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Kampo medicines are widely used in Japan; however, their potential to cause drug interactions still remains unclear and needs to be further investigated. The effects of goreisan on the P-glycoprotein (P-gp) and the cytochrome P-450 (CYP), which are associated with drug interactions, were investigated.The inhibitory effect of goreisan extract on P-gp was evaluated using a Caco-2 cell permeability assay. The results indicated that it inhibited P-gp function in a concentration-dependent manner.The inhibitory effect of three goreisan ingredients (alisol A, tumulosic acid, and ( E )-cinnamic acid) on seven CYP isoforms was evaluated using human liver microsomes (HLM). Of these, tumulosic acid and ( E )-cinnamic acid exhibited less than 16% inhibition at concentrations of 10 µmol/L against any of the CYP isoforms tested. Alisol A inhibited only CYP3A but showed no inhibitory effect with pre-incubation.These results indicate that goreisan extract has inhibitory activity against P-gp and that alisol A, a goreisan ingredient, exhibits an inhibitory effect on CYP3A. However, these are thought to be minor or negligible  in vivo . Overall, these findings will be useful to evaluate possible drug interactions and provide support for the interpretation of future clinical drug–drug interaction studies involving goreisan. Kampo medicines are widely used in Japan; however, their potential to cause drug interactions still remains unclear and needs to be further investigated. The effects of goreisan on the P-glycoprotein (P-gp) and the cytochrome P-450 (CYP), which are associated with drug interactions, were investigated. The inhibitory effect of goreisan extract on P-gp was evaluated using a Caco-2 cell permeability assay. The results indicated that it inhibited P-gp function in a concentration-dependent manner. The inhibitory effect of three goreisan ingredients (alisol A, tumulosic acid, and ( E )-cinnamic acid) on seven CYP isoforms was evaluated using human liver microsomes (HLM). Of these, tumulosic acid and ( E )-cinnamic acid exhibited less than 16% inhibition at concentrations of 10 µmol/L against any of the CYP isoforms tested. Alisol A inhibited only CYP3A but showed no inhibitory effect with pre-incubation. These results indicate that goreisan extract has inhibitory activity against P-gp and that alisol A, a goreisan ingredient, exhibits an inhibitory effect on CYP3A. However, these are thought to be minor or negligible  in vivo . Overall, these findings will be useful to evaluate possible drug interactions and provide support for the interpretation of future clinical drug–drug interaction studies involving goreisan.

xenobiotica

In vitro  assessment of the inhibitory effect of goreisan extract and its ingredients on the P-glycoprotein drug transporter and cytochrome P-450 metabolic enzymes