RMIT University10th SCICC, Guangzhou, China, 2008 Recent Progress in the Evidence-Based Application of Herbal Medicines for Cardiovascular Diseases Professor Shufeng Zhou, MD, PhD School of Health Sciences WHO Collaborating Center for Traditional Medicine RMIT University, Bundoora, Victoria 3083 Australia Phone: Tel: +61 3 9925 7794; Fax: +61 3 9925 7178 Email: shufeng.zhourmit.edu.au11 April 2008RMIT University10th SCICC, Guangzhou, China, 2008 An Overview of Global Herbal UseAll folk medicine includes the use of plant products.11,145 species of herbal plants worldwide; 534 species of plants for Chinese Medicine.WHO definition botanical origin, without adulteration of any synthetic drugs.Legal status: food supplements (FDA drugs/health foods (SFDA of China).US$25 billion; market value 1015%/per year. 2 billion in Australia.40% Caucasian and 80% Asians use or used herbs.RMIT University10th SCICC, Guangzhou, China, 2008 Active ComponentsBiotransformation ExcretionAbsorptionResponse/Toxicity?RMIT University10th SCICC, Guangzhou, China, 2008 Preclinical StagePhase IPhase IIPhase IIIPhase IVClinical Trials of Herbal MedicinesGeneral acceptance of humansSafety and EfficacyMore data on safety and EfficacyRMIT University10th SCICC, Guangzhou, China, 2008 Challenges for Herbal Clinical trials Dosage poor clinical studies Lack of ADR reporting systemRMIT University10th SCICC, Guangzhou, China, 2008 Types of Clinical Reports on Herb-Drug InteractionsN = 85RMIT University10th SCICC, Guangzhou, China, 2008 What Herbs Interact with Drugs?N = 85RMIT University10th SCICC, Guangzhou, China, 2008 What Drugs Interact with Herbs?N = 85Drug Properties: narrow therapeutic index; extensive metabolism; substrates of CYPs and/or PgP.RMIT University10th SCICC, Guangzhou, China, 2008 HerbInteracting drugsDangguiWarfarinDanshen WarfarinGarlic Saquinavir, ritonavir, warfarin, chlorpropamide Ginkgo Trazodone, warfarin, digoxinGinsengAlcohol, phenelzine, warfarin HawthornDigoxin (no change)KavaAlcohol, alprazolam, bromazepam, L-dopaMilk thistleIndinavirPiperinePropranolol, rifampin, sparteine, theophylline, phenytoinRMIT University10th SCICC, Guangzhou, China, 2008 Toxicity due to Herb-Drug InteractionsHerb + DrugToxicitySJW + cyclosporine AOrgan rejectionSJW + oral contraceptivesBreakthrough bleeding SSRIs (sertraline Zoloft) Anticancer drug: irinotecan (CPT-11) Anticoagulants: warfarin (coumadin), phenprocoumon Antihistamine: fexofenadine Anti-HIV agents: PI: indinavir; RTI: nevirapine Bronchodilator: theophylline Hypoglycemics: tolbutamide Cardiovascualr drugs: digoxin, simvastatin Opiates: methadone, loperamide Oral contraceptives Sedatives: alprazolam & midazolam Immunosuppressants: cyclosporine & tacrolimusRMIT University10th SCICC, Guangzhou, China, 2008 RMIT University10th SCICC, Guangzhou, China, 2008 Mechanisms for Herb-Drug InteractionsDrug ResponseMetabolizing enzymes (CYPs) Identical TargetsTransporters (PgP)Different TargetsPharmacokinetics (PK)Pharmacodynamics (PD)RMIT University10th SCICC, Guangzhou, China, 2008 Herb-CYP InteractionsHerbCYPs affectedSJWMost CYP (mainly CYP3A4)GarlicCYP2C, 2D, 2E, 3APiperineCYP1A, 2C, 3ALicorice CYP1A, 2A, 2C, 3AKavaCYP1A, 2C, 2D, 3A Ginseng CYP3A4, 2D, 2CGinkgo CYP2B, 3ABaizhiCYP1A, 2D, 2E, 3ADangguiCYP1A, 3ARMIT University10th SCICC, Guangzhou, China, 2008 Herb-PgP InteractionsHerbModulation of PgPCurcumininhibitionHawthorn?GarlicInhibitionGinsengMostly inhibitionGreen teaInhibitionMilk thistleInhibitionPiperineInhibition SJWInductionRosemaryInhibitionRMIT University10th SCICC, Guangzhou, China, 2008 RMIT University10th SCICC, Guangzhou, China, 2008 RMIT University10th SCICC, Guangzhou, China, 2008 Herbal Labeling What: identity, quantity of contents, identified active ingredient by common name or proprietary blend. How to use: route, dose daily, etc Who: name and place of manufacturer, packer or distributor. What to claim “This statement has not been evaluated by the Food and Drug Administration”. “This product is not intended to diagnose, treat, cure, or prevent any diseases”.- “It is not advisable to use in combination with”RMIT University10th SCICC, Guangzhou, China, 2008 AcknowledgmentsProf. Guangji Wang Prof. Xiyong Yu Prof. Charlie Xue and Chunguang Li Prof. Eli Chan Prof. Wen Xie Prof. Tony Koon Prof. James W Paxton & Bruce Baguley Prof. John O Miners Prof. Ronald G Dickinson Prof. Min Huang & Anlong Xu Prof. Wei Duan Prof. Xiaotian Lee Prof. Ge Lin Prof. Qiang Zhang Prof. Yi-Zhun Zhu National University of Singapore Academic Research Funds Singapore Cancer Syndicate RMIT University Grant for New Institute NICM grant of Australia Auckland Medical Research Foundation New Zealand Cancer Society Funds Maurice & Phyllis Paykel Trust Hu Zeping Tian Quan Zhang Jing Sun Zhuming Sun Feng Zhang Yaochung Linlin Wang Meredith Payne Liping Ya