Structure-Activity Relationship and Substrate-Dependent Phenomena in Effects of Ginsenosides on Activities of Drug-Metabolizing P450 Enzymes
(0) Ginseng, a traditional herbal medicine, may interact with several co-administered drugs in clinical settings, and ginsenosides, the major active components of ginseng, may be responsible for these ginseng-drug interactions (GDIs). Results from previous studies on ginsenosides effects on human drug-metabolizing P450 enzymes are inconsistent and confusing. Herein, we first evaluated the inhibitory effects of fifteen ginsenosides and sapogenins on human CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 enzymes by using commercially available fluorescent probes. The structure-activity relationship of their effects on the P450s was also explored and a pharmacophore model was established for CYP3A4. Moreover, substrate-dependent phenomena were found in ginsenosides effects on CYP3A4 when another fluorescent probe was used, and were further confirmed in tests with conventional drug probes and human liver microsomes. These substrate-dependent effects of the ginsenosides may provide an explanation for the inconsistent results obtained in previous GDI reports.
Miao Hao Yuqing Zhao Peizhan Chen He Huang Hong Liu Hualiang Jiang Ruiwen Zhang Hui Wang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes Shenyang Pharmaceutical University, Shenyang, Peoples Republic of China Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Department of Pharmacology 4Toxicology, Division of Clinical Pharmacology, Comprehensive Cancer Cent Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes
国际会议
广州
英文
327-336
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）