In Vitro Studies on the Oxidative Metabolism of 20(S)-Ginsenoside Rh2 in Human, Monkey, Dog, Rat, and Mouse Liver Microsomes, and Human Liver S9
文献类型：期刊论文
| 作者 | Li, Liang ; Chen, Xiaoyan; Zhou, Jialan; Zhong, Dafang
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| 刊名 | DRUG METABOLISM AND DISPOSITION
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| 出版日期 | 2012-10 |
| 卷号 | 40期号:10页码:2041-2053 |
| ISSN号 | 0090-9556 |
| DOI | 10.1124/dmd.112.046995 |
| 文献子类 | Article |
| 英文摘要 | 20(S)-Ginsenoside Rh2 (Rh2)-containing products are widely used in Asia, Europe, and North America. However, extremely limited metabolism information greatly impedes the complete understanding of its clinical safety and effectiveness. The present study aims to systematically investigate the oxidative metabolism of Rh2 using a complementary set of in vitro models. Twenty-five oxidative metabolites were found using liquid chromatography-electrospray ionization ion-trap mass spectrometry. Six metabolites and a metabolic intermediate were synthesized. The metabolites were structurally identified as 26-hydroxy Rh2 (M1-1), (20S,24S)-epoxydammarane-12,25-diol-3-beta-D-glucopyranoside (M1-3), (20S,24R)-epoxydammarane-12,25-diol-3-beta-D-glucopyranoside (M1-5), 26,27-dihydroxy Rh2 (M3-6), (20S,24S)-epoxydammarane-12,25,26-triol-3-beta-D-glucopyranoside (M3-10), (20S,24R)-epoxydammarane-12,25,26-triol-3-beta-D-glucopyranoside (M3-11), and 26-aldehyde Rh2 on the basis of detailed mass spectrometry and nuclear magnetic resonance data analysis. Double-bond epoxidation followed by rearrangement and vinyl-methyl group hydroxylation represent the initial metabolic pathways generating monooxygenated metabolites M1-1 to M1-5. Further sequential metabolites (M2-M5) from the dehydrogenation and/or oxygenation of M1 were also detected. CYP3A4 was the predominant enzyme involved in the oxidative metabolism of Rh2, whereas alcohol dehydrogenase and aldehyde dehydrogenase mainly catalyzed the metabolic conversion of alcohol to the corresponding carboxylic acid. No significant differences were observed in the phase I metabolite profiles of Rh2 among the five species tested. Reactive epoxide metabolite formation in both humans and animals was evident. However, GSH conjugate M6 was detected only in cynomolgus monkey liver microsomal incubations. In conclusion, Rh2 is a good substrate for CYP3A4 and could undergo extensive oxidative metabolism under the catalysis of CYP3A4. |
| WOS关键词 | DRUG-METABOLISM ; MASS-SPECTROMETRY ; GINSENOSIDE RH2 ; INHIBITION ; ACTIVATION ; IDENTIFICATION ; APOPTOSIS ; PATHWAY ; DESIGN ; CELLS |
| 资助项目 | National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program," China[2009ZX09301-001] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000309001400021 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277926]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Liang,Chen, Xiaoyan,Zhou, Jialan,et al. In Vitro Studies on the Oxidative Metabolism of 20(S)-Ginsenoside Rh2 in Human, Monkey, Dog, Rat, and Mouse Liver Microsomes, and Human Liver S9[J]. DRUG METABOLISM AND DISPOSITION,2012,40(10):2041-2053. |
| APA | Li, Liang,Chen, Xiaoyan,Zhou, Jialan,&Zhong, Dafang.(2012).In Vitro Studies on the Oxidative Metabolism of 20(S)-Ginsenoside Rh2 in Human, Monkey, Dog, Rat, and Mouse Liver Microsomes, and Human Liver S9.DRUG METABOLISM AND DISPOSITION,40(10),2041-2053. |
| MLA | Li, Liang,et al."In Vitro Studies on the Oxidative Metabolism of 20(S)-Ginsenoside Rh2 in Human, Monkey, Dog, Rat, and Mouse Liver Microsomes, and Human Liver S9".DRUG METABOLISM AND DISPOSITION 40.10(2012):2041-2053. |
入库方式： OAI收割
来源：上海药物研究所
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