Impacts of Kampo medicine on induction of CYP3A4 and ABCB1 in gastrointestinal cell model LS180

Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)

Kana Hashimoto ¹ , Daichi Enomoto ² , Shion Ohsawa ³ , Saki Aoki ⁴ , Kai Tanaka ⁵ , Runa Yamauchi ⁶ , Yuko Nakayama ⁷ , Kohji Takara ⁸

1 - Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan
2 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan
3 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan
4 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan
5 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan
6 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan
7 - Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University; Himeji, Japan
8 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University

Received: 2023-03-15 Accepted : 2023-06-22 Published : 2023-06-22

Keywords: Cyp3a4, Kampo medicine, ABCB1, LS180 cell,

Abstract :

Background & Aim: The clinical use of some Kampo medicines has increased rapidly, and opportunities to be used concomitantly with Western medicines more frequently. Although the inhibition of cytochrome P450(CYP)-mediated drug metabolism and ABCB1-mediated transport by Kampo medicine has been reported, little information is available regarding the induction of CYP enzymes or P-glycoprotein—which is encoded by the highly polymorphic ATP-binding cassette transporter B1 (ABCB1) gene—by Kampo medicine. This study aimed to evaluate the induction of CYP enzymes and ABCB1 using Kampo medicines.Experimental: Four Kampo medicines, namely Saireito, Shosaikoto, Goreisan, and Daikenchuto, were selected. The induction of CYP3A4 and ABCB1mRNA expressionwas evaluated in human-derived colon adenocarcinoma LS180 cells, which are an established model for investigating gene induction mediated by the pregnane X receptor.Results: Exposure to Saireito caused a dose-dependent increase in CYP3A4 mRNA expression. A significant increase in CYP3A4 mRNA expression was also observed with Goreisan and Daikenchuto, but not with Shosaikoto. Exposure to Saireito, Shosaikoto, and Goreisan significantly upregulated the expression of ABCB1 mRNA in a dose-dependent manner, but exposure to Daikenchuto had no such effect. These results indicate the differing induction effects of Kampo medicines and the distinct profiles of CYP3A4 and ABCB1, suggesting the upregulation of CYP3A4 or ABCB1 expression by Kampo medicines in enterocytes.Recommended applications/industries: Collectively, our results show that Kampo medicines can potentially induce the expression of CYP enzymes and ABCB1, and provide useful clinical information on the safety and efficacy of the combined use of Kampo and Western medicines.

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