DICP OpenIR
Subject Area物理化学
Inhibitory effects of sanguinarine on human liver cytochrome P450 enzymes
Qi, Xiao-Yi1; Liang, Si-Cheng2,3; Ge, Guang-Bo2; Liu, Yong2; Dong, Pei-Pei4; Zhang, Jiang-Wei2; Wang, Ao-Xue1; Hou, Jie4; Zhu, Liang-Liang2; Yang, Ling2; Tu, Cai-Xia1; Yang L(杨凌); Tu CX(涂彩霞)
KeywordSanguinarine Human Liver Microsomes Cytochrome P450 Enzyme Drug-drug Interaction Time-dependent Inhibition
Source PublicationFOOD AND CHEMICAL TOXICOLOGY
2013-06-01
DOI10.1016/j.fct.2013.02.054
Volume56Pages:392-397
Indexed BySCI
Cooperation Status
SubtypeArticle
Department18
Funding Project1806
Contribution Rank待补充
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding Organization2,2 ; 2,2 ; 2,2 ; 2,2
WOS SubjectFood Science & Technology ; Toxicology
WOS Research AreaFood Science & Technology ; Toxicology
WOS KeywordXENOBIOTIC-METABOLIZING ENZYMES ; ST JOHNS WORT ; ALKALOID SANGUINARINE ; DRUG-METABOLISM ; EPIDEMIC DROPSY ; CHELERYTHRINE ; PHARMACOGENOMICS ; ACTIVATION ; PREDICTION ; OXIDATION
AbstractSanguinarine (SAG) has been recognized as an anticancer drug candidate. However, the drug-drug interactions (DDI) potential for SAG via the inhibition against human cytochrome P450 (CYP) enzymes remains unclear. In the present study, the inhibitory effects of SAG on seven major human CYP isoforms 1A2, 2A6, 2E1, 2D6, 2C8, 2C9 and 3A4 were investigated with human liver microsomes (HLM). The results showed that SAG was a potent noncompetitive inhibitor of CYP2C8 activity (K-i = 8.9 mu M) and competitive inhibitor of CYP1A2, CYP2C9 and CYP3A4 activities (K-i = 2.7, 3.8 and 2.0 mu M, respectively). Furthermore, SAG exhibited time- and NADPH-dependent inhibition towards CYP1A2 and CYP3A4 with K-i/k(inact) values of 13.3/0.087 and 5.58/0.029 min(-1) mu M-1, respectively. Weak inhibition of SAG against CYP2E1, CYP2D6 and CYP2A6 was also observed. In vitro-in vivo extrapolation (IV-IVE) from HLM data showed that more than 35.9% of CYP1A2, CYP2C9, CYP2C8 and CYP3A4 activities in vivo could be inhibited by SAG, suggesting that harmful DDIs could occur when SAG or its medical preparations are co-administered with drugs primarily cleared by these CYP isoforms. Further in vivo studies are needed to evaluate the clinical significance of the data presented herein. (C) 2013 Elsevier Ltd. All rights reserved.
Language英语
Funding Organization2,2 ; 2,2 ; 2,2 ; 2,2
URL查看原文
WOS IDWOS:000318960100046
Citation statistics
Cited Times:43[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/119431
Collection中国科学院大连化学物理研究所
Corresponding AuthorYang L(杨凌); Tu CX(涂彩霞)
Affiliation1.Dalian Med Univ, Affiliated Hosp 2, Dalian, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China
3.Dalian Anim Hlth Supervis Inst, Dalian, Peoples R China
4.Dalian Med Univ, Dalian, Peoples R China
Recommended Citation
GB/T 7714
Qi, Xiao-Yi,Liang, Si-Cheng,Ge, Guang-Bo,et al. Inhibitory effects of sanguinarine on human liver cytochrome P450 enzymes[J]. FOOD AND CHEMICAL TOXICOLOGY,2013,56:392-397.
APA Qi, Xiao-Yi.,Liang, Si-Cheng.,Ge, Guang-Bo.,Liu, Yong.,Dong, Pei-Pei.,...&涂彩霞.(2013).Inhibitory effects of sanguinarine on human liver cytochrome P450 enzymes.FOOD AND CHEMICAL TOXICOLOGY,56,392-397.
MLA Qi, Xiao-Yi,et al."Inhibitory effects of sanguinarine on human liver cytochrome P450 enzymes".FOOD AND CHEMICAL TOXICOLOGY 56(2013):392-397.
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