| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Zhou, Xiao-wen Ma, Zheng Geng, Ting Wang, Zhen-zhong Ding, Gang Yu-an, Bi Xiao, Wei |
| Description |
Country affiliation: China Author Affiliation: Zhou XW ( The First Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China.); Ma Z ( State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Processes, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China.); Geng T ( State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Processes, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China.); Wang ZZ ( State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Processes, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China.); Ding G ( State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Processes, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China.); Yu-an B ( State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Processes, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China.); Xiao W ( State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Processes, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China. Electronic address: kanionxw2010@126.com.) |
| Abstract |
ETHNOPHARMACOLOGICAL RELAVANCE: The extracts of Ginkgo biloba leaves are effective in treating cerebral infarction, of which ginkgolides have been demonstrated to be the active ingredients. The purpose of this study was to determine whether hydrolyzed ginkgolides would cause potential drug-drug interactions (DDI) during its clinical use via inhibition or induction of the major human cytochrome P450s (CYPs). MATERIALS AND METHODS: The inhibition (direct and metabolism-dependent inhibiton on CYP activities) and induction (mRNA expression level and activity of CYPs) by the hydrolyzed ginkgolides were evaluated in human liver microsomes and cryopreserved human hepatocytes, respectively. RESULTS: Within 0.1 to 10µg/mL, the hydrolyzed ginkgolides showed negligible direct inhibition against CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4m (midazolam as substrate) and 3A4t (testosterone as substrate), with IC50 values determined to be >10µg/mL (concentrations expressed as the sum of equivalent concentrations of ginkgolide A, B and K). For the metabolism-dependent inhibition studies, the preincubation of 30min did not substantially alter the IC50 values when compared with the corresponding values in the direct inhibition studies. The activities and mRNA expression levels for CYP1A2 and 2B6 within each drug-treated group (0.1, 1 and 10µg/mL) were not affected after the 48-h incubation. For CYP3A4, the activity and mRNA expression level were not altered when incubated with 0.1 and 1µg/mL of hydrolyzed ginkgolides. When incubated with hydrolyzed ginkgolides at 10µg/mL, the relative activity and relative mRNA expression level of CYP3A4 remarkably increased to 4.59±3.67 and 17.2±9.16-fold of the corresponding vehicle control values, respectively. CONCLUSIONS: The hydrolyzed ginkgolides is not likely to cause DDI via inhibition of the major human CYPs. However, the CYP3A4 induction might be clinically relevant. |
| File Format |
HTM / HTML |
| ISSN |
03788741 |
| Volume Number |
158 Pt A |
| e-ISSN |
18727573 |
| Journal |
Journal of Ethnopharmacology |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-12-02 |
| Publisher Place |
Ireland |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Ethnopharmacology Cytochrome P-450 Enzyme System Drug Effects Ginkgolides Pharmacology Lactones Cytochrome P-450 Enzyme Inducers Administration & Dosage Cytochrome P-450 Enzyme Inhibitors Genetics Metabolism Dose-response Relationship, Drug Female Gene Expression Regulation, Enzymologic Ginkgo Biloba Chemistry Hepatocytes Enzymology Humans In Vitro Techniques Inhibitory Concentration 50 Male Microsomes, Liver Plant Leaves Rna, Messenger Journal Article Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Drug Discovery Pharmacology |
