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• W2901253721 abstract "In light of the widespread use of herbal medicines containing rosmarinic acid (RA) and limited literature available thereon, we investigated the metabolic interactions of RA with human cytochrome P450 monooxygenases (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs). The involvement of selected enzymes (CYP1A2, CYP2C19, CYP2E1, CYP3 A4, UGT1A1, UGT1A6, and UGT2B7) in the metabolism of RA and the inhibitory effect of RA on the enzyme activity were comprehensively evaluated using human recombinant isozyme system. Additionally, concentration-dependent RA metabolism mediated by phase I enzymes (including CYPs) or UGT was investigated in human liver microsome (HLM) system. A significant disappearance of RA was observed in the seven CYP and UGT isoforms studied, indicating their possible involvement in the metabolism of RA. Based on Michaelis-Menten kinetics, the metabolism study using HLM suggests that the UGT system may have a higher capacity and lower affinity for the metabolism of RA than phase I enzyme (including CYP) systems. Moreover, RA weakly inhibited CYP2C9 and 2E1 activities with IC50 values of 39.6 and 61.0 μM, respectively, while moderately inhibiting UGT1A1, 1A6, and 2B7 with IC50 values of 9.24, 19.1, and 23.4 μM, respectively. By constructing Line weaver–Burk plots, the type of inhibition exhibited by RA on CYP and UGT activities was determined as follows: CYP2C19, mixed inhibition; CYP2E1, UGT1A1, UGT1A6, and UGT2B7, competitive inhibition. Based on the comparison of the IC50 and Ki values obtained in the current study with the previously reported plasma concentrations of RA after oral dosing in humans, it is suggested that RA may significantly inhibit the activities of the tested UGTs, rather than CYPs, in clinical settings. Thus, the present study could provide a basis for further studies on clinically significant interactions between UGT substrate drugs and herbal medicines containing RA." @default.
• W2901253721 created "2018-11-29" @default.
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• W2901253721 date "2019-02-01" @default.
• W2901253721 modified "2023-09-27" @default.
• W2901253721 title "Metabolic interactions of rosmarinic acid with human cytochrome P450 monooxygenases and uridine diphosphate glucuronosyltransferases" @default.
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• W2901253721 doi "https://doi.org/10.1016/j.biopha.2018.11.040" @default.
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