SCHOOL OF CHINESE MEDICINE

Researcher : Cao K



List of Research Outputs

 

Cao K., 補腎、健脾、活血中藥對環磷醯胺造模小鼠骨髓抑制影響的實驗研 究 , 第二屆粵港澳腫瘤大會學術論文集, 廣州, 2007, 171-173.

 

Chen R.Q., Cao K., Lam T.H. and Wong C.M., Symptom characteristics of Kidney-Yin deficiency and Kidney-Yang deficiency in Hong Kong Chinese midlife women, Journal of Alternative and Complementary Medicine. 2008, 14(5): 457-460.

 

Chen R.Q., Wong C.M., Cao K. and Lam T.H., The Development Of A Questionnaire For Diagnostic Evaluation Of Kidney-Yin Deficiency And Kidney-Yang Deficiency, In: Felix Wong, Basil Roufogalis , Third International Congress on Complementary Medicine Research. Sydney, Australia, International Society for Complementary Medicine Research, 2008, 27.

 

Chen R.Q., Lam C.L.K., Wong C.M., Cao K. and Lam T.H., The HRQoL measured by SF-12 in Hong Kong Chinese Middle Aged Women with Kidney Deficiency Syndrome, 2008 Asian Chinese Quality of Life Conference . 2008.

 

Chen R.Q., Wong C.M., Cao K. and Lam T.H., The measurement properties of a kidney deficiency syndrome questionnaire in Hong Kong Chinese midlife women (abstract and oral presentation), 12th Research Postgraduate Symposium, 12 & 14 December 2007, Hong Kong. Hong Kong, LKS Faculty of Medicine, HKU, 2007, 146.

 

Researcher : Chen H



List of Research Outputs

 

Chen H., Cho W.C.S., Sze C.W. and Tong Y., A Systematic Review on Efficacy of Erxian Decoction Treated Menopausal Symptoms, 3rd International Congress Complementary Medicine Research. Sydney, Australia, 2008.

 

Chen H., Cho W.C.S., Sze C.W. and Tong Y., Treatment of Menopausal Symptoms with Er-xian Decoction: A Systematic Review, America Journal of Chinese Medicine. 2008, 36(2): 233-244.

 

Researcher : Chen J



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/ProblemsThese 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. and Loo T.Y., Immunomulatory effect of YPF on human lymphocytes in vitro , The 6th biennial meeting of the Asian breast cancer society . 2007.

 

Chen J., Loo T.Y. and Chou W.K., Juzen-taiho-to enhances immune activity in vitro and minimizes cyto-toxicity in vivo, the 6th Biennial meeting of Asian Breast cancer society. 2007.

 

Chen J., WDY' conference , Breast cancer treatment strategy in Chinese medicine. 2007.

 

Chen J., prevention and treatment Breast cancer by Chinese Medicine , 2007TWGHs Eddie wang symposium on integrated chinese and western Medicine. 2007.

 

Chen J., treatment strategy of Chinese medicine on Breast caner, WDY's academically conference . 2007.

 

Diao J J., Chen J. and Lao Y J., 柴胡用治发热的临床应用概况, 廣州中醫藥大學學報, Guanzhou, 2008, 3(25)2008: 259.

 

Li Y., Chen J. and Loo T.Y., Immunomodulatory effect of Yupingfeng (YPF) on human lymphocytes in vitro, Organisation for Oncology and Translational Research (OOTR) 4th Annual Conference. 2007.

 

Li Y., Loo T.Y., Guan X.Y. and Chen J., anticancer effect if Dioscin in breast and esopageal cancer cells, the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Loo T.Y., Chen J. and Chow W.C., A 3-year Prospective Study in Monitoring Bone Mineral Density of Mandible in 180 Fully Edentulous Patients after chemotherapy., the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Loo T.Y., Chen J. and Chow W.C., A non-toxic herbal remedy which enhance lymphocyte activity and cytokine secretion: Takayama Ganoderma Lucidum, the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Loo T.Y., Chen J. and Chow W.C., Traditional Chinese medicine, Rhodia, prevents oral membrane ulceration in patients undergoing chemotherapy: a novel discovery, the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Wang D.N., Lin S.H., Yang D.P., Jin J., Tong Y. and Chen J., Characterization of steroidal saponins in crude extract from Dioscorea Nipponica Makino by liquid chromatography tandem multi-stage mass spectrometry, Analytica Chimica Acta. France, Analytica Chimica Acta, 2007, 599:: 9(2007, 599: 98-106).

 

Wang S., Yang X., jiang S., Chen J., houng S. and Lu F., 弓形虫感染宫内垂直传播的免疫特点, 热带医学杂志, guanzhou, 热带医学杂志, 2008, 8(5): 505.

 

sui L., Li J.M., wang D.M., zhu L.P., Chen J. and Yang D., 应用QuikPrep HSCCC 系统 实现共轭亚油酸及其异构体的分离, 分析试验室, 2008, 27: 253.

 

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)

 

List of Research Outputs

 

Chen R.Q., Clinical evaluation of classic theoretical literatures on Kidney-deficiency syndromes, 腎虛證相關經典文獻理論的初步臨床驗證, The Chinese University of Hong Kong School of Chinese Medicine. 2008.

 

Chen R.Q., Cao K., Lam T.H. and Wong C.M., Symptom characteristics of Kidney-Yin deficiency and Kidney-Yang deficiency in Hong Kong Chinese midlife women, Journal of Alternative and Complementary Medicine. 2008, 14(5): 457-460.

 

Chen R.Q., Wong C.M., Cao K. and Lam T.H., The Development Of A Questionnaire For Diagnostic Evaluation Of Kidney-Yin Deficiency And Kidney-Yang Deficiency, In: Felix Wong, Basil Roufogalis , Third International Congress on Complementary Medicine Research. Sydney, Australia, International Society for Complementary Medicine Research, 2008, 27.

 

Chen R.Q., Lam C.L.K., Wong C.M., Cao K. and Lam T.H., The HRQoL measured by SF-12 in Hong Kong Chinese Middle Aged Women with Kidney Deficiency Syndrome, 2008 Asian Chinese Quality of Life Conference . 2008.

 

Researcher : Chu OM



List of Research Outputs

 

Chu O.M., <中醫藥治療頭頸部腫瘤>的講座, "農本方"特約新城電台節目:"中醫藥透視", 2007.

 

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, 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., Luo W.Q. and Zhu S.Q., Explore new clinical application of Huanglian and corresponding compound prescriptions from their traditional use. , In: Editor-in-Chief: Xiao Pei-gen, China Journal of Chinese Materia Medica. Beijing, Institute of Chinese Materia Medica, China Academy of CMS, 2008, 33(10): 1221-1225.

 

Feng Y., HKU TCM workshop 2007, Coptidis Rhizoma: new drug for liver diseases?. Hong Kong, 2007.

 

Feng Y., Linnaeus and medicinal products. An international conference on drugs of natural origin in the honour of Carl Linnaeus. , The misuse of Aristolochia-related species (ARSs) due to confused herbal names in Hong Kong (Short lecture). . Uppsala, Sweden., 2007, SL06,28.

 

Feng Y., Tsao G.S.W., Tong Y. and Ng K.M., Matching Grant (4th Phase)-Research project on alternative drug for bear bile, UGC (Government Matching Grant Scheme). 2008, HK$402,500.

 

Feng Y., Tsao G.S.W., Tong Y. and Ng K.M., Research project on alternative drug for bear bile, Yiqingzhai Foundation (The Pong Ding Yueng Endowment Fund for Education & Research in Chinese-Western Medicine). 2008, HK$805,000.

 

Feng Y. and Tong Y., 从中药现代研究看中医学的基本特点, 香港中医杂志. Hong Kong, 香港中医杂志出版部, 2008, 3(1): 17-21.

 

Feng Y., Ye X. and Tong Y., 建立香港中藥不良反應監測系統和發揮中醫藥在香港藥物濫用防治中的作用, 中國藥物濫用防治雜誌. Beijing., Publisher of Chinese Journal of Drug Abuse Prevention and Tr, 2007, 13(4): 220-223.

 

Feng Y., 中華中醫中藥促進會註冊中醫學術講座., 古今縱橫: 黃連及其複方., 2008.

 

Feng Y., 中國中醫中藥行: 2007(香港)國際中醫中藥高級論壇, 從中藥現代研究看中醫學的基本特點, Hong Kong, 2007.

 

Feng Y., 香港註冊中醫學會學術講座, 中藥不良反應和中毒概述, Hong Kong, 2007.

 

Tang J., Feng Y., Tong Y., Jia R., Sy L.K. and Man R.Y.K., The Mucilage Cavity is a Distinct Microscopic Characteristic Showing in the Phloem but not Pith of Rhizomes for the Identification of Radix et Rhizoma Rhei., In: Editoral Department of Wuhan University Journal of Natural Sciences, Wuhan University Journal of Natural Sciences. Wuhan, China, Wuhan University Journals Press, 2008, 13(5): 1007-1202.

 

Ye X., Feng Y., Tong Y. and Tsao G.S.W., The effects of coptis extract on hepatoprotection in rats with liver damage., 2007 Hong Kong-Macau postgraduate Symposium on Chinese Medicine. Hong Kong, 2007, 92-93.

 

Zhang Y., Tong Y., Sze C.W., Feng Y., Song J.X., Wong R.N.S. and NG T.B., Application of sequence characterized amplified region (SCAR) analysis to authenticate Lycium barbarum and its adulterants., In: Stephen Sze CW, Song JX, Ricky Wong NS, Ng TB, Tong Y, Kalin Zhang YB. , Biotechnology and Applied Biochemistry . 2007, 51: 15-21.

 

Researcher : Jia R



List of Research Outputs

 

Tang J., Feng Y., Tong Y., Jia R., Sy L.K. and Man R.Y.K., The Mucilage Cavity is a Distinct Microscopic Characteristic Showing in the Phloem but not Pith of Rhizomes for the Identification of Radix et Rhizoma Rhei., In: Editoral Department of Wuhan University Journal of Natural Sciences, Wuhan University Journal of Natural Sciences. Wuhan, China, Wuhan University Journals Press, 2008, 13(5): 1007-1202.

 

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.

 

List of Research Outputs

 

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 Formulatrion ISF-1 Enables the Selection of Multiple Marker Genes as a Potential Metric for Quality Control , Journal of Ethno-Pharmacology . 2007, 113: 35-44.

 

Rong J., Cheung C.Y.H., Lau A.S.Y., Shen J., Tam P.K.H. and Cheng Y.C., Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress, International Journal of Molecular Medicine. 2008, 21(4): 405-411.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Developing method to screen for endocrine-active Chinese medicine formulation to relieve the menopausal syndrome, Sixth Meeting of Consortium for Globalization of Chinese Medicine (Poster). Beijing, 2007, Bio-028: P.95.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Erxian Decoction Stimulates Estrogen Secretion Via Steroidogenic Signaling Transduction Pathway In Vivo., 3rd International Congress Complementary Medicine Research . Sydney, Australia, 2008.

 

Sze C.W., Lau A.S.Y., Zhang Y., Tong Y. and Zhang Z., Mechanical Study of Erxian Decoction for Peri-menopausal Syndrome., Third International Symposium on Healthy Aging: Improving the Health of an Aging Population. (Speaker). 2008.

 

Tong Y., Sze C.W., Zhang Y., Zhang Z. and Lau A.S.Y., "Mechanical Study of Erxian Decoction for Peri-menopausal Syndrom”, Third International Healthy Aging - Improving the Health of an Aging Population”, Hong Kong (Speaker). 2008.

 

Researcher : Li H



List of Research Outputs

 

Li H., Sze C.W. and Tong Y., Immunomodulation Induced By Chinese Medicine Herb, Rhodiola algida, On Th1- and Th2-dependent Cytokine Production., 3rd International Congress Complementary Medicine Research (Poster Abstract, p118). Sydney, Australia, 2008.

 

Shi J., Tong Y., Shen J. and Li H., Effectiveness and safety of herbal medicines in the treatment of irritable bowel syndrome: A systematic review., World Journal of Gastroenterology. 2008, Iss. 14(3): 454-462.

 

Researcher : Li H



List of Research Outputs

 

Li H., Sze C.W. and Tong Y., Immunomodulation Induced By Chinese Medicine Herb, Rhodiola algida, On Th1- and Th2-dependent Cytokine Production., 3rd International Congress Complementary Medicine Research (Poster Abstract, p118). Sydney, Australia, 2008.

 

Shi J., Tong Y., Shen J. and Li H., Effectiveness and safety of herbal medicines in the treatment of irritable bowel syndrome: A systematic review., World Journal of Gastroenterology. 2008, Iss. 14(3): 454-462.

 

Researcher : Li L



List of Research Outputs

 

Li L., The Different Effects of Electro-acupuncture at Different Time on The plasma cAMPs, cGMPs and cAMPcGMP ratios of Normal Young Adults , Chinese-French & Chinese-European International Forum of Chronomedicine. 2007.

 

Li L., 穴位別講, 香港大學中醫藥學院主辦龐鼎元系列中醫專題講座, 2007.

 

Li L., 《黃帝內經》、《素問》、《靈樞》諸書名的文化內涵, 香港《黃帝內經》學術研討會, 2008.

 

Researcher : Li Y



List of Research Outputs

 

Li Y., Chen J. and Loo T.Y., Immunomodulatory effect of Yupingfeng (YPF) on human lymphocytes in vitro, Organisation for Oncology and Translational Research (OOTR) 4th Annual Conference. 2007.

 

Li Y., Loo T.Y., Guan X.Y. and Chen J., anticancer effect if Dioscin in breast and esopageal cancer cells, the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Researcher : Liu C



Project Title:

Systematic Determination and Compilation of DNA Barcodes for Medicinal Plants Used In Traditional Chinese Medicines

Investigator(s):

Liu C

Department:

Medical Faculty

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2006

 

Abstract:

During the past decades, interest in Traditional Chinese Medicine (TCM) has grown worldwide. Among the many barriers for TCM to enter the mainstream medicines is the inconsistent quality of TCMs. This complicating factor has hindered the research, development and testing of TCMs. As a result, recent guideline from the US Food and Drug Administration has outlined the required quality control measures (www.fda.gov/cder/guidance/4592fnl.htm) for botanical raw materials (that is, fresh or processed part of a single species of plant or a fresh or processed alga or macroscopic fungus), botanical drug substances (that is, materials derived from one or more plants, algae, or macroscopic fungi by certain processes.) and botanical drug products (that is, a finished, labeled product that contains vegetable matter processed from one or many botanical substance). Among all these quality control requirements, the first step is to make sure that the correct botanical species have been used in the formulation. Unfortunately, there is no universal standard species determination method available at present time. Our hypothesis is that a short DNA sequence (100-650bp long) can be used for species identification of medicinal plants. This kind of short DNA sequence is called a DNA barcode in the following text. Our long term goal is to (1) systematically determine DNA barcode(s) that can be used for the species identification of most, if not all, medicinal plants used in the TCMs, and compile them into a DNA barcode library; and (2) establish a standard procedure to amplify the barcode sequence(s) from a test sample and compare it to sequences from the DNA barcode library for species identification. The present study is a pilot study in an attempt to lay the ground for the future large scale DNA barcode identification project in all important medicinal plants used in TCM. This study intends to address the problem of misidentification of botanical raw materials that has been well-reported in the literature and media. For example, a “Siberian Ginseng” (Eleutherococcus Senticosus) product implicated in a case of neonatal androgenisation was found upon analysis to be an unrelated species, Chinese silk vine “Periploca Sepium” (1). In Hong Kong, encephalopathy and neuropathy associated with a Chinese herbal preparation purportedly made from the roots of Long-Dan-Cao (Gentiana Regescens) turned out to be due to another plant Podophyllum Emodi. In another example, more than 48 cases of renal poisoning attributed to fang-ji (Stephania Tetrandra) in weight-loss preparation were actually caused by Guang-Fang-Ji (Aristolochia Fangchi); aristolochic acid is a known nephrotoxin (2). The exactly extent of this problem can be much greater than what have been reported considering that only the cases having the most severe consequences would be reported. The result obtained from this study will lay the foundation for the development of a standard method that will eventually limit, if not able to eliminate the problems of misidentification, adulteration and contamination of botanical raw materials and botanical drug products. We plan to accomplish our goal through three specific aims: SPECIFIC AIM 1: To select the DNA sequence that can be used as DNA barcode for species determination of medicinal plants. Recent study has led to the concept of “DNA barcode”, which is a short to very short (100-650bp) sequence that server as a DNA marker or fingerprint and has the power to identify most, if not all organisms on Earth based on variability in the barcode sequences (3). An international consortium has been formed to systematically barcode life in different domains (http://barcoding.si.edu/index_detail.htm). A proof-of-concept study has showed that the cytochrome c oxidase I (COI) sequences can server as the core of a global bio-identification system for many animals. These studies suggest that using a single DNA barcode for species identification of medicinal plants is also possible. With very few sequence information available for most medicinal plants, we will depend on literature search to select the sequence most likely to represent the DNA barcode. SPECIFIC AIM 2: To establish a standard experimental procedure for species determination of medicinal plants under test. The procedure will mainly involve Polymerase Chain Reaction (PCR) following by automatic DNA sequencing. Although the standard procedure of PCR has been well established, we might still encounter several problems since we are trying to amplify DNA from samples containing botanical species belonging to a wide range of taxonomic groups. First, our PCR primers might not be universal enough to effectively and specifically amplify the intended DNA barcode from certain samples. Second, the DNA purification method might require substantial modification to extract DNA from certain botanical samples. Third, specific measures might have to be taken to remove potential DNA polymerase inhibitors in the botanical samples. Consequently, significant amount of efforts are expected to optimize the experimental conditions. The goal of this aim to establish a procedure that can be used in the future large scale project. SPECIFIC AIM 3: To build a pilot database of DNA barcodes from approximately two hundred medicinal plants. Using DNA fingerprinting for species identification in specific medicinal plants have been reported before. However, systematic efforts to identify universal DNA barcodes and to use these barcodes for species determination and identification have not been reported. After the successful completion of specific aim 1 and 2, we will extend the study to approximate 200 medicinal plants. This survey type of study will help us to evaluate the usefulness and robustness of the selected DNA barcode and the standard procedure developed above. This information will facilitate the design of the following large-scale DNA barcode determination project. In summary, this proposed study intends to carry out the pilot study that will eventually solve the practically critical problem of species identification of medicinal plants. The data generated from this study can have broad applications in a wide range of research areas. For example, it will generate important new insights into the diversification of life and the rules of molecular evolution. In addition, it will lay the ground work for the future development of a systematic, reliable, cost-effective and accessible solution to authenticate the botanical materials used for making TCMs.

 

Project Title:

Identification and characterization of chromosomal functional domains in completely sequenced genomes

Investigator(s):

Liu C, Lau ASY

Department:

Medical Faculty

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

08/2006

 

Abstract:

(1) To develop statistical methods/software tools that can identify clusters of adjacent genes sharing similar expression patterns based on data derived from whole genome mRNA expression profiling experiments; (2) To apply these methods and tools to identify and characterize chromosomal functional domains in the genomes of lower and higher eukaryotes, and to build a Functional Domain Database to store these results; (3) To apply the tools and results obtained from (1) and (2) to solve specific biological problems. Specifically, the tools and results will be used to : i) identify regulatory elements for individual and all genes in these functional domains; and ii) identify potential chromosomal rearrangements in disease samples, especially those of cancer samples.

 

Project Title:

Identification of Chem- and Bio- Markers of Fritillaria Species Using High Performance Liquid Chromatography, Microarray and Multivariate Data Analysis Methods: Principle Component Analysis and Partial Least Square Modeling

Investigator(s):

Liu C

Department:

Medical Faculty

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

03/2007

 

Abstract:

Two of the main challenging tasks in the studies of traditional Chinese medicine (TCM) are (i) to identify the active components of TCM drugs; and (ii) to identify the molecular targets of these active components. These tasks become even more difficult as many TCM drugs exert their therapeutic effects through the coordinated activities of multiple active components on multiple molecular targets. Our long term goal is to develop methodologies to identity the set of active components of TCM drugs and their corresponding set of molecular targets. The determination of these molecules will lay the foundation to (i) elucidate the mechanisms of actions of TCM drugs, (ii) to provide better quality control of already-proven TCM drug products and (iii) to develop novel TCM drug products.Chromatographic and Spectrometric methods have been used extensively to identify the active components of TCM drugs. More recently, with the microarray technology become common place, gene expression profiles have been proposed to be used as markers of biological activities of TCM drugs. Thus, the combinatorial use of chemical profiling and microarray profiling technologies becomes technically feasible. However, many challenging experimental and computational issues remain, for example, (i) how to identify chemo-markers (that is, the set of chemical compounds or active components that contribute to the biological activity of a TCM drug); (ii) how to identify bio-response markers or bio-markers (that is, the set of genes that represent the biological response of the cells to the treatment of a TCM drug, and also represent the biological activity of the TCM drug); (iii) how to quantify the importance of individual component of the chemo- or bio- markers; (iv) how chemo-markers correlate with the bio-markers quantitatively. To our knowledge, systematic study using advance multivariate data analysis methods to address these problems have not been reported. The current study is designed as a very first attempt to address these important problems in a systematic manner.Our hypothesis is that (i) the gene expression profile of bio-markers can be used to quantify the biological activity of a TCM drug and the biological response of cells after treatment; and (ii) the abundance profile of chemo-markers correlate with the expression profile of bio-markers. In this pilot study, we are intended to test the hypothesis and also to establish the necessary methodologies. We will use Fritillaria species as our model TCM herbs. The bulbs of Fritillaria species have been widely used in folk medicines as antitussive and expectorant. We will use the technology of High Performance Liquid Chromatography (HPLC) coupled with Evaporative Light Scattering Detection (ELSD) to generate the chemical compound profiles, which we will use to identify the chemo-markers. On the other hand, we will use Affymetrix GeneChip technology to generate gene expression profiles, which we will use to identify the bio-markers. The identification of chemo- and bio- markers and the determination of their correlations will be carried out using multivariate data analysis methods such as Principle Component Analysis and Partial Least Square Modeling. This pilot study consists of three specific aims: Specific Aim 1: To obtain chemical profiles of Fritillaria species using HPLC-ELSD technology.Specific Aim 2: To obtain gene expression profiles of human cells treated with extracts of Fritillaria species using Affymetrix GeneChip technology.Specific Aim 3: To identify chemo-markers, bio-markers and to determine their correlations using multivariate data analysis methods.If successfully completed, we will extend the proposed study to utilize more sophisticated technologies and more specific assays, and to include more Fritillaria species. For example, we will use the technology of Liquid Chromatography (LC) and Mass Spectrometry (MS) to generate the chemical profiles instead. Real-time PCR, instead of whole genome microarray study, will be used to measure the expression profiles of a list of marker genes identified in the pilot study. Furthermore, more Fritillaria species with greater diversity in chemical compositions and biological activities can be subjected to the above analysis to increate the power of the analysis. These follow-up studies will constitute a RGC grant proposal.

 

 

Researcher : Liu Q



List of Research Outputs

 

Liu Q., Loo W.T.Y., Sze C.W., Tong Y. and Chow L.W.C., Curcumin’s effect on breast cancer cell – a preclinical trial, The 6th Biennial Meeting of the Asian Breast Cancer Society (ABCS). 2007, 20-22.

 

Tong Y., Zhang N.X. and Liu Q., Study on the Action Mechanism of "ShuGan LiFei" Therapy on Experimental Rats with Asthma and under Stress, World Conference of Stress, Badapest, Hungary (Poster). 2007, 391-396.

 

Researcher : Liu Q



List of Research Outputs

 

Liu Q., Loo W.T.Y., Sze C.W., Tong Y. and Chow L.W.C., Curcumin’s effect on breast cancer cell – a preclinical trial, The 6th Biennial Meeting of the Asian Breast Cancer Society (ABCS). 2007, 20-22.

 

Tong Y., Zhang N.X. and Liu Q., Study on the Action Mechanism of "ShuGan LiFei" Therapy on Experimental Rats with Asthma and under Stress, World Conference of Stress, Badapest, Hungary (Poster). 2007, 391-396.

 

Researcher : Loo TY



List of Research Outputs

 

Chen J. and Loo T.Y., Immunomulatory effect of YPF on human lymphocytes in vitro , The 6th biennial meeting of the Asian breast cancer society . 2007.

 

Chen J., Loo T.Y. and Chou W.K., Juzen-taiho-to enhances immune activity in vitro and minimizes cyto-toxicity in vivo, the 6th Biennial meeting of Asian Breast cancer society. 2007.

 

Li Y., Chen J. and Loo T.Y., Immunomodulatory effect of Yupingfeng (YPF) on human lymphocytes in vitro, Organisation for Oncology and Translational Research (OOTR) 4th Annual Conference. 2007.

 

Li Y., Loo T.Y., Guan X.Y. and Chen J., anticancer effect if Dioscin in breast and esopageal cancer cells, the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Loo T.Y., Chen J. and Chow W.C., A 3-year Prospective Study in Monitoring Bone Mineral Density of Mandible in 180 Fully Edentulous Patients after chemotherapy., the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Loo T.Y., Chen J. and Chow W.C., A non-toxic herbal remedy which enhance lymphocyte activity and cytokine secretion: Takayama Ganoderma Lucidum, the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Loo T.Y., Chen J. and Chow W.C., Traditional Chinese medicine, Rhodia, prevents oral membrane ulceration in patients undergoing chemotherapy: a novel discovery, the 6th Biennial meeting of Asian Breast cancer society . 2007.

 

Researcher : Mo F



List of Research Outputs

 

Mo F., Clinical Observation on the Application of 650nm Laser Acupoint Irradiation in the Treatment of the Benign Prostatic Hyperplasia . , 洪文,莫飛智,李建強,趙燕平,曾長春,劉頌豪.650nm鐳射穴位照射治療良性前列腺增生症30例臨床觀察.新中醫,2008401):60-61, New Journal of Traditional Chinese Medicine.2008401):60-61. 新中醫, Guangzhou,China, Guangzhou University of Traditional Chinese Medicine, 2008, 40(1): 60-61.

 

Mo F., Mo Feizhi. Forum on Teaching of Chinese Medicine Classical Text "Yellow Emperor Canon of Chinese Medicine", 莫飛智.《黃帝內經》教學探討, Research papers for the Conference on Research of "Yellow Emperor's Canon of Chinese Medicine". Hong Kong, June 2008 :24 (Abstract). 香港《黃帝內經》學術研討會論文資料,20086月:24 (摘要), 2008.

 

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.

 

List of Research Outputs

 

Lee D.C.W., Chik S.C.C., Li C.B., Yang L.H., Rong J., Tam P.K.H. and Lau A.S.Y., Application of Platform Technologies to Investigate the Immunomodulatory Effects of Ginseng, 14th Hong Kong International Cancer Congress, Hong Kong, 14-16 November 2007.

 

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 Formulatrion ISF-1 Enables the Selection of Multiple Marker Genes as a Potential Metric for Quality Control , Journal of Ethno-Pharmacology . 2007, 113: 35-44.

 

Rong J., Cheung Y.H., Lau A.S.Y., Shen J., Tam P.K.H. and Cheng Y.C., Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress, Int J Mol Med. Athens, Greece, D.A. Spandidos, 2008, 21: 405-11.

 

Rong J., Cheung C.Y.H., Lau A.S.Y., Shen J., Tam P.K.H. and Cheng Y.C., Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress, International Journal of Molecular Medicine. 2008, 21(4): 405-411.

 

Researcher : Shen F



List of Research Outputs

 

Shen F., 中藥6類新藥丹仙康骨膠囊研製 獲貴州省科學技術進步三等獎 (課題主持人), 2007.

 

Shen F., 龐鼎元系列中醫專題講座 - 股骨頭缺血壞死的中醫藥治療空間的探討, 香港大學中醫藥學院, 2007.

 

Shen F., 腰椎間盤突出症的診斷與中醫治療, 蘭靈閣圖書國際有限公司與香港中醫骨傷科學會, 2007.

 

Shen F., 中西醫綜合病例討論 -- 肌骨病, 香港醫院管理局, 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.

 

List of Research Outputs

 

Liu B.Y. and Shen J., Effects of Buyang Huanwu Decoction on caveolin-1 and 2 of cerebral ischemia in rats, Journal of Hunan TCM University. 2008, 28(1): 22-28.

 

Ren J., Fung P.C.W., Chang C., Shen G.G., Chan F.H.Y., Liu K.J. and Shen J., A comparative ESR study on blood and tissue nitric oxide concentration during renal ischemia-reperfusion injury , Applied Magnetic Resonance. Springer-Verlag, 2007, 32: 243-255.

 

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 Formulatrion ISF-1 Enables the Selection of Multiple Marker Genes as a Potential Metric for Quality Control , Journal of Ethno-Pharmacology . 2007, 113: 35-44.

 

Rong J., Cheung Y.H., Lau A.S.Y., Shen J., Cheng Y.C. and Tam P.K.H., Induction of heme oxygenase-1 by the Chinese herbal formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress, The Sixth Meeting of Consortium for Globalization of Chinese Medicine (CGCM). Beijing, China, 2007.

 

Rong J., Cheung Y.H., Lau A.S.Y., Shen J., Tam P.K.H. and Cheng Y.C., Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress, Int J Mol Med. Athens, Greece, D.A. Spandidos, 2008, 21: 405-11.

 

Rong J., Cheung C.Y.H., Lau A.S.Y., Shen J., Tam P.K.H. and Cheng Y.C., Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress, International Journal of Molecular Medicine. 2008, 21(4): 405-411.

 

Shen J., Integration of Multiple Comprehensive Approaches for Exploration of Therapeutic Principle of BHD-01 in Post-stroke Treatment, HKU TCM Workshop 2007. Hong Kong, 21.

 

Shen J., Rong J., So K.F., Lau A.S.Y. and Tam P.K.H., Integration of multiple comprehensive approaches for exploration of therapeutic principle of BHD-01 in post-stroke treatment, HKU TCM Workshop 2007.

 

Shen J., Rong J., Tong Y., So K.F., Lau A.S.Y., Liu K.J., Tam P.K.H. and Cheng Y.C., Integration of systemic biology, chemical profile fingerprint and functional imaging technology for understanding therapeutic principle of Chinese medicinal formula: a study on classical Post-Stroke Formula, The Sixth Meeting of Consortium for Globalization of Chinese Medicine (CGCM). Beijing, China, 2007.

 

Shen J., Reagents for highly specific detection of peroxynitrite. , Patent: U.S. CN2006002177. 2008.

 

Shi J., Tong Y., Shen J. and Li H., Effectiveness and safety of herbal medicines in the treatment of irritable bowel syndrome: A systematic review., World Journal of Gastroenterology. 2008, Iss. 14(3): 454-462.

 

Zeng H.P., Wang T.T., Chen W., Wang C.Y., Chen D.F. and Shen J., Characterization of chemical components in extracts from Si-wu decoction with proliferation-promoting effects on rat mesenchymal stem cells., Bioorg Med Chem. . 2008, 16(9): 5109-5114.

 

Researcher : Shi J



List of Research Outputs

 

Shi J., Tong Y., Shen J. and Li H., Effectiveness and safety of herbal medicines in the treatment of irritable bowel syndrome: A systematic review., World Journal of Gastroenterology. 2008, Iss. 14(3): 454-462.

 

Researcher : Song J



List of Research Outputs

 

Sze C.W., Song J., Chang R.C.C., Wong R.N.S., Tong Y. and Zhang Y., Research Advances on the Anti-aging Profile of Fructus lycii: an Ancient Chinese Herbal Medicine, Journal of Complementary and Integrative Medicine. 2008, Vol. 5: Iss. 1, Art. 8.

 

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., A Systematic Review on Efficacy of Erxian Decoction Treated Menopausal Symptoms, 3rd International Congress Complementary Medicine Research. Sydney, Australia, 2008.

 

Chen H., Cho W.C.S., Sze C.W. and Tong Y., Treatment of Menopausal Symptoms with Er-xian Decoction: A Systematic Review, America Journal of Chinese Medicine. 2008, 36(2): 233-244.

 

Chu E.S., Sze C.W., Tong Y., Wong T.K. and Yow C.M., Differential Inhibition of Hedyotis diffusa (HD) and Scutellaria barbata (SB) on human nasopharyngeal carcinoma cells, American association for cancer research. USA, 2008, 49: 30.

 

Li H., Sze C.W. and Tong Y., Immunomodulation Induced By Chinese Medicine Herb, Rhodiola algida, On Th1- and Th2-dependent Cytokine Production., 3rd International Congress Complementary Medicine Research (Poster Abstract, p118). Sydney, Australia, 2008.

 

Liu Q., Loo W.T.Y., Sze C.W., Tong Y. and Chow L.W.C., Curcumin’s effect on breast cancer cell – a preclinical trial, The 6th Biennial Meeting of the Asian Breast Cancer Society (ABCS). 2007, 20-22.

 

Sze C.W., Zhang Y., Shaw P.C., But P.P.H., Ng T.B. and Tong Y., A DNA microarray for differentiation of the Chinese medicinal herb Dendrobium officinale (Fengdou Shihu) by its 5 S ribosomal DNA intergenic spacer region, Biotechnology and Applied Biochemistry. 2008, 49: 149-154.

 

Sze C.W., Chinese Medicine for the peri-menopausal sydrome: theory and experiment, Department of Health Technology & Informatics, the Hong Kong Polytechnic University. 2008.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Developing method to screen for endocrine-active Chinese medicine formulation to relieve the menopausal syndrome, Sixth Meeting of Consortium for Globalization of Chinese Medicine (Poster). Beijing, 2007, Bio-028: P.95.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Erxian Decoction Stimulates Estrogen Secretion Via Steroidogenic Signaling Transduction Pathway In Vivo., 3rd International Congress Complementary Medicine Research . Sydney, Australia, 2008.

 

Sze C.W., Zhang Y., Zhang Z., Lau A.S.Y. and Tong Y., Erxian decoction stimulates estrogen secretion via steroidogenic signalling transduction pathway in vivo, 3rd International Congress on Complementary Medicine Research, Sydney, Australia, 29-31 March 2008 (Poster Abstract, p120). 2008, 60.

 

Sze C.W., Lau A.S.Y., Zhang Y., Tong Y. and Zhang Z., Mechanical Study of Erxian Decoction for Peri-menopausal Syndrome., Third International Symposium on Healthy Aging: Improving the Health of an Aging Population. (Speaker). 2008.

 

Sze C.W., Song J., Chang R.C.C., Wong R.N.S., Tong Y. and Zhang Y., Research Advances on the Anti-aging Profile of Fructus lycii: an Ancient Chinese Herbal Medicine, Journal of Complementary and Integrative Medicine. 2008, Vol. 5: Iss. 1, Art. 8.

 

Sze C.W., Zhang Z. and Tong Y., Traditional Chinese Medicine for Parkinson’s Disease: Basic Theory and Preclinical Screening., Croucher Advanced Study Institute: Innovative Therapies of Movement Disorders: Basic and Clinical Sciences.. 2007.

 

Sze C.W., Traditional Chinese Medicine for Parkinson’s Disease: Basic Theory and Preclinical Screening, Croucher Advanced Study Institute: Innovative Therapies of Movement Disorders: Basic and Clinical Sciences.. 2007.

 

Tong Y., Sze C.W., Zhang Y., Zhang Z. and Lau A.S.Y., "Mechanical Study of Erxian Decoction for Peri-menopausal Syndrom”, Third International Healthy Aging - Improving the Health of an Aging Population”, Hong Kong (Speaker). 2008.

 

Yuan H.N., Wang C.Y., Sze C.W., Tong Y., Tan Q.R., Feng X.J., Jiu R.M., Zhang J.Z., Zhang Y. and Zhang Z., A Randomized Crossover Comparison of Herbal Medicine and Bromocriptine against Risperidone-Induced Hyperprolactinemia in Patients with Schizophrenia, Journal of Clinical Psychopharmacology. 2008, 28: 264-370.

 

Zhang Y., Tong Y., Sze C.W., Feng Y., Song J.X., Wong R.N.S. and NG T.B., Application of sequence characterized amplified region (SCAR) analysis to authenticate Lycium barbarum and its adulterants., In: Stephen Sze CW, Song JX, Ricky Wong NS, Ng TB, Tong Y, Kalin Zhang YB. , Biotechnology and Applied Biochemistry . 2007, 51: 15-21.

 

Zhang Y., Tong Y. and Sze C.W., PI: HK$200,000 (2007).Donation from the Li Ka Shing Foundation : Matching Grant for Seed Funding Programme. Donation from LKS Faculty of Medicine.No. 20460016. , In: Zhang YB, Sze CW, Tong Y. , LKS Faculty of Medicine. 2007.

 

Researcher : Tang J



List of Research Outputs

 

Tang J., Feng Y., Tong Y., Jia R., Sy L.K. and Man R.Y.K., The Mucilage Cavity is a Distinct Microscopic Characteristic Showing in the Phloem but not Pith of Rhizomes for the Identification of Radix et Rhizoma Rhei., In: Editoral Department of Wuhan University Journal of Natural Sciences, Wuhan University Journal of Natural Sciences. Wuhan, China, Wuhan University Journals Press, 2008, 13(5): 1007-1202.

 

Researcher : Tong Y



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., A Systematic Review on Efficacy of Erxian Decoction Treated Menopausal Symptoms, 3rd International Congress Complementary Medicine Research. Sydney, Australia, 2008.

 

Chen H., Cho W.C.S., Sze C.W. and Tong Y., Treatment of Menopausal Symptoms with Er-xian Decoction: A Systematic Review, America Journal of Chinese Medicine. 2008, 36(2): 233-244.

 

Chu E.S., Sze C.W., Tong Y., Wong T.K. and Yow C.M., Differential Inhibition of Hedyotis diffusa (HD) and Scutellaria barbata (SB) on human nasopharyngeal carcinoma cells, American association for cancer research. USA, 2008, 49: 30.

 

Feng Y., Tsao G.S.W., Tong Y. and Ng K.M., Matching Grant (4th Phase)-Research project on alternative drug for bear bile, UGC (Government Matching Grant Scheme). 2008, HK$402,500.

 

Feng Y., Tsao G.S.W., Tong Y. and Ng K.M., Research project on alternative drug for bear bile, Yiqingzhai Foundation (The Pong Ding Yueng Endowment Fund for Education & Research in Chinese-Western Medicine). 2008, HK$805,000.

 

Feng Y. and Tong Y., 从中药现代研究看中医学的基本特点, 香港中医杂志. Hong Kong, 香港中医杂志出版部, 2008, 3(1): 17-21.

 

Feng Y., Ye X. and Tong Y., 建立香港中藥不良反應監測系統和發揮中醫藥在香港藥物濫用防治中的作用, 中國藥物濫用防治雜誌. Beijing., Publisher of Chinese Journal of Drug Abuse Prevention and Tr, 2007, 13(4): 220-223.

 

Li H., Sze C.W. and Tong Y., Immunomodulation Induced By Chinese Medicine Herb, Rhodiola algida, On Th1- and Th2-dependent Cytokine Production., 3rd International Congress Complementary Medicine Research (Poster Abstract, p118). Sydney, Australia, 2008.

 

Liu Q., Loo W.T.Y., Sze C.W., Tong Y. and Chow L.W.C., Curcumin’s effect on breast cancer cell – a preclinical trial, The 6th Biennial Meeting of the Asian Breast Cancer Society (ABCS). 2007, 20-22.

 

Luk J.M.C., Wang X., Liu P., Wong K.F., Chan K.L., Tong Y., Hui C.K., Lau G. and Fan S.T., Traditional Chinese herbal medicines for treatment of liver fibrosis and cancer: from laboratory discovery to clinical evaluation, Liver International. 2007, 27(7): 879-890.

 

Shen J., Rong J., Tong Y., So K.F., Lau A.S.Y., Liu K.J., Tam P.K.H. and Cheng Y.C., Integration of systemic biology, chemical profile fingerprint and functional imaging technology for understanding therapeutic principle of Chinese medicinal formula: a study on classical Post-Stroke Formula, The Sixth Meeting of Consortium for Globalization of Chinese Medicine (CGCM). Beijing, China, 2007.

 

Shi J., Tong Y., Shen J. and Li H., Effectiveness and safety of herbal medicines in the treatment of irritable bowel syndrome: A systematic review., World Journal of Gastroenterology. 2008, Iss. 14(3): 454-462.

 

Sze C.W., Zhang Y., Shaw P.C., But P.P.H., Ng T.B. and Tong Y., A DNA microarray for differentiation of the Chinese medicinal herb Dendrobium officinale (Fengdou Shihu) by its 5 S ribosomal DNA intergenic spacer region, Biotechnology and Applied Biochemistry. 2008, 49: 149-154.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Developing method to screen for endocrine-active Chinese medicine formulation to relieve the menopausal syndrome, Sixth Meeting of Consortium for Globalization of Chinese Medicine (Poster). Beijing, 2007, Bio-028: P.95.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Erxian Decoction Stimulates Estrogen Secretion Via Steroidogenic Signaling Transduction Pathway In Vivo., 3rd International Congress Complementary Medicine Research . Sydney, Australia, 2008.

 

Sze C.W., Zhang Y., Zhang Z., Lau A.S.Y. and Tong Y., Erxian decoction stimulates estrogen secretion via steroidogenic signalling transduction pathway in vivo, 3rd International Congress on Complementary Medicine Research, Sydney, Australia, 29-31 March 2008 (Poster Abstract, p120). 2008, 60.

 

Sze C.W., Lau A.S.Y., Zhang Y., Tong Y. and Zhang Z., Mechanical Study of Erxian Decoction for Peri-menopausal Syndrome., Third International Symposium on Healthy Aging: Improving the Health of an Aging Population. (Speaker). 2008.

 

Sze C.W., Song J., Chang R.C.C., Wong R.N.S., Tong Y. and Zhang Y., Research Advances on the Anti-aging Profile of Fructus lycii: an Ancient Chinese Herbal Medicine, Journal of Complementary and Integrative Medicine. 2008, Vol. 5: Iss. 1, Art. 8.

 

Sze C.W., Zhang Z. and Tong Y., Traditional Chinese Medicine for Parkinson’s Disease: Basic Theory and Preclinical Screening., Croucher Advanced Study Institute: Innovative Therapies of Movement Disorders: Basic and Clinical Sciences.. 2007.

 

Tang J., Feng Y., Tong Y., Jia R., Sy L.K. and Man R.Y.K., The Mucilage Cavity is a Distinct Microscopic Characteristic Showing in the Phloem but not Pith of Rhizomes for the Identification of Radix et Rhizoma Rhei., In: Editoral Department of Wuhan University Journal of Natural Sciences, Wuhan University Journal of Natural Sciences. Wuhan, China, Wuhan University Journals Press, 2008, 13(5): 1007-1202.

 

Tong Y., Sze C.W., Zhang Y., Zhang Z. and Lau A.S.Y., "Mechanical Study of Erxian Decoction for Peri-menopausal Syndrom”, Third International Healthy Aging - Improving the Health of an Aging Population”, Hong Kong (Speaker). 2008.

 

Tong Y., "Physical condition and healthcare”, HKSAR Civil Servant Training and Development Institute (CSTDI). 2007.

 

Tong Y., "The Mechanical Study of EXD for Peri-menopausal Syndrom”, Department of Pharmacology, School of Medicine, Yale Universiy. 2008.

 

Tong Y., "The development of research of Prevention from oncology with Chinese Medicine” at its Press Conference for educational books for cancer prevention “Integration medicine-Love makes miracles” (癌症防治科普讀物 "中西合璧, 愛顯奇跡"), China Resources Retail (Group) Co., Ltd.. 2008.

 

Tong Y., "The roles of the Universities in the training of TCM professionals in Hong Kong" under main theme session “Training and Professional Development of Chinese Medicine practitioners”, 2007 TWGHs Eddie Wang Symposium on Integrated Chinese and Western Medicine, Hong Kong (speaker). Hong Kong, 2007.

 

Tong Y., "The roles of the Universities in the training of TCM professionals in Hong Kong” under main theme session “Training and Professional Development of Chinese Medicine practitioners”, 2007 TWGHs Eddie Wang Symposium on Integrated Chinese and Western Medicine, Hong Kong. 2007.

 

Tong Y., Comparison of the liver system between Chinese medicine "Gan" and Western medicine "liver", Hong Kong - Shanghai International Liver Congress (Speaker). 2008.

 

Tong Y., Comparison of the liver system between Chinese medicine”Gan” and western Medicine “liver”, Hongkong – Shanghai International Liver Congress (Speaker). 2008.

 

Tong Y., Mechanical Study of Erxian Decoction for Peri-menopausal Syndrome, HKU TCM Workshop. 2007.

 

Tong Y., Zhang N.X. and Liu Q., Study on the Action Mechanism of "ShuGan LiFei" Therapy on Experimental Rats with Asthma and under Stress, World Conference of Stress, Badapest, Hungary (Poster). 2007, 391-396.

 

Tong Y., to visit the pharmacology college and brain research center and gave a presentstion” the research status of school of Chinese Medicine of HKU”, The University of New Mexico. 2008.

 

Tong Y., "Chinese medicine for the good health of the Elderly” 創新老年痴呆症活動工作坊2008, 醫院管理局職業治療統籌委員會, 香港老年痴呆症協會, 2008.

 

Tong Y., 中醫的觀念II, University Health Service, HKU, 2008.

 

Tong Y., 中醫的觀念 I, University Health Service, HKU, 2008.

 

Wang D.N., Lin S.H., Yang D.P., Jin J., Tong Y. and Chen J., Characterization of steroidal saponins in crude extract from Dioscorea Nipponica Makino by liquid chromatography tandem multi-stage mass spectrometry, Analytica Chimica Acta. France, Analytica Chimica Acta, 2007, 599:: 9(2007, 599: 98-106).

 

Ye X., Feng Y., Tong Y. and Tsao G.S.W., The effects of coptis extract on hepatoprotection in rats with liver damage., 2007 Hong Kong-Macau postgraduate Symposium on Chinese Medicine. Hong Kong, 2007, 92-93.

 

Yuan H.N., Wang C.Y., Sze C.W., Tong Y., Tan Q.R., Feng X.J., Jiu R.M., Zhang J.Z., Zhang Y. and Zhang Z., A Randomized Crossover Comparison of Herbal Medicine and Bromocriptine against Risperidone-Induced Hyperprolactinemia in Patients with Schizophrenia, Journal of Clinical Psychopharmacology. 2008, 28: 264-370.

 

Zhang Y., Tong Y., Sze C.W., Feng Y., Song J.X., Wong R.N.S. and NG T.B., Application of sequence characterized amplified region (SCAR) analysis to authenticate Lycium barbarum and its adulterants., In: Stephen Sze CW, Song JX, Ricky Wong NS, Ng TB, Tong Y, Kalin Zhang YB. , Biotechnology and Applied Biochemistry . 2007, 51: 15-21.

 

Zhang Y. and Tong Y., Nature Anti-cancer Medicine- Ganoderma and cordyceps. , In: Xie Yong Zheng (Ed)., lovingness ferly- integrate of Chinese Medicine and western medicine.. Hong Kong: Tuo Sheng health and developing Ltd Press, 2008.

 

Zhang Y., Tong Y. and Sze C.W., PI: HK$200,000 (2007).Donation from the Li Ka Shing Foundation : Matching Grant for Seed Funding Programme. Donation from LKS Faculty of Medicine.No. 20460016. , In: Zhang YB, Sze CW, Tong Y. , LKS Faculty of Medicine. 2007.

 

Zhang Z., Tan Q.R., Tong Y., Li Q., Kang W.H., Zhen X.C. and Post R.M., The effectiveness of carbamazepine in unipolar depression: a double-blind, randomized, placebo-controlled study. , Journal of Affective Disorders. 2008, 109: 91-97.

 

Researcher : Wang TT



List of Research Outputs

 

Zeng H.P., Wang T.T., Chen W., Wang C.Y., Chen D.F. and Shen J., Characterization of chemical components in extracts from Si-wu decoction with proliferation-promoting effects on rat mesenchymal stem cells., Bioorg Med Chem. . 2008, 16(9): 5109-5114.

 

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

 

Feng Y., Ye X. and Tong Y., 建立香港中藥不良反應監測系統和發揮中醫藥在香港藥物濫用防治中的作用, 中國藥物濫用防治雜誌. Beijing., Publisher of Chinese Journal of Drug Abuse Prevention and Tr, 2007, 13(4): 220-223.

 

Ye X., Feng Y., Tong Y. and Tsao G.S.W., The effects of coptis extract on hepatoprotection in rats with liver damage., 2007 Hong Kong-Macau postgraduate Symposium on Chinese Medicine. Hong Kong, 2007, 92-93.

 

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

 

Ng S.M., Tsui E.Y.L. and Yiu Y.M., Acupuncture and chronic fatigue syndrome: A Randomized controlled trial, World Mental Health Congress. Hong Kong, 2007, 106.

 

Tsui E.Y.L., Ng S.M. and Yiu Y.M., Co-occurrence of irritable bowel symptoms and chronic fatigue syndrome: Prevalence in Hong Kong, World Mental Health Congress. Hong Kong, 2007, 119.

 

Yiu Y.M., Ng S.M., Tsui E.Y.L. and Chan Y.L., A clinical trial of acupuncture for chronic fatigue syndrome, 針刺治療慢性疲勞綜合征的臨床研究, Hong Kong Chinese Medical Journal. 香港中醫雜誌, Hong Kong, 2008, 3(1): 76-79.

 

Yiu Y.M., Ng S.M., Tsui E.Y.L. and Chan Y.L., A clinical trial of acupuncture for treating chronic fatigue syndrome in Hong Kong, Journal of Chinese Integrative Medicine (Zhong Xi Yi Jie He Xue Bao). 2007, 5: 630-633.

 

Yiu Y.M., Tsui E.Y.L. and Ng S.M., The seasonal effect of acupuncture in the treatment of chronic fatigue syndrome, World Mental Health Congress. Hong Kong, 2007, 107.

 

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., Shaw P.C., But P.P.H., Ng T.B. and Tong Y., A DNA microarray for differentiation of the Chinese medicinal herb Dendrobium officinale (Fengdou Shihu) by its 5 S ribosomal DNA intergenic spacer region, Biotechnology and Applied Biochemistry. 2008, 49: 149-154.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Developing method to screen for endocrine-active Chinese medicine formulation to relieve the menopausal syndrome, Sixth Meeting of Consortium for Globalization of Chinese Medicine (Poster). Beijing, 2007, Bio-028: P.95.

 

Sze C.W., Zhang Y., Lau A.S.Y. and Tong Y., Erxian Decoction Stimulates Estrogen Secretion Via Steroidogenic Signaling Transduction Pathway In Vivo., 3rd International Congress Complementary Medicine Research . Sydney, Australia, 2008.

 

Sze C.W., Zhang Y., Zhang Z., Lau A.S.Y. and Tong Y., Erxian decoction stimulates estrogen secretion via steroidogenic signalling transduction pathway in vivo, 3rd International Congress on Complementary Medicine Research, Sydney, Australia, 29-31 March 2008 (Poster Abstract, p120). 2008, 60.

 

Sze C.W., Lau A.S.Y., Zhang Y., Tong Y. and Zhang Z., Mechanical Study of Erxian Decoction for Peri-menopausal Syndrome., Third International Symposium on Healthy Aging: Improving the Health of an Aging Population. (Speaker). 2008.

 

Sze C.W., Song J., Chang R.C.C., Wong R.N.S., Tong Y. and Zhang Y., Research Advances on the Anti-aging Profile of Fructus lycii: an Ancient Chinese Herbal Medicine, Journal of Complementary and Integrative Medicine. 2008, Vol. 5: Iss. 1, Art. 8.

 

Tong Y., Sze C.W., Zhang Y., Zhang Z. and Lau A.S.Y., "Mechanical Study of Erxian Decoction for Peri-menopausal Syndrom”, Third International Healthy Aging - Improving the Health of an Aging Population”, Hong Kong (Speaker). 2008.

 

Yuan H.N., Wang C.Y., Sze C.W., Tong Y., Tan Q.R., Feng X.J., Jiu R.M., Zhang J.Z., Zhang Y. and Zhang Z., A Randomized Crossover Comparison of Herbal Medicine and Bromocriptine against Risperidone-Induced Hyperprolactinemia in Patients with Schizophrenia, Journal of Clinical Psychopharmacology. 2008, 28: 264-370.

 

Zhang Y., Anti-Osteoporosis Activity of Naringin in the Retinoic Acid-Induced Osteoporosis Model , In: Min Wei, Ping Li, Kalin Yanbo Zhang, Zhonglin Yang, American Journal of Chinese Medicine . 2007.

 

Zhang Y., Tong Y., Sze C.W., Feng Y., Song J.X., Wong R.N.S. and NG T.B., Application of sequence characterized amplified region (SCAR) analysis to authenticate Lycium barbarum and its adulterants., In: Stephen Sze CW, Song JX, Ricky Wong NS, Ng TB, Tong Y, Kalin Zhang YB. , Biotechnology and Applied Biochemistry . 2007, 51: 15-21.

 

Zhang Y., Authentication of Lycium barbarum and its adulterants by sequence characterized amplified region (SCAR) analysis., In: Zhang Yanbo, Tong Yao, Sze Cho Wing, 3rd International Congress on Complementary Medicine Research. . 2008.

 

Zhang Y., Chemical and Molecular Identification of Hong Dangshen, A Unique Medicinal Material for Diarrhea in Hong Kong , In: Zhang Yan-Bo, Jiang Ren-Wang, Li Song-Lin, Qiao Chun-Feng, Han Quan-Bin, Xu Hong-Xi, Wong Ka-Lok, But Paul Pui-Hay, Shaw Pang-Chui, Chinese Journal of Pharmaceutical Science . 2007.

 

Zhang Y., Council member in Journal of Pharmaceutical and Biological Technology., In: Zhangyanbo, Journal of Pharmaceutical and Biological Technology. 2007.

 

Zhang Y., DNA microarray for identification of Chinese Medicine., In: Zhang Yanbo, Chinese Medicine Serial Active of China in Hong Kong.. Olympian City, Hong Kong, 2007.

 

Zhang Y., Development of DNA Microarray for High Throughput Identification of Chinese Medicinal Formulations., In: Zhang Yanbo, Sixth Meeting of Consortium for Globalization of Chinese Medicine (CGCM).. Bejing, China, 2007.

 

Zhang Y., Molecular Authentication of Chinese Medicines, In: Zhang YB, International Conference & Exhibition of the Modernization of Chinese Medicine & Health Products. 2007.

 

Zhang Y. and Tong Y., Nature Anti-cancer Medicine- Ganoderma and cordyceps. , In: Xie Yong Zheng (Ed)., lovingness ferly- integrate of Chinese Medicine and western medicine.. Hong Kong: Tuo Sheng health and developing Ltd Press, 2008.

 

Zhang Y., PI: HK$100,000 (2007). Top-up fund for support the Postgraduate Studentships of MPhil or PhD students admitted. Funding from LKS Faculty of Medicine., In: Zhang YB , LKS Faculty of Medicine. 2007.

 

Zhang Y., Tong Y. and Sze C.W., PI: HK$200,000 (2007).Donation from the Li Ka Shing Foundation : Matching Grant for Seed Funding Programme. Donation from LKS Faculty of Medicine.No. 20460016. , In: Zhang YB, Sze CW, Tong Y. , LKS Faculty of Medicine. 2007.

 

Zhang Y., PI: HK$50,000 (2008). Donation from the Li Ka Shing Foundation : CERG Incentive Award. Project No 20460013. 30/05/2008., In: Zhang YB, LKS Faculty of Medicine. 2008.

 

Zhang Y., Parmacology study in Blueberry Extract, In: Zhang Yanbo , Doctor health company . 2007.

 

Zhang Y., Special topic lecture: toxicity Chinese Medicine-Bufo bufo gargarizans Canror., In: Zhang Yanbo, In the Hong Kong Society of Chinese Medicines. . 2007.

 

Zhang Y., death case on toxicity Chinese Medicine-Bufo bufo gargarizans Canror., In: Zhang Yanbo, In the law court of Xi Wan Ho, Hong Kong.. 2007.

 

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

 

Sze C.W., Zhang Y., Zhang Z., Lau A.S.Y. and Tong Y., Erxian decoction stimulates estrogen secretion via steroidogenic signalling transduction pathway in vivo, 3rd International Congress on Complementary Medicine Research, Sydney, Australia, 29-31 March 2008 (Poster Abstract, p120). 2008, 60.

 

Sze C.W., Lau A.S.Y., Zhang Y., Tong Y. and Zhang Z., Mechanical Study of Erxian Decoction for Peri-menopausal Syndrome., Third International Symposium on Healthy Aging: Improving the Health of an Aging Population. (Speaker). 2008.

 

Sze C.W., Zhang Z. and Tong Y., Traditional Chinese Medicine for Parkinson’s Disease: Basic Theory and Preclinical Screening., Croucher Advanced Study Institute: Innovative Therapies of Movement Disorders: Basic and Clinical Sciences.. 2007.

 

Tong Y., Sze C.W., Zhang Y., Zhang Z. and Lau A.S.Y., "Mechanical Study of Erxian Decoction for Peri-menopausal Syndrom”, Third International Healthy Aging - Improving the Health of an Aging Population”, Hong Kong (Speaker). 2008.

 

Yu Y., Wang J.R., Sun P.H., Guo Y., Jin G.Z., Zhang Z. and Zhen X., Neuroprotective effects of atypical D1 receptor agonist SKF83959 are mediated via D1 receptor-dependent inhibition of glycogen synthase kinase-3 beta and a receptor-independent anti-oxidative action., Journal of Neurochemistry. 2008, 104: 946-956.

 

Yuan H.N., Wang C.Y., Sze C.W., Tong Y., Tan Q.R., Feng X.J., Jiu R.M., Zhang J.Z., Zhang Y. and Zhang Z., A Randomized Crossover Comparison of Herbal Medicine and Bromocriptine against Risperidone-Induced Hyperprolactinemia in Patients with Schizophrenia, Journal of Clinical Psychopharmacology. 2008, 28: 264-370.

 

Zhang Z., Chinese herbal medicine and acupuncture therapy of major psychiatric disorders , 2007 World Mental Health Congress of the World Federation for Mental Health, Hong Kong, August 21, 2007.

 

Zhang Z., Tan Q.R., Tong Y., Li Q., Kang W.H., Zhen X.C. and Post R.M., The effectiveness of carbamazepine in unipolar depression: a double-blind, randomized, placebo-controlled study. , Journal of Affective Disorders. 2008, 109: 91-97.



-- End of Listing --