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
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
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DOI：
10.1080/00498254.2022.2078750
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发表时间：
2022-07-25
期刊：
影响因子：
1.8
通讯作者：
Mizoguchi，Kazushige
中科院分区：
文献类型：
--
作者：
Takiyama，Mikina;Matsumoto，Takashi;Mizoguchi，Kazushige
汉方药物在日本被广泛使用；然而，它们引起药物相互作用的可能性仍不清楚，需要进一步研究。研究了 goreisan 对与药物相互作用相关的 P-糖蛋白 (P-gp) 和细胞色素 P-450 (CYP) 的影响。使用 Caco-2 细胞通透性测定评估了 goreisan 提取物对 P-gp 的抑制作用。结果表明，它以浓度依赖性方式抑制P-gp功能。利用人肝微粒体（HLM）评估了三种Goreisan成分（泽泻醇A、土木洛酸和（E）-肉桂酸）对七种CYP亚型的抑制作用。其中，肿瘤酸和 (E)-肉桂酸在浓度为 10μmol/L 时对任何测试的 CYP 亚型表现出低于 16% 的抑制作用。泽泻醇 A 仅抑制 CYP3A，但在预孵育时没有显示出抑制作用。这些结果表明，goreisan 提取物对 P-gp 具有抑制活性，并且 goreisan 成分泽泻醇 A 对 CYP3A 表现出抑制作用。然而，这些在体内被认为是次要的或可以忽略不计的。总体而言，这些发现将有助于评估可能的药物相互作用，并为解释未来涉及 goreisan 的临床药物相互作用研究提供支持。
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 negligiblein 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.