Food and Drug Interactions: Effect of <i>Acanthopanax senticosus</i> Harms on CYP2C9 Activity (Part 2) / 日本補完代替医療学会誌

<b>Objective:</b> <i>Acanthopanax senticosus</i> Harms extract (ASE) is an ingredient of functional foods, such as health supplements, in Japan. We investigated the effects of ASE on CYP2C9 activity.<br> <b>Methods and Results:</b> CYP2C9-catalyzed diclofenac 4′-hydroxylase activities in human intestinal and liver microsomes (abbreviated as HIM and HLM, respectively) were significantly decreased by the addition of ASE in a concentration-dependent manner. Kinetic studies of diclofenac 4′-hydroxylase in HLM revealed that ASE addition significantly decreased <i>V</i>_max but had no effect on <i>K</i>_m. These results suggest that diclofenac 4′-hydroxylase activity is suppressed by ASE addition in a non-competitive manner. Then, we investigated the time courses of diclofenac 4′-hydroxylase activity in rat liver microsomes after ASE oral administration (50 to 400 mg/kg). Diclofenac 4′-hydroxylase activities were significantly lowered by the administration of 200 and 400 mg/kg ASE at 0.5 to 4 hr compared with control (0 hr). Furthermore, we investigated the effects of ASE oral administration on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. The area under the concentration-time curve of tolbutamide after ASE oral administration (400 mg/kg) was enhanced by approximately 1.6 times compared with that without ASE oral administration.<br> <b>Conclusion:</b> These findings indicated that ASE inhibits human intestinal and hepatic CYP2C9 activities.<br>

Food and Drug Interactions: Effect of <i>Acanthopanax senticosus</i> Harms on CYP3A4 and CYP2C9 Activities (Part 3) / 日本補完代替医療学会誌

<b>Objective:</b> By using human liver microsomes (HLM), we analyzed the effects of 14 known components of <i>A.senticosus</i> Harms on the activities of CYP2C9 and CYP3A4.<br> <b>Methods and Results:</b> Sesamin and quercetin inhibited both enzyme activities, whereas quercitrin strongly inhibited CYP3A4 activity. The 50% inhibitory concentrations (IC₅₀s) of sesamin and quercetin on CYP2C9 activity were approximately 124- and 59-fold higher and the IC₅₀s of sesamin, quercetin, and quercitrin on CYP3A4 activity were approximately 427-, 135-, and 22-fold higher than that of <i>A. senticosus</i> Harms extract (ASE), respectively. All these components inhibited both CYP3A4 and CYP2C9 in a non-competitive manner. However, these components are present in small amounts in ASE.<br> <b>Conclusion:</b> Therefore, the food-drug interactions caused by <i>A. senticosus </i>Harms are presumed to be due to the additive or synergistic interaction of these components or the other existing components, including their metabolites.<br>