DICP OpenIR
Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7
Ma, Hai-Ying1; Sun, Dong-Xue2; Cao, Yun-Feng3,4; Ai, Chun-Zhi4; Qu, Yan-Qing5; Hu, Cui-Min4,7; Jiang, Changtao6; Dong, Pei-Pei8; Sun, Xiao-Yu4; Hong, Mo4; Tanaka, Naoki6; Gonzalez, Frank J.6; Ma, Xiao-Chi3,4,8,9; Fang, Zhong-Ze3,4,6
KeywordAndrographolide Derivatives Herb-drug Interaction (Hdi) Udp-glucuronosyltransferases (Ugts) Adverse Effects
Source PublicationTOXICOLOGY AND APPLIED PHARMACOLOGY
2014-05-15
DOI10.1016/j.taap.2014.02.021
Volume277Issue:1Pages:86-94
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS KeywordZIDOVUDINE GLUCURONIDATION ; PANICULATA EXTRACT ; IN-VITRO ; ACID ; 4-METHYLUMBELLIFERONE ; PHARMACOKINETICS ; SELECTIVITY ; 1-NAPHTHOL ; BINDING ; SITES
AbstractHerb-drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4catalyzed trifluoperazine ( IFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (KO were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (KO and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb-drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7. (C) 2014 Elsevier Inc. All rights reserved.
Language英语
WOS IDWOS:000335095200010
Citation statistics
Cited Times:54[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/145787
Collection中国科学院大连化学物理研究所
Affiliation1.China Med Univ, Affiliated Hosp 4, Shenyang 110032, Peoples R China
2.Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang 110016, Peoples R China
3.Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China
4.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China
5.Yantaishan Hosp, Yantai, Shandong, Peoples R China
6.NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA
7.Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA
8.Dalian Med Univ, Acad Integrat Med, Dalian 116044, Peoples R China
9.Med Univ, Coll Pharm, Pharmacokinet & Drug Transport Key Lab, Dalian, Peoples R China
Recommended Citation
GB/T 7714
Ma, Hai-Ying,Sun, Dong-Xue,Cao, Yun-Feng,et al. Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2014,277(1):86-94.
APA Ma, Hai-Ying.,Sun, Dong-Xue.,Cao, Yun-Feng.,Ai, Chun-Zhi.,Qu, Yan-Qing.,...&Fang, Zhong-Ze.(2014).Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7.TOXICOLOGY AND APPLIED PHARMACOLOGY,277(1),86-94.
MLA Ma, Hai-Ying,et al."Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7".TOXICOLOGY AND APPLIED PHARMACOLOGY 277.1(2014):86-94.
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