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Inhibition of human CYP3A4 and CYP3A5 enzymes by gomisin C and gomisin G, two lignan analogs derived from Schisandra chinensis
Zhao, Jin1; Sun, Tao2; Wu, Jing-Jing3,4; Cao, Yun-Feng3,4,5; Fang, Zhong-Ze4,6; Sun, Hong-Zhi4; Zhu, Zhi-Tu4; Yang, Kun6; Liu, Yong-Zhe6; Gonzalez, Frank J.7; Yin, Jun1
KeywordGomisin c Gomisin g Cyp3a4 Cyp3a5 Inhibition Herb-drug Interactions
Source PublicationFITOTERAPIA
2017-06-01
DOI10.1016/j.fitote.2017.03.010
Volume119Pages:26-31
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectChemistry, Medicinal ; Pharmacology & Pharmacy
WOS Research AreaPharmacology & Pharmacy
WOS KeywordIN-VITRO ; LIVER-MICROSOMES ; DRUG-INTERACTIONS ; METABOLISM ; MIDAZOLAM ; TESTOSTERONE ; NIFEDIPINE ; PREDICTION ; EXTRACT ; PROBE
AbstractGomisin 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.
Language英语
WOS IDWOS:000404307800005
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/152105
Collection中国科学院大连化学物理研究所
Affiliation1.Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang 110016, Peoples R China
2.Liaoning Canc Hosp & Inst, Dept Breast Med, Shenyang 110042, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
4.Key Lab Liaoning Tumor Clin Metabol KLLTCM, Jinzhou, Liaoning, Peoples R China
5.Shanghai Inst Planned Parenthood Res, Key Lab Contracept & Devices Res NPFPC, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Shanghai, Peoples R China
6.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China
7.NIH, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA
Recommended Citation
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.
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