Inhibition of human CYP3A4 and CYP3A5 enzymes by gomisin C and gomisin G, two lignan analogs derived from Schisandra chinensis
文献类型：期刊论文
| 作者 | Zhao, Jin2; Sun, Tao3; Wu, Jing-Jing4,5; Cao, Yun-Feng4,5,6; Fang, Zhong-Ze5,7; Sun, Hong-Zhi5; Zhu, Zhi-Tu5; Yang, Kun7; Liu, Yong-Zhe7; Gonzalez, Frank J.1 |
| 刊名 | FITOTERAPIA
 |
| 出版日期 | 2017-06-01 |
| 卷号 | 119页码:26-31 |
| 关键词 | Gomisin c Gomisin g Cyp3a4 Cyp3a5 Inhibition Herb-drug Interactions |
| DOI | 10.1016/j.fitote.2017.03.010 |
| 英文摘要 | Gomisin C (GC) and gomisin G (GG) are two lignan analogs isolated from the Traditional Chinese Medicine Schisandra chinensis which possesses multiple pharmacological activities. However, the potential herb-drug interactions (HDI) between these lignans and other drugs through inhibiting human cytochrome P450 3A4 (CYP3A4) and CYP3A5 remains unclear. In the present study, the inhibitory action of GC and GG on CYP3A4 and CYP3A5 were investigated. The results demonstrated that both GC and GG strongly inhibited CYP3A-mediated midazolam 1 '-hydroxylation, nifedipine oxidation and testosterone 6 beta-hydroxylation. Notably, the inhibitory intensity of GC towards CYP3A4 was stronger than CYP3A5 when using midazolam and nifedipine as substrates. While inhibition of GC towards CYP3A5 was weaker than CYP3A4 when using testosterone as substrate. In contrast, GG showed a stronger inhibitory activity on CYP3A5 than CYP3A4 without substrate-dependent behavior. In addition, docking simulations indicated that the pi-pi interaction between CYP3A4 and GC, and hydrogen-bond interaction between CYP3A5 and GG might result in their different inhibitory actions. Furthermore, the AUC of drugs metabolized by CYP3A was estimated to increase by 8%-321% and 2%-3190% in the presence of GC and GG, respectively. These findings strongly suggested that GC and GG showed high HDI potentials, and the position of methylenedioxy group determined their different inhibitory effect towards CYP3A4 and CYP3A5, which are of significance for the application of Schisandra chinensis-containing herbs. 2017 Elsevier B.V. All rights reserved. |
| 语种 | 英语 |
| WOS记录号 | WOS:000404307800005 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/152105]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.NIH, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA 2.Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang 110016, Peoples R China 3.Liaoning Canc Hosp & Inst, Dept Breast Med, Shenyang 110042, Peoples R China 4.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China 5.Key Lab Liaoning Tumor Clin Metabol KLLTCM, Jinzhou, Liaoning, Peoples R China 6.Shanghai Inst Planned Parenthood Res, Key Lab Contracept & Devices Res NPFPC, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Shanghai, Peoples R China 7.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Jin,Sun, Tao,Wu, Jing-Jing,et al. Inhibition of human CYP3A4 and CYP3A5 enzymes by gomisin C and gomisin G, two lignan analogs derived from Schisandra chinensis[J]. FITOTERAPIA,2017,119:26-31. |
| APA | Zhao, Jin.,Sun, Tao.,Wu, Jing-Jing.,Cao, Yun-Feng.,Fang, Zhong-Ze.,...&Yin, Jun.(2017).Inhibition of human CYP3A4 and CYP3A5 enzymes by gomisin C and gomisin G, two lignan analogs derived from Schisandra chinensis.FITOTERAPIA,119,26-31. |
| MLA | Zhao, Jin,et al."Inhibition of human CYP3A4 and CYP3A5 enzymes by gomisin C and gomisin G, two lignan analogs derived from Schisandra chinensis".FITOTERAPIA 119(2017):26-31. |
入库方式： OAI收割
来源：大连化学物理研究所
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