School of Chinese Medicine

SCHOOL OF CHINESE MEDICINE

Researcher : Cao K

List of Research Outputs

Cao K., 中醫內科學臨床全攻略, HONGKONG, 靈蘭閤圖書國際公司, 2007, 254.

Researcher : Chen H

List of Research Outputs

Chen H., Cho W.C.S., Sze C.W. and Tong Y., Treatment of Menopausal Symptoms with Er-Xian Decoction: A Systematic Review, 2nd Int'l Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007, 17b.

Sze C.W., Zhang Y., Chen H. and Tong Y., Molecular Mechanism of Erxian Decoction in Estrogen Secretion in vitro, 2nd Int'l Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population". 2007, 17a.

Tong Y. and Chen H., 仲景運用細辛規律研究, 上海中醫藥大學學報, 2007, 21(3): 12-14.

Researcher : Chen H

List of Research Outputs

Tong Y. and Chen H., 仲景運用細辛規律研究, 上海中醫藥大學學報, 2007, 21(3): 12-14.

Researcher : Chen J

Project Title:	Mechanisms of extracts of Dioscorea Panthaica Prain et Burkill (黃山葯) in protecting cardiomyocytes from hypoxia-reoxygenation injury and regulating lipid metabolism
Investigator(s):	Chen J, Shen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding for New Staff
Start Date:	08/2004
Completion Date:	10/2006

Abstract:

To evaluate the properties of antioxidant, lipid-modulation and cardioprotection of the herbal medicine Dioscorea Panthaica Prain et Burkill (黃山葯).

Project Title:	The effects of quickening blood circulation & transforming blood stasis on feminine tumours by Chinese herbs (DC0618)
Investigator(s):	Chen J, Chan YS
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2006

Abstract:

Purpose: This study is designed to evaluate the properties of treatment for feminine tumours such as ovarian and breast tumours by quickening blood circulation & transforming blood stasis. The designed prescription has been named DC0618 which consists of Chinese herbs that work by the above approach. Issues/Problems：These prescriptions have been widely used for the prevention and treatment of tumours. A lot of articles have reported that these herbs can inhibit tumour cell growth by releasing cytotoxin; inducing tumour cell apoptosis; lowering blood viscosity; improving micro-circulation and modulating immune system etc. Many researchers believe that herbal compounds do not have direct cytotoxic effects [8]. Rather, the anticancer properties of these herbs are thought to be related to the activation and release of cytokines that then induce apoptosis [9]. Apoptosis is usually regulated tightly and its execution may be initiated by many different signals, either from within or outside the cell [10]. While different genes such as p53, c-myc or Bcl-2/Bax have been shown to shift the balance from cell survival to cell death, apoptosis may also be modulated by signals from ligand-receptor interactions, as has been shown for TNF-/TNF-receptor [11, 12]. It is well documented that cytotoxic drugs exert their effects through the induction of apoptosis [13].

List of Research Outputs

Chen J., Tong Y. and Wong T.M., Diosgenin against myocardial injury induced by ischemia and reperfusion in rats, 　Fifth CGCM. zhuhai, 2006.

Chen J. and Wong T.M., Protective effects of Diosgenin against myocardial injury induced by ischemia and reperfusion , In: Bao KX, 　2006 international symposium for traditional Chinese medicine and integration of traditionalchinese & western medicine. seattle, 2006.

Chen J. and Loo T.Y., The therapeutic effect of Shugansanjie Tang on human breast tumor tissue , The Third Annual Conference of the Organisation for Oncology and Translational Research. The Third Annual Conference of the, 2006.

Chen J. and Han F., 　Be coming easy to learn Chinese Medicine Prescriptions, In: AMEE Association for Medical Education in Europe , AMEE Association for Medical Education in Europe . 2006.

Chen J., 方劑全攻略, 香港靈蘭閣圖書國際公司, 2007.

Loo T.Y. and Chen J., 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. USA, Biomedicine et Pharmacotherapy, 2007, 2007 61(9):601-5.

Mo S.M., Law Y.H. and Chen J., 《傷寒雜病論》中麻黃与甘草配伍規律探討, In: 新中医, 新中医, Guan Zhou, 新中医, 2006, 37ï¼12ï¼2005: 9－10.

li X.I.A.O.F.A.N.G. and Chen J., 黃山藥提取物緩釋片的研制 , 廣東藥學院學報, 广东　, 廣東藥學院學報, 2006, 22-03: 223-225.

Researcher : Chen RQ

Project Title:	Developing a novel scientific approach for clinical research of Chinese medicine using menopause as a model
Investigator(s):	Chen RQ
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2005

Abstract:

B) To analyse gene expression in subjects with KDS-Yin and KDS-Yang, who are identified with the validated KDS Scale. (Note: KDS-Yin: A pattern of pathogenesis in Chinese medicine: Kidney-Yin-deficiency syndrome KDS-Yang: A pattern of pathogenesis in Chinese medicine: Kidney-Yang-deficiency syndrome)

Researcher : Feng Y

Project Title:	Development of Animal models and cell culture for Evaluating the bioactive effect of Chinese Medicines Series1: bioactive Screening and Estimation of Chinese Medicines by using rats with hepatic damage models (including liver cancer models), rats with renal disease models and relevant cell culture
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:	11/2005

Abstract:

Chinese medicines have thousands of years’ history of use in China, but its research by modern scientific methods was not initiated until the early twentieth century. Today, there have been over 8,000 chemical ingredients identified from Chinese medicines. Extensive bioactive studies have been conducted regarding the application of Chinese medicines in modern medical practice (e.g. qinghaosu, ephedrine, vincristine, tetramethylpyrazine, indirubin, berberine, polysaccharide from Ganoderma lucidum and Panax ginseng etc.). There are two strategies for research of Chinese medicines: the first is to extract chemical ingredients from a single kind of Chinese crud drug, and then analyze it by various scientific methods, including bioactive screening methods. This is a process from laboratory study to clinical application and is similar to western medicine research. The other strategy is research of Chinese medicinal formulations. For the latter one, the bioactive action is confirmed or discovered in the laboratory according to evidences from clinical observation, and the outcome is applied to clinical setting. This kind of study needs to recombine modern scientific methods with the unique characteristics of TCM. Chinese medicines use therapeutic approach of compound formulations. Therefore, the 2nd type of research has important significance in the modernization of Chinese medicines. The question is how to evaluate the compound formulas. Some standard animal models have been established for some diseases in western medicine, but how to apply them to syndromes in Chinese medicine and then evaluation of Chinese medicines remain to be explored. This project aims to establish standard animal models and cell culture for evaluation of the bioactive action of Chinese medicines and the mechanism of drug derived there from. The designation and development of drugs in Chinese medicines are based on updated studies from various scientific fields, which are combined with unique characteristics of TCM. Furthermore, we expect the outcome of this study to be useful in setting up standard systems for evaluating the bioactive action of drugs derived from Chinese medicines and providing scientific evidence and mechanism of Chinese herb medicine. Researchers who participate in this project all have extensive research experience in both Chinese medicines and western medicine.

List of Research Outputs

Feng Y. and Chan K.S., Basic status and comments on adverse reaction and poisoning of Chinese medicines in national and international databases, 国内外资料库中对中药不良反应和中毒的基本情况及评述, In: 陈抗生，王炳岐，赵中正等, Hong Kong Chinese Medical Journal . 香港中医杂志, Hong Kong, The Pblisher of Hong Kong Chinese Medical Journal, 2007, 2(1): 27-33.

Feng Y., Tong Y. and Lau E.P.W., Research methodology of TCM Formulas, 中药复方研究之探讨, In: Chan Kongsheng, Wang Bingqi, Zhao zhongzheng etc., Hong Kong Chinese Medical Journal. 香港中医杂志, Hong Kong, The Publisher of Hong Kong Chinese Medical Journal, 2006, 1(2): 64-66.

Lau E.P.W., Tsao G.S.W., Tong Y. and Feng Y., Study on the anti proliferative effect and its mechanism of berberine in various cancer cell lines. , 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. . Hong Kong, MCMIA, 2006, 1: pp30-31.

Ye X., Feng Y., Tong Y. and Zhang X.D., The Protective effects of chlorgenic acid on damaging of intestinal cosal microvascular endothelial cells caused by lipopolysaccharide., 2006 Hong Kong-Macau postgraduate Symposium on Chinese Medicine. . Hong Kong., MCMIA, 2006, pp132-133.

Researcher : Lau ASY

Project Title:	Mechanism of SARS-coronavirus pathogenesis - identification of viral genes implicated in immune dysregulation
Investigator(s):	Lau ASY, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To investigate the pathogenesis of SARS-Coronavirus-induced pulmonary injury and multi-organ dysfunctions in humans: (a) to identify the viral determinants of proinflammatory cytokine induction: candidate envelope genes to be examined include Spike (S), Envelope (E) and Membrane (M); (b) to investigate the signaling pathways including kinases and transcription factors involved in the cytokine induction.

Project Title:	A role for apoptogenic gene PKR in regulating TNF and cytokine expression in Avian influenza H5N1 infections
Investigator(s):	Lau ASY, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2003

Abstract:

To investigate whether H5N1/97 is a potent inducer of specific signaling kinases, compared to H1N1 or H3N2, leading to enhanced cytotoxicity in the host cell; to investigate whether H5N1/97 induction of TNF-[alpha] and related proinflammatory cytokines is dependent on the expression of these signaling kinases; the mechanism of H5N1/97-induced TNF-[alpha] and related cytokine expression; to identify transcription factors (TF) operative in H5N1-induced and kinase-mediated pathways; the role of these signaling kinases in H5N1/97-induced cytotoxicity: to identify kinase-regulated downstream pathways and induction of apoptogenic genes.

Project Title:	Immune dysregulation in HIV infection - mechanism of mycobacterial pathogenesis
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To confirm the role of HIV tat on monocytic cells in TH2 cytokine induction and TH1 reponse suppression; to identify the signaling pathways and transcription factors operative in Tat activation of IL-10 promoter; to investigate the effects of BCG or mycobacterial cell wall submits on IL-10 induction; to examine whether Tat interacts with TLR-associated kinases and factors directly or via PKR; to delineate whether exogenous IFN-[gamma] and other TH1 cytokines can counteract the effects of Tat and MTB in IL-10 induction.

Project Title:	Immunotherapy of mycobacterial infections: a cell and molecular model
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:	02/2005

Abstract:

To examine the profile of cytokine expression including proinflammatory cytokines and anti-inflammatory cytokines in BCG and mycobacterial cell wall subunits-treated cells; to confirm the role of PKR and related kinases in signaling pathways operative in the BCG- and cell wall subunit-induced cytokine expression; to examine the role of IL-10 in inhibition of IFN signaling and macrophage functions; to examine whether IL-10 induces the expression of SOCS to inhibit IFN-gamma signaling; to delineate whether exogenous IFN-gamma and other TH1 cytokines can modulate and reverse the effects of BCG and IL-10 in SOCS induction and restore the effects of IFN-gamma macrophage function.

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:	Mechanisms of inteferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections
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:	10/2006

Abstract:

To examine the signaling pathways in IFN-beta super-induction by avian influenza viruses including H5N1/97, as compared to human viruses including H1N1; to investigate whether there is a preferential activation of IFN regulatory factors (IRFs) during IFN induction in avian virus infections; to determine the transcriptional activation of IFNs by electrophorectic mobility shift, IFN promoter-driven luciferase and steady-state quantitative-PCR assays, in addition to Western blots; to delineate whether there is differential induction of cytotoxicity and apoptotic genes by the avian viruses from the human ones.

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:	Competitive Earmarked Research Grants (CERG)
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:	Regulation of Matrix Metalloproteinases by Epstein-Barr Virus Latent Membrane Protein 1
Investigator(s):	Lau ASY, Chua DTT, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006

Abstract:

Objectives: In this project, we will investigate the role of Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in the expression of Matrix Metalloproteinases (MMPs) and their consequent effects on cell migration. Our Specific Aims are: 1) We will generate LMP1-expressing cells including fibroblasts or epithelial cells by transient transfection of the cells with LMP1 cDNA. 2) We will delineate the mechanisms of Epstein-Barr Virus, specifically LMP1 gene, in the regulation of MMPs induction and the promotion of cell invasion. Background Epstein-Barr Virus (EBV) is a human herpesvirus that infects a large percentage of the world’s population (1). EBV has been known to be highly associated with human malignancies, including Burkitt’s lymphoma, post-transplant lymphomas, AIDS-associated lymphoma, gastric carcinoma, and the highly invasive nasopharyngeal carcinoma (NPC), putatively related to and as a consequence of the latent infection state (1,2). Specific EBV latent genes including LMP1, 2A, and 2B, as well as EBV nuclear antigen-1 (EBNA1) and EBV non-polyadenylated RNAs (EBER) are expressed in NPC cells (1). LMP1 has been shown to have transforming properties in mouse fibroblasts (3). It also plays an important role in EBV-induced B-cell immortalization and association with metastasis in nasopharyngeal carcinoma (3, 4). In in vitro study, LMP1 regulates Matrix Metalloproteinase 1 (MMP1) expression in epithelial cells, as well as MMP2 and -9 in B-cells. The transmembrane component of the LMP1 C-terminal contains two important signaling domains, namely CTAR1 and CTAR2. The interactions of CTAR domains with TRAFs or TRADD result in the activation of NF-kB, p38 MAPK, JNK and/or JAK/STAT signaling pathways (5). Matrix Metalloproteinase, with a total of 23 family members, are endopeptidases involved in the degradation of extracellular matrix proteins and their upregulation in cancer samples implicates their role in tumor metastasis (6). Selected MMPs are highly expressed in malignant cancers, in particular in the areas of active invasion such as the interface of tumor and stroma. For example, MMP-3 induced by cytokines and cellular factors in cancer and non-cancerous stromal cells may result in the deregulation of E-cadherin, a prototype adhesion molecule in maintaining the intercellular matrix (3). Thus destruction of E-cadherin and associated proteins promotes tumor invasion. Our previous studies indicate that LMP1 regulates the expression of proinflammatory cytokines including TNF and IL-6 as well as anti-inflammatory cytokines including IL-10. In light of the role of LMP1 in cytokine regulation and the fact that MMPs are regulated by TNF, we hypothesize that LMP1 promotes the progression and metastasis of highly invasive NPC via the induction of MMPs.

Researcher : Lau EPW

List of Research Outputs

Feng Y., Tong Y. and Lau E.P.W., Research methodology of TCM Formulas, 中药复方研究之探讨, In: Chan Kongsheng, Wang Bingqi, Zhao zhongzheng etc., Hong Kong Chinese Medical Journal. 香港中医杂志, Hong Kong, The Publisher of Hong Kong Chinese Medical Journal, 2006, 1(2): 64-66.

Lau E.P.W., Tsao G.S.W., Tong Y. and Feng Y., Study on the anti proliferative effect and its mechanism of berberine in various cancer cell lines. , 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. . Hong Kong, MCMIA, 2006, 1: pp30-31.

Researcher : Law YH

List of Research Outputs

Mo S.M., Law Y.H. and Chen J., 《傷寒雜病論》中麻黃与甘草配伍規律探討, In: 新中医, 新中医, Guan Zhou, 新中医, 2006, 37ï¼12ï¼2005: 9－10.

Researcher : Lee WS

List of Research Outputs

Lee W.S., Shen J., So K.F. and Tong Y., NITRIC OXIDE STIMULATES CAVEOLIN-1 EXPRESSION AND INTERACTION OF CAVEOLIN-1 AND NITRIC OXIDE SYNTHASE REGULATES NITRIC OXIDE PRODUCTION IN HUMAN SK-N-MC NEURAL CELLS UNDER HYPOXIA CONDITION, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”. Hong Kong, 2007.

Researcher : Li L

List of Research Outputs

Li L., , In: 張豐, 《百病單穴針灸驗方》, 香港九龍觀塘偉業街171號偉業工業大廈十樓A3室, 靈蘭閣圖書國際公司, 2007, 265.

Li L., 不同時辰電針內關與十二經五輸穴對正常人白細胞介素—2的影響, In: 第六屆上海國際針灸臨床與科研學術研討會, 第六屆上海國際針灸臨床與科研學術研討會論文彙編, 中國上海, 上海中醫藥大學, 2006, 196~199.

Li L., In: 張豐, 《<周易>導讀》, 香港九龍觀塘偉業街171號偉業工業大廈十樓A3室, 靈蘭閣圖書國際公司, 2007, 300.

Researcher : Liu KJ

List of Research Outputs

Shen J., Tong Y. and Liu K.J., Development of Electronic Paramagnetic Resonance Imaging: A Promising Imaging Technology for in vivo Mapping Brain Oxygen Distribution and Infarction in Ischemic Stroke, 2007 World Congress on Ageing and Dementia in Chinese Communities . Hong Kong, 2007.

Researcher : Loo TY

List of Research Outputs

Chen J. and Loo T.Y., The therapeutic effect of Shugansanjie Tang on human breast tumor tissue , The Third Annual Conference of the Organisation for Oncology and Translational Research. The Third Annual Conference of the, 2006.

Loo T.Y. and Chen J., 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. USA, Biomedicine et Pharmacotherapy, 2007, 2007 61(9):601-5.

Researcher : Mo F

List of Research Outputs

Mo F., HONG Wen, MO Fei-zhi, LI Jian-qiang, ZHAO Yan-ping, LIU Song-hao. (2007) Observation on the Therapeutic Effectiveness of the Rectal LED Irradiation in the Treatment of the Benign Prostatic Hyperplasia. , 洪文，莫飛智，李建強，趙燕平，劉頌豪. LED直腸內照射治療良性前列腺增生症療效觀察, Guangxi Traditional Chinese Medicine. 廣西中醫藥, 2007, 30(3): 38-39.

Mo F., HONG Wen, MO Fei-zhi, LI Jian-qiang, ZHAO Yan-ping, LIU Song-hao. Clinical Observation on the Therapeutic Effectiveness of the Rectal LED Irradiation in the Treatment of the Benign Prostatic Hyperplasia. , 洪文，莫飛智，李建強，趙燕平，劉頌豪. 鐳射穴位照射治療良性前列腺增生症臨床觀察.中華中醫藥學會.中醫、中西醫結合治療常見病研討會議交流論文. 中國黃山，2007年6月23--27, Treatment of Common Diseases by Chinese Medicine and Integrated Chinese-Western Medicine Conference. China Association of Chinese Medicine. Huangshan,China.Jun, 2007. (Thesis Presentation). 中華中醫藥學會.中醫、中西醫結合治療常見病研討會議交流論文., 2007.

Mo F., HONG Wen, MO Fei-zhi, LI Jian-qiang, ZHAO Yan-ping, ZENG Chang-chun, LIU Song-hao. Clinical Study on the Progress of the Rectal LED Irradiation in the Treatment of the Benign Prostatic Hyperplasia, 洪文，莫飛智，李建強，趙燕平，劉頌豪.（2006）鐳射照射治療慢性前列腺炎臨床研究進展., Abstracts of 2006' General Meeting of Chinese Optical Society. Guangzhou, Guangdong, China. September:134. 中國光學學會2006年學術大會論文摘要集, 中國廣東廣州, 2006年9月:134, 2006.

Mo F., HONG Wen, MO Fei-zhi, LI Jian-qiang, ZHAO Yan-ping, ZENG Chang-chun, LIU Song-hao. Observation on the Comparison in Therapeutic Effects between the 650 nm Laser Acupoint Irradiation and Acupuncture on the Treatment of Benign Prostatic Hyperplasia. , 洪文，莫飛智，李建強，趙燕平，劉頌豪. 650nm鐳射穴位照射與針灸治療良性前列腺增生症的療效對比觀察., Acta Laser Biology Sinica. 鐳射生物學報, 2007, 16(2): 230-233.

Mo F., Mo Feizhi. (2006) Discussion on Teaching of Classic Traditional Chinese Medicine. , 莫飛智．經典中醫教學探討., The 4th China Guangzhou International Conference of Traditional Chinese Medicine & the 3rd International Symposium on Education of Traditional Chinese Medicine. Guangzhou, November. 第四屆中國廣州國際中醫藥學術會議暨第三屆國際中醫藥教育研討會．2006 年11 月, 2006.

Mo F., Mo Feizhi. (2006) Using Classical Formula Based on Time Differentiation. , 莫飛智．時間辨證用經方.第四屆中國廣州國際中醫藥學術會議暨第三屆國際中醫藥教育研討會．廣州，2006 年11 月：15（摘要）, The 4th China Guangzhou International Conference of Traditional Chinese Medicine & the 3rd International Symposium on Education of Traditional Chinese Medicine. Guangzhou, November :15 (Abstract). 第四屆中國廣州國際中醫藥學術會議暨第三屆國際中醫藥教育研討會．廣州，2006 年11 月：15（摘要）, 2006.

Researcher : Mo SM

List of Research Outputs

Mo S.M., Law Y.H. and Chen J., 《傷寒雜病論》中麻黃与甘草配伍規律探討, In: 新中医, 新中医, Guan Zhou, 新中医, 2006, 37ï¼12ï¼2005: 9－10.

Researcher : Rong J

Project Title:	Modulation of heme oxygenase-1 expression by traditional Chinese medicine: Implications for antioxidant therapy
Investigator(s):	Rong J
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	07/2006

Abstract:

Heme oxygenase (HO) is the rate-limiting enzyme degrading heme into biliverdin, ferrous iron and carbon monoxide. Among the three isoenzymes isolated to date. HO-1 is highly inducible in response to diverse stimuli that often provoke oxidative injury to the tissues/organs [1-4]. The induction of HO-1 expression has been implicated in a variety of disease states such as atherosclerosis, hypertension, transplant rejection, acute renal injury, hyperoxia and hypoxia-induced lung injury, diabetes, cancer, cerebrovascular accident and cardiovascular diseases [5, 6]. Notably, the HO-1 pathway is widely recognized as an intrinsic defense against numerous pathological challenges. Pharmacological modulation of HO-1 expression therefore offers potential therapeutics to overcome the oxidative injury and inflammatory tissue damage. Many traditional Chinese medicine (TCM) products have been claimed to possess antioxidant and anti-inflammatory activities. However, the mechanisms underlying the actions of TCM products against the oxidative stress have not been well defined. We have recently investigated the biological response fingerprints of human liver cells to a TCM decoction ISF-1, a famous formula widely prescribed to treat ischemia reperfusion injury. We found for the first time that HO-1 was up-regulated up to 27-fold by the decoction ISF-1. Moreover, some heme/iron transporters and iron regulated transcriptional factors were also up-regulated to certain extent [7]. Based on our preliminary results, we hypothesize that the heme/iron homeostasis is one of the major targets for the decoction ISF-1. Presumably, most of the TCM products exert the antioxidant and anti-inflammatory activities in a similar fashion. Our long term goal is to investigate and resolve the problem of the mysterious correlation between the chemical compositions and the therapeutic efficacy of TCM drugs. Understanding on the molecular mechanisms of TCM actions is the key to develop evidence-based TCM drugs according to the international standards. Our strategy fingerprints the biological responses by the powerful oligonucleotide GeneChips at the genome-wide scale [8, 9]. Based on the global gene expression profiles, a number of representative mechanisms are selected to approach the complexity of TCM pharmacological effects. Subsequently, the active components responsible for the specific pathways are isolated through the bioactivity-guided fractionation. We anticipate that an optimal combination of active components (OCAC) will mimic the parent TCM drug in terms of the potency and efficacy. As a proof of principle, the proposed study will use a well-known post-stroke rehabilitation formula ISF-1 as an example and focus on ISF-1 mediated regulation of HO-1 pathway, one of the key pathways in ischemia reperfusion injury [7, 10]. The following specific aims will demonstrate how we will elucidate the mechanisms of ISF-1 actions and identify the individual active components from the complex formula. On the basis of the identified active components from this study and further related studies, we can develop a new optimized formula. Specific Aim 1: To identify the active compounds responsible for the induction of HO-1. Identification of the active components plays a key role in translating the experience-based TCM to modern evidence-based medicine. The decoction ISF-1 is the popular formula for the therapy of ischemia reperfusion injury. Intriguingly, most of the herbal ingredients are widely used to treat inflammation and oxidative stress. The antioxidant activity appears to be cytoprotective during reperfusion. However, both the active components and the regulated pathways have not been well characterized. We have recently demonstrated that the decoction ISF-1 can induce the high level expression of HO-1 in the cultured cells [7]. Considering the potential of HO-1 pathway in the antioxidant therapy, therefore, this study will identify the active components responsible for induction of HO-1. Pilot experiments will be performed using six herbs and the earthworm used in decoction ISF-1. To facilitate rapid identification of the active components, RT-PCR techniques will be used to detect HO-1 mRNA expression in the cells treated with various chromatographic fractionations. The cytoprotective effects of the active components against H2O2-induced oxidative stress will be evaluated by various assays for cell viability, xanthine oxidase and lipid peroxidation in the cultured cells. Specific Aim 2: To elucidate the molecular mechanism underlying the pharmacological regulation of HO-1. The genomic structure of human HO-1 gene indicates that the regulatory region is consisting of a 500-bp promoter, a proximal enhancer and 2 or more distal enhancers, and contains the specific binding sites for various transcriptional factors like AP-1, NF-kB and HIF-1. These response elements render that the expression of HO-1 can be induced by its substrate heme and various stress stimuli. Upon stimulation, an array of the cellular kinases including PKC PKA PI3K, ERK, JNK and MAPK may be activated in a specific manner. In order to elucidate the mechanisms of actions, a luciferase reporter plasmid construct with the human HO-1 promoter (The construct is ready to go for plasmid preparation in the Lab) will be introduced into HepG2 cells. Stable clones will be used as the reporter system. A small scale of phenotypic assay for the luciferase activity will be performed using a panel of different specific kinase inhibitors or siRNAs. We anticipate that such effort will result in identification of novel active components, which trigger the expression of HO-1 through different pathways. Furthermore, a global transcriptional analysis will help us to fingerprint the biological responses, providing some useful information to define the mechanisms. In summary, we will elucidate the molecular mechanisms underlying the regulation of HO-1 expression by the active components of ISF-1 and define the importance of HO-1 regulation to the overall biological activities of the decoction ISF-1. Successful identification of the single active components will help us to further characterize the cellular pathways contributing to the modulation of HO-1 expression. Thus, this study will not only provide useful information to develop novel HO-1 based therapies, but also provide experience to identify the herbal components responsible for different molecular pathways. These results will be valuable for developing novel TCM drugs in the near future.

Project Title:	Integrative transcriptomic and proteomic analysis of the cellular responses of human liver cells to the bioactive saponin Astragaloside IV: Towards the mechanisms underlying the antioxidant activity of Chinese medicine Radix Astragali
Investigator(s):	Rong J
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2007

Abstract:

Radix Astragali, known as Huang-Qi in traditional Chinese medicine, has been shown to possess a variety of biological and pharmacological activities such as anti-aging, anti-inflammation, and anti-oxidation in the central nerve system, cardiovascular system, and immune system [1-5]. Interestingly, we have recently demonstrated that the induction of heme oxygenase-1 (HO-1) expression is a key event to account for the antioxidant activity of traditional Chinese medicines. The induction of HO-1 enzyme was significantly enhanced by combination of Radix Astragali with other Chinese medicines such as Radix Chuangxiong and Lumbricus [6]. Furthermore, we have successfully demonstrated that astragaloside IV is the active compound responsible for regulating HO-1 expression. HO-1 is known to be cytoprotective against oxidative insults [7], suggesting that our results well pertain to the broad pharmacological activities of astragaloside IV, for example, inhibition of NF-kB activation [8] and suppression of excess accumulation of intracellular calcium [9]. Thus, we hypothesize that astragaloside IV is able to activate several intracellular pathways and consequently HO-1 is induced to a greater extent. The purpose of this study is to identify the cellular protein targets for drug discovery based on the genome-wide biological response profiles of human cells astragaloside IV and understand how astragaloside IV enhances the induction of HO-1 expression.Specific Aim # 1. To determine the differential gene expression profiles of human cells with/without the treatment of astragaloside IV. This specific aim is based on the hypothesis that astragaloside IV exhibit its activities through regulating cellular gene expression. Under this specific aim, we will perform a genome-wide analysis of the cellular gene expression modulated by astragaloside IV. The alteration of gene expression pattern should suggest the cellular protein targets for astragloside IV. In the future studies (beyond this proposal), the mRNA expression of candidate genes will be verified by quantitative RT-PCR. Protein expression will be quantified by Western blotting and its cellular localization will be determined by immunohistochemical staining. The results from this study will provide evidence for further characterization of the cellular proteins targeted by astragaloside IV.Specific Aim # 2. To determine the differential proteomic profiles of human cells with/without the exposure to astragaloside IV. This specific aim is based on the hypothesis that astragaloside IV may regulate post-transcriptional modifications of proteins. Under this specific aim, we will apply the proteomic approach to determine how astragaloside IV affects the cellular proteomic profiles by 2D gel electrophoresis and protein identification. Protein expression will be analyzed by western blotting (for quantification) and immunohistochemistry (for localization). The results of proteomic analysis will clarify whether astragaloside IV alters the post-transcriptional modification spectrum of the cellular proteins or not.Specific Aim # 3. To elucidate the role of astragaloside IV in the regulation of HO-1 expression. Our hypothesis is that astragaloside IV regulates HO-1 expression by activating a specific intracellular pathway. Based on the transcriptomic and proteomic profiles obtained in Specific Aim #1 & 2, we will first use specific inhibitors to determine which intracellular pathway is involved in regulating HO-1 expression. Candidate pathways may include NF-kB, nitric oxide production or calcium homeostasis. A promoter-reporter system, in which the reporter luciferase is under the control of 4.9 kb upstream DNA sequence of HO-1 gene, will be used to facilitate the detection of HO-1 expression.This project represents our new attempts to apply the state-of the-art genomics and proteomics technologies to characterize the biological response fingerprints (BioReF) of Chinese traditional medicines in human cells. The results from the proposed studies should be informative as to what types of biological pathways are targeted by the purified active component astragaloside IV. This knowledge will advance current understanding of the molecular changes that characterized the pharmacological activities of astragaloside IV and the molecular basis for its role in regulating HO-1 expression. Ultimately, this study will provide direct evidence to make use of the biological activities of astragaloside IV, especially enhancement of HO-1 induction, for therapeutic purpose.

Researcher : Shen F

List of Research Outputs

Shen F., 中醫骨傷科學, 中國中醫藥出版社, 2007, ç¬¬äºç: 326-349.

Shen F., 自擬皮疹1號方加減治療濕熱證濕瘡37例總結, 中西醫結合防治皮膚病學術研討會, 香港, 2007.

Shen F., 中醫骨傷名師, 中華中醫藥學會, 2007.

Researcher : Shen J

Project Title:	Effects of Buyang Huanwu Decoction on neuronal regeneration after ischemic brain injury
Investigator(s):	Shen J, Fung PCW
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To evaluate the effects of Buyang Huanwu Decoction, a classical formula of Traditional Chinese Medicine (TCM), and its major component Astragalus membranaceus on the regeneration of neurons after ischemic brain injury.

Project Title:	Plasma membrane cholesterol homeostasis and oxidative stress: implication for neuronal oxidative damage in ischemia stroke
Investigator(s):	Shen J, Cheung RTF, Fung PCW
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005
Completion Date:	12/2006

Abstract:

To investigate the reole of plasma membrane cholesterol in regulating cellular oxygen supply and ROS production in MCAO ischemia-reperfused model; to investigate which cholesterol pools, free cholesterol, choelsterol ester or oxysterols, would aggravate neuronal oxidative damage in ischemia-reperfused neuronal cells; to test the hypothesis that caveolin-1 may be a important target protein linking with neuronal oxidative damage and abnormal choletserol metabolism.

List of Research Outputs

Cai G., Liu B., Liu W., Tan X., Rong J., Chen X., Tong L. and Shen J., Buyang Huanwu Decoction Can Improve Recovery of Neurological Function, Reduce Infarction Volume, Stimulate Neural Proliferation and Modulate VEGF and Flk1 Expressions in Transient Focal Cerebral Ischaemic Rat Brains, Journal of Ethnopharmacology. 2007, 113: 292-299.

Chen B.Y., Lam K.S.L., Wang Y., Wu D., Lam C.W., Shen J., Wong L.C., Hoo R.L.C., Zhang J. and Xu A., Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes., Biochemical and Biophysical Research Communications . 2006, 341: 549-556.

LU G., Shen J., Fung P.C.W. and Chu K.W., 直結腸癌細胞線粒體超微結構與細胞凋亡的關系., 中國誤診學雜誌, China, 2006, 6(17): 3277-3279.

Lee W.S., Shen J., So K.F. and Tong Y., NITRIC OXIDE STIMULATES CAVEOLIN-1 EXPRESSION AND INTERACTION OF CAVEOLIN-1 AND NITRIC OXIDE SYNTHASE REGULATES NITRIC OXIDE PRODUCTION IN HUMAN SK-N-MC NEURAL CELLS UNDER HYPOXIA CONDITION, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”. Hong Kong, 2007.

Miyake M., Shen J., Liu S.M., Shi H.L., Liu W.L., Yuan Z.R., Pritchard A., Kao J.P.Y., Liu K.J. and Rosen G.M., Acetoxymethoxycarbonyl nitroxides as electron paramagnetic resonance proimaging agents to measure O2 levels in mouse brain: a pharmacokinetic and pharmacodynamic study. , Journal of Pharmacology and Experimental Therapeutics. USA, 2006, 318(3): 1187-1193.

Rong J., Shen J., Ng K.M., Liu C., Tam P.K.H. and Lau A.S.Y., Application Of Biological Response Fingerprinting (BioReF) To Define Marker Genes As Potential Quality Control Of Botanical Drug Products, 2006 World Congress on Chinese Medicine (CM2006). 2006.

Rong J., Shen J., Ng K.M., Liu C., Tam P.K.H. and Lau A.S.Y., Genome-wide biological response fingerprinting (BioReF) enables selection of multiple marker genes as potential quality control of botanical drug products, Fifth Meeting of Consortium for Globalization of Chinese Medicine (CGCM). 2006.

Rong J., Cheung Y.H., Shen J., Tam P.K.H. and Lau A.S.Y., 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, The 7th International Conference of System Biology. 2006.

Rong J., Tilton R., Shen J., Ng K.M., Liu C., Tam P.K.H., Lau A.S.Y. and Cheng Y.C., Genome-wide biological response fingerprinting (BioReF) of the Chinese botanical formulation ISF-1 enables the selection of multiple marker genes as a potential metric for quality control, Journal of Ethnopharmacology. 2007, 113: 35-44.

Shen J., Liu B.Y. and Tong Y., Buyang Huanwu Decoction Can Improve Recovery of Neurological Function via Stimulating Neural Proliferation and Differentiation and Modulating VEGF and Flk1 Expressions in Transient Focal Cerebral Ischaemic Rat Brains, 2nd International Symposium on Nutrition, Oxygen Biology and Medicine. Paris, France, 2007.

Shen J., Buyang Huanwu Decoction Can Improve Recovery of Neurological Function via Stimulating Neural Proliferation and Differentiation and Modulating VEGF and Flk1 Expressions in Transient Focal Cerebral Ischaemic Rat Brains, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”. Hong Kong, 2007.

Shen J., Liu S., Miyake M. and Liu K.J., Cerebral Tissue Oxygenation: Transportation, Metabolism, Measurement, And Significance In The Ischemic Brain, In: John Zhang, Hyperbaric Oxygen for Neurological Disorders. Flagstaff, Arizona, USA, Best Publishing Co., USA, 2007, 65-84.

Shen J., Chairman in the Session of Neuroimaging for Neurodegenative Disorders, 2007 World Congress on Ageing and Dementia in Chinese Communities. Hong Kong, 2007.

Shen 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 and infarction in ischemic brain, 2007.

Shen J., Tong Y., Rosen G.M. and Liu K.J., Development of Electron Paramagnetic Resonance Imaging: A Potential Imaging Technology for Evaluation of Traditional Chinese Medicine in Ischemiv Stroke, 2006 World Congress on Chinese Medicine:Charting the Course of Development. 2006.

Shen J., Tong Y. and Liu K.J., Development of Electronic Paramagnetic Resonance Imaging: A Promising Imaging Technology for in vivo Mapping Brain Oxygen Distribution and Infarction in Ischemic Stroke, 2007 World Congress on Ageing and Dementia in Chinese Communities . Hong Kong, 2007.

Shen J., Tong Y. and Tang X.H., Ginkgo biloba Extracts (EGb 761) Can Reduce Neurological Deficit Scores via Stimulating Neural Proliferation and Differentiation in Transient Focal Cerebral Ischaemic Rat Brains, 2007 Diet and Optimum Health Conference. 2007.

Tong L., Tan X.H. and Shen J., Comparative study of buyang huanwu decoction and the different combinations of its ingredients on neurogenesis following ischemic stroke in rats, Chinese Journal of Intergrated Medicine. 2007, 27(6): 519-22.

Researcher : Shi Y

List of Research Outputs

Shi Y., 中醫骨傷科: 臨床全攻略; 骨礦與臨床, Hong Kong, 靈閣圖書國際公司, 2007, 1: 232.

Researcher : Sze CW

Project Title:	Mechanistics Study on the Molecular Actions of a Modern Chinese Medicine Decoction (GFP) in Estrogen Secretion in Rat Granulose Cell via Aromatase Activation in vitro.
Investigator(s):	Sze CW, Tong Y, Zhang Y
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2006

Abstract:

Objective:According to a review of 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 is expected to rise to 1.1 billion after 20 years .GFP decoction has been widely used for more than 50 years in Chinese Medicine relieving peri-menopausal syndrome. Peri-menopause is the period of gradual degeneration of ovarian function, which in turn lowers the estrogen level. However, GFP can elevate the estrogen level of estrogenic depletion patients undergoing peri-menopause back to their normal level.Based on the fact that the main role of granulose cells is estrogen secretion and the results of our clinical study showed that the estrogen level of peri-menopausal patients increases after treated by GFP, we are now intending to find out how GFP can stimulate the estrogen secretion in ovarian granulose cells in vitro.Hypothesis: GFP treatment results in increased estrogen level. This increased secretion of estrogen is attributed to the activation of aromatase in ovarian granulose cells. Aromatase is an enzyme that produces estrogen in granulose cells.The purpose of this study: To find out the action mechanism of GFP-induced estrogen secretion in rat granulose cell via aromatase activation in vitro. If the Hypothesis can be verified, the study should shed novel light on the relationship between GFP and aromatase activation. This will benefit the therapeutic approach to peri-menopausal syndromes.Key Issues of this study:Special Aim 1: To determine and compare the compounds in GFP by High Performance Liquid Chromatograph (HPLC) which can establish the chemical fingerprint maps of GFP for quality control purpose.Special Aim 2: To establish a suitable cell model for studying the molecular event regulating granulosa cell steroidogenesis by GFP. Special Aim 3: To test the implication of the hypothesis, i.e. GFP-induced estrogen secretion in granulosa cells via aromatase activation, and to find out the brief action mechanism of GFP-induced estrogen secretion in rat granulose cells via aromatase activation in vitro.

List of Research Outputs

Chen H., Cho W.C.S., Sze C.W. and Tong Y., Treatment of Menopausal Symptoms with Er-Xian Decoction: A Systematic Review, 2nd Int'l Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007, 17b.

Sze C.W., Zhang Y., Chen H. and Tong Y., Molecular Mechanism of Erxian Decoction in Estrogen Secretion in vitro, 2nd Int'l Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population". 2007, 17a.

Sze C.W., Zhang Y. and Tong Y., Stimulation of Estrogen Secretion in Rat Granulose Cell via Steroidogenic Enzyme Activation by Modern Chinese Medicine Decoction (GFP)., Fifth Meeting of Consortium for Globalization of Chinese Medicine. 2006, 5: 108.

Zhang Y., Sze C.W. and Tong Y., A DNA Microarray for Differentiation of Fengdou Shihu (Dendrobium officinale) by 5S Ribosomal DNA Intergenic Spacer Region, Fifth Meeting of Consortium for Globalization of Chinese Medicine. 2006, 5: 35.

Zhang Y., Tong Y. and Sze C.W., Development of sequence characterized amplified region (SCAR) markers to differentiate Fengdou Shihu and its adulterants , In: Tong Yao, Zhang Yanbo, Sze Cho-Wing , HKU. 2006.

Zhang Y., Shaw P.C., Sze C.W., Wang Z.T. and Tong Y., Molecular Authentication of Chinese Herbal Materials, Journal of Food and Drug Analysis. 2007, 15: 1-9.

Researcher : Tong Y

Project Title:	Experimental study of Erxian Decoction on blocking apoptosis of ovary granulosa cells in middle-aged female rats
Investigator(s):	Tong Y, Chen J
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2005
Completion Date:	12/2006

Abstract:

The main objective of this project is to investigate the efficacy and certain mechanisms of Erxian Decoction in blocking apoptosis of ovary graanulosa cells in middle-aged female rats.

Project Title:	Development of Sequence Characterized Amplified Region (SCAR) Markers to Differentiate Fengdou Shihu (枫斗石斛) and Its Adulterants.
Investigator(s):	Tong Y, Zhang Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

Fengdou Shihu (FDSH) from Dendrobium Officinale (铁皮石斛) (Family: orchidaceae) is a valuable and tonic Chinese medicine, which have gained considerable favor in Hong Kong citizens. For this reason FDSH are commanded high prices in Hong Kong and adulterated frequently. Owing to be processed to same apparent shape, use of traditional authentication method cannot distinguish crude from its adulterant. Therefore, molecular method will be explored in this study. A random amplified polymorphic DNA (RAPD) fragment from Dendrobium officinale will be converted to a sequence characterized amplified region (SCAR) marker. The main difference between the SCAR of D. officinale and its adulterants will be found in the sequences. Primers deriving from this sequence will be used to differentiate D. officinale species and its adulterants. SCAR is expected to be a usefully approach for authentication of FDSH.

Project Title:	To evaluate the anti-invasion, anti-metastasis, multidrug resistance property and chemoprevention effect of curcumin for the treatment of breast cancer.
Investigator(s):	Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2007

Abstract:

The purpose of this study is to evaluate the anti-invasion, anti-metastasis, multidrug resistance property and chemoprevention effect of curcumin for the treatment of breast cancer.Breast cancer, is the most common cancer among women in Hong Kong as well as other developed countries (1). Breast cancer has increased dramatically in China with 3% to 4% annual increments during the past two decades (2, 3).Therefore, there is great interest in developing novel molecular-based therapeutics targeted at inhibition of breast cancer cell proliferation pathways (14, 15). The use of compounds from natural products for breast cancer treatment is currently being explored (16). 5-fluorouracil, Epirubicin and Capecitabine are common cytotoxic agents for the treatment of breast cancers with anti-invasion and anti-metastasis properties (10-12). Capecitabine, is a fluoropyrimidine carbamate which is rapidly absorbed via the oral route (13). However, we still have no effective therapy for breast cancer treatment. Therefore, novel therapy approaches, such as Chinese Medicine, are needed.Curcumin (diferuloylmethane), Chinese medicine, the most active constituent of turmeric preparations, have been the subject of hundreds of published papers for its antioxidant, anti-inflammatory, cancer chemopreventive and potentially chemotherapeutic properties (4). Recent studies show that curcumin can induce apoptosis in multiple cancer cell including colon cancer cells (5) and lung cancer cell (6, 7) as well as ovarian cancer cells (8). Curcumin has been found to induce apoptosis in MCF-7 breast cancer cells by regulation of multiple signaling pathways (9). Our previous studies have showed that curcumin inhibit proliferation of breast cancer cell at progress through G1 into S phase of cell cycle by down-regulating the NFκB on ER positive BT-483 breast cancer cell and ER-negative MDA-MB-231 breast cancer. However, the effects of curcumin on anti-invasion, anti-metastasis, multidrug resistance property and chemoprevention effect remain unclear. We therefore hypothesized that curcumin possess the properties of anti-invasion, anti-metastasis, multidrug resistance and chemoprevention for breast cancer treatment. Matrix metalloproteinases (MMPs) are important prerequisite for tumor invasion and metastasis (17). Usually, patients refractory to chemotherapy exhibit resistance to multiple cytotoxic agents of different structure (and often function), termed as multidrug resistance (MDR), which overexpression can be expected in around 30-40% of primary and 50% of metastatic breast cancers (18). Cancer chemoprevention involves the use of either natural or synthetic chemicals to prevent the initiation, promotion, or progression of cancer.Therefore, the objectives in this study are:1. To investigate and compare the anti-invasion and anti-metastasis effects of curcumin and common cytotoxic agents (5-fluorouracil, Epirubicin and Capecitabine).2. To investigate and compare the multidrug resistance property of curcumin and common cytotoxic agents (5-fluorouracil, Epirubicin and Capecitabine).3. To investigate and compare the chemoprevention effect of curcumin and common cytotoxic agents (5-fluorouracil, Epirubicin and Capecitabine).Reference:1. Simpson P. Hong Kong families and breast cancer: beliefs and adaptation strategies. Psychooncology 2005,14(8):671-683.2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005,55(2):74-108.3. Zhang WJ, Gao YJ, Li QB, Xu D. Breast cancer in China: demand for genetic counseling and genetic testing. Genet Med. 2006,8(3):196-7.4. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer. 2005 Sep;41(13):1955-19685. Chauhan DP. Chemotherapeutic potential of curcumin for colorectal cancer. Curr Pharm Des. 2002, 8:1695-1706.6. Lee J, Im YH, Jung HH, Kim JH, Park JO, Kim K, Kim WS, Ahn JS, Jung CW, Park YS, Kang WK, Park K. Curcumin inhibits interferon-alpha induced NF-kappaB and COX-2 in human A549 non-small cell lung cancer cells. Biochem Biophys Res Commun. 2005, 334(2):313-318.7. Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E. Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett. 2004,208(2):163-70.8. Zheng L, Tong Q,Wu C. Growth inhibitory effects of curcumin on ovary cells and its mechanism. J Huazhong Univ Sci Technolog Med Sci. 2004;24:55-589. Ramachandran C, Rodriguez S, Ramachandran R, Raveendran Nair PK, Fonseca H, Khatib Z, Escalon E, Melnick SJ. Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res. 2005, 25(5):3293-302.10. Esteva FJ, Valero V, Pusztai L, Boehnke-Michaud L, Buzdar AU, Hortobagyi GN. Chemotherapy of metastatic breast cancer: what to expect in 2001 and beyond. Oncologist. 2001;6(2):133-46.11. Decatris MP, Sundar S, O'Byrne KJ. Platinum-based chemotherapy in metastatic breast cancer: current status. Cancer Treat Rev. 2004,30(1):53-81.12. Camaggi CM, Strocchi E, Carisi P et al. Epirubicin metabolism and pharmacokinetics after conventional- and high-dose intravenous administration: a cross-over study. Cancer Chemother Pharmacol 1993;32:301-309.13. Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H. Design of a novel oral fluoropyrimidine carbamate, Capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998; 34: 1274-128114. Sporn MB: Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res 1976;36:2699-2702.15. Greenwald P, Kelloff G, Cynthia Burch-Whitman Barnett S. Kramer. Chemoprevention. Cancer J Clin1995;45: 31-4916. Tamimi RM, Lagiou P, Adami HO, Trichopoulos D. Prospects for chemoprevention of cancer. J Intern Med. 2002, 251(4):286-300.17. Shon YH, Park SD, Nam KS. Effective chemopreventive activity of genistein against human breast cancer cells. J Biochem Mol Biol. 2006, 39(4):448-451.18. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001, 47(4):293-303.19. Fujimoto-Ouchi K, Sekiguchi F, Tanaka Y. Antitumor activity of combinations of anti-HER-2 antibody trastuzumab and oral fluoropyrimidines capecitabine/5'-dFUrd in human breast cancer models. Cancer Chemother Pharmacol. 2002, 49(3):211-216.

List of Research Outputs

Chen H., Cho W.C.S., Sze C.W. and Tong Y., Treatment of Menopausal Symptoms with Er-Xian Decoction: A Systematic Review, 2nd Int'l Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007, 17b.

Chen J., Tong Y. and Wong T.M., Diosgenin against myocardial injury induced by ischemia and reperfusion in rats, 　Fifth CGCM. zhuhai, 2006.

Feng Y., Tong Y. and Lau E.P.W., Research methodology of TCM Formulas, 中药复方研究之探讨, In: Chan Kongsheng, Wang Bingqi, Zhao zhongzheng etc., Hong Kong Chinese Medical Journal. 香港中医杂志, Hong Kong, The Publisher of Hong Kong Chinese Medical Journal, 2006, 1(2): 64-66.

Lau E.P.W., Tsao G.S.W., Tong Y. and Feng Y., Study on the anti proliferative effect and its mechanism of berberine in various cancer cell lines. , 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. . Hong Kong, MCMIA, 2006, 1: pp30-31.

Lee W.S., Shen J., So K.F. and Tong Y., NITRIC OXIDE STIMULATES CAVEOLIN-1 EXPRESSION AND INTERACTION OF CAVEOLIN-1 AND NITRIC OXIDE SYNTHASE REGULATES NITRIC OXIDE PRODUCTION IN HUMAN SK-N-MC NEURAL CELLS UNDER HYPOXIA CONDITION, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”. Hong Kong, 2007.

Luk J.M., Wang X.L., Liu P., Wong K.F., Chan K.L., Tong Y., Hui C.K., Lau G.K. and Sheung T.F., Traditional Chinese herbalmedicines for treatmentof liver￠brosis and cancer: fromlaboratorydiscovery to clinical evaluation , LiverInternationnal ISSN. 2007, 1478-3223.

MAN P.M., Tong Y. and Zhang Z., Advance in Acupuncture Treatment of Drug Withdrawal Syndrome, The 6th Shanghai International Symposium on Clinical and Academic Research of Acupuncture & Moxibustion. , 2006.

Shen J., Liu B.Y. and Tong Y., Buyang Huanwu Decoction Can Improve Recovery of Neurological Function via Stimulating Neural Proliferation and Differentiation and Modulating VEGF and Flk1 Expressions in Transient Focal Cerebral Ischaemic Rat Brains, 2nd International Symposium on Nutrition, Oxygen Biology and Medicine. Paris, France, 2007.

Shen J., Tong Y., Rosen G.M. and Liu K.J., Development of Electron Paramagnetic Resonance Imaging: A Potential Imaging Technology for Evaluation of Traditional Chinese Medicine in Ischemiv Stroke, 2006 World Congress on Chinese Medicine:Charting the Course of Development. 2006.

Shen J., Tong Y. and Liu K.J., Development of Electronic Paramagnetic Resonance Imaging: A Promising Imaging Technology for in vivo Mapping Brain Oxygen Distribution and Infarction in Ischemic Stroke, 2007 World Congress on Ageing and Dementia in Chinese Communities . Hong Kong, 2007.

Shen J., Tong Y. and Tang X.H., Ginkgo biloba Extracts (EGb 761) Can Reduce Neurological Deficit Scores via Stimulating Neural Proliferation and Differentiation in Transient Focal Cerebral Ischaemic Rat Brains, 2007 Diet and Optimum Health Conference. 2007.

Sze C.W., Zhang Y., Chen H. and Tong Y., Molecular Mechanism of Erxian Decoction in Estrogen Secretion in vitro, 2nd Int'l Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population". 2007, 17a.

Sze C.W., Zhang Y. and Tong Y., Stimulation of Estrogen Secretion in Rat Granulose Cell via Steroidogenic Enzyme Activation by Modern Chinese Medicine Decoction (GFP)., Fifth Meeting of Consortium for Globalization of Chinese Medicine. 2006, 5: 108.

Tan Q.R., Wang X.Z., Wang C.Y., Liu X.J., Chen Y.C., Wang H.H., Zhang R.G., Zhen X.C., Tong Y. and Zhang Z., Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells, European Neuropsychopharmacology. 2007, 17: 768-773.

Tong Y., Research of Mechanism on Regulating Stress to Prevent and Cure Psychological Desease by Treatment Liver (TCM), Hong Kong Health Expo and International Conference on Traditional Chinese Medicine (TCM) and The Fourth Pong Ding Yuen International symposium on Traditional Chinese Medicine. 2006.

Tong Y., 中醫藥防治傳染病研究的進展, 國際現代化中醫藥及健康產品展覽會暨會議, 2006, 17-18.

Tong Y. and Chen H., 仲景運用細辛規律研究, 上海中醫藥大學學報, 2007, 21(3): 12-14.

Tong Y., 中醫調肝法調節應激防治心身疾病機理研究, 香港健康展暨國際中醫藥發展論壇暨第四屆龐鼎元中醫藥國際研討會, 2006, 28-30.

Ye X., Feng Y., Tong Y. and Zhang X.D., The Protective effects of chlorgenic acid on damaging of intestinal cosal microvascular endothelial cells caused by lipopolysaccharide., 2006 Hong Kong-Macau postgraduate Symposium on Chinese Medicine. . Hong Kong., MCMIA, 2006, pp132-133.

Zhang Y., Sze C.W. and Tong Y., A DNA Microarray for Differentiation of Fengdou Shihu (Dendrobium officinale) by 5S Ribosomal DNA Intergenic Spacer Region, Fifth Meeting of Consortium for Globalization of Chinese Medicine. 2006, 5: 35.

Zhang Y., Tong Y. and Sze C.W., Development of sequence characterized amplified region (SCAR) markers to differentiate Fengdou Shihu and its adulterants , In: Tong Yao, Zhang Yanbo, Sze Cho-Wing , HKU. 2006.

Zhang Y. and Tong Y., Donation HK$200.000 for research developing and postgraduate education, In: Zhang Yanbo, Tong Yao, from private . 2007.

Zhang Y., Shaw P.C., Sze C.W., Wang Z.T. and Tong Y., Molecular Authentication of Chinese Herbal Materials, Journal of Food and Drug Analysis. 2007, 15: 1-9.

Zhang Y., Tong Y. and Zhang Y., Zhang Yanbo. Mechanistics study on the molecular actions of a modern Chinese medicine decoction (GFP) in estrogen secretion in rat granulose cell via aromatase activation in vitro , In: Sze Cho-Wing, Tong Yao, Zhang Yanbo , HKU . 2006.

Zhang Z., Tong Y., Wang X., Yao S.M., Jin G.X. and Wang X.P., Huperzine A as add-on therapy in patients with treatment-resistant schizophrenia: An open-labeled trial, Schizophrenia Research . 2007, 92: 273–275.

Researcher : Wong YY

List of Research Outputs

Ng S.M., Chan C.L.W., Wong Y.Y. and Ho T.H., Overattachment, mind/body stagnation and depression, Consultation on Holistic Health & Care. Hong Kong, 2006.

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 : Ye X

List of Research Outputs

Ye X., Feng Y., Tong Y. and Zhang X.D., The Protective effects of chlorgenic acid on damaging of intestinal cosal microvascular endothelial cells caused by lipopolysaccharide., 2006 Hong Kong-Macau postgraduate Symposium on Chinese Medicine. . Hong Kong., MCMIA, 2006, pp132-133.

Researcher : Yiu YM

Project Title:	The clinical effectiveness of acupuncture in the treatment of chronic fatigue syndrome (CFS)
Investigator(s):	Yiu YM, Ng SM
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2006

Abstract:

The main objective of this research is to conduct a randomized controlled clinical trial to evaluate the effectiveness of acupuncture on CFS

List of Research Outputs

Yiu Y.M. and Ting H.D., 針灸配合食療醫治慢性疲勞綜合症, 香港中醫雜志. Hong Kong, 2006, 2: 77-78.

Yiu Y.M. and Qiu M.Y., 香港地區慢性疲勞綜合征與中醫證型的流行病學調查, 香港中醫雜志, HK, 1, 2006, 1: 27-29.

Researcher : Zhang Y

Project Title:	Comparison of Pharmacological Effects and Chemical Constituents between Different Dendrobium Species
Investigator(s):	Zhang Y, Tong Y, Sze CW
Department:	School of Chinese Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2007

Abstract:

Objectives:The Chinese crude drug "Shihu", which is derived from the dried or fresh stems of Dendrobium species (Orchidaceae), is a valuable and tonic Chinese medicine and have gained considerable favor in Hong Kong citizens. Today, there are about 35 Dendrobium species used as "Shihu" in market [1]. However, it have been remained unknown that whether all the Dendrobium species used today can be applied as the same clinical effect as authentic "Shihu", and what are the differences in both pharmacological and chemical level between each species. Therefore, the objective of this project is to investigate the differences in their pharmacological effects and chemical constituents between each species.

List of Research Outputs

Sze C.W., Zhang Y., Chen H. and Tong Y., Molecular Mechanism of Erxian Decoction in Estrogen Secretion in vitro, 2nd Int'l Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population". 2007, 17a.

Sze C.W., Zhang Y. and Tong Y., Stimulation of Estrogen Secretion in Rat Granulose Cell via Steroidogenic Enzyme Activation by Modern Chinese Medicine Decoction (GFP)., Fifth Meeting of Consortium for Globalization of Chinese Medicine. 2006, 5: 108.

Zhang Y., Sze C.W. and Tong Y., A DNA Microarray for Differentiation of Fengdou Shihu (Dendrobium officinale) by 5S Ribosomal DNA Intergenic Spacer Region, Fifth Meeting of Consortium for Globalization of Chinese Medicine. 2006, 5: 35.

Zhang Y., Authentication method in Codonopsis species , In: Shaw PC, Xu HX, But PPH, Zhang YB , China . 2007.

Zhang Y., Tong Y. and Sze C.W., Development of sequence characterized amplified region (SCAR) markers to differentiate Fengdou Shihu and its adulterants , In: Tong Yao, Zhang Yanbo, Sze Cho-Wing , HKU. 2006.

Zhang Y. and Tong Y., Donation HK$200.000 for research developing and postgraduate education, In: Zhang Yanbo, Tong Yao, from private . 2007.

Zhang Y., Shaw P.C., Sze C.W., Wang Z.T. and Tong Y., Molecular Authentication of Chinese Herbal Materials, Journal of Food and Drug Analysis. 2007, 15: 1-9.

Zhang Y., Molecular Authentication of Chinese Medicines , 　International Conference & Exhibition of the Modernization of Chinese Medicine & Health Products . 2006.

Zhang Y., Tong Y. and Zhang Y., Zhang Yanbo. Mechanistics study on the molecular actions of a modern Chinese medicine decoction (GFP) in estrogen secretion in rat granulose cell via aromatase activation in vitro , In: Sze Cho-Wing, Tong Yao, Zhang Yanbo , HKU . 2006.

Researcher : Zhang Z

Project Title:	Therapeutic effects of ligustilide and mechanisms of its actions against premenstrual dysphoric disorder (PMDD)
Investigator(s):	Zhang Z
Department:	School of Chinese Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	12/2006

Abstract:

1. Objective The objective of the proposed project is to determine therapeutic effects of ligustilide, an essential oil initially derived from the Chinese medicine Angelica sinensis (Dang-Gui), and mechanisms of its actions against premenstrual dysphoric disorder (PMDD). PMDD symptoms mainly include severe depressed mood, anxiety, anger, and increased interpersonal conflicts. Although the antidepressants selective serotonin reuptake inhibitors (SSRIs) have been first-line therapy of PMDD, over 50% of the patients cannot obtain clinically defined responses. The incompleteness of SSRI therapy is largely because the etiology and pathogenesis of PMDD are apparently different from major depressive disorders. Since decreased sensitivity of central gamma-aminobutyric acid (GABA) receptors induced by dramatic fluctuation in ovarian steroids during the cycle is the major pathogenesis of PMDD is. Therefore, it is reasonable to believe that agents that can restore GABA receptor sensitivity by stabilizing ovarian steroid fluctuation should yield better clinical efficacy than SSRIs in the treatment of PMDD. Angelica sinensis is the most commonly used Chinese medicine in treating menstrual cycle-linked mood disorders. Ligustilide is an essential oil which initially derived from Angelica and accounts for nearly 45% of total Angelica essential oils. Behavioral studies have shown that ligustilide possesses broad psychotropic effects, in particular, anxiolytic, social conflict-improved, and antidepressant effects; the effects are modulated by central GABAergic systems. Furthermore, ligustilide also possesses estrogenic and neurosteroid-like activities. These observations have led to the hypotheses that ligustilide may have specific therapeutic effects against PMDD by stabilizing ovarian steroid fluctuation during the cycle, and the effects are regulated by certain GABA and 5-HT receptor subtypes. To test these hypotheses, the following specific aims are proposed: 1) To evaluate the therapeutic effects of ligustilide against anxiety, depressive, and social conflict behavior observed in a PMDD model (female rats in the estrous phase); 2) To characterize GABAA and 5-HT2 receptor subtypes in the prefrontal cortex, hippocampus, and amygdala that modulate behavioral actions of ligustilide; and 3) To determine if ligustilide pretreatment could normalize dysfunction of GABAA receptor subtypes induced by withdrawal from exposure to the neurosteroid allopregnanolone in cultured neuronal cells. Through achieving these specific aims, we attempt to answer the following questions: (1) Does ligustilide have comparable even better effects in inhibiting PMDD-like behavior compared to reference drugs? (2) Are behavioral effects of ligustilide correlated with decreases in the amplitude of fluctuation in ovarian steroids? (3) Can GABAA and 5-HT2 receptor antagonists abolish behavioral effects of ligustilide observed in PMDD models? and (4) How does ligustilide treatment change the expression of GABAA receptor subtypes in specific brain regions and cultured neuronal cells? 2. Background The idea that comes from our previous studies: Jia-Wei-Xiao-Yao-San (Free and Easy Wanderer Plus, FEWP) is a well known Chinese herbal mixture which principal indications are menstrual cycle-associated mood symptoms, including premenstrual tension and menopausal syndrome. In previous studies, we have shown the beneficial effects of FEWP as adjunctive therapy and monotherapy in patients with mood disorders. In particular, FEWP monotherapy yields significantly greater improvement than placebo in patients with unipolar and bipolar depression, and this greater improvement appears to be more significant in female patients. These findings have triggered our interest to further explore potential constituents contained in FEWP that may have specific effects against menstrual cycle-linked mood disorders, such as PMDD. Since Angelica sinensis is a principal herb in the FEWP formula and most commonly used for menstrual cycle-linked illnesses, its major constituent ligustilide naturally came into our first consideration. What is known about ligustilide: Ligustilide is a low molecular compound (C12H14O2: MW: 190.24), easily penetrating into the blood-brain barrier. Ligustilide has been shown to have broad psychotropic effects. Acute administration of ligustilide significantly improves anxiety-like and depressive behavior in male rats. Ligustilide treated animals also display significant improvements on aggressive in social interaction test. Moreover, ligustilide reverses heightened social isolation induced by FG7142, a GABAA receptor blocker. However, these effects of ligustilide remain to be evaluated. Ligustilide has moderate to high affinity at estrogen receptors and GABA receptors. It also up-regulates progesterone receptor mRNA and enhances the release of 5-hydroxytryptamine (5-HT) and noradrenaline (NA), suggesting that ligustilide has both estrogenic and neurosteroid effects, including regulating GABA, NA and 5-HT activities. It is therefore reasonable to believe that ligustilide may have specific effects against the etiology and pathogenesis of PMDD. What is known about PMDD: Dramatic fluctuation in the ovarian hormone progesterone (P) and its metabolite allopregnanolone (ALLO) during the cycle is believed to be a major etiological factor of PMDD. Since ALLO is a potent positive modulator of GABAA receptor that enhances central GABAergic inhibition, high levels of ALLO during the cycle may induce excessive inhibition and low level or sharp drop may induce withdrawal effects, resulting in negative mood, anxiety, irritability, and social conflict in certain individuals. Furthermore, reduced sensitivity of GABAA receptor subtypes in specific brain regions was found to be associated with changes in ALLO levels, recurrence and severity of PMDD experienced during the cycle. These observations have led to a belief that restoration of GABAA receptors by stabilizing the steroid fluctuations is an effective strategy in the treatment of PMDD. On the other hand, it has been known that the 5-HT2 receptor plays an important role in regulating therapeutic effects of SSRIs in the treatment of PMDD. We will evaluate effects of ligustilide on the expression of 5-HT2 receptor subtypes in brain regions. Models of PMDD: The most widely used model is female rats in the estrus phase. Behavioral responses of estrous-phase animals in the elevated plus-maze (EPM), forced swimming test (FST), and social interaction (SI) test are nearly 70%-110% higher than diestrous-phase animals, which well resemble anxiety, depression, and social conflict observed in PMDD patients. We will utilize the three paradigms to test anti-PMDD effects of ligustilide. Cultured rat hippocampal neurons express abundant various GABAA receptor subtypes, and changes in the expression induced by withdrawal from the exposure to neurosteroids are consistent with the pathogenesis of PMDD. We will use the cultured cellsto detect molecular mechanisms of ligustilide’s actions.

List of Research Outputs

MAN P.M., Tong Y. and Zhang Z., Advance in Acupuncture Treatment of Drug Withdrawal Syndrome, The 6th Shanghai International Symposium on Clinical and Academic Research of Acupuncture & Moxibustion. , 2006.

Tan Q.R., Wang X.Z., Wang C.Y., Liu X.J., Chen Y.C., Wang H.H., Zhang R.G., Zhen X.C., Tong Y. and Zhang Z., Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells, European Neuropsychopharmacology. 2007, 17: 768-773.

Zhang Z., A randomized crossover comparison of an herbal preparation and bromocriptine against risperidone induced hyperprolactinemia in patients with schizophrenia, The Third Annual Current Concepts in Complementary and Alternative Medicine, Johns Hopkins University, Baltimore, Maryland, USA. 2007.

Zhang Z., Kang W.H., Li Q., Wang X.Y., Yao S.M. and Ma A.Q., Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: A double-blind, randomized, placebo-controlled study, Schizophrenia Research . 2006, 88: 102–110.

Zhang Z., Huperzine A add-on therapy improves cognitive function in patients with treatment-resistant schizophrenia - an open-labeled trial, The World Congress on Ageing and Dementia in Chinese Communities. 2007.

Zhang Z., Tong Y., Wang X., Yao S.M., Jin G.X. and Wang X.P., Huperzine A as add-on therapy in patients with treatment-resistant schizophrenia: An open-labeled trial, Schizophrenia Research . 2007, 92: 273–275.

Zhang Z., Kang W.H., Li Q. and Tan Q.R., The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP) for mood disorders: Double-blind, placebo-controlled studies, Journal of Psychiatric Research . 2006, 41: 828–836.

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