TITLE:
Potential Mechanism of Herb-Drug Interaction Mediated by Angelica dahurica: Inhibition on CYP3A Enzymes in Rats
AUTHORS:
Fan Yang, Ally R. Mussa, Lijun An, Rongjia Liang, Xiaoyan Shi, Justin N. Kabera, Xin He
KEYWORDS:
Angelica dahurica, Total Coumarin Extract (TCE), Inhibition, CYP3A, Herb-Drug Interactions (HDIs)
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.7 No.4,
April
20,
2016
ABSTRACT: Angelica dahurica is commonly referred to as ‘Baizhi’ in China and has been noted for its therapeutic significance. The major active ingredients of Angelica dahurica is coumarin, which is reported as a kind of potent inhibitor of cytochrome P450 enzymes (CYP450s). The aim of this study was to investigate the inhibition of CYP3A enzymes by total coumarin extract (TCE) obtained from dried root of Angelica dahurica by using in situ single pass intestinal perfusion (SPIP) and in situ liver perfusion in rats. When midazolam (MDZ) which is a substrate of CYP3A co-perfused with TCE (198 μg/mL) from Baizhi in duodenum and ileum segments, the Peff of MDZ has increased significantly compared with the MDZ single perfused group (p 0.05) (n = 6). During in situ liver perfusion study, the results demonstrated that, 3 days oral administration of TCE obtained from Baizhi could significantly reduce the elimination rate of MDZ in the perfusate (p Angelica dahurica extract co-administrated with drugs which are the substrates of CYP3A, much more attention should be paid rather than that of other CYP450 enzymes. These findings may facilitate in predicting possible herb-drug interactions (HDIs) when Angelica dahurica is used in combination with other drugs, and decrease the incidence of the CYP450-mediated HDIs.