate the molecular mechansims underlying the regulation of LTB4DH. Leukotrienes (e.g. LTB4) are important proinflammatory lipid mediators in the cardiovascular diseases including arteriosclerosis, myocardial infarction, and stroke [29, 30]. LTB4DH is an endogenous regulator of LTB4-mediated inflammatory signals by converting the LTB4 to the less bioactive metabolite [31]. Previous studies showed that LTB4DH expression could be induced pharmacologically. Our preliminary results showed that Radix Astragali and Radix Paeoniae Rubrae may induce LTB4DH expression in a synergistic fashion. However, little is known about the cellular signaling pathways that regulate LTB4DH expression. Following the identification of the active compounds in Specific Aim 1, this study is designed to elucidate the molecular mechansims underlying the regulation of LTB4DH by the active herbal compounds. Transcriptomics is widely used to study the molecular mechanisms undelying the action of various drugs. We will fingerprint the cellular responses to the active compounds by DNA GeneChips at the genome-wide scale. The transcriptional profile will reveal the target genes for the active compounds. Subsequently, we will verify the candidate targets by introducing the full length cDNA sequence into the neuronal cells or knocking down the expression of the candidate genes by RNAi contructs. Alternatively, we will clone the promoter sequence of LTB4DH gene from the genomic DNA library purchased from Stratagene earlier. Our hypothesis is that LTB4DH gene carries with specific transcriptional regulatory elements responsive to Radix Astragali and Radix Paeoniae Rubrae. Identification of transcriptional regulatory elements may be helpful to decipher the intracellular signaling networks regulated by the active compounds. Thus, this study will make it possible to develop chemically defined and mechanism specific new Chinese medicine formulation for the prevention and treatment of post-stroke disorders.

Project Title:	Inhibitory effect of gallic acid and caffeoyl glucose in combination on the proliferation of human liver cancer HepG2 cells: A role of leukotriene B4 12-hydroxydehydrogenase (LTB4DH)
Investigator(s):	Rong J
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2010

Abstract:

Hepatocarcinogenesis is a multistep process including initiation, promotion and progression [1, 2]. Although multiple etiologies exist, viral infection and chronic inflammation are the major risk factors for the pathogenesis of hepatocellular carcinoma [3, 4]. Chronic inflammation is characterized by aberrant arachidonic acid metabolism that is implicated in the development of various cancers [5]. Arachidonic acids are converted to prostaglandins (PGs) and leukotrienes (LTs) by cyclooxygenase (COX) and lipoxygenase (LOX) pathways, respectively [6]. Leukotriene B4 (LTB4) is a key proinflammatory mediator derived from arachidonic acid by 5-lipoxygenase (5-LOX) pathway [7, 8]. It was recently found that LTB4 level could be 10-30 fold higher in oral squamous cell cancers compared to control normal tissues [6, 9]. LTB4 also promotes the growth and survival of cancer cells [5, 10]. These results suggest a role for LTB4 in the pathogenesis of various cancers. Recent in vitro and in vivo studies also showed that blockage of LTB4 production resulted in the suppression of tumor development [10, 11]. However, selective control of the cellular LTB4 level is an ongoing challenge. With the support of a previous internal seed grant, we recently discovered that gallic acid and 1-O-caffeoyl-β-D-glucose in combination strongly induced the expression of LTB4 12-hydroxydehydrogenase (LTB4DH) mRNA and protein (Figure 1&2). LTB4DH is a key endogenous enzyme converting LTB4 to less active metabolite 12-keto-LTB4. Remarkably, we confirmed that elevated LTB4DH expression either through transfection of LTB4DH cDNA or synergistic induction of by gallic acid and 1-O-caffeoyl-β-D-glucose inhibited the growth of cancer cells (Figure 3&4). The inhibition of the growth of HepG2 cells by gallic acid and 1-O-caffeoyl-β-D-glucose was largely attenuated by RNAi-mediated knockdown of LTB4DH expression (Figure 5). These preliminary results suggest a role for LTB4DH in the anticancer activity of gallic acid and 1-O-caffeoyl-β-D-glucose. Thus, we hypothesize that LTB4DH induction may attenuate the proliferation of cancer cells via specific control of LTB4 level. We will test this hypothesis through addressing two specific questions: (1) Does LTB4DH play a role in the inhibitory effect of gallic acid and 1-O-caffeoyl-β-D-glucose on the proliferation of cancer cells? (2) Is it possible to use gallic acid and 1-O-caffeoyl-β-D-glucose in the treatment of hepatocarcinogenesis in vivo? The goal of this project is to demonstrate a novel anticancer mechanism by pharmacological induction of LTB4DH. The results from this project will improve current understanding on the role of LTB4DH in the selective control of LTB4 levels and subsequent inhibition of hepatocellular carcinoma. Objectives 1. To investigate the role of LTB4DH in the inhibitory effect of gallic acid and caffeoyl glucose on the proliferation of liver cancer HepG2 cells. Our pilot results suggest that LTB4DH is highly induced by gallic acid and caffeoyl glucose in cultured HepG2 cells, which is positively correlated with the inhibition of cell proliferation. Importantly, RNAi-mediated downregulation of LTB4DH expression attenuated the inhibitory effects of gallic acid and caffeoyl glucose on the growth of HepG2 cells. Thus, the objective of this study is to investigate the role of LTB4DH in the inhibition of cell proliferation by gallic acid and caffeoyl glucose in liver cancer HepG2 cells. We will determine the effects of LTB4DH induction on the focus formation, colony formation, morphological changes and cell motility as described [12-14]. The results of this study will not only demonstrate the chemopreventive role of LTB4DH in hepatocarcinogenesis, but also open a new avenue for the therapeutic intervention of hepatocarcinogenesis based on traditional Chinese medicines. 2. To examine the effect of gallic acid and caffeoyl glucose on hepatocarcinogenesis in an animal model We recently discovered that gallic acid and caffeoyl glucose inhibited the proliferation of cancer cells in cell culture. Others showed that Radix Astragali extracts inhibited carcinogenesis in animal models [15, 16]. Thus, this study is designed to further investigate the effects of gallic acid and caffeoyl glucose on tumor growth in vivo. Human hepatoma xenograft will be made in nude mice as described [17]. This study will demonstrate the therapeutic potential of gallic acid and caffeoyl glucose in liver cancer.

List of Research Outputs

Feng Y., Liu K.J., Wang J., Shen J., Zhang Y., Rong J., Tong Y., Chan K.S. and Wong B.W., Basic and clinical Toxicology of Chinese Medicines, 基礎和臨床中藥毒理學, Hong Kong, Commercial Press (HK) Ltd., 2009, p394.

Lee D.C.W., Yang L.H., Chik S.C.C., Li J., Rong J., Chan G.C.F. and Lau A.S.Y., Immunomodualtory effect of Panax ginseng on human promonocytic U937 cells, Journal of Translational Medicine. 2009, 7: 34-40.

Qi H., Wei L., Han Y., Zhang Q., Lau A.S.Y. and Rong J., Proteomic characterization of the cellular response to chemopreventive triterpenoid astragaloside IV in human hepatocellular carcinoma cell line HepG2, In: Professor DEMETRIOS A. SPANDIDOS, International Journal of Oncology. Athens, Greece, Spandidos Publications, 2010, 36: 725-735.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolide isomers H and I from Rhizoma Chuanxiong attenuate hydrogen peroxide-induced oxidative stress in human liver HepG2 cells via induction of heme oxygenase-1, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM). Nottingham, UK, 2009.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1, Chemico-Biological Interactions. 2010, 183(3): 380-389.

Qi H. and Rong J., Z-ligustilide protects neuronal PC12 cells from oxidative stress by inducing heme oxygenase-1 via the Nrf2 and PI3K/Akt mediated pathways, Gordon Research Conference: 2010 High Throughput Chemistry and Chemical Biology. 2010.

Tong L., Shen J., Qu H.D., Cai G.X., Peng K., Liu B.Y., Rong J., Tan X.H., Liao C.L., Chen Y.Y. and Luo Q.W., 補陽還五湯對缺血性中風後神經元保護及增殖作用的相關機制研究, 2009年度中華中醫藥學會科學技術獎三等獎, 2010.

Tong L., Shen J., Qu H., Cai G.X., Peng K., Liu B.Y., Rong J., Tan X.H., Liao C.L. and Chen Y., 补阳还五汤对缺血性中风后神经元保护及增殖作用的相关机制研究, 2009年广东省科学技术奖, 2009.

Wei L., Liu J., Le X.C. and Rong J., Induction of LTB4 12-hydroxydehydrogenase (LTB4DH)expression by coordination of the active compounds isolated from the plants Radix Astragli and Radix Paeoniae Rubra, ASCB 2009 (49th Annual Meeting). 2009.

Researcher : Shen F

List of Research Outputs

Shen F., Lin X., Zhang Y., Tong Y. and Sze C.W., 複方黃苦膏劑對濕疹外治消炎止癢作用的實驗研究, 江蘇中醫藥雜誌, 2010.

Researcher : Shen J

Project Title:	Biochemical Society Meeting 679 University of Essex UK - Stress, Signalling and Control Reactive Oxygen Species Mediate Intracellular Cholesterol Accumulation via Modulating Caveolin-1 Pathway in Chinese Hamster Ovary Cells
Investigator(s):	Shen J
Department:	Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2003

Abstract:

N/A

Project Title:	Development of Nano-salvianic Acids for Protecting Neural Cells from Oxidative Injury
Investigator(s):	Shen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

Background: Ischemic stroke is the third killer in human diseases. Disruption of blood brain barrier (BBB) and enlargement of infarction volume are frequently found in stroke patients after blood circulation is restored. This phenomenon is commonly called cerebral ischemia-reperfusion injury. Free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), are found in ischemic brains. Both ROS and RNS are important cytotoxic factors in cerebral ischemia-reperfusion injury. ROS, including superoxide (O2.-) and hydroxyl radicals (OH.), etc., induces lipid peroxidation of plasma membrane and destroys membrane structures and functions of neural cells and brain microvascular endothelial cells, resulting in BBB breakdown, enlargement of infarction and neural apoptotic cell death. RNS, including nitric oxide (NO) and peroxynitrite (ONOO-), contributes to neural oxidative damage as well. High concentration of NO produced from inducible NOS (iNOS) and neuronal NOS (nNOS) is detrimental to ischemic brain, inducing inflammation, cell death, BBB hyperpermeability, and infarction enlargement. NO reacts with superoxide (O2.-) to generate ONOO-. The later can easily penetrate lipid bilayers, leading to peroxidation of membrane lipids and apoptotic cell death during cerebral ischemia-reperfusion injury. Therefore, development of novel antioxidants for scavenging free radicals becomes a critical therapeutic strategy for the treatment of ischemic stroke. Danshen, the dried root of salvia miltiorrhiza, is a commonly used traditional Chinese Medicine (TCM) for the treatment of ischemic heart disease and ischemic cerebrovascular diseases. A number of clinical trials have reported its efficacy on improving clinical outcome and quality of life in the treatment of ischemic stroke. The chemical constituents of Danshen have been studied and at least 50 hydrophilic compounds and 30 lipophilic compounds have been identified. Among them, salvianolic acids and tanshinones are considered as the major constituents contributing to Danshen's neuroprotective effects. Salvianolic acids have showed to scavenge free radicals, inhibit lipid peroxidation and mitochondrial membrane permeability transition, improve regional cerebral blood flow, protect neural cells and improve neurogenesis in experimental stroke models. Salvianolic acids can be potentially developed into new botanical drugs for stroke treatment. However, as hydrophilic compounds, salvianolic acids are difficult to penetrate BBB, greatly limiting its application. Development of novel antioxidants based on the traditional antioxidants form herbal medicine like salvianolic acids with enhanced antioxidant capacity and BBB permeability is an important stretegy of drug discovery for the treatment of ischemic stroke. Current research in neuro nanomedicine have proposed to use nanotechnology for featuring brain repair, brain imaging and drug delivery for crossing the BBB. Recent progress in the development of new biological materials nanotechnology provides great opportunities for drugs and small molecular delivery across the BBB. The promise of nanotechnology is that the selective delivery of therapeutics can be delivered through to the brain without causing secondary damage. In our recent study, we found that the antioxidant activity and bioavailability of tocopherol can be dramatically enhanced by assembling it on the surface of nanoparticles (see Free Rad Biol Med 43:1243-1254, 2007). Therefore, with the discovery, we hypothesize that the assembly of antioxidant ligands on nanoparticles could provide the possiblity of improving antioxidant activity and enhancing drug delivery into the brains. In this proposal we will design self-assembled nanoantioxidants based on salvianolic acid A and evaluate its antioxidant and neuroprotective effects on neural cells under oxidative stress. Objectives: (1) To design and prepare self-assembled nano-salvianolic acids. (2) To compare the antioxidant effects of the nano-salvianolic acids and natural salvianolic acid A in human neuroblastoma SK-N-MC cells under oxidative stress. (3) To compare the effects of the nano-salvianolic acid A and natural salvianolic acid A against apoptotic cell death in human neuroblastoma SK-N-MC cells under oxidative stress.

Project Title:	Interactions of Reactive Nitrogen Species, Caveolins and Matrix Metalloproteinases: A Novel Signal Mechanism in Disruption of Blood Brain Barrier during Ischemic Stroke
Investigator(s):	Shen J, Chung SK, So KF, Yang D
Department:	School of Chinese Medicine
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2008

Abstract:

(1) To test the hypothesis that ONOO- would contribute to NO-induced down-regulation of caveolin-1 and activation of MMPs in cerebral ischemia-reperfusion injury. The experiments will be conducted in hypoxia-reoxygenated brain microvascular endothelial cells (BMECs) in vitro and middle cerebral artery occlusion (MCAO)-induced cerebral ischemia-reperfusion injury in vivo; (2) To address the question whether diminished caveolin-1 expression will be linked to activation of MMPs, increase of BBB permeability and enlargement of infarction volume in cerebral ischemia-reperfusion injury. Several conventional approaches including caveolin-1 knockdown BMECs, caveolin-1 knockout mice and cell-permeable peptide encoding caveolin-1 scaffolding domain will be used to elucidate the roles of caveolin-1 in regulating MMPs expression and BBB permeability; (3) To test the hypothesis that caveolin-1 will control BBB peremability via protecting tight junction-associated proteins from degradation of MMPs in ischemia-reperfused BMECs and brain tissues.

Project Title:	Development of caveolin-1 as a target molecule for screening active compounds from herbal medicine in promoting neurogenesis for ischemic stroke
Investigator(s):	Shen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2008

Abstract:

Stroke is the third leading cause of death and a major human disease associated with disability. Currently, no reliable therapy is available to improve the regeneration of neurons and the recovery of neurological functions for the treatment of ischemic brain injury, inducing long-term disability in post-stroke patients. Mammalian central nervous system (CNS) was believed to be incapable of self-repair or regeneration. Recent evidence found that stem/progenitors cells in adult CNS could potentially generate new functional neurons and repair the damaged CNS. Adult CNS in dentate gyrus of hippocampus, subventricular zone (SVZ) of lateral ventricle and cortex contains a range of progenitors or stem cells with limited capacities of growth and differentiation. As pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, they are selectively destroyed after cerebral ischemia. After transient global ischemia, newborn cells migrate into the granule cells. Enhanced neurogenesis in the dentate gyrus could promote functional recovery of the ischemia brain injury. However, only one neuronal subtype, granule cells in the dentate gyrus, is able to regenerate, and the production of new neurons in other hippocampal regions appears to be very limited in adults. Growth-factors showed to stimulate massive regeneration of hippocampal pyramidal neurons after ischemia injury. The result is interpreted as an evidence for direct migration of neuronal precursors toward injured areas, possibly triggering brain repair. Neuronal replacement strategies to rely on endogenous progenitors avoid many potential technical ethical limitations associated with fetal or stem cell transplantation. The mechanisms of neural regeneration at ischemic brains are largely unknown. Recent studies bring attentions to the connection between hypoxia and the proliferation of neural stem/progenitor cells. Enhanced proliferation of stem cells in response to hypoxia has been shown in vivo in neural stem/progenitor cells after hypoxic brain injury in neonatal mice, in adult rats and in aged humans. Hypoxia could be a proliferation stimulus in neural stem/progenitor cells. However, most of proliferated neural stem/progenitor cells in ischemia area could not be finally developed into newly formed neurons and integrated in neurological network. It is important to find out why the newly proliferated neural stem/progenitor cells could not further developed into neurons in the ischemic brains. Neural stem/progenitor cells are found in close proximity to blood vessels and surrounded by glial cells in the hippocampus and SVZ. The proliferation and differentiation of neural stem/progenitor cells depend on microenvironment niche signals, including a number of growth factors. Recent studies have drawn attention to the roles of vascular endothelial growth factors (VEGF) and its receptors in neural regeneration. VEGF was originally identified as a major mediator of angiogenesis. VEGF exerts its action via its receptor, VEGFR-2/Flk-1, in endothelial cells, hematopoietic stem/progenitor cells and tumor cells. VEGF stimulates the expension of neural stem/progenitor cells and neurogenesis in various animal models, resulting in improved learning ability. VEGF-overexpressing transgenic mice show enhanced post-ischemic neurogenesis, neuromigration, angiogenesis and functional recovery. Both vascular endothelial cells and glial cells expressing VEGF and bFGF serve as niche signals for neural stem/progenitor cells. Neural stem/progenitor cells proliferate in response to bFGF during neurogenic phase. In addition, VEGF and brain-drived neurotrophic factor (BDNF) mediate cross-talk between neural stem cells and endothelial cells in the niche. Therefore, VEGF and its receptor Flk-1 could be therapeutic target for brain repair in post-stroke treatment. Caveolae, invaginations of the plasma membrane, participates in many cellular events. Caveolins are integral membrane proteins located at the caveolae. The subtypes of caveolin-1 and -2 are widely expressed in neuronal cell types and brain regions, while caveolin-3 is specifically expressed in skeleton muscle cells and cardiomyocytes. Caveolins are cholesterol trafficking proteins as well as negative regulating protein in a variety of signal transduction pathways, such as G proteins, nitric oxide synthases (NOS), Src tyrosine kinases, ras, esterogen receptors, PKC, intergrins, EGF-R, etc. Caveolin-1 suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF in mesangial cells. Upregulation of VEGFR-2/Fik-1 by bFGF treatment is essential for VEGF-mediated promotion of neural stem/progenitor cell proliferation. Overexpression of caveolin-1 inhibits the activity of VEGFR-2/Fik-1, resulting in G0/G1 arrest in endothelial cells. Caveolin-1 appears to play important roles on post-injury reactive neural plasticity. Caveolin-1 can inhibit the bFGF signal pathway and block the formation of neurites upon bFGF treatment in N2a cells. Caveolin-1 is present in neural stem/progenitor cells. However, whether caveolin-1 modulates the proliferation and differentiation of neural stem/progenitor cells are unknown yet. In Traditional Chinese Medicine (TCM), many formulae have clinically used for treating stroke-induced disability for centuries. Buyang Huanwu Decoction (BHD), a representative formula, has been commonly used for functional recovery of stroke-induced disability for more than 300 years. BHD is composed of Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, Ligusticum chuanxiong, Carthamus tinctorius, Prunus persica and Lumbricus. The neuroprotective effects of BHD on ischemic stroke patients were reported clinically. Experimental evidence shows that BHD could promote growth and differentiation of neural progenitor cells [44]. BHD can promote neurite outgrowth and differentiation of neuroepithelial stem cells. However, the mechanisms for promoting neural growth and regeneration and its active ingredients with promoting neural regeneration are unclear yet. Further studies in those aspects would lead to drug discovery for the treatment of post-stroke disability. The purpose of the proposal is to verify the roles played by caveolin-1 in inhibiting VEGF signal and neurogenesis. Following key issues will be addressed: Central Hypothesis Caveolin-1 is a critical negative regulation protein for proliferation and differentiation of neural stem cells via inhibiting neural growth signals including VEGF and its receptor VEGFR-2/Flk-1. Key issues and problem to be addressed: 1. To understand the roles played by caveolin-1 in modulating proliferation and differentiation of neural stem cells under hypoxia /ischemia 2. To test the hypothesis that caveolin-1 could inhibit the expression and activity of VEGF and its receptor VEGFR-2/Flk-1 3. To use caveolin-1 as a target protein for screening bioactive ingredients with promoting neural regeneration properties from Buyang Huanwu Decoction, a classic TCM formula for recovery of neurological functions in post-stroke treatment

Project Title:	Effects of Baicalin on promoting differentiation of neural stem cells into neurons in post-ischemic stroke rats
Investigator(s):	Shen J, Tong Y
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009
Completion Date:	03/2010

Abstract:

Mammalian central nervous system (CNS) has long been believed to be incapable of neuronal repair or regeneration. In the past decade, one of the most important discoveries in Neurobiology is that ischemia-injured brains have the potential capability to repair itself by stimulating the proliferation and differentiation of neural stem/progenitor cells, and by the direct migration of the neuronal precursors toward injured areas and replaced damaged neurons. The compensatory replacement of striatal neurons from resident progenitors and neuronal recruitment into the neostriatum have been identified in experimental stroke models. Apparent compensatory neurogenesis has been also found in the striatum of Huntington’s disease patients and in the dentate gyrus of hippocampus of Alzheimer’s patients, indicating the potentials for recruiting new neurons from resident neural progenitor cells as a means of treating degenerative conditions. Those discoveries offer a hope for the development of therapeutic approaches for the recovery of neurological functions in post-stroke patients and in those with neurodegenerative diseases. The strategy of cell replacement by endogenitors raises optimism for regenerative therapies, avoiding many potential technical and ethical limitations associated with fetal or stem cell transplantation. Therefore, recent efforts have focused on stimulating the formation and preventing the death of neurons and glial cells produced by endogenous stem cells in the adult CNS. Neurogenesis is a multistep process including proliferation, fate determination, migration, and neuronal maturation of endogenous neural progenitor cells. Among these processes, one of critical steps during NSCs differentiation is the decision to generate neuronal or glial cells. Recent evidences indicate that Stat3 could maintain the propagation and pluripotency of embryonic stem cells. Targeted disruption of the Jak/Stat3 gene in mice results in early embryonic lethality. Especially, suppression of Jak/Stat3 directly induced neurogenesis and inhibited astrogliogenesis in neural stem cells. In contrast, the activator-type bHLH genes including Mash1, Math and Neurogenin are expressed by differentiating neurons. Misexpression of these genes in neural stem cells induces the pan-neuronal gene expression and determines the neuronal fate. In addition, Mice lacking Mash1 present defects in the specification of progenitors in the autonomic ganglia, olfactory epithelium, and ventral forebrain, while Neurogenin 1 and Neurogenin 2 mutant mice present similar phenotypes in the dorsal root and cranial ganglia and in the dorsal telencephalons. Those studies suggest that Stat 3 and Mash1 participate in the signal modulations during the differentiations of neural progenitors. The natural plant world is a vast resource that can be used in drug discovery for neurogenesis. Many botanical ingredients such as ginsenoside Rb1, M1, and withanolide A, have been reported to improve neuritic regeneration and synaptic reconstruction in cultured neurons in vitro. Baicalin, a flavonoid isolated from the root of Scutellaria baicalensis G, has showed multiple biological functions, such as anti-inflammatory activity, and inhibition of nitric oxide producing activity. Baicalin has neuroprotective effects on the oxygen/glucose deprivation- and NMDA-induced injuries in primary cultured neurons and rat hippocampus slice. Recent experiments indicate that Baicalin can pass through BBB and reach the CNS. Interestingly, Baicalin has been shown to promote the differentiation of human umbilical cord blood mesenchymal stem cells and rat bone marrow stromal cells into neuron. Those results lead us hypothesize that Baicalin could promote the differentiation of neural progenitor cells in post-ischemic brains. To verify this hypothesis, we conducted pilot studies on primiary cultured neural progenitor cells and found that baicalin could promote the differentiation of neural progenitor cells but inhibit glial generation of neural progenitor cells. Baicalin can suppress Stat3 pathway and activate the Mash1 gene expression in the neural progenitor cells. This proposal is specifically designed to further verify this hypothesis in both in vitro neural progenitor cells and in vivo animal model. Central hypothesis: Baicalin could promote the differentiation of neural progenitor cells but inhibit glial generation of neural progenitor cells in post-ischemic brains via suppressing Stat3 pathway and activating the basic helix-loop-helix (bHLH) transcription factors in the neural progenitor cells.

Project Title:	6th World Congress for Brain Mapping and Image Guided Therapy 1. Development of 3-actoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an electron paramagnetic resonance imaging reagent for in vivo mapping brain oxygen distribution and infarction in ischemic brain 2. INTERACTION OF CAVEOLIN-1, NITRIC OXIDE AND NITRIC OXIDE SYNTHASES IN HYPOXIC HUMAN SK-N-MC NEUROBLASTOMA CELLS AND RAT ISCHEMIC BRAINS
Investigator(s):	Shen J
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

Project Title:	Elucidating Effects and Mechanisms of Isoflavonoids from Astragalus Mongholicus in Improving Neurogenesis for Post-stroke Treatment
Investigator(s):	Shen J, Fu S
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Mammalian central nervous system (CNS) has long been believed to be incapable of neuronal repair or regeneration. However, in the past decade, one of the most important discoveries in Neurobiology is that ischemic injured brains have the potential capability to repair itself by stimulating the proliferation and differentiation of neural stem/progenitor cells, and by the direct migration of the neuronal precursors toward injured areas. This discovery offers a hope for the development of therapeutic approaches for the recovery of neurological functions in post-stroke patients and in those with neurodegenerative diseases. The production of new neurons in the ischemic brain itself appears to be very limited in adults. Neural stem/progenitor cells within the adult brain germinal centers reside in a specialized microenvironmental niche. These cells are found in close proximity to blood vessels and are surrounded by glial cells in the adult hippocampus and the SVZ. The proliferation and differentiation of neural stem/progenitor cells and neural growth depend on the microenvironment niche signals, which include a number of growth factors such as basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and epidermal growth factor (EGF) [1]. Vascular endothelial growth factor (VEGF) seems to play a key role in neural regeneration. Originally, VEGF was identified as a major mediator of angiogenesis, but it can also mediate vascular permeability and tissue regeneration. VEGF exerts its action via phosphotyrosine kinase receptors including VEGFR1/fms-like tyrosine kinase (Flt) and Flk-1 in endothelial cells, in hematopoietic stem/progenitor cells, and in tumor cells. VEGF binds to Flk-1 in brain cells. The VEGF stimulates the extension of neural stem/progenitor cells and neurogenesis, consequently improving the learning ability in several animal models [1-4]. VEGF has the enhanced neurogenesis, neuromigration, angiogenesis, and improves recovery of sensorimotor and cognitive deficits in post focal cerebral ischemic rats [5-7]. Both vascular endothelial cells and glial cells expressing VEGF and bFGF function as niche signals for neural stem/progenitor cells, which proliferate in response to bFGF signal during neurogenic phase [8-11]. Both VEGF and BDNF mediate cross-talking between neural stem cells and endothelial cells in the niche [12]. Hypoxia-induced up-regulation of VEGF and Flk-1 stimulates proliferation and differentiation of adult neural stem cells in vitro and promotes neurogenesis in vivo [4,7,13]. Therefore, the niche signals are important cellular signal molecules mediating neural regeneration. Traditional Chinese Medicine is potentially useful for recovery of neurological functions in post-stroke treatment. Astragalus mongholicus (AM), which is a commonly used Chinese medicinal plant, has been reported to improve recovery of neurological function and promote neural regeneration in the rat brains. AM can reverse A beta(25-35)-induced memory loss and prevent the loss of axons and synapses in the cerebral cortex and hippocampus in mice [14]. The mechanisms of AM on promotion of neural regeneration are still unclear. AM is reported to promote the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells [15]. DNA microarray analysis showed that AM remarkably up-regulated the expressions of epiregulin, fibroblast growth factor, and basic helix-loop-helix (bHLH) transcription factors (Mash1, Neurogenin1, Neurogenin2) in the induction of BMSCs into neuronal cells [16]. Astragalosides, the major components of AM, can improve memory in aged mice [17]. Astragaloside IV, a representative compound of Astragalosides, can reduce brain infarction in mice after focal ischemia [18]. The active herbal ingredients of AM could hold promise for the discovery of novel drugs that could promote neurogenesis. However, the active ingredients and molecular mechanisms of AM for promoting neurogenesis are largely unclear. Isoflavonoids are one of the important active components in AM. Previous studies suggest that the isoflavonoids isolated from AM. have strong antioxidant activities and can protect neural cells from toxicity induced by L-glutamine (19-20). Our preliminary data showed that the isoflavonoids including formononetin, calycosin and 9,10-dimethoxypterocarpan-3-O-b- D-glucoside, could promote proliferation and differentiation of neural stem cells in vitro. In this proposal, we will further investigate the effects of formononetin, 9,10-dimethoxypterocarpan-3-O-b-D-glucoside, and calycosin on promoting neural regeneration and its mechanisms involved. Objectives: To test the hypothesis that AM isoflavonoids can promote proliferation and differentiation of neural stem cells via regulating niche signals Special Aim 1. To investigate the effects of the AM isoflavonoids on improving proliferation and differentiation in cultured neural progenitor cells in vitro. Special Aim 2. To explore the molecular mechanisms of the AM isoflavonoids for promoting proliferation and differentiation of neural progenitor/stem cells under normoxic and hypoxic conditions. Special Aim 3. To study the effects of the AM isoflavonoids on improving neural progenitors / stem cells to develop into new neurons in ischemia rat brains in vivo References: 1. Mocchetti I, Wrathall JR. J Neurotrauma 1995; 12:853-870. 2. Jin K, Zhu Y, Sun Y, et al. PNAS 2002; 99:11946-11950. 3. Fabel K, Tam B, Kaufer D, et al. Eur J Neurosci 2003; 18:2803-2812. 4. Cao L, Jiao X, Zuzga DS, et al. Nat Genet 2004; 36:827-835. 5. Schänzer A, Wachs FP, Wilhelm D, et al. Brain Pathol 2004; 14:237-248. 6. Wang Y, Galvan V, Gorostiza O, et al. Brain Res 2006; 1115(1):186-193. 7. Wang Y, Jin K, Mao XO, et al. Neurosci Res 2007; 85(4):740-7. 8. Lee HJ, Kim KS, Park IH, et al. PLoS One 2007; 2(1):e156. 9. Ciccolini F, Svendsen CN. J Neurosci 1998; 18:7869-7880. 10. Vaccarino FM, Schwartz ML, Raballo R, et al. Nat Neurosci 1999; 2:246-253. 11. Raballo R, Rhee J, Lyn-Cook R, et al. J Neurosci 2000; 20:5012-5023. 12. Li Q, Ford MC, Lavik EB, et al. J Neurosci 2006; 84:1656-1668. 13. Meng H, Zhang Z, Zhang R, et al. Neurosci lett 2006; 393:97-101. 14. Tohda C, Matsuyama S, Komatsu K. Br J Pharmacol 2006; 149:532-541. 15. Yang XW, Wang Y, Tissues Engineering Research 2008: 12(25):4996-5000. 16. Leng S, Dong X. Nervous Diseases and Mental Health 2005: 5(4): 251-256. 17. Lei H, Wang B, Li WP, et al. Acta Pharmacol Sin 2003; 24: 230-234. 18. Luo Y, Qin Z, Hong Z, et al. Neurosci Lett 2004; 363:218-223. 19. Yu D, Duan Y, Bao Y, et al. J Ethnopharmacol 2005; 98(1-2):89-94; 20. Yu DH, Bao YM, Wei CL, et al. Biomed Environ Sci 2005; 18(5):297-301

Project Title:	Development of Hydroxysafflor Yellow A (HSYA) as a Botanical Drug for Reducing Blood Brain Barrier Permeability and Preventing Infarction Enlargement in Stroke Treatment
Investigator(s):	Shen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	06/2010

Abstract:

Stroke is the third major cause of death worldwide and is the leading cause of disability in human diseases. Few therapeutic drugs are available for saving neural cells from cerebral ischemic injury. Recombinant tissue-plasminogen activator (rt-PA) is the only thrombolytic drug approved for rebuilding cerebral circulation in the treatment of acute ischemic stroke. However, rt-PA has the restraint of use within 3 hours after stroke with potential risk of hemorrhagic transformation. It is desirable to develop new drugs for saving neural cells from ischemic brain injury. After stroke, elevated blood brain barrier (BBB) permeability and infarction enlargement are major complications contributing to ischemic brain injury. Activating matrix metalloproteinases (MMPs) is a key step in BBB disruption during stroke [1-3]. MMPs are a large family of proteolytic zinc-containing enzymes responsible for degradation of extracellular matrix around cerebral blood vessels and neurons, and their action leads to BBB opening, brain edema, hemorrhage and cell death. MMP-2, -3, and -9 are the main soluble MMPs in brain. MMP-3 has a broad spectrum of activity against extracellular matrix, while MMP-2 and -9 show narrow ranges of substrates, but these include important elements of the basement membrane. MMP-2 is normally present in astrocytic end feet surrounding cerebral blood vessels. Ischemia-reperfusion causes the induction of MMP-9 in blood vessels and subsequent invasion of neutrophils. Increased activation of MMPs contributes to BBB opening following thrombolysis with rt-PA in focal cerebral ischemic experiments [4]. Development of new drugs particularly targeting on protection of BBB integrity is an attractive strategy for drug discovery to protect ischemic brains in stroke treatment. Free radicals are important mediators for activating MMPs and inducing BBB breakdown and infarction enlargement. Fee radicals include reactive oxygen species (ROS) like superoxide (O2.-) and hydroxyl radicals (.OH) and reactive nitrogen species (RNS) such as nitric oxide (NO) and peroxynitrite (ONOO-), etc. Both ROS and RNS are important cytotoxic factors in neural oxidative damage. NO mediates BBB disruption through MMPs activation [3]. NOS inhibitor L-NAME shows to reduce both the disruption of BBB and MMP-9 expression [5]. NO can react with superoxide (O2.-) to generate ONOO-. Peroxynitrite mediates NO-induced BBB damage. Peroxynitrite can easily penetrate lipid bilayers, leading to peroxidation of membrane lipids. More and more evidences indicate that the formation of peroxynitrite is a key pathway of ischemic brain injury, inducing inflammation, cell death, BBB high-permeability and infarction enlargement. For example, 3-nitrotyrosine (3-NT), an oxidative product of tyrosine by ONOO–, is widely used as a biomarker for ONOO– detection. The increase of 3-NT was found in the penumbral cortex of ischemic brains [5,6]. By co-localizing of 3-NT, MMP-9 and Evans blue leakage, a recent study suggests that ONOO- is associated with MMP-9 activation and BBB opening in focal cerebral ischemia-reperfusion rats [7]. Peroxynitrite decomposition catalysts (PDCs) potentates the reduction of NO and O2.- and isomerizes ONOO- to nitrate and decreases its decomposition to other reactive intermediates. Even delayed treatments of PDCs can reduce apoptosis, infarction volume, edema and neurological deficits in focal ischemic rat brains [8]. Those results suggest a role of NO and ONOO- in activation of MMPs and BBB opening during cerebral ischemia-reperfusion injury. Therefore, seeking for the drugs with the properties of scavenging ONOO- and inhibiting MMPs activation can lead to drug discovery for preventing BBB breakdown and infarction enlargement in stroke treatment. The dried flower of the safflower plant, Carthamus tinctorius L. (紅花), a herbal medicine with the properties of improving circulation, has been used extensively in Traditional Chinese Medicine (TCM) to treat ischemic heart diseases, hypertension, cerebrovascular and gynecological diseases [9, 10]. Phytochemical studies have proved that safflower yellow is the main constituent in water soluble extracts of safflower. Safflower yellow consists of hydroxysafflor yellow A, safflor yellow B, safflomin A, etc, and has a wide range of pharmacological activities, including coronary dilation, platelet activator factor antagonists, antioxidation, myocardial and cerebral protection, and immunosuppression, etc. Hydroxysafflor yellow A (HSYA) is considered as the main active component of safflor yellow contributing to the myocardial and cerebral protective effects and is chosen as an active marker component for controlling the quality of safflower in Chinese Pharmacopoeia [9]. The chemical structure of HSYA is showed in Fig 1 of Attachment. HSYA can extend the coagulation time and has anti-thrombotic effect. Accumulating evidence indicates that HSYA can be potentially developed into a new drug for the treatment of ischemic stroke. HSYA has showed the neuroprotective effects against ischemic brain injury in vivo and in vitro. Previous studies have showed the multiple pharmacological activities of HSYA such as scavenging active oxygen species, suppressing p65 binding activity and inflammatory cytokines including TNF-alpha, IL-1beta and IL-6, promoting anti-inflammatory cytokine IL-10, and inhibiting mitochondrial permeability transition pores, etc.[11-14]. HSYA can reduce infarction size, edema and improve the neurological deficit scores in focal cerebral ischemic rats [11]. HSYA has showed to significantly inhibit glutamate and sodium cyanide (NaCN)-mediated neuronal injury in the in vitro cultured fetal cortical cells and remarkably attenuate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mediated neurotoxicity in mice [15-16]. In our pilot study, we found that HSYA reduced infarction volumes in the ischemic brains in vivo and protected brain microvascular endothelial cells from oxidative injury in vitro. Further study showed that HYSA inhibited MMPs activation and degradation of tight-junction proteins (key proteins in BBB permeability). In order to develop HSYA as a potential drug for protecting BBB from oxidative damage in ischemic stroke treatment, we propose to further investigate the effects of HSYA on inhibiting RNS production, MMPs activation-induced degradation of the tight junction proteins and preventing blood brain barrier disruption in focal brain ischemia-reperfusion injury. References 1. Gasche Y, et al. Front Biosci. 2006;11:1289-301. 2. Rosenberg GA, Yang Y. Neurosurg Focus. 2007;22(5):E4. 3. Liu KJ, Rosenberg GA. Free Rad Biol Med 2005; 39: 71-80 4. Kelly MA, et al. Exp Neurol. 2006; 200(1):38-49 5. Gursoy-Ozdemir Y, et al.Stroke 2000;31:1974-81 6. Suzuki M, et al. Brain Res 2002; 951: 113-20 7. Gursoy-Ozdemir Y, et al. Stroke. 2004; 35(6):1449-53. 8. Thiyagarajan M, et al. Br J Pharmacol 2004; 142, 899-911 9. The State Pharmacopoeia Commission of China, Pharmacopoeia of the People’s Republic of China, Part I. Chemical Industury Press. Beijing, China. 2005. p10 10. Nie QR. Shizhen Med Materia Med Res 2003 14(8): 503-5 11. Ye SY, Gao WY. Arch Pharm Res 2008; 31(8): 1010-5 12. Li ZY, Tu XH. Tradit Chin Drug Res Clin Pharmacol 2005;16(2): 153-6 13. Tian J, et al. Pharmacology 2008:82(2);121-6 14. Chen TT, et al. Yao Xue Xue Bao 2008; 43(6):570-5. 15. Zhu H, et al. Planta Med 2003; 69(5): 429-33. 16. Han B, Zhao H. Neurochem Res 2010; 35(1):107-13

List of Research Outputs

Deng R., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui Buxue Tang (DBT) and its major components on hematopoiesis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Deng R.X., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui and its component Ferulic Acid on haematopoiesis and platelet production, Blood [Abstract in 2009 American Society of Hematology], 20 November 2009. 114.

Feng Y., Liu K.J., Wang J., Shen J., Zhang Y., Rong J., Tong Y., Chan K.S. and Wong B.W., Basic and clinical Toxicology of Chinese Medicines, 基礎和臨床中藥毒理學, Hong Kong, Commercial Press (HK) Ltd., 2009, p394.

Feng Y., Chen X., Wang N. and Shen J., Current Progress on Medicinal Plants and their Biological Properties in Contemporary China, In: Govil J.N. , Recent Progress in Medicinal Plants Vol. 28: Ethnomedicine: Source & Mechanism-II. Houston, USA, Studium Press LLC, 2009, 28: 529-588.

Mao W.W., Wang T.T., Zeng H.P., Wang Z., Chen J. and Shen J., Synthesis and evaluation of novel substituted 5-hydroxycoumarin and pyranocoumarin derivatives exhibiting significant antiproliferative activity against breast cancer cell lines , Bioorganic & Medicinal Chemistry Letters. 2009, 19: 4570-4573.

Shen J., Crosstalk between vascular endothelial growth factor and Notch signaling: A novel signal pathway that mediates neurogenesis in post stroke brains, The 12th National Cerebrovascular Diseases Rehabilitation Conference, Wenzhou . Wenzhou, China, 2009, 53.

Shen J., Rosen C.M. and Liu K.J., Development of 3-actoxymethoxycarbonyl- 2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an Electron Paramagnetic Resonance Imaging Reagent for In Vivo Mapping Brain Oxygen Distribution in Ischemic Brain, 6th Annual World Congress for Brain Mapping and Image Guided Therapy, Boston, . 2009.

Shen J., Rosen G.M. and Liu K.J., Development of 3-actoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an Electron Paramagnetic Resonance Imaging Reagent for In Vivo Mapping Brain Oxygen Distribution in Ischemic Brain , 6th Annual World Congress for Brain Mapping and Image Guided Therapy. Harvard Medical School, Boston, USA, 2009.

Shen J., Sood R., Weaver J., Timmins G.S., Schnell A., Miyake M., Kao J.P., Rosen G.M. and Liu K.J., Direct visualization of mouse brain oxygen distribution by electron paramagnetic resonance imaging: Application to focal cerebral ischemia., Journal of Cerebral Blood Flow & Metabolism. Nature Group Publishing, 2009, 29: 1695-1703.

Shen J., Effects of Buyang Huanwu Decoction on improving neurogenesis and recovery of neurological functions in post-stroke treatment, The 5th Symposium on Collateral Disease Theory, Guangzhou, China. 2009.

Shen J., Effects of hydroxysafflor yellow A (HSYA) on protecting myocardia and brains from ischemia-reperfusion injury, A contract research project awarded HK$ 376,530. 2010.

Shen J. and Li Y., Elucidating Caveolin-1 as a Negative Regulating Protein for Proliferation and Neural Differentiation of Neural stem/progenitor Cells in Post-ischemic Brain with Fluorescent Imaging Technology, 7th Annual World Congress for Brain Mapping and Image Guided Therapy at UNIFORMED SERVICES UNIVERSITY HEALTH SCIENCES (MAY 24-27th 2010). 2010.

Shen J., Lee W.S., Li Y. and Fung M.L., INTERACTION OF CAVEOLIN-1, NITRIC OXIDE AND NITRIC OXIDE SYNTHASES IN HYPOXIC HUMAN SK-N-MC NEUROBLASTOMA CELLS AND RAT ISCHEMIC BRAINS, 6th World Congress for Brain Mapping and Image Guided Therapy. Harvard Medical School, Boston, USA, 2009.

Shen J., Integration of Multiple Comprehensive Approaches for Understanding Therapeutic Principles of BHD-01 in Post-stroke Treatment , Invited lecture at Wuhan Science and Technology University. 2010.

Shen J., Interaction of Caveolin-1 and Nitric Oxide Impacts on Regulation of Blood Brain Barrier Permeability and Infarction Enlargement in Cerebral Ischemia and Reperfusion Injury, Invited lecture at Wuhan . 自由基生物学医学发展战略研讨会暨海峡两岸会议, 2010.

Tong L., Shen J., Qu H.D., Cai G.X., Peng K., Liu B.Y., Rong J., Tan X.H., Liao C.L., Chen Y.Y. and Luo Q.W., 補陽還五湯對缺血性中風後神經元保護及增殖作用的相關機制研究, 2009年度中華中醫藥學會科學技術獎三等獎, 2010.

Tong L., Shen J., Qu H., Cai G.X., Peng K., Liu B.Y., Rong J., Tan X.H., Liao C.L. and Chen Y., 补阳还五汤对缺血性中风后神经元保护及增殖作用的相关机制研究, 2009年广东省科学技术奖, 2009.

Tu T.Z., Shen J. and Jiang J., Studies on constituents from the roots of astrgalus membranaceus (Fisch.) Bge. Hisao., West China Journal of Pharmaceutical Sciences. 2009, 24(5): 27-29.

Yang D., Sun Z., Peng T., Wang L.H., Shen J., Chen Y. and Tam P.K.H., Synthetic fluorescent probes for imaging of peroxynitrite and hypochlorous acid in living cells, Methods Mol Biol.. 2010, 591: 93-103.

Zheng G., Li Y., Gu Y., Chen X., Zhou Y., Zhao S. and Shen J., Beyond Water Channel: Aquaporin-4 in Adult Neurogenesis., Neurochemistry International. 2010, 56(5): 651-654.

Researcher : Song J

List of Research Outputs

Song J., Li Y., Ge J., Duan Y., Sze C.W., Tong Y., Shaw P.C., Ng T.B., Tsui K.C. and Zhang Y., Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC), Phytotherapy Research. 2010, 24 (4): 520-540.

Song J., Li Y.Q., Shaw P.C., Ng T.B., Tong Y., Sze C.W. and Zhang Y., Protective effects of Bilberry (Vaccinium myrtillus L.) extract on beta-Amyloid 25-35 and homocysteine induced neurotoxicity, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM ). UK, 2009.

Song J., Lin X., Sze C.W., Tong Y., Wong N.S., Shaw P.C. and Zhang Y., Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells, In: Song JX, Lin X, Ricky NS Wong, Stephen CW Sze, Tong Y, Shaw PC, Zhang YB, Phytotherapy, accepted . 2010.

Researcher : Sun S

List of Research Outputs

Sun S., (The Various Branches of Acupuncture Studies). 針灸流派概論, 人民衛生出版社, 2009.

Researcher : Sze CW

Project Title:	Molecular Actions of Isolated Dioscorea Batatas Decne protein (Chinese Yam Protein) in Estrogen Secretion via Follicle-Stimulating Hormone Receptor Activation in vitro.
Investigator(s):	Sze CW, Tong Y
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	02/2008
Completion Date:	07/2009

Abstract:

The purpose of the proposed investigation is to find out the action mechanisms of Chinese Yam Protein-induced estrogen secretion in SD-rat ovarian granulose cell via follicle-stimulating hormone receptor (FSHR) activation in vitro. Estrogen is an ovarian hormone, and plays a very important role in triggering the maturation of reproductive organs, helps in the development of sexual characteristics, maintains, regulates and triggers the production of other hormones, and facilitates in the development of menses (1). Peri-menopause is the period of gradual degeneration of ovarian function, during which the estrogen secreted by the ovaries gradually decline. Peri-menopausal women therefore have irregular menses and much higher incidences of physiological changes. These physiological changes induce symptoms, such as hot flashes, night sweats, heart palpitations, loss of bladder control, frequent urination, joint pains, etc. For some females, these physiological changes are severe and significantly disrupt their quality of life. According to a review by the Women's Health Initiative (WHI) and Data and Safety Monitoring Board (DSMB) in 2004, there were more than 477 million peri-menopausal women in the world, and the figure is expected to rise to 1.1 billion after 20 years (2). The solution to overcome menopausal symptoms seems simple – Hormone Replacement Therapy (HRT). This has been a widely accepted practice for the past 40 years, but the bad news is that this therapy also increases the risk of some forms of cancer, including breast, ovarian, and uterine cancer (3-5). Therefore, the need for a novel approach in treating peri-menopausal symptoms is crucial. Chinese Yam, a Chinese Medicine, has been used to treat menopausal symptom folklorically. Peri-menopause is the period of gradual degeneration of ovarian function, which in turn lowers the estrogen level. However, Chinese Yam can elevate the estrogen level of estrogenic depletion patients undergoing peri-menopause. Preivous clinical and experimental study reveals that Chinese Yam possess the estrogenic effect to improve the status of estrogen in menopausal women (6, 7). However this mechanism is still unclear. Besides, it also might reduce the risk of cancer and cardiovascular diseases though the improving the status of lipids and antioxidants in postmenopausal women. (6, 8). Chinese Yam is edible, a sweet soothing herb, which possess the tonic effect on the lung and kidneys and stimulating effect on stomach and spleen in Chinese Medicine (9). Previous studies also showed that proteins isolated from Chinese Yam possess variety biological activities, including antioxidative, carbonic anhydrase and trypsin inhibitor activities etc (10, 11). However, the estrogenic activity of isolated protein from Chinese Yam has still not been reported. Hypothesis: Chinese Yam treatment results in increased estrogen level. This increased secretion of estrogen is attributed to the activation of FSHR in ovarian granulose cells. Activation of FSHR can also trigger to produce estrogen in granulose cells. Therefore, we hypothesize is that Molecular Actions of Isolated Dioscorea Batatas Decne protein in Estrogen Secretion via FSHR Activation in vitro. The purpose of this study: To find out the action mechanism of Chinese Yam-induced estrogen secretion in rat granulose cell via FSHR activation in vitro. If the Hypothesis can be verified, the study should shed novel light on the relationship between Chinese Yam and FSHR activation. Results obtained from this study may benefit the therapeutic approach to peri-menopausal syndromes though FSHR activation. To test the hypothesis, we propose the following specific aims. Special Aim 1: To isolate and purify the estrogenic protein from Chinese Yam by Fast Performance Liquid Chromatograph (FPLC). Special Aim 2: In order to test the implication of the hypothesis, our well-established cell model will be used for studying the molecular event regulating granulosa cell steroidogenesis by Chinese Yam protein, i.e. Chinese Yam protein-induced estrogen secretion in granulosa cells via FSHR activation, and to find out the brief action mechanism of Chinese Yam protein-induced estrogen secretion in rat granulose cells via FSHR activation in vitro. References: 1. James R. Slauterbeck; Stephen F. Fuzie; Michael P. Smith; Russell J. Clark; K.Tom Xu; David W. Starch; Daniel M. Hardy (2002) The Menstrual Cycle, Sex Hormones, and Anterior Cruciate Ligament Injury. Journal of Athletic Training 37(3):275–280 2. Wulf Utian, MD. (2002) Menopause Core Curriculum Study Guide (2nd Edition) 3. David J. Winchester (2003) Hormone Replacement Therapy: A Promoter and Modulator of Breast Cancer. Annals of Surgical Oncology, 11(1):9–10 4. AILA TIITINEN (2002) Hormonal replacement therapy and ovarian cancer. Acta Obstet Gynecol Scand 2002: 81: 479–481 5. V. Loizzi, G. Cormio, M. Vicino, N. Fattizzi, S. Bettocchi & L. Selvaggi (2005)Hormone replacement therapy on ovarian and uterine cancer risk and cancer survivors: how shall we do no harm? International Journal of Gynecological Cancer.15:420. 6. Wu WH et al. (2005) Estrogenic Effect of Yam Ingestion in Healthy Postmenopausal Women. Journal of the american college of nutrition. 24 (4), 235-243. 7. Russell L et al. (2002) Phytoestrogens: a viable option? Am J Med Sci. 324 (4): 185-8. 8. Mckoy et al. (2003) Investigation of the effects of a sapogenin-rich preparation from a Jamaican yam (Dioscorea sp.) on blood cholesterol levels in rats. Proc West Pharmacol Soc. 46; 156-159. 9. Liao YH et al (2004) Compositional and Conformational Analysis of Yam Proteins by Near Infrared Fourier Transform Raman Spectroscopy. J. Agric Food Chem. 52, 8190-8196. 10. Hou WC et al. (2001) Antioxidant Activities of Dioscorin, the Storage Protein of Yam (Dioscorea batatas Decne) Tube. J. Agric. Food Chem., 49 (10), 4956 -4960 11. Hou WC et al. (1999) Dioscorin, the Major Tuber Storage Protein of Yam (Dioscorea batatas Decne) with Carbonic Anhydrase and Trypsin Inhibitor Activities. J. Agric. Food Chem. 47(5) pp 2168 – 2172 12. Santoro N. (2005) The Menopausal transition. The Amercian Journal of Medicine. 118(12B), 8. 13. Uno Y. (1987) Aging Phenomena of Granulosa Cells in the Human Ovary. Hokkaido Igaku Zasshi. 62(4), 558. 14. Mikko Anttonen. (2005) Ovarian Development, Function, and Granulosa cell Tumorigenesis. Academic Dissertation. Pediatric Graduate School, Hospital for Children and Adolescents, University of Helsinki, Finland.

Project Title:	Bioactive components of Tian Xian Liquid as a potential drug candidate for the treatment of colon cancer
Investigator(s):	Sze CW, Tong Y, Hu KY
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	03/2009
Completion Date:	08/2010

Abstract:

The aim of this study is to have primary preclinical research for a new drug development which is useful for the treatment of colon cancer: 1. The bioactive components of Chinese Medicine commercial product, Tian Xian Liquid (TXL), will be extracted and fractioned. 2. And, their pharmacological effect will be evaluated for the further development of a new drug for the treatment of colon cancer. Colon cancer is one of the most common malignancies and the second leading cause of cancer death in the western world, representing one million new cases and half a million deaths annually worldwide [1]. Similar to western countries, Asians are also considered to have high incidence rate of colon cancer. In Hong Kong, colon cancer is the second most common cancer, and the second most frequent cause of cancer death. Every year more than three thousand new cases are diagnosed, and more than one thousand people die of the disease [2]. It is more likely to develop this cancer in those aged over 50, and the risk increases with age. The average age of colon cancer sufferers in Hong Kong is 60 years old. Surgery is the main treatment for colon cancer and adjuvant treatment with chemotherapy and/or radiotherapy may also be used in some situations. Despite years of intensive research, conventional treatments including hormone therapy, radiotherapy, chemotherapy and surgical approaches have not been able ensure a cure. Chinese Medicine has been widely used as for treatment or adjuvant treatment of various cancers or in China for centuries. There is considerable interest among oncologist to find anticancer drugs in Chinese Medicine. Tian-Xian liquid (TXL) has been commercially used as an anticancer dietary supplement for more than 10 years [3] without side effects. It is an aqueous extraction from Chinese herbal mixture and consists mainly of 14 Chinese medicinal herbs: Cordyceps sinensis, Oldenlandia diffusa, Indigo pulverata levis, Polyporus umbellatus, Radix astragali, Panax ginseng, Solanum nigrum L., Pogostemon cablin, Atractylodis macrocephalae rhizoma, Trichosanthes radix, Clematis radix, Margarite, Ligustrum lucidum Ait, and Glycyrrhiza radix [4]. Previous study reported that TXL could induce apoptosis in human cancer cell lines, but not in normal human cells [3]. Besides, our recent findings indicated that the 1% (V/V) of TXL could not only induce apoptosis in colon cancer HT-29 at 48 hour (Fig 1a), but also induce p21-dependent growth arrest (Fig 1b & c). Interestingly 5% (V/V) TXL treatment does induce the proliferation of immune cells, not induce apoptosis (Fig 2). Therefore, all of these phenomenon not only support that TXL is a good drug for colon cancer treatment, but also support us to further explore the pharmacological effect of the bioactive TXL fractions in this study. References: 1. Ferlay J, Bray F, Pisani P, Parkin DM: GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0. IARC CancerBase No 5 IARC, Lyon, France, 2001. 2. Hong Kong Cancer Registry, Hospital Authority, 2005. 3. Sun A, Chia JS, Chiang CP, Hsuen SP, Du JL, Wu CW, Wang WB: The chinese herbal medicine tien-hsien liquid inhibits cell growth and induces apoptosis in a wide variety of human cancer cells. Journal of Alternative & Complementary Medicine 2005;11:245-256. 4. Sun A, Chia JS, Wang WB, Chiang CP: Immunomodulating effects of "Tien-hsien liquid" On peripheral blood mononuclear cells and t-lymphocytes from patients with recurrent aphthous ulcerations. American Journal of Chinese Medicine 2004;32:221-234.

Project Title:	The 8th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM) Micro-computed Tomography for the Evaluation of the Anti-Osteoporotic Activity of Erxian Decoction in Menopausal Rat Model
Investigator(s):	Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

Project Title:	A Novel Estrogenic Protein from Edible Chinese Yam (Dioscorea Opposita Thunb.) as a Potential Drug Candidate for Relieving Menopausal Syndrome
Investigator(s):	Sze CW, Zhang Y, Tong Y
Department:	School of Chinese Medicine
Source(s) of Funding:	Innovation and Technology Support Programme (Tier 2)
Start Date:	12/2009

Abstract:

1. To evaluate the efficacy of the protein drug derived from Chinese yam for menopausal treatment by measuring the serum level of estrogen bio-synthesis in vivo. 2. To study its underlying mechanisms on estrogen biosynthesis in vivo. 3. To further evaluate the efficacy of the protein drug derived from Chinese yam for treating menopausal osteoporosis by measuring the bone mineral density in vivo.

Project Title:	Proteomic study on ovary during menopausal transition
Investigator(s):	Sze CW, Tong Y, Zhang Y
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Menopause is often defined as a period that the ovarian production of estrogens is gradually declined as a result of ovarian senescence [1]. As the ovary’s follicular function is losing, menopause is also defined as “permanent cessation of mense” due to such loss of follicular activity [2]. Although pieces of evidences demonstrating the unique expression of genes during menopause are revealed, the complete biochemical mechanism of the menopausal transition in ovary is yet to be elucidated. During the menopausal transition, ovarian production of estrogen declines which can be reflected from the serum estrogen level [3]. Such decline is often related to the alteration of the steroidogenic pathway. Steroidogenesis refers to the function of synthesis of steroid hormones from the cholesterol precursor. In normal young ovary, steroidogenesis involves the cholesterol being transported into the mitochondrial membrane with the help of steroidogenic acute regulatory (StAR) protein [4]. The cholesterol precursor will then be converted into androgen – androstenedione, and aromatized by aromatase to form estrogen -- estradiol (E2). Some researchers have demonstrated that the steroidogenic pathway is altered during menopause using the microarray and real-time PCR approach [5]. For example, they have revealed that the expression of CYP19 gene coding for aromatase was down-regulated. As a result, production of E2 will be decreased. The negative feedback of E2 to the pituitary and hypothalamus will thus be lessened, leading to elevated production of FSH and LH. The other featured characteristic gene expression during menopausal transition is the up-regulation of StAR protein. Findings from researches using either old mice [5] or VCD-treated mice [6] coincided with each other that, with the deprivation of ovarian function, the StAR protein level in ovary will be increased. This observation sounds consistent with the elevated FSH and LH level observed in menopausal female, as the LH binds to the LH receptor, which triggers cAMP-dependent cascade to stimulate StAR transcription [4]. The researches mentioned unearthed parts of the complicated changes during the menopause. However, questions about what and how the body lead to the transition throughout menopause and aging remains unsolved. A previous research done in 2006 gave a glimpse of the molecular basis of menopausal transition to scientists. By using oligonucleotide array, scientists identified a number of genes showed differential expression between aged and young mice ovary, including genes for steroid and growth factor, transcription factor, cell signaling and stress induced genes [7]. Their research have proved that the aging process in ovary resemble the general functional pathway in other tissues, though tissue specific aging response was also shown. However, how the differential expression of genes in different menopausal stages is mediated and the signaling of the aging process has yet to be determined. Thus by using proteomic approach, this proposed investigation is to find out the protein markers in menopausal transition that can shed light on the understanding of the biology of ovarian aging and its underlying mechanisms during the menopausal transition. There are three objectives in this proposed study. Objective: 1. To set up rat model of different reproductive ages to verify different menopausal transition stages by tracking the serum estrogen level. 2. To identify specific protein markers in each menopausal stages with the use of 2-dimensional gel electrophoresis approach followed by mass spectrometry. 3. To confirm the key protein markers identified in each stage using Western blotting analysis. Reference: [1] F. Al-Azzawi and S. Palacios. (2009) Hormonal Changes During Menopause. Maturitas 63: 135-137. [2] Holly Mattix Kramer MD, Gary C. Curhan MD, ScD, Ajay Singh MD and HELP Study Group. (2003) Permanent cessation of menses and postmenopausal hormone use in dialysis-dependent women: The HELP study. American Journal of Kidney Diseases 41 (3): 643-650. [3] G. Rannevik, S. Jeppsson, 0. Johnell, B. Bjerre, Y. Laurell-Borulf and L. Svanberg. (1995) A Longitudinal Study of the Perimenopausal Transition: Altered Profiles of Steroid and Pituitary Hormones, SHBG and Bone Mineral Density. Maturitas 21: 103-113. [4] P. R. Manna, M.T. Dyson and D. N. Stocco. (2009) Regulation of the Steroidogenic Acute Regulatory Protein Gene Expression: Present and Future Perspectives. Molecular Human Reproduction 15(6): 321-333. [5] J.C. Havelock, W.E. Rainey, K.D. Bradshaw and B.R. Carr. (2006) The Post-menopausal Ovary Displays a Unique Pattern of Steroidogenic Enzyme Expression. Human Reproduction 21(1): 309-317. [6] Z. Rivera, P.J. Christian, S.L. Marison, H.L. Brooks and P.B. Hoyer. (2009) Steroidogenic Capacity of Residual Ovarian Tissue in 4-Vinylcyclohexene Diepoxide Treated Mice. Biology of Reproduction 80: 328-336. [7] A. Zimon, A. Erat, T. von Wald, B. Bissell, A. Koulova, C.H. Choi, D. Bachvarov, R.H. Reindolla and A. Usheva. (2006) Genes Invoked in the Ovarian Transition to Menopause. Nucleic Acid Research 34(11): 3279-3287.

Project Title:	A Novel Estrogenic Protein from Edible Chinese Yam (Dioscorea Opposita Thunb.) as a Potential Drug Candidate for Relieving Menopausal Syndrome
Investigator(s):	Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Innovation and Technology Fund Internship Programme
Start Date:	02/2010

Abstract:

Project Title:	A Novel Estrogenic Protein from Edible Chinese Yam (Dioscorea Opposita Thunb.) as a Potential Drug Candidate for Relieving Menopausal Syndrome
Investigator(s):	Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Innovation and Technology Fund Internship Programme
Start Date:	02/2010

Abstract:

List of Research Outputs

Chu S.M.E., Sze C.W. and Tong Y., Modulation of MMP2 and VEGF expression by Chinese medicine decoction TXL in human colorectal cancer cells, International Conference on Traditional Medicine 2009 – Evaluation on the efficacy, safety and quality control of Traditional medicine, Guangzhou, China. 2009, pp96.

Hu Y.M., Wu J.J., Liu Q., Sze C.W., Zhong L. and Tong Y., Identification of the Multiple Chemical Constituents from a Chinese Medicinal Prescription- Erxian Decoction by LC-DAD-ESI-MS, International Conference on Traditional Medicine. Guangzhou, China, 2009.

Li H.X., Tong Y., Sze C.W. and Ng T.B., Production of Th1- and Th2-dependent Cytokines Induced by the Chinese Medicine Herb,Rhodiola algida, on Human Peripheral Blood Monocytes., Journal of Ethnopharmacology. 2009, 123: 257–266.

Lin X., Sze C.W., Tong Y., Zhang Z., Feng Y., Chen J., Ng T.B., Lin X., Shaw P.C. and Zhang Y., Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren’s Syndrome, Journal of Complementary and Integrative Medicine . 2010, in press.

Liu Q., Sze C.W. and Tong Y., Chinese Medicine Decoction (Tian-Xian Liquid) induces apoptosis in HT-29 Colon Cancer Cells via Mitochondrial Dysfunction, International Conference on Traditional Medicine. Guangzhou, China, 2009.

Shen F., Lin X., Zhang Y., Tong Y. and Sze C.W., 複方黃苦膏劑對濕疹外治消炎止癢作用的實驗研究, 江蘇中醫藥雜誌, 2010.

Song J., Li Y., Ge J., Duan Y., Sze C.W., Tong Y., Shaw P.C., Ng T.B., Tsui K.C. and Zhang Y., Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC), Phytotherapy Research. 2010, 24 (4): 520-540.

Song J., Li Y.Q., Shaw P.C., Ng T.B., Tong Y., Sze C.W. and Zhang Y., Protective effects of Bilberry (Vaccinium myrtillus L.) extract on beta-Amyloid 25-35 and homocysteine induced neurotoxicity, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM ). UK, 2009.

Song J., Lin X., Sze C.W., Tong Y., Wong N.S., Shaw P.C. and Zhang Y., Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells, In: Song JX, Lin X, Ricky NS Wong, Stephen CW Sze, Tong Y, Shaw PC, Zhang YB, Phytotherapy, accepted . 2010.

Sze C.W., Chu S.M.E., Wong K.L., Liu Q., Yow C.M.N., Liu W.K., Ng T.B. and Tong Y., Anti-Cancer Effect of Tian Xian Liquid, a Chinese Medicine Formula, in Human Colon Carcinoma HT29, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Tsang K.W., Wong H.K., Liu Q. and Zhong L., Identification Of The Major Chemical Constituents And Their Metabolites In Rat Plasma And Various Organs After Oral Administration Of Effective Exd Fraction By Liquid Chromatography-mass Spectrometry , In: Lim, Chang Kee , Biomedical Chromatography. 2009.

Sze C.W., Tong Y., Lai Y.M., Zhang Y. and Yow C.M.N., Micro-computed Tomography for the Evaluation of the Anti-Osteoporotic Activity of Erxian Decoction in Menopausal Rat Model, The 8th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM) . 2009.

Sze C.W., Tong Y. and Ye W.C., Quality Assessment Of Cortex Phellodendri By High-performance Liquid Chromatography Coupled With Electrospray Ionization Mass Spectrometry , In: Dr. Chang Kee Lim , Biomedical Chromatography. Biomedical Chromatography, 2009.

Sze C.W. and Tong Y., Regulation of p21, MMP-1 and MDR-1 expression in Human colon carcinoma HT29 by Tian Xian Liquid, a Chinese Medicine Formula, in vitro and in vivo, 7th Annual Congress of International Drug Discovery Science and Technology. Shanghai, China, 2009.

Sze C.W., Tong Y., Yow C.M.N., Liu W.K., Ng T.B., Liu Q. and Chu S.M.E., Regulation of p21, MMP-1 and MDR-1 expression in Human colon carcinoma HT29 by Tian Xian Liquid, a Chinese Medicine Formula, in vitro and in vivo, The 7th Annual Congress of IDDST 2009, Shanghai, China. 2009.

Sze C.W., Tong Y. and Zhang X.I.A.O. .Q.I., Simultaneous Analysis Of Lipid-soluble Constituents Of Erxian Decoction By Using Gas Chromatography And Mass Spectrometry , In: T. A. Berger ；K.-S. Boos; H. Lingeman; G. Massolini; E. R. Adlard; K. D. Altria; I. W. Davies, Chromatographia. Chromatographia, 2009.

Sze C.W., Wong K.L., Chu S.M.E., Zhong L. and Tong Y., Synergistic Effect of Six Estrogenic Compounds isolated from Erxian Decoction for Relieving Menopausal Syndrome, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N., Lai Y.M. and Ng T.B., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis., IEEE PUBLICATION: Biomedical Engineering and Informatics, BMEI 2009. 2009, 1: 47-49.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N. and LAI Y.M., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis, The 2nd International Conference on BioMedical Engineering and Informatics (BMEI'09). 2009.

Tong Y. and Sze C.W., To Unveil Synergistic Effect of TXL in Anti-tumorigencity on Colon Cancer in vitro and in vivo, China-Japan Feida Ltd . 2010.

Zhang Y. and Sze C.W., A formulation of Chinese Medicines to improve diabetic disease., China. China, 2010.

Zhang Y., Feng Y., Sze C.W., Tong Y., Mo F., Yiu Y.M., Xiao L., Wong JH Y., Ng T.B., Shaw P.C., Xiao Y. and Li Z.M., Dendrobium candidum Extract Increases the Expression of Aquaporin 5 in Labial Glands from Patients with Sjögren’s Syndrome. , In: Lin Xiao, Tzi Bun Ng, Yi-Bin Feng, Tong Yao, Jack Ho Wong, Ren-Min Yao, Lei Li, Fei-Zhi Mo, Yin Xiao, Pang-Chui Shaw, Ze-Min Li, Stephen Cho Wing Sze, Kalin Yanbo Zhang, Phytomedicine, Accepted. 2010.

Zhang Y. and Sze C.W., HKD 150,000. Study on the formulation LD209 to improve diabetes. Project No. 20006061., In: Zhang YB, Sze CW. , Oriental Int'l Health Products Co., Ltd.. 2010.

Zhang Y., Sze C.W., Ng T.B., Wong J.H. and Wang H.X., Isolation of a mitogenic agglutinin with relatively high thermostability from seeds of the variegated shell ginger., In: Wong JH, Ng TB, Zhang KY, Sze SC, Wang HX., Protein Pept Lett.. 2010, 17: 38-43.

Zhang Y., Sze C.W., Tong Y., Feng Y., Ng T.B., Shaw P.C., Xiao L. and Xiao K., Protective effect of Dendrobium officinale polysaccharides on experimental Sjögren’s Syndrome, In: Xiang Lin, Stephen Cho-Wing Sze, Yao Tong, Zhangjin Zhang, Yibin Feng, Jian ping Chen, Tzi Bun Ng, Xiao Lin, PC Shaw, and Kalin Yanbo Zhang., Journal of Complementary and Integrative Medicine. 2010, 17: 1-18.

Zhang Y., Sze C.W., Ng T.B. and Wang J.H., Purification and Characterization of a Laccase with Inhibitory Activity toward HIV-1 Reverse Transcriptase and Tumor Cells from an Edible Mushroom (Pleurotus cornucopiae), In: Wong JH, Ng TB, Jiang Y, Liu F, Cho S, Sze W, Zhang KY., Protein Pept Lett.. 2009, 10: [Epub ahead of print].

Zhang Y., Sze C.W. and Tong Y., The Novel Mechanisms Study: the Chrysotoxine, a Compound from Dendrobium chrysotoxum, Treats Sjögren's Syndrome., In: Stephen CW Sze, Tong Y, Kalin Zhang YB, Chinese Medicine Society. 2009.

Researcher : Tang J

List of Research Outputs

Tang J., Feng Y., Tsao G.S.W., Wang N., Curtain R.P. and Wang Y., Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations. , Journal of Ethnopharmacology. . 2009, 126: 5-17.

Researcher : Tong Y

Project Title:	Bioactive Components of Erxian Decoction as a Potential Drug Candidate for Peri-menopausal Syndrome
Investigator(s):	Tong Y, Sze CW, Zhang Y
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	06/2008
Completion Date:	05/2010

Abstract:

The aim of this study is to have primary preclinical research for a new drug development which is useful for the relieving the peri-menopausal syndrome: 1. The bioactive components of Chinese Medicine Formulation, Erxian Decoction, will be extracted and fractioned. 2. And, their pharmacological effect will be evaluated for the further development of a new drug for relieving peri-menopausal syndrome. Peri-menopause is the period of gradual degeneration of ovarian function, during which the estrogen secreted by the ovaries gradually decline [1]. Menopausal women suffer from hot flashes, night sweats, mood swings and insomnia, etc. It is believed that low levels of estrogen and high levels of FSH in patients are responsible for the peri-menopausal symptoms [2]. Hormone replacement therapy (HRT) is clinically used as effective medications. This has been a widely accepted practice for the past 40 years, but the bad news is that this therapy also increases the risk of developing breast cancers, stroke, osteoporosis and Alzheimer’s disease etc [3-15]. Therefore, it is desirable and urgent to explore the use of alternative medicine, especially Chinese Medicine [16-18]. Erxian Decoction (EXD), a Chinese Medicine experienced formula, has been used to treat menopausal syndrome for fifty years [19, 20-22]. No toxic reaction was reported. Only some symptoms such as vomiting and diarrhea were reported when the dosage used was equivalent to 60-80 times of the dosage applied in clinical practice [23]. EXD has six herbs including rhizome curculiginis orchioidis, herba epimedii, Radix morindae officinalis, radix angelicae sinenisis, cortex phellodendri and rhizome anemarrhenae. Interestingly EXD treatment does induce estrogen secretion in peri-menopausal women and rats [11, 24-28]. Besides, our recent findings indicated that the EXD could increase the estrogen secretion (Fig 1A) via the aromastase signialling pathway in female aged SD-rat (Fig 1B). Therefore, all of these phenomenons support us to further explore the pharmacological effect of the bioactive EXD fractions in this study. References: 1. Greendale GA et al. Lancet 1999;353:571-580 2. Simoni M et al. Endocrine reviews 1997;18:739-773 3. Goldstein LB et al. Circulation 2006;113:873-923 4. Uno Y et al. The Hokkaido journal of medical science 1987;62:558-563 5. Utian W. Menopause Core Curriculum Study Guide (2nd Edition). In; 2002. 6. Mora S et al. Current Treatment Options in Cardiovascular Medicine 2001;3:67-79 7. Miller KJ. Current psychiatry reports 2003;5:439-444 8. Rossouw JE et al. Journal of the American Medical Association 2002;288:321-333 9. Lertsanguansinchai P et al. Journal of the Medical Association of Thailand 2002;85 Supplement 1:S193-202 10. Lien LL et al. Journal Clinical Pharmacology and Therapeutics 1996;21:101-111 11. Zhang CZ et al. Journal of ethnopharmacology 2005;98:295-300 12. Lobo RA et al. Medscape general medicine 2006;8:40 13. Vera PGC et al. Review Medical Chile 2003;131:951-953 14. Anderson GL et al. Journal of the American Medical Association 2004;291:1701-1712 15. Rossouw JE et al. Journal of the American Medical Association 2002;288:321-333 16. Eisenberg DM et al. Journal of the American Medical Association 1998;280:1569-1575 17. Low Dog T et al. The American journal of medicine 2005;118 Suppl 12B:98-108 18. Newton KM et al. Obstetrics and gynecology 2002;100:18-25 19. Wang CH et al. Shanxi Journal of Traditional Chinese Medicine 1997;18 (6):253 20. Zhang L et al. Fujian Journal of Traditional Chin Medicine 2004;35 (1):19-22 21. Zhang B et al. Chinese Journal of Internal Medicine 1965;13(6):501-503 22. Li. Y et al. Shanghai Journal of Internal Medicine 2004;38 (2):43-44 23. GS Z et al. Pharmacy Acta 1962;9 (5):287 24. Nian H et al. Journal of ethnopharmacology 2006;108:96-102 25. Lu SB et al. Shandong Journal of Traditional Chinese Medicine 1998;17(12): 547 26. Li JJ et al. Chinese Journal of integrative medicine 2007;13:67-73 27. Liu Q et al. China Journal of Chinese Materia Medica 2005;30:1023-1026 28. ZQ Fang et al. China Journal of Traditional Chinese Medicine and Pharmacy 1992;7 (5):24-26 29. Santoro N. The menopausal transition. The American journal of medicine 2005;118 Suppl 12B:8-13 30. Miller MM et al. Experimental Gerontology 1998;33:729-757 31. Danilovich N et al. Biology of reproduction 2002;67:370-378 32. Wu JM et al. Exp Biol Med (Maywood) 2005;230:818-828 33. Aschheim P et al. Experientia 1974;30:213 34. Wilkes MM et al. Advances in experimental medicine and biology 1978;113:127-147 35. Gore AC et al. Endocrine 2000;13:315-323 36. Danilovich N et al. Experimental Gerontology 2004;39:1669-1678 37. Danilovich N et al. Experimental Neurology 2003;183:559-572 38. Danilovich N et al. Experimental gerontology 2006;41:117-122 39. Rehman HU et al. Gender Medicine 2005;2:41-56 40. Urban RJ et al. Endocrinology and Metabolism Clinics of North America 1992;21:921-931 41. Te Velde ER et al. Molecular and cellular endocrinology 1998;145:67-73 42. Wise PM et al. Recent progress in hormone research 2002;57:235-256 43. SCW Sze et al. Beijing Conference Center location diagram; 2007 44. ZQ Fang et al. Chinese Journal of Basic Medicine in Traditional Chinese Medicine 2003;9:78-81 45. ZQ Fang et al. Chinese Journal of Basic Medicine in Traditional Chinese Medicine 1998;4 (1):23-25 46. ZQ Fang et al. Acta University Traditions Medicals Sinensis Pharmacology Shanghai 1998;12 (1):59-61 47. ZQ Fang et al. Journal of Shandong College of Traditional Chinese Medicine 1996;20 (6):399-401

Project Title:	Mechanical Study of Tian Xian Liquid (TXL), Chinese Medicine Formula, in Treatment of Colon Cancer in vitro
Investigator(s):	Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2008

Abstract:

Colon cancer is one of the most common malignancies and the second leading cause of cancer death in the western world, representing one million new cases and half a million deaths annually worldwide [1]. Similar to western countries, Asians are also considered to have high incidence rate of colon cancer. In Hong Kong, colon cancer is the second most common cancer, and the second most frequent cause of cancer death. Every year more than three thousand new cases are diagnosed, and more than one thousand people die of the disease [2]. It is more likely to develop this cancer in those aged over 50, and the risk increases with age. The average age of colon cancer sufferers in Hong Kong is 60 years old. Surgery is the main treatment for colon cancer and adjuvant treatment with chemotherapy and/or radiotherapy may also be used in some situations. However, the etiology of colon cancer is still unclear, most studies have showed that dietary and genetic factors are closely related to the disease. Carcinogenesis contains three stages: initiation, progression and promotion. Initiation is a result of initial uptake of a carcinogen and the subsequent stable genotoxic damage [3]. Other causes of cancer initiation include oxidative stress, chronic inflammation, and hormonal imbalance [4]. Promotion process is caused by deregulated signal transduction pathways such as nuclear factor kappa B (NFκB), Ras, Wnt/beta-catenin, mitogen-activated protein kinase (MAPK) pathways. Inflammation acts as a key regulator during the progression, possibly by providing initiated cells with proliferating signals and by preventing apoptosis. Cancer growth follows fine balance disturbance in cell proliferation, differentiation and death. The balance between proliferation and apoptosis is crucial in determining the overall growth or regression of the tumor. [4,5] Neo-angiogenesis is required for tumor development and progression. Many solid tumors induce vascular proliferation by production of angiogenic factors, prominently vascular endothelial growth factor (VEGF), which is regulated by hypoxia-inducible factor (HIF)-1 expression and transcriptional activation.[6] Despite years of intensive research, conventional treatments including hormone therapy, radiotherapy, chemotherapy and surgical approaches have not been able ensure a cure. Chinese Medicine has been widely used as for treatment or adjuvant treatment of various cancers or in China for centuries. There is considerable interest among oncologist to find anticancer drugs in Chinese Medicine. Tian-Xian liquid (TXL) has been commercially used as an anticancer dietary supplement for more than 10 years [7] without side effects. It is an aqueous extraction from Chinese herbal mixture and consists mainly of 14 Chinese medicinal herbs: Cordyceps sinensis, Oldenlandia diffusa, Indigo pulverata levis, Polyporus umbellatus, Radix astragali, Panax ginseng, Solanum nigrum L., Pogostemon cablin, Atractylodis macrocephalae rhizoma, Trichosanthes radix, Clematis radix, Margarite, Ligustrum lucidum Ait, and Glycyrrhiza radix [8]. Bradford et al reported TXL had no acute toxicity test with two week's oral administration in two species. The micronucleus test had mutagenic action in a dose-dependent manner. Their research found TXL had some harmful and toxic action on the heredity of germ cells while normal in Ames test [9]. Ding et al also indicated TXL had inhibitory effects on hepatic carcinoma foci [10]. Zhao et al also reported TXL had inhibitory effects on S180, and had inhibitory effects on hepatic carcinoma foci [11]. Bradford et al also reported that TXL had some effect on phagocytic function of mononuclear macrophage, spleen index and thymus index, splenic lymphocyte transformation, serum hemolysin formation, host spleen reaction coefficient and stimulate coefficient & stimulus index [12]. Sun et al indicated TXL could induce apoptosis in human cancer cell lines, but not in normal human cells [7]. Hypothesis: In our previous study, the proliferation effect of Tian Xian Liquid (TXL) on colon cancer cell HT-29 has been studied. However, the mechanism of its anti-cancer effect is still unknown. In this study, we hypothesized that TXL possess the properties of anti-angiogenesis and reversion of multidrug-resistance (MDR) in treatment of colon cancer in vitro. Objectives: 1. To conduct quality control study of TXL 2. To determine whether the TXL possesses anti-angiogenesis property for the treatment of colon cancer or not 3. To determine whether the TXL possesses reversion of multidrug-resistance for the treatment of colon cancer or not References: 1. Ferlay J, Bray F, Pisani P, Parkin. IARC CancerBase No 5 IARC, Lyon, France, 2001. 2. Hong Kong Cancer Registry, Hospital Authority, 2005. 3. Hahn WC, Weinberg. New Engl J Med 2002;347:1593-1603. 4. Tamm I, Schriever F, Dorken B. Lancet Oncol 2001;2:33-42. 5. Reed JC. Curr Opin Oncol 1999;11:68-75. 6. Rhee J, Hoff PM. Expert Opin Pharmacother 2005;6:1701-1711. 7. Sun A, Chia JS, Chiang CP, Hsuen SP, Du JL, Wu CW, Wang WB. Journal of Alternative & Complementary Medicine 2005;11:245-256. 8. Sun A, Chia JS, Wang WB, Chiang CP. American Journal of Chinese Medicine 2004;32:221-234. 9. Bradford RW, Ding KX: The study on the toxicology of frc001 (China no.1 tian xian liquid), 2007. 10. Ding KX, Su CW, Bradford RW: The study on the inhibition effects of frc001 (china no. 1 tian xian sarcoma liquid), 2007. 11. Zhao BL, Xin WJ, Kao CY, Zhang H: Scavenging effects of frc001 china no.1 tian xian liquid on oxygen free radicals, 2007. 12. Bradford RW, Ding KX: The experimental study on the effect of frc001 (china no. 1 tian xian liquid), 2007. 13. Tabruyn SP, Griffioen. Biochem Biophys Res Commun 2007;355:1-5. 14. Yoysungnoen P, Wirachwong P, Bhattarakosol P, Niimi H, Patumraj S. Clin Hemorheol Microcirc 2006;34:109-115. 15. Hao LS, Wang G, Qian K, Luo T, Li XJ, Wu XT]. Sichuan Da Xue Xue Bao Yi Xue Ban 2007;38:60-63. 16. Sarkar FH, Adsule S, Li Y, Padhye S. Mini Rev Med Chem 2007; 7: 599-608. 17. Shimizu M, Deguchi A, Joe AK, Mckoy JF, Moriwaki H, Weinstein IB. J Exp Ther Oncol 2005; 5: 69-78. 18. Toffoli G, Viel A, Tumiotto L, Biscontin G, Rossi C, Boiocchi M. Br J Cancer 1991. 63: 51-56. 19. Lazaris AC, Kavantzas NG, Zorzos HS, Tsavaris NV, Davaris. J Cancer Res Clin Oncol 2002; 128: 114-118.

Project Title:	8th Meeting of the Consortium for Globalization of Chinese Medicine The Characteristics of Chinese Medicine Education in the University of Hong Kong
Investigator(s):	Tong Y
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

Project Title:	A pilot study of teaching Chinese Medicine Diagnostics with problem-based learning tutorials
Investigator(s):	Tong Y, Shen J, Diu CK
Department:	School of Chinese Medicine
Source(s) of Funding:	Run Run Shaw Research and Teaching Endowment Fund - Teaching Grants
Start Date:	09/2009

Abstract:

Problem-based learning (PBL) tutorials have played a more and more important role in the medical education. It was initiated and used extensively at McMaster University, Hamilton, Ontario, Canada and widely accepted and developed by the other universities in the North America in the past 20 years. In Asia, the Faculty of Medicine, Hong Kong University was one of the earliest pioneers in reforming the curriculum into a system-based programme with the use of student-centred and problem-based approach since 1997. It has marked an important breakthrough in medical education and gained great reputation in the region. It is quite important to implement PBL in the teaching of traditional Chinese Medicine, because the knowledge systems of the traditional Chinese Medicine are totally different from the modern scientific theories and they are combination of medicine, humanities, philosophy, sociology, and psychology,etc. The thinking pattern of traditional Chinese Medicine is quite difficult to understand if it is learned by lectures and totally self-directed learning. But the PBL tutorial is an excellent educational method for the students to mature in their professional attitude, as well as to gain communication skills, enhance the ability of discovering and solving problem, and gain practical knowledge, especially for meeting the demands of new generation of Chinese Medicine practitioners. So it is a valuable issue to be considered for how to make balance between the traditional lecture-based learning and the problem-based learning in the teaching of the traditional Chinese Medicine Some Chinese medicine schools in mainland China have tried to implement PBL tutorials since 2003 but these implementations were independent of the existing curricula and resulted in additional overloaded schedules for both the students and the educators. On the other hand, the number of the students in these Chinese medicine schools is usually large, 70-80 students per class, and the teachers are only 3-4 in one tutorial class, so each group is more than 10 students which results in the poor quality of the discussions and participation of the students. Based on all these experiences, a pilot study in adding problem-based learning tutorials to a traditional lectured-lecture-based curriculum "Diagnostics of Traditional Chinese Medicine" will be conducted in the School of Chinese Medicine, LKS Faculty of Medicine, HKU. The aim of this study is to evaluate whether PBL tutorials will improve the motivation of self-learning and how to implement the PBL tutorials into the total curricula of traditional Chinese Medicine. The key issues of this study include the selection of PBL tutors, creating the PBL scenario, team size and random allocation.

Project Title:	An Innovative Approach for Research and Development of Novel Scientific Chinese Medicine Formula: Erxian Decoction for Relieving Menopause Syndrome as a Study Model
Investigator(s):	Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	01/2010

Abstract:

Chinese medicine is widely used throughout the world. Thus, the current trend is to research and develop high quality, effective and safe multi-ingredient-based drugs derived from prescribing formulas for treating diseases which are hard to treat with Western medicine. Prescribing formulas is very common in Chinese medicine. Each herb is understood to carry out distinctive functions at specific organs. When used in combination, Chinese herbs not only synergistically enhance their therapeutic effects, but also simultaneously offset their adverse effects. Therefore, a Chinese medicine formula (CMF) is extremely safe when prescribed correctly by a qualified Chinese medicine practitioner. However, due to the complexity of its chemical constituents, it is hard to address the essence of the formulas, making it difficult to study the potential mechanisms of action as well as introducing it to the world. In this study, we propose to develop an innovative approach for addressing the essence of the CMF, developing the novel scientific medicine formula and elucidating its underlying mechanism of action at specific organs for treating disease. Erxian Decoction (EXD) is selected as a model in this proposed study, which has been extensively used in the clinical menopausal therapy for the last fifty years. Previous findings [1-6] and our recent publications [7-8] revealed that EXD has effectiveness in relieving menopausal syndrome via increasing the circulatory estrogen level. The menopause-related changes in the hypothalamic-pituitary-ovarian (H-P-O) axis have lead to the decrease of circulatory estrogen level. In this proposal, we intend to use pharmacology and system biology approaches to develop a novel strategy for seeking the corresponding multi-constituents responsible for the efficacy of EXD formula and studying their underlying synergistic mechanisms of action in H-P-O axis for relieving menopausal syndrome. In addition, the quality control and quality consistency of preparations of EXD in our previous study [9-10] was also assessed using modern chemical fingerprint technologies, but the complexity of its chemical constituents in fact makes it hard to address the essence of this Chinese medicine formula, and so as a result, it is very difficult to properly introduce it to the world. Therefore, in this proposed study, we use EXD for relieving menopause syndrome as a study model to elucidate the science behind Chinese medicine formula in the concept of holism. We hypothesized that corresponding therapeutic constituents of EXD can research and function synergistically at the multiple target sites of hypothalamic-pituitary-ovarian (H-P-O) axis for reliving menopause syndrome. Although some bio-active constituents of EXD have been reported and isolated [11], the rationale of having them together in EXD has never been explored. Having newly developed technology in bio-analytical chemical and proteomics analysis, our objectives are: (1) to seek the EXD’s constituents detected in H-P-O axis and serum of the SD-rat after treating with EXD; (2) to isolate the corresponding EXD’s constituents from its raw material (3) to study their individual and synergistic effect in endocrine aspect on their target sites in vitro and elucidate their underlying mechanism using our well-established proteomic analysis. The identification of regulated protein (s) in proteomic analysis could help us to understand the rationale of holism in Chinese medicine and synergistic action mechanism of Novel Scientific Chinese Medicine Formulas at target specific organs. In addition, this study provides useful insights to set up a strong rationale for enhancing the quality and efficacy of Chinese medicine, i.e. developing the multi-ingredients-based drug (Novel Scientific Chinese Medicine Formula), and set up a model to promote the modernization and globalization of Chinese medicine. If the proposed study is awarded, we will apply the ITF to verify the efficacy of corresponding EXD’s constituents in vivo. (i.e. to develop the Novel Scientific Chinese Medicine Formula; to study their synergistic effect in endocrine and proteomic aspects on their target sites and elucidate their underlying mechanism in vivo) Reference: (refer to attachment)

Project Title:	A pilot study on the effects of a Chinese herbal formula on menopause
Investigator(s):	Tong Y, Chu SME
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Objectives: The main menopausal symptoms include vasomotor symptoms (hot flushes, night sweats), mood and sleep disturbances .The population of Chinese women aged 45-60 years old is about 120 millions . In Hong Kong, it is predicted that by 2010, the percentage of women aged 50 years old will be about 31.8% . A research in Hong Kong indicated that 48% of the perimenopausal women experienced four or more symptoms compared with 23% of premenopausal, and 29% of the postmenopausal women . The standard treatment for menopausal symptoms was hormone replacement therapy (HRT). However, the long-term large-scale study of HRT by the Women’s Health Initiative (WHI) indicated that HRT can increase the risks of breast cancer, coronary heart disease and thromboembolic disease. HRT in the US for menopausal symptoms declined from 91 million women in 2001 to 57 million in 2003 . Events have led to considerable public attention and encouraged clinicians to search for alternative options that may possess comparable efficacy and safety without significant side effects In recent years, more and more women have turned to traditional Chinese medicine (TCM) to manage their menopausal symptoms. Among various Chinese medicine formulae, Erxian Decoction (EXD) is one of the most acceptable Chinese medicine formulae to relieve menopausal symptoms11. EXD is composed of rhizome curculiginis (仙茅)，herba epimedii (淫羊藿), radix morindae officinalis (巴戟天), rhizome anemarrhenae（知母）, cortex phellodendri（黄柏） and radix angelicae sinenisis(當歸) The applicants have studied the efficacy of EXD with multi-disciplinary approaches for nearly four years. Previous work and our unpublished experimental data indicated that EXD treatment shows a significant increase of estrogen level in the sera of twenty-month-old female SD-rats compared with the control group and in the culture medium of cultured ovarian granulosa cells . Clinical trials of EXD are small-sample observational trials to evaluate the efficacy and safety of this formula, which have shown satisfactory efficacy for menopause symptoms relief and osteoporosis with no adverse effects reported. However, there is no RCT study has been done before to evaluate the efficacy of EXD. The objective of this pilot project is to conduct a small sample clinical trial to evaluate whether Erxian Decoction could improve menopausal symptoms with the standard Menopause Rating Scale (MRS) [Annex A]and also improve the quality of life with the Menopause-Specific Quality of Life Questionnaire (MENQOL) [Annex B].

List of Research Outputs

Cheung K.F., Ye D., Yang Z., Lu L., Liu C.H., Wang X.L., Poon R.T.P., Tong Y., Liu P., Chen Y. and Lau G., Therapeutic efficacy of Traditional Chinese Medicine 319 recipe on hepatic fibrosis induced by carbon tetrachloride in rats, Journal of Ethnopharmacology. 2009, 124(1): 142-150.

Chu S.M.E., Sze C.W. and Tong Y., Modulation of MMP2 and VEGF expression by Chinese medicine decoction TXL in human colorectal cancer cells, International Conference on Traditional Medicine 2009 – Evaluation on the efficacy, safety and quality control of Traditional medicine, Guangzhou, China. 2009, pp96.

Feng Y., Liu K.J., Wang J., Shen J., Zhang Y., Rong J., Tong Y., Chan K.S. and Wong B.W., Basic and clinical Toxicology of Chinese Medicines, 基礎和臨床中藥毒理學, Hong Kong, Commercial Press (HK) Ltd., 2009, p394.

Feng Y., Cheung K.F., Wang N., Liu P., Nagamatsu T. and Tong Y., Chinese medicines as a resource for liver fibrosis treatment , In: Hin Wing Yeung, Chinese Medicine . Macau, International association of Chinese Medicine, 2009, 4(1): 16.

Hu K.Y., Wang Y.T., Sze S.C., Tsang K.W., Wong H.K., Liu Q., Zhong L. and Tong Y., Identification of the major chemical constituents and their metabolites in rat plasma and various organs after oral administration of effective Erxian Decoction (EXD) fraction by liquid chromatography-mass spectrometry., Biomed Chromatogr. 2010 May;24(5):. 2010, 479-89.

Hu Y.M., Wu J.J., Liu Q., Sze C.W., Zhong L. and Tong Y., Identification of the Multiple Chemical Constituents from a Chinese Medicinal Prescription- Erxian Decoction by LC-DAD-ESI-MS, International Conference on Traditional Medicine. Guangzhou, China, 2009.

Li H.X., Tong Y., Sze C.W. and Ng T.B., Production of Th1- and Th2-dependent Cytokines Induced by the Chinese Medicine Herb,Rhodiola algida, on Human Peripheral Blood Monocytes., Journal of Ethnopharmacology. 2009, 123: 257–266.

Lin X., Sze C.W., Tong Y., Zhang Z., Feng Y., Chen J., Ng T.B., Lin X., Shaw P.C. and Zhang Y., Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren’s Syndrome, Journal of Complementary and Integrative Medicine . 2010, in press.

Liu Q., Sze C.W. and Tong Y., Chinese Medicine Decoction (Tian-Xian Liquid) induces apoptosis in HT-29 Colon Cancer Cells via Mitochondrial Dysfunction, International Conference on Traditional Medicine. Guangzhou, China, 2009.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolide isomers H and I from Rhizoma Chuanxiong attenuate hydrogen peroxide-induced oxidative stress in human liver HepG2 cells via induction of heme oxygenase-1, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM). Nottingham, UK, 2009.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1, Chemico-Biological Interactions. 2010, 183(3): 380-389.

Shen F., Lin X., Zhang Y., Tong Y. and Sze C.W., 複方黃苦膏劑對濕疹外治消炎止癢作用的實驗研究, 江蘇中醫藥雜誌, 2010.

Song J., Li Y., Ge J., Duan Y., Sze C.W., Tong Y., Shaw P.C., Ng T.B., Tsui K.C. and Zhang Y., Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC), Phytotherapy Research. 2010, 24 (4): 520-540.

Song J., Li Y.Q., Shaw P.C., Ng T.B., Tong Y., Sze C.W. and Zhang Y., Protective effects of Bilberry (Vaccinium myrtillus L.) extract on beta-Amyloid 25-35 and homocysteine induced neurotoxicity, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM ). UK, 2009.

Song J., Lin X., Sze C.W., Tong Y., Wong N.S., Shaw P.C. and Zhang Y., Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells, In: Song JX, Lin X, Ricky NS Wong, Stephen CW Sze, Tong Y, Shaw PC, Zhang YB, Phytotherapy, accepted . 2010.

Sze C.W., Chu S.M.E., Wong K.L., Liu Q., Yow C.M.N., Liu W.K., Ng T.B. and Tong Y., Anti-Cancer Effect of Tian Xian Liquid, a Chinese Medicine Formula, in Human Colon Carcinoma HT29, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Tong Y., Lai Y.M., Zhang Y. and Yow C.M.N., Micro-computed Tomography for the Evaluation of the Anti-Osteoporotic Activity of Erxian Decoction in Menopausal Rat Model, The 8th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM) . 2009.

Sze C.W., Tong Y. and Ye W.C., Quality Assessment Of Cortex Phellodendri By High-performance Liquid Chromatography Coupled With Electrospray Ionization Mass Spectrometry , In: Dr. Chang Kee Lim , Biomedical Chromatography. Biomedical Chromatography, 2009.

Sze C.W. and Tong Y., Regulation of p21, MMP-1 and MDR-1 expression in Human colon carcinoma HT29 by Tian Xian Liquid, a Chinese Medicine Formula, in vitro and in vivo, 7th Annual Congress of International Drug Discovery Science and Technology. Shanghai, China, 2009.

Sze C.W., Tong Y., Yow C.M.N., Liu W.K., Ng T.B., Liu Q. and Chu S.M.E., Regulation of p21, MMP-1 and MDR-1 expression in Human colon carcinoma HT29 by Tian Xian Liquid, a Chinese Medicine Formula, in vitro and in vivo, The 7th Annual Congress of IDDST 2009, Shanghai, China. 2009.

Sze C.W., Tong Y. and Zhang X.I.A.O. .Q.I., Simultaneous Analysis Of Lipid-soluble Constituents Of Erxian Decoction By Using Gas Chromatography And Mass Spectrometry , In: T. A. Berger ；K.-S. Boos; H. Lingeman; G. Massolini; E. R. Adlard; K. D. Altria; I. W. Davies, Chromatographia. Chromatographia, 2009.

Sze C.W., Wong K.L., Chu S.M.E., Zhong L. and Tong Y., Synergistic Effect of Six Estrogenic Compounds isolated from Erxian Decoction for Relieving Menopausal Syndrome, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N., Lai Y.M. and Ng T.B., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis., IEEE PUBLICATION: Biomedical Engineering and Informatics, BMEI 2009. 2009, 1: 47-49.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N. and LAI Y.M., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis, The 2nd International Conference on BioMedical Engineering and Informatics (BMEI'09). 2009.

Tong Y. and Zhong L., Comparative Study of Five Organs between Chinese and Western Medicine, 中西醫五臟比較研究, Hong Kong, The Commercial Press (H.K.), 2009, 2.

Tong Y., The Characteristics of Chinese Medicine Education in the University of Hong Kong, The 8th Meeting of the Consortium for Globalization of Chinese Medicine 2009 (CGCM 2009). 第八屆中藥全球化聯昷會議 (2009), Nottingham, UK, 2009.

Tong Y., The Investigation and Implementation of Innovative, Training System in Chinese Medicine , The 41st Annual Meeting of The Japan Society for Medical Education. Osaka, Japan, 2009.

Tong Y. and Sze C.W., To Unveil Synergistic Effect of TXL in Anti-tumorigencity on Colon Cancer in vitro and in vivo, China-Japan Feida Ltd . 2010.

Tsang C.M., Lau P.W.E., Di K., Cheung P.P.Y., Hau P.M., Ching Y.P., Wong Y.C., Cheung A., Wan T.S.K., Tong Y., Tsao G.S.W. and Feng Y., Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells, International Journal of Molecular Medicine. 2009, 24: 131-138.

Zhang Y., Feng Y., Sze C.W., Tong Y., Mo F., Yiu Y.M., Xiao L., Wong JH Y., Ng T.B., Shaw P.C., Xiao Y. and Li Z.M., Dendrobium candidum Extract Increases the Expression of Aquaporin 5 in Labial Glands from Patients with Sjögren’s Syndrome. , In: Lin Xiao, Tzi Bun Ng, Yi-Bin Feng, Tong Yao, Jack Ho Wong, Ren-Min Yao, Lei Li, Fei-Zhi Mo, Yin Xiao, Pang-Chui Shaw, Ze-Min Li, Stephen Cho Wing Sze, Kalin Yanbo Zhang, Phytomedicine, Accepted. 2010.

Zhang Y., Sze C.W., Tong Y., Feng Y., Ng T.B., Shaw P.C., Xiao L. and Xiao K., Protective effect of Dendrobium officinale polysaccharides on experimental Sjögren’s Syndrome, In: Xiang Lin, Stephen Cho-Wing Sze, Yao Tong, Zhangjin Zhang, Yibin Feng, Jian ping Chen, Tzi Bun Ng, Xiao Lin, PC Shaw, and Kalin Yanbo Zhang., Journal of Complementary and Integrative Medicine. 2010, 17: 1-18.

Zhang Y., Sze C.W. and Tong Y., The Novel Mechanisms Study: the Chrysotoxine, a Compound from Dendrobium chrysotoxum, Treats Sjögren's Syndrome., In: Stephen CW Sze, Tong Y, Kalin Zhang YB, Chinese Medicine Society. 2009.

Zhang Z., Tan Q.R., Zhen X.C. and Tong Y., The potential benefits of herbal medicines for schizophrenia: from empirical observations to clinical trials (chapter 16). In: Hertzman M & Adler L (ed): Clinical Trials in Psychopharmacology. , Wiley-Blackwell, UK, 2010, 311-335.

Zhong L. and Tong Y., Quality Assessment of the Clinical Trials with Chinese Medicine on Menopausal Syndrome in the Last Five Years: From the View of Evidence-based Medicine, 5th International Congress On Complementary Medicine Research. 2010, P-105.

Zhong L. and Tong Y., The Roles Of Er-xian Decoction As A Basic Formula For The Management Of Menopause-related Symptoms: A Systematic Evidence Review, The 9th National Conference Of TCM Gynecology. 2009.

Researcher : Tsang KW

List of Research Outputs

Hu K.Y., Wang Y.T., Sze S.C., Tsang K.W., Wong H.K., Liu Q., Zhong L. and Tong Y., Identification of the major chemical constituents and their metabolites in rat plasma and various organs after oral administration of effective Erxian Decoction (EXD) fraction by liquid chromatography-mass spectrometry., Biomed Chromatogr. 2010 May;24(5):. 2010, 479-89.

Sze C.W., Tsang K.W., Wong H.K., Liu Q. and Zhong L., Identification Of The Major Chemical Constituents And Their Metabolites In Rat Plasma And Various Organs After Oral Administration Of Effective Exd Fraction By Liquid Chromatography-mass Spectrometry , In: Lim, Chang Kee , Biomedical Chromatography. 2009.

Researcher : Wang N

List of Research Outputs

Feng Y., Cheung K.F., Wang N., Liu P., Nagamatsu T. and Tong Y., Chinese medicines as a resource for liver fibrosis treatment , In: Hin Wing Yeung, Chinese Medicine . Macau, International association of Chinese Medicine, 2009, 4(1): 16.

Feng Y., Chen X., Wang N. and Shen J., Current Progress on Medicinal Plants and their Biological Properties in Contemporary China, In: Govil J.N. , Recent Progress in Medicinal Plants Vol. 28: Ethnomedicine: Source & Mechanism-II. Houston, USA, Studium Press LLC, 2009, 28: 529-588.

Tang J., Feng Y., Tsao G.S.W., Wang N., Curtain R.P. and Wang Y., Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations. , Journal of Ethnopharmacology. . 2009, 126: 5-17.

Researcher : Wang N

List of Research Outputs

Researcher : Wang TT

List of Research Outputs

Mao W.W., Wang T.T., Zeng H.P., Wang Z., Chen J. and Shen J., Synthesis and evaluation of novel substituted 5-hydroxycoumarin and pyranocoumarin derivatives exhibiting significant antiproliferative activity against breast cancer cell lines , Bioorganic & Medicinal Chemistry Letters. 2009, 19: 4570-4573.

Researcher : Wang Z

List of Research Outputs

Mao W.W., Wang T.T., Zeng H.P., Wang Z., Chen J. and Shen J., Synthesis and evaluation of novel substituted 5-hydroxycoumarin and pyranocoumarin derivatives exhibiting significant antiproliferative activity against breast cancer cell lines , Bioorganic & Medicinal Chemistry Letters. 2009, 19: 4570-4573.

Wang Z., Guan X.Y. and Chen J., Anti-tumor effects and mechanisms of Spatholobus suberectus water extracts in vitro and in vivo., HK, 2009, 98.

Wang Z., Loo T.Y., Wang D., Cheng Y., Guan X.Y. and Chen J., Spatholobus suberectus, a potential Chinese herb for cancer treatment, In: OOTR the 6th Annual Conference, OOTR the 6th Annual Conference. Kyoto, Japan, 2010.

Researcher : Wang Z

List of Research Outputs

Wang Z., Guan X.Y. and Chen J., Anti-tumor effects and mechanisms of Spatholobus suberectus water extracts in vitro and in vivo., HK, 2009, 98.

Researcher : Wei L

List of Research Outputs

Qi H., Wei L., Han Y., Zhang Q., Lau A.S.Y. and Rong J., Proteomic characterization of the cellular response to chemopreventive triterpenoid astragaloside IV in human hepatocellular carcinoma cell line HepG2, In: Professor DEMETRIOS A. SPANDIDOS, International Journal of Oncology. Athens, Greece, Spandidos Publications, 2010, 36: 725-735.

Wei L., Liu J., Le X.C. and Rong J., Induction of LTB4 12-hydroxydehydrogenase (LTB4DH)expression by coordination of the active compounds isolated from the plants Radix Astragli and Radix Paeoniae Rubra, ASCB 2009 (49th Annual Meeting). 2009.

Researcher : Wong HK

List of Research Outputs

Hu K.Y., Wang Y.T., Sze S.C., Tsang K.W., Wong H.K., Liu Q., Zhong L. and Tong Y., Identification of the major chemical constituents and their metabolites in rat plasma and various organs after oral administration of effective Erxian Decoction (EXD) fraction by liquid chromatography-mass spectrometry., Biomed Chromatogr. 2010 May;24(5):. 2010, 479-89.

Sze C.W., Tsang K.W., Wong H.K., Liu Q. and Zhong L., Identification Of The Major Chemical Constituents And Their Metabolites In Rat Plasma And Various Organs After Oral Administration Of Effective Exd Fraction By Liquid Chromatography-mass Spectrometry , In: Lim, Chang Kee , Biomedical Chromatography. 2009.

Researcher : Wong KL

List of Research Outputs

Sze C.W., Chu S.M.E., Wong K.L., Liu Q., Yow C.M.N., Liu W.K., Ng T.B. and Tong Y., Anti-Cancer Effect of Tian Xian Liquid, a Chinese Medicine Formula, in Human Colon Carcinoma HT29, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Wong K.L., Chu S.M.E., Zhong L. and Tong Y., Synergistic Effect of Six Estrogenic Compounds isolated from Erxian Decoction for Relieving Menopausal Syndrome, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Researcher : Wu J

Project Title:	Anti-cystic hyperplasia of breast herbal medicine research
Investigator(s):	Wu J, Chow LWC
Department:	School of Chinese Medicine
Source(s) of Funding:	Other Funding Scheme
Start Date:	05/2001

Abstract:

To study anti-cystic hyperplasia of breast herbal medicine.

Project Title:	Anti-prostatomegaly herbal medicine research
Investigator(s):	Wu J, Leung SYL
Department:	School of Chinese Medicine
Source(s) of Funding:	Other Funding Scheme
Start Date:	06/2001

Abstract:

To study the effectiveness of anti-prostatomegaly herbal medicine.

Researcher : Yip WK

List of Research Outputs

Mo F., Zhong L. and Yip W.K., Ju Ching Chu Secondary School (Yuen Long) Chinese Medicine Talk and Demonstration, 元朗裘錦秋中學座談分享及手法示範, In: Ju Ching Chu Secondary School (Yuen Long) , 2009.

Yip W.K. and Yuen S.F., Pope Paul VI College Chinese Medicine Talk and Demonstration, 葵涌石籬保祿六世書院座談分享及手法示範, In: Pope Paul VI College, 2010.

Yip W.K., Public Talk at Shek Tong Tsui Public Library, 石塘咀公共圖書館講座-秋冬保健湯水, In: Shek Tong Tsui Public Library, 2009.

Yip W.K., Public talk at Hong Kong S.K.H.Tseung Kwan O Aged Care Complex , 從中醫角度了解心臟病的治療和保健方法, In: Hong Kong S.K.H.Tseung Kwan O Aged Care Complex , 2009.

Yip W.K. and Yuen S.F., Queen Elizabeth Secondary School visit sharing talk and demonstrations, 2010, 伊利莎伯中學中醫分享坐座及示範, In: Queen Elizabeth Secondary School, 2010.

Researcher : Yiu YM

List of Research Outputs

Yiu Y.M. and Ng S.M., Efficacy study of Chinese medicine hot pad for chronic fatigue syndrome, The 6th World Congress of Chinese Medicine. 2009, 145-148.

Zhang Y., Feng Y., Sze C.W., Tong Y., Mo F., Yiu Y.M., Xiao L., Wong JH Y., Ng T.B., Shaw P.C., Xiao Y. and Li Z.M., Dendrobium candidum Extract Increases the Expression of Aquaporin 5 in Labial Glands from Patients with Sjögren’s Syndrome. , In: Lin Xiao, Tzi Bun Ng, Yi-Bin Feng, Tong Yao, Jack Ho Wong, Ren-Min Yao, Lei Li, Fei-Zhi Mo, Yin Xiao, Pang-Chui Shaw, Ze-Min Li, Stephen Cho Wing Sze, Kalin Yanbo Zhang, Phytomedicine, Accepted. 2010.

Researcher : Yuen SF

List of Research Outputs

Yip W.K. and Yuen S.F., Pope Paul VI College Chinese Medicine Talk and Demonstration, 葵涌石籬保祿六世書院座談分享及手法示範, In: Pope Paul VI College, 2010.

Yip W.K. and Yuen S.F., Queen Elizabeth Secondary School visit sharing talk and demonstrations, 2010, 伊利莎伯中學中醫分享坐座及示範, In: Queen Elizabeth Secondary School, 2010.

Researcher : Zhang Y

Project Title:	A novel DNA microarray for differentiation of Tiepi Fengdou (Dendrobium officinale) by 5S ribosomal DNA intergenic spacer region
Investigator(s):	Zhang Y, Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2008
Completion Date:	04/2010

Abstract:

Objectives: This study aims to develop an accurate and high-throughput method to differentiate D. officinale and other Dendrobium species. The key issues and problem: D. officinale is an important medicinal plant and tonic which is usually used to produce a high-value product, Tiepi Fengdou (TPFD). Due to its great demand, the price of TPFD has soared up to US$5,000 per kg. For this reason, TPFD is frequently adulterated by other Dendrobium species [1]. There are approximately 1100 species of Dendrobium distributed all over the world [2], and over 45 Dendrobium species have been found to counterfeit TPFD frequently as sold in the market [3]. Many Dendrobium species are over-collected and are now endangered. Due to too much adulterant species in this medicinal material and TPFD’s shape change by the process, traditional authentication methods, such as morphology or histology, have been limited. It is thus necessary to develop a high-throughput and accurate method for authenticating the plant sources of TPFD. Over the last years, DNA microarray technology has become one of the principal platform technologies for the high-throughput analysis of biological systems. Starting with the construction of the first DNA microarrays in the 1990s, the DNA microarray technology has flourished in the last years, and many different new formats have been developed [4]. We attempted an ITS microarray for the differentiation of Dendrobium species [5-7]. The great base differences were found between species [1]. However, this study also shows that four species that cannot be distinguished as sequences are very similar [6]. This includes the differentiation of TPFD and its adulterants. Therefore, this study aims to develop a novel 5S microarray for the fast and accurate authentication of TPFD. The use 5S microarray has several significant advantages: 1) The sample can be compared once with even up to over 1100 Dendrobium species in the future as high-throughput screening; 2) Accuracy is increased as 5S rDNA region variation is abundant; and 3) DNA can be detected from a small amount of sample as high sensitivity. The 5S microarray-based authentication of Dendrobium plant source may be useful as an inexpensive and rapid tool. In this study, the 5S microarray will be attempted for differentiating D. officinale and 11 Dendrobium species. Presequently we will apply industry funding (such as ITF) support to develop this scientific technology for authentication of more Dendrobium plant resource. Reference: 1. Zhang YB. 2003. DNA microarray for authentication of medicinal Dendrobium species. PhD thesis. Department of Biochemistry, the Chinese University of Hong Kong. 2. Wang XK, Zhao TF. 1990. A discussion of the chemical constituents of Dendrobium plants and of the Chinese herbal drug Shi-hu. Inter J Orient Med 15: 146-155. 3. Ma GX, Xu GJ, Xu LS, Li MF. 1995. Survey and identification of Herba Dendrobii (III). Chin Trad Herb Drug 26: 370-372. 4. Sobek J, Bartscherer K, Jacob A, Hoheisel JD, Angenendt P. 2006. Microarray technology as a universal tool for high-throughput analysis of biological systems. Comb. Chem. High Throughput Screen 9: 365-380. 5. Zhang YB, Wang J, Wang ZT, But PP, Shaw PC. 2003. DNA microarray for identification of the herb of Dendrobium species from Chinese medicinal formulations. Planta Med 69: 1172-1174. 6. Zhang YB, But PPH, Wang ZT, Shaw PC. 2005. Current approaches for the authentication of medicinal Dendrobium species and its products. P. G. R. 3: 144-148. 7. Zhang YB, Shaw PC, Sze CW, Wang ZT, Tong Y. 2007. Molecular authentication of Chinese herbal materials. Journal of Food and Drug Analysis, 15: 1-9.

Project Title:	The primary preclinical study of a potential new drug extracted from Dendrobium officinale for treating Sjögren's syndrome
Investigator(s):	Zhang Y, Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

The aim of this study is to have primary preclinical research for a new drug which is useful for the treatment of Sjögren’s syndrome (SS). The drug is extracted from a traditional Chinese medicinal herb, Dendrobium officinale. The pharmacological effect and active fraction will be investigated for the further development of a new drug for treating SS. Sjögren’s syndrome (SS) is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands [1]. A general clinical feature of patients with SS is the progressive dryness of mouth and eyes due to insufficient salivary and lacrimal secretions. Other symptoms associated with SS, especially in patients complaining of dry mouth, include diffuse oral burning, dysphagia, dysgeusia, and hoarseness [2]. Thus, for the clinical improvement of patients with SS, development new drug to enhance tear and salivary secretion would be inevitable. The Dendrobium species (Orchidaceae), locally known as ‘Shihu’, especially Tiepi Fengdou (TPFD) from Dendrobium officinale has a better quality. It has long been used in traditional Chinese medicine for antipyretic, eye benefiting, immunomodulatory as well as anti-aging effects [3]. Our clinical research indicated that TPFD could increase salivary and tear secretion of SS patients. Therefore, our findings support the focus of the pharmacological effect and active fraction of TPFD addressed in this proposal. The overall hypothesis for the current proposal is that active fraction of TPFD prevents the development of salivary and lacrimal gland exocrinopathy in SS model mice.

Project Title:	Molecular Mechanisms of Dengibsin I and II against human hepatocellular carcinoma by epigenetic processes
Investigator(s):	Zhang Y, Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	10/2008

Abstract:

Objective: To investigate the efficacy and certain mechanisms of Dengibsin against human hepatocellular carcinoma by epigenetic processes for development of a new drug for the treatment of liver cancer. Stratagems: 1. The components, Dengibsin I & II will be extracte, siolate and then purify from Dendrobium nobile, a Chinese medicine. 2. The pharmacological effect will be tested by HpG2 cell line. 3. The active component (Dengibsin I or II, or Dengibsin I and II) will be investigated for the further development of a new drug for treating liver cancer.

Project Title:	Study on the Taxol: an Herb Compound, Prominent Effecacy in Anti-cancer, Production by Endophytic Fungus Fermentation
Investigator(s):	Zhang Y, Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	06/2009
Completion Date:	07/2010

Abstract:

Objective: This study aim to develop a high output approach-endophytic fungus fermentation for industry production of taxol Special aim 1: To clarify the biosynthesis routes of taxol by fermentation from endophytic fungus. Special aim 2: To isolate and determine the function of related genes in taxol synthesis by microbe fermentation. Special aim 3: To supply target genes for constructing gene-engineering strains with high output. Cancer is intimidating human health. Up to nowadays, no a lear effect drug control it. A compound, taxol from medicine plant Taxus celebica have been found of prominent effecacy against many cancers [1, 2]. However, this ingredient is too little in the plant so that it can not be used enough on clinic to cure cancers. Due to the rapid growing market, current industrial production of taxol by semi-synthesis that consumes large amount of yew trees cannot meet the demand of the market. Therefore, new generation approaches were investigated [3,4]. The discovery of taxol-producing fungus Taxomyces andeanae, an endophyte of T. brevifolia, by Stierle et al [5]. Paves a new way to the production of this drug, that is, employing large-scale fungal fermentation to make taxol at a lower cost, and yet a higher yield. But no stable and high output taxol synthesis-associated genes have been found for industry production so far. This study aims to clarify the biosynthesis routes of taxol by fermentation from endophytic fungus, isolate the function of related genes in taxol synthesis and supply target genes for constructing gene-engineering strains with high output for market demand. This study will use the homogeneous conformity of Agrobacterium tumefaciens (ATMT) to target the taxol obtained related candidate genes by Synchronized Switch Harvesting (SSH) method to realize gene knockout. The candidate gene through Heringsdorf 68 (HDF-68) taxol synthesis-related gene will be determined by the changes of taxol output from the transform bodies, including increase, decrease or no taxol production. Meanwhile, ATMT is still used for HDF-68 transformation to acquire transformation factor library. TLC and HPLC will be used to screen mutagens with different taxol output. TAIL-PCR will be used for isolating genes related to HDF-68 taxol production. Functional study will be performed on gene expression features, and protein expression levels. This study may provide new gene technology for the biosynthesis pathway of taxol production by taxol-producing fungus, and for the construction of genetic engineering strains with high output. References: 1. Tran TA, Gillet L, Roger S, Besson P, White E, Le Guennec JY. Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness. Biochem Biophys Res Commun. 2009, 379:304-8. 2. Pushkarev VM, Starenki DV, Saenko VA, Pushkarev VV, Kovzun OI, Tronko MD, Popadiuk ID, Yamashita S. Differential effects of low and high doses of Taxol in anaplastic thyroid cancer cells: possible implication of the Pin1 prolyl isomerase. Exp Oncol. 2008, 30:190-4. 3. Li YC, Tao WY, Cheng L. Paclitaxel production using co-culture of Taxus suspension cells and paclitaxel-producing endophytic fungi in a co-bioreactor. Appl Microbiol Biotechnol. 2009, [Epub ahead of print] 4. Filion KB, Roy AM, Baboushkin T, Rinfret S, Eisenberg MJ. Cost-effectiveness of drug-eluting stents including the economic impact of late stent thrombosis. Am J Cardiol. 2009, 103:338-44. 5. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Stierle A, Strobel G, Stierle D. Science. 1993, 260:214-6.

Project Title:	The 8th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM) Protective effects of Bilberry (Vaccinium myrtillus L.) extract on beta-Amyloid 25-35 and homocysteine induced neurotoxicity
Investigator(s):	Zhang Y
Department:	School of Chinese Medicine
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

List of Research Outputs

Feng Y., Liu K.J., Wang J., Shen J., Zhang Y., Rong J., Tong Y., Chan K.S. and Wong B.W., Basic and clinical Toxicology of Chinese Medicines, 基礎和臨床中藥毒理學, Hong Kong, Commercial Press (HK) Ltd., 2009, p394.

Huang W., Cai Y. and Zhang Y., Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention, Nutrition and Cancer – An International Journal. 2010, 62(1): 1-20.

Lin X., Sze C.W., Tong Y., Zhang Z., Feng Y., Chen J., Ng T.B., Lin X., Shaw P.C. and Zhang Y., Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren’s Syndrome, Journal of Complementary and Integrative Medicine . 2010, in press.

Shen F., Lin X., Zhang Y., Tong Y. and Sze C.W., 複方黃苦膏劑對濕疹外治消炎止癢作用的實驗研究, 江蘇中醫藥雜誌, 2010.

Song J., Li Y., Ge J., Duan Y., Sze C.W., Tong Y., Shaw P.C., Ng T.B., Tsui K.C. and Zhang Y., Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC), Phytotherapy Research. 2010, 24 (4): 520-540.

Song J., Li Y.Q., Shaw P.C., Ng T.B., Tong Y., Sze C.W. and Zhang Y., Protective effects of Bilberry (Vaccinium myrtillus L.) extract on beta-Amyloid 25-35 and homocysteine induced neurotoxicity, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM ). UK, 2009.

Song J., Lin X., Sze C.W., Tong Y., Wong N.S., Shaw P.C. and Zhang Y., Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells, In: Song JX, Lin X, Ricky NS Wong, Stephen CW Sze, Tong Y, Shaw PC, Zhang YB, Phytotherapy, accepted . 2010.

Sze C.W., Tong Y., Lai Y.M., Zhang Y. and Yow C.M.N., Micro-computed Tomography for the Evaluation of the Anti-Osteoporotic Activity of Erxian Decoction in Menopausal Rat Model, The 8th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM) . 2009.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N., Lai Y.M. and Ng T.B., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis., IEEE PUBLICATION: Biomedical Engineering and Informatics, BMEI 2009. 2009, 1: 47-49.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N. and LAI Y.M., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis, The 2nd International Conference on BioMedical Engineering and Informatics (BMEI'09). 2009.

Zhang Y. and Sze C.W., A formulation of Chinese Medicines to improve diabetic disease., China. China, 2010.

Zhang Y., Authenticated Chinese medicines for the clinic and experiment study of professors, In: Zhang YB , School of Chinese Medicine . 2009.

Zhang Y., Feng Y., Sze C.W., Tong Y., Mo F., Yiu Y.M., Xiao L., Wong JH Y., Ng T.B., Shaw P.C., Xiao Y. and Li Z.M., Dendrobium candidum Extract Increases the Expression of Aquaporin 5 in Labial Glands from Patients with Sjögren’s Syndrome. , In: Lin Xiao, Tzi Bun Ng, Yi-Bin Feng, Tong Yao, Jack Ho Wong, Ren-Min Yao, Lei Li, Fei-Zhi Mo, Yin Xiao, Pang-Chui Shaw, Ze-Min Li, Stephen Cho Wing Sze, Kalin Yanbo Zhang, Phytomedicine, Accepted. 2010.

Zhang Y., Developed clinic preparation laboratory and provided preparations in decoction, powder, soft creams and aqua (07/2007-07/2009), In: Zhang YB, School of Chinese Medicine. 2009.

Zhang Y. and Sze C.W., HKD 150,000. Study on the formulation LD209 to improve diabetes. Project No. 20006061., In: Zhang YB, Sze CW. , Oriental Int'l Health Products Co., Ltd.. 2010.

Zhang Y., Sze C.W., Ng T.B., Wong J.H. and Wang H.X., Isolation of a mitogenic agglutinin with relatively high thermostability from seeds of the variegated shell ginger., In: Wong JH, Ng TB, Zhang KY, Sze SC, Wang HX., Protein Pept Lett.. 2010, 17: 38-43.

Zhang Y., Sze C.W., Tong Y., Feng Y., Ng T.B., Shaw P.C., Xiao L. and Xiao K., Protective effect of Dendrobium officinale polysaccharides on experimental Sjögren’s Syndrome, In: Xiang Lin, Stephen Cho-Wing Sze, Yao Tong, Zhangjin Zhang, Yibin Feng, Jian ping Chen, Tzi Bun Ng, Xiao Lin, PC Shaw, and Kalin Yanbo Zhang., Journal of Complementary and Integrative Medicine. 2010, 17: 1-18.

Zhang Y., Provided the standard samples and extractions of Chinese Medicines for Clinic study and experiment study (2006-2009), In: Zhang YB , School of Chinese Medicine . 2009.

Zhang Y., Sze C.W., Ng T.B. and Wang J.H., Purification and Characterization of a Laccase with Inhibitory Activity toward HIV-1 Reverse Transcriptase and Tumor Cells from an Edible Mushroom (Pleurotus cornucopiae), In: Wong JH, Ng TB, Jiang Y, Liu F, Cho S, Sze W, Zhang KY., Protein Pept Lett.. 2009, 10: [Epub ahead of print].

Zhang Y., Sze C.W. and Tong Y., The Novel Mechanisms Study: the Chrysotoxine, a Compound from Dendrobium chrysotoxum, Treats Sjögren's Syndrome., In: Stephen CW Sze, Tong Y, Kalin Zhang YB, Chinese Medicine Society. 2009.

Zhang Y., The regulation and quality control of Traditional Chinese Medicine, In: Zhang YB, The Hong Kong Polytechnic University. 2010.

Researcher : Zhang Z

Project Title:	The Establishment of Neurobehavioral Experiments into the Acupuncture Course (BCHM3003, 針灸學) of Undergraduate Chinese Medicine Programs
Investigator(s):	Zhang Z, Tong Y
Department:	School of Chinese Medicine
Source(s) of Funding:	Run Run Shaw Research and Teaching Endowment Fund - Teaching Grants
Start Date:	07/2007

Abstract:

The objective of this proposed project is to establish neurobehavioral experiments into the acupuncture course (BCHM3003, 針灸學) currently delivered by School of Chinese Medicine for five-year undergraduate program. As an ancient healing art, acupuncture is a core part in the modern education of Chinese medicine. This is not only because the traditional theory of acupuncture, such as acupoints and meridian doctrine, is fundamental knowledge for students to understand the whole Chinese medicine theory system, but also because acupuncture has become the most widely recognized alternative therapy by the mainstream medical community. Indeed, the effectiveness of acupuncture therapy for many conditions and diseases has been well demonstrated in contemporary clinical practice. Numerous basic and clinical studies also have clearly revealed modern scientific basis of acupuncture’s effects, which are reflected in the facts that over ten thousands of research papers related to acupuncture have been published in the past four decades. Obviously, the introduction of the achievements in acupuncture research into the current Chinese medicine teaching programs will set a bridge between traditional and contemporary knowledge hierarchies. It is also of greatly valuable in improving students’ skills in communication with the mainstream medical professionals and then enhancing their capacity in the practice of acupuncture. Nevertheless, these evidence-based acupuncture knowledge accumulated over the past four decades has not yet been included in our current 5-year undergraduate acupuncture course (BCHM3003, 針灸學), in which only the traditional theory of acupuncture is taught. This obviously fails to meet the School’s mission that graduates from our School should become comprehensive professionals firmly possessing both traditional and contemporary knowledge of Chinese medicine. Thus, the introduction of contemporary knowledge of acupuncture into the course has become a matter of great urgency. Among the therapeutic effects of acupuncture, analgesic (pain-depressing) and anti-drug addiction effects are the most determined and have been well confirmed in both animal experiments and clinical settings. In general, behavioral approaches are the most commonly used in determining both effects of acupuncture in animal experiments. For instance, hot-plate test is used to detect analgesic effects of acupuncture and anti-cocaine craving effects are tested in conditioned place preference paradigm. Based on these, we propose to establish these two neurobehavioral experiments into the current acupuncture course (BCHM3003, 針灸學). If the experiments are successful, we will further set up other experiments and eventually create an independent acupuncture experimental course for Chinese medicine teaching programs.

Project Title:	Behavioral and genomic/proteomic mechanisms of D1 agonistic-D2 antagonistic dual action of stepholidine against negative and cognitive symptoms of schizophrenia
Investigator(s):	Zhang Z
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2008
Completion Date:	06/2010

Abstract:

Stepholidine (SPD), initially isolated from the Chinese herb Stephania, is a compound known to have dopamine D1 receptor agonistic and D2 antagonistic dual effects. Drugs with such distinct pharmacological properties are believed to be specifically effective in treating the negative and cognitive symptoms of schizophrenia. However, the therapeutic advantages of SPD and the underlying mechanisms have not yet been characterized. Therefore, the objectives of the proposed project are designed: (1) to determine the therapeutic effects in various animal models of schizophrenia that can mimic the positive, negative, and cognitive deficit symptoms of patients with schizophrenia; and (2) to correlate the behavioral effects of SPD of various symptom clusters with changes in expression levels of genes and proteins involved in the pathogenesis of schizophrenia using high-throughput genomic and proteomic approaches. The main reason that schizophrenia is the most incurable mental illness is because of persistent negative symptoms and a range of cognitive impairments. Numerous studies have shown that the currently available antipsychotic therapies, conventional and atypical, are ineffective or less effective in treating both clusters of symptoms. Conversely, long-term use of some antipsychotic treatments may reduce and even damage cognitive function. These shortcomings have led to a search of other novel antipsychotic agents that may have distinct pharmacological properties. The reduced function of dopamine D1 receptors in the medial prefrontal cortex (mPFC) has been found to be associated with the negative symptoms and cognitive deficits of schizophrenia, whereas the D2 receptor hyperactivity in subcortical regions (e.g., the nucleus accumbens) might result in the positive symptoms. These observations have led to a hypothesis that drugs that possess D1 agonistic and D2 antagonistic dual effects might be effective in improving negative and cognitive symptoms of this disorder. To date, stepholidine (SPD) is the only drug known to possess such distinct properties. SPD was initially isolated from the Chinese herb Stephania and is a leading compound of tetrahydroprotoberberines (THPBs). Our previous pharmacological studies have shown that SPD displays the highest affinity to D1- and D2-like receptors of all known THPBs and only low affinities to 5-HT2 receptors and α2-adrenoceptors, and rare affinity to several other transmitter receptors. Functional assays suggest that SPD possesses an agonist effect on D1 receptors and an antagonist effect on D2 receptors. This dual action has been confirmed in electrophysiological, biochemical, and immunohistochemical studies. Moreover, our recent preliminary studies found that systemic administration of SPD not only suppresses an increase in locomotion and the disruption of prepulse inhibition (PPI) induced by phencyclidine (PCP), but also significantly ameliorates PCP-induced social withdrawal and cognitive impairments, suggesting the therapeutic potential of SPD in the treatment of negative and cognitive symptoms of schizophrenia. Despite the fact that recent genomic and proteomics studies have revealed various presumed susceptibility genes and their products that may be involved in the etiology and pathogenesis of schizophrenia, such as neuregulin-1 (NRG1), dysbindin (DTNBP1), regulator of G-protein signaling 4 (RGS4), catechol-o-methyltransferase (COMT), proline dehydrogenase (PRODH) and disrupted-in-schizophrenia 1 (DISC1), little is known about relationships between these biomarkers and specific symptom clusters of schizophrenia, especially negative and cognitive symptoms, and antipsychotic actions. We therefore hypothesize that SPD is effective in improving the negative and cognitive symptoms of schizophrenia and such improvement is associated with alterations in gene and protein biomarkers related to the negative and cognitive symptoms. To test this hypothesis, the following specific aims are proposed: (1) To characterize the therapeutic advantages of SPD in animal models of the positive, negative symptoms and cognitive impairments of schizophrenia; and (2) To correlate the behavioral effects of SPD on various symptom clusters with changes in expression levels of gene and proteins involved in the pathogenesis of schizophrenia using high-throughput genomic and proteomic approaches. We will focus on the following genes and their products: catecholamine and serotonin synthesis, reuptake, and metabolite genes and their products, neuregulin-1 (NRG1), dysbindin (DTNBP1), regulator of G-protein signaling 4 (RGS4), catechol-o-methyltransferase (COMT), proline dehydrogenase (PRODH) and disrupted-in-schizophrenia 1 (DISC1).

Project Title:	Pharmacokinetic and therapeutic characterization of liguslitide nasal spray (藁苯內酯鼻喷雾剂) for premenstrual syndromes
Investigator(s):	Zhang Z
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	08/2008
Completion Date:	07/2010

Abstract:

Liguslitide is an essential oil contained in the Chinese herbal medicine Angelica sinensis (Dang-Gui). The objective of the proposed project is to characterize pharmacokinetic profile and therapeutic effects of ligustilide nasal spray preparation in the animal models of premenstrual syndromes (PMSs). PMSs are among the most common health problems in women, affecting 20–40% of women of reproductive age. A severe form of PMSs is premenstrual dysphoric disorder (PMDD) that occurs in 3–9% of patients with PMSs. PMS/PMDD is characterized by mood and behavioral changes, mainly including severe depressed mood, anxiety, and increased interpersonal conflicts. Although many classes of pharmacological drugs have been introduced into the treatment of PMS/PMDD, over 50% of the patients cannot obtain satisfactory outcomes. Thus, a search of novel pharmaceutical therapy is greatly needed. Angelica sinensis is a Chinese herbal medicine commonly used for the treatment of various menstrual cycle-related disorders, particularly mood symptoms, in Chinese medicine clinical practice. Ligustilide is an essential oil initially extracted from Angelica sinensis. Previous studies have suggested that ligustilide may possess broad psychotropic effects, including anti-anxiety effects. Most recently, our preliminary studies have found that intraperitioneal (i.p.) administration of ligustilide with a dose range of 25-75 mg/kg produces significant anxiolytic and social conflict-improved effects in female rat models of PMS by withdrawn from repeated treatment with progesterone, measured in the open field and social interaction tests. However, there are many shortcomings in regular delivery routes (e.g., i.m., p.o. or i.p.) of essential oil preparations. For example, a large volume is generally required when the preparations are delivered clinically via regular routes (e.g., i.m. or p.o.) due to large degradation in hepatic system and poor bioavailability. In contrast, nasal sprays are of practical use for their high bioavailability, particularly in the central nervous system by rapidly and easily entering the blood-brain barrier (BBB), with easy-to-use and rapid-to-act features. Since these advantages, this form of formulation has been widely introduced into pharmaceutical preparations of Chinese medicine and many nasal spray products of Chinese medicine, including essential oil nasal sprays have been available in market. The working hypothesis of the proposed project is that intranasal administration of ligustilide yields more efficient and effective pharmacokinetic profile and comparable therapeutic effects compared to other route administration (e.g., i.p.). To test this hypothesis, we will determine whether there are differences in the in vivo time course of changes in pharmacokinetic indices between single-dose ligustilide via intranasal and intraperitioneal routes. We also will compare behavioral effects of the two route administration in animal models of PMS.

Project Title:	The development of a clinical-case search system to introduce case-study learning mode into Chinese medical curricula
Investigator(s):	Zhang Z, Wong HK
Department:	School of Chinese Medicine
Source(s) of Funding:	Leung Kau Kui Research and Teaching Endowment Fund - Teaching Grants
Start Date:	09/2008

Abstract:

In order to introduce case-study learning mode into Chinese medical curricula at HKU School of Chinese Medicine, the objective of this proposed project is to develop a clinical-case search system that provides a search tool to quickly find the desired clinical cases from a huge number of patients’ medical charts currently available in two Chinese medicine clinics of the School. Unlike contemporary medical education, which emphasizes concept-oriented, problem-based, practice for transfer and stimulations in clerkship, most traditional Chinese medicine (TCM) curricula in HKU School of Chinese Medicine still implements traditional pedagogical fashion, characterized by didactic presentations and unidirectional communications. This mode has largely lagged behind the demand of learners, desiring a new learning model that could yield higher impacts and more transferable knowledge. It is well known that Chinese medicine is an ancient healing art with empirical knowledge. However, the acquisition of the empirical knowledge, especially those relevant to the skill of Chinese medical diagnosis and clinical therapeutics, largely relies on case-by-case studies through classroom teaching, internship and clinical practice. This has been in fact reflected in a vast number of various disease cases recorded in ancient Chinese pharmacopoeias. Thus, the introduction of case-study learning mode will be of great significance in improving the quality of our School’s TCM curricula by enhancing transferability and practicality of TCM knowledge, heightening learner’s interest, and increasing impacts between teachers and learners. Obviously, a buildup of accessible and searchable clinical cases is the first step in the establishment of case-study learning mode. To date, there has been an accumulation of nearly 12,000 patients visited at two Chinese medical clinics in our School. And, at least 1,500 new patients are expected to be added annually. The information of the patients is recorded in paper-based medical charts which are stored in archives. Apparently, the development of a search system for a huge number of medical charts is a requisite to conducting case-study learning mode.

Project Title:	A single-blind, randomized, sham controlled study of electroacupuncture in accelerating the onset antidepressant action of selective serotonin reuptake inhibitors via serotonergic mechanisms
Investigator(s):	Zhang Z, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Health and Health Services Research Fund - Full Grants
Start Date:	01/2009

Abstract:

(1) To confirm that the patients in active EA intervention has significantly greater improvements on depressive symptoms than in sham intervention in the initial phase of treatment; (2) to compare the effects of sham and active EA intervention combination with paroxetine on platelet 5-HT levels, 5-HT!A/1B receptors, and 5-HT transporters; (3) to determine correlations between clinical efficacy measures and platelet 5-HT indices.

Project Title:	Central mechanisms involved in dense cranial electroacupuncture stimulation in treating major depression - a positron emission topographic (PET) study
Investigator(s):	Zhang Z
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2010

Abstract:

The central theme of the proposed project is to determine whether the clinical efficacy of dense cranial electroacupuncture stimulation (DCEAS), a novel acupuncture modality, is equivalent to selective serotonin reuptake inhibitors (SSRIs) in treating depressive symptoms and whether the two treatment regimes share a similar mechanism in normalizing functional activities in the related brain regions of patients with major depressive disorder (MDD), using positron emission topography (PET). Although the development of various classes of antidepressant drugs, represented by SSRIs, has considerably improved the prognosis and tolerability in the treatment of depressive disorders, the currently available antidepressant therapy is still incomplete. There are a large portion of depressed individuals who cannot obtain full response and experience recurrent episodes. High incidences of various adverse events (e.g., sexual, cardiovascular side effects and discontinuation syndrome) and delay in onset of the action also have hampered the use of antidepressants. Hence, the development of effective alternative strategies is in a great demand. As a well recognized alternative therapy, electroacupuncture (EA) has been shown to have beneficial effects in the treatment of various psychiatric conditions, including depression. Our recent meta-analysis showed that acupuncture monotherapy is comparable to antidepressants in improving depressive symptoms. It is documented that the therapeutic effects of EA are achieved mainly via spinal/trigeminal-reticular-forebrain tracts, and the prefrontal cortex, cingulate cortex and other forebrain regions play a dominant role in the pathogenesis of mood disorders. We believe that DCEAS in which electrical stimulation is directly delivered on a density of acupoints (in general 6-8 pairs) located on the frontal, parietal, and temporal scalp areas, most innervated by the trigeminal nerve, could produce robust therapeutic effects. Indeed, our pilot studies have shown the effectiveness of DCEAS in various psychiatric conditions, including major depression and refractory obsessive compulsive disorder (OCD). Therefore, its mechanisms deserve to be further explored. Over the past decade, various functional neuroimaging approaches, especially PET and functional magnetic resonance imaging (fMRI) have been utilized in the investigation of mood disorders. Altered functional activities of certain brain regions are thought to be a universal characteristic in the pathogenesis of MDD. This is initially evidenced by the fact that several abnormalities of regional cerebral blood flow and glucose metabolism - a surrogate of neuronal function - are widely observed in MDD patients, particularly in those related to the encoding of mood and cognitive signals, such as the prefrontal cortex, cingulate cortex, and amygdala. Furthermore, the therapeutic responses to antidepressants were found to be associated with the normalization of dysfunction of certain brain regions, which are then considered as predictors for the outcomes of antidepressant treatment. Thus, the neuroimaging identification of changes in activities in the related brain regions is a valid approach to delineating central mechanisms of novel therapies, such as DCEAS. A large number of previous studies aimed at exploring acupoint specificity and analgesic effects of EA have shown that the stimulation of different acupoints could elicit the response in multiple brain areas, including the prefrontal cortex, cingulate cortex, and amygdala, suggesting that EA may possess the therapeutic actions for mood disorders by normalizing mood processing-related brain activities. Our preliminary PET study confirms this normalizing effect of DCEAS in MDD patients. We therefore hypothesize that DCEAS and SSRI treatments could yield equivalent efficacy in improving depressive symptoms and the treatment effects may be associated with normalization of mood processing-related brain region activities. To test this hypothesis, a 3-week, single-blind, randomized study of DCEAS intervention versus SSRI treatment in 78 first-episode, drug-free patients with MDD is proposed to investigate the following three objectives with the employment of PET scanning measures. The proposed study may lead to a better understanding of the applicability and mechanisms of DCEAS effects. Considering a heavy burden of Hong Kong mental healthcare and the incompleteness of conventional antidepressant treatment, the proposed study will provide necessary scientific evidence for introducing this novel therapy into the treatment of depression and other psychiatric conditions. The proposed project will also open a new avenue towards developing novel treatment strategies from alternative medicines. Two apparently innovative and unique aspects of this application may deserve to be addressed: (1) DCEAS is a novel acupuncture modality established on neuroanatomic basis and evidence-based studies; and (2) the application of neuroimaging approaches to acupuncture therapy of depression is the very first and original. (1) To compare clinical improvements on depressive symptoms between DCEAS and fluoxetine (FLX, a SSRI) monotherapy in MDD subjects; (2) To determine the effects of DCEAS intervention on glucose metabolic levels in related brain regions in comparison with FLX treatment and healthy subjects, using PET scanning; and (3) To correlate between clinical improvements and changes in PET-measured activities of the related brain regions in a pool of the subjects treated with DCEAS and FLX.

List of Research Outputs

Gao H., Chu H.Y., Jin G.Z., Zhang Z., Wu J. and Zhen X.C., l-Stepholidine-excited dopamine neurons in rat ventral tegmental area is associated with its 5-HT1A receptor partial agonistic activity, Synapse. 2010, in press.

Jiang X., Zhang Z., Zhang S., Gamble E.H., Jia M., Ursano R.J. and Li H., 5-HT2A receptor antagonism by MDL 11,939 during inescapable stress prevents subsequent exaggeration of acoustic startle response and reduced body weight in rats, J Psychopharmacol. 2009, [Epub ahead of print].

Lin X., Sze C.W., Tong Y., Zhang Z., Feng Y., Chen J., Ng T.B., Lin X., Shaw P.C. and Zhang Y., Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren’s Syndrome, Journal of Complementary and Integrative Medicine . 2010, in press.

Wang H.H., Zhang Z., Tan Q.R., Yin H., Chen Y.C., Wang H.N., Zhang R.G., Wang Z.Z., Guo L. and Tang L.H., Psychopathological, biological, and neuroimaging characterization of posttraumatic stress disorder in survivors of a severe coalmining disaster in China, Journal of Psychiatric Research . 2010, 44: 385-392.

Wang H.N., Peng Y., Tan Q.R., Wang H.H., Chen Y.C., Zhang R.G., Wang Z.Z., Guo L., Liu Y. and Zhang Z., Free and Easy Wanderer Plus (FEWP), a polyherbal preparation, ameliorates PTSD-like behavior and cognitive impairments in stressed rats, Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2009, 33(8): 1458-1463.

Wong W., Zhang Z. and Ng R., Mentality, Traditional Chinese Medicine (TCM) and Mental-emotional Disorders, International Handbook of Psychiatry: A Concise Guide for Medical Students, Residents and Medical Practitioners. 2010.

Zhang Z., Wang X.Y., Tan Q.R., Jin G.X. and Yao S.M., Electroacupuncture for refractory obsessive-compulsive disorder - a pilot, waitlist-controlled trial, Journal of Nervous and Mental Disease. 2009, 197(8): 619-622.

Zhang Z., Herbal medicine for major psychiatric disorders, XXVII CINP Congress (symposium Chair). 2010, 6-10 June, 2010.

Zhang Z., Psychoparmacology (textbook, Chinese version) 精神药理学 (教科书), In: 主编: 刘吉成, Psychopharmacology of Chinese medicine and its clinical application (Chapter 14). (14章: 中药精神药理和临床应用). Peoples’ Health Press, Beijing, China, 2009, 252-262.

Zhang Z., Tan Q.R., Zhen X.C. and Tong Y., The potential benefits of herbal medicines for schizophrenia: from empirical observations to clinical trials (chapter 16). In: Hertzman M & Adler L (ed): Clinical Trials in Psychopharmacology. , Wiley-Blackwell, UK, 2010, 311-335.

Zhang Z., memeber of editorial board, Chinese Medicine (Macau). 2010.

Researcher : Zheng G

List of Research Outputs

Zheng G., Li Y., Gu Y., Chen X., Zhou Y., Zhao S. and Shen J., Beyond Water Channel: Aquaporin-4 in Adult Neurogenesis., Neurochemistry International. 2010, 56(5): 651-654.

Researcher : Zhong L

List of Research Outputs

Hu K.Y., Wang Y.T., Sze S.C., Tsang K.W., Wong H.K., Liu Q., Zhong L. and Tong Y., Identification of the major chemical constituents and their metabolites in rat plasma and various organs after oral administration of effective Erxian Decoction (EXD) fraction by liquid chromatography-mass spectrometry., Biomed Chromatogr. 2010 May;24(5):. 2010, 479-89.

Hu Y.M., Wu J.J., Liu Q., Sze C.W., Zhong L. and Tong Y., Identification of the Multiple Chemical Constituents from a Chinese Medicinal Prescription- Erxian Decoction by LC-DAD-ESI-MS, International Conference on Traditional Medicine. Guangzhou, China, 2009.

Mo F., Zhong L. and Yip W.K., Ju Ching Chu Secondary School (Yuen Long) Chinese Medicine Talk and Demonstration, 元朗裘錦秋中學座談分享及手法示範, In: Ju Ching Chu Secondary School (Yuen Long) , 2009.

Sze C.W., Tsang K.W., Wong H.K., Liu Q. and Zhong L., Identification Of The Major Chemical Constituents And Their Metabolites In Rat Plasma And Various Organs After Oral Administration Of Effective Exd Fraction By Liquid Chromatography-mass Spectrometry , In: Lim, Chang Kee , Biomedical Chromatography. 2009.

Sze C.W., Wong K.L., Chu S.M.E., Zhong L. and Tong Y., Synergistic Effect of Six Estrogenic Compounds isolated from Erxian Decoction for Relieving Menopausal Syndrome, 2nd International Conference on Drug Discovery and Therapy. Dubai, 2010.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N., Lai Y.M. and Ng T.B., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis., IEEE PUBLICATION: Biomedical Engineering and Informatics, BMEI 2009. 2009, 1: 47-49.

Sze C.W., Tong Y., Zhang Y., Zhong L., Lau A.S.Y., Yow C.M.N. and LAI Y.M., The Use of a Noninvasive and Nondestructive Method, Microcomputed Tomography, to Evaluate the Anti-Osteoporotic Activity of Erxian Decoction, a Chinese Medicinal Formula, in a Rat Model of Menopausal Osteoporosis, The 2nd International Conference on BioMedical Engineering and Informatics (BMEI'09). 2009.

Tong Y. and Zhong L., Comparative Study of Five Organs between Chinese and Western Medicine, 中西醫五臟比較研究, Hong Kong, The Commercial Press (H.K.), 2009, 2.

Zhong L. and Tong Y., Quality Assessment of the Clinical Trials with Chinese Medicine on Menopausal Syndrome in the Last Five Years: From the View of Evidence-based Medicine, 5th International Congress On Complementary Medicine Research. 2010, P-105.

Zhong L., The Efficacy And Safety Of A Chinese Medicine Formula (zsq) On Light And Moderate Systemic Lupus Erythematosus, Journal of Evidence-based Chinese Medicine. Tai Wan, 2009, 2: 56-65.

Zhong L. and Tong Y., The Roles Of Er-xian Decoction As A Basic Formula For The Management Of Menopause-related Symptoms: A Systematic Evidence Review, The 9th National Conference Of TCM Gynecology. 2009.

Researcher : Zhong L

List of Research Outputs

Tong Y. and Zhong L., Comparative Study of Five Organs between Chinese and Western Medicine, 中西醫五臟比較研究, Hong Kong, The Commercial Press (H.K.), 2009, 2.

Zhong L., The Efficacy And Safety Of A Chinese Medicine Formula (zsq) On Light And Moderate Systemic Lupus Erythematosus, Journal of Evidence-based Chinese Medicine. Tai Wan, 2009, 2: 56-65.

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