CN: 32-1845/R
ISSN: 2095-6975
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YAO Qing-Qing, LI Li, XU Ming-Cheng, HU Hai-Hong, ZHOU Hui, YU Lu-Shan, ZENG Su. The metabolism and hepatotoxicity of ginkgolic acid (17:1) in vitro[J]. Chinese Journal of Natural Medicines, 2018, 16(11): 829-837

The metabolism and hepatotoxicity of ginkgolic acid (17:1) in vitro

YAO Qing-Qing1, LI Li2, XU Ming-Cheng1, HU Hai-Hong1, ZHOU Hui1, YU Lu-Shan1, ZENG Su1
1 Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Hangzhou 310058, China;
2 Department of Pharmacy & Geriatrics Institute of Zhejiang Province, Zhejiang Hospital, Hangzhou 310013, China
Abstract:
Pharmacological activities and adverse side effects of ginkgolic acids (GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few reports on their hepatotoxicity. In the present study, the metabolism and hepatotoxicity of GA (17:1), one of the most abundant components of GAs, were investigated. Kinetic analysis indicated that human and rat liver microsomes shared similar metabolic characteristics of GA (17:1) in phase I and Ⅱ metabolisms. The drug-metabolizing enzymes involved in GA (17:1) metabolism were human CYP1A2, CYP3A4, UGT1A6, UGT1A9, and UGT2B15, which were confirmed with an inhibition study of human liver microsomes and recombinant enzymes. The MTT assays indicated that the cytotoxicity of GA (17:1) in HepG2 cells occurred in a time-and dose-dependent manner. Further investigation showed that GA (17:1) had less cytotoxicity in primary rat hepatocytes than in HepG2 cells and that the toxicity was enhanced through CYP1A-and CYP3A-mediated metabolism.
Key words:    Ginkgolic acid (17:1)    Cytotoxicity    Liver microsomes    Recombinant enzyme    Hepatotoxicity   
Received: 2018-04-28   Revised:
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Articles by YAO Qing-Qing
Articles by LI Li
Articles by XU Ming-Cheng
Articles by HU Hai-Hong
Articles by ZHOU Hui
Articles by YU Lu-Shan
Articles by ZENG Su
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