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Inhibition of cytochrome P450 2B6 by Astragalus extract mixture HT042

Journal name:Nature Briefing
Literature No.:
Literature Url: https://link.springer.com/article/10.1007/s43188-019-00027-z
Date publication:04 December 2019

Astragalus extract mixture (AEM) HT042 is a functional food approved by the MFDS (Korean FDA) for increasing height. It comprises a mixture of three standardized extracts from Astragalus membranaceus root, Eleutherococcus senticosus stem, and Phlomis umbrosa root. In this study, drug–functional food interaction was analyzed using six major human cytochrome P450 enzymes. The inhibitory effect of AEM HT042 on P450 activities was studied using a P450–NADPH P450 reductase reconstitution system. Among the six P450 enzymes (1A2, 2A6, 2B6, 2D6, 2C9, and 3A4), only P450 2B6 activity was markedly decreased by AEM HT042 addition. The bupropion hydroxylation activity of P450 2B6 was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS). A calculated IC50 value of 10.62 µg/ml was obtained. To identify the inhibitory compounds in the mixture, four active compounds in AEM HT042 were analyzed. Shanzhiside methylester exhibited inhibitory effects on P450 2B6, whereas formononetin, eleutheroside E, and sesamoside did not affect P450 2B6 activity at all. Our results suggest that shanzhiside methylester in AEM HT042 is responsible for the inhibitory effect on P450 2B6 metabolism. Characterization of the inhibitory effect on P450 can help determine the safe administration of functional foods along with many clinical drugs that are metabolized by P450.

… St. Louis, MO, USA). Shanzhiside methylester was purchased from Target Molecule Corp (Wellesley Hills, MA, USA). Sesamoside was purchased from Chengdu Biopurify Phytochemicals Ltd. (Chengdu, Sichuan, China). All … 
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