An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone

Youfa Qin; Yongkun Zhu; Xiaoyan Xue; Guanghui Zhou; Huibo Li; Jian Wang

doi:10.1155/2020/5267684

An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone

Evid Based Complement Alternat Med. 2020 Sep 13:2020:5267684. doi: 10.1155/2020/5267684. eCollection 2020.

Authors

Youfa Qin¹, Yongkun Zhu¹, Xiaoyan Xue¹, Guanghui Zhou², Huibo Li³, Jian Wang⁴

Affiliations

¹ Department of Clinical Pharmacy, SSL Central Hospital of Dongguan City, Dongguan, China.
² Rehabilitation Department of Traditional Chinese Medicine, Dongguan Third People's Hospital, Dongguan, China.
³ Department of Pharmacy, Peking University Third Hospital, Beijing, China.
⁴ School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.

Abstract

Kurarinone is a major component found in the dried roots of Sophora flavescens Ait. that participates in vital pharmacological activities. Recombinant CYP450 supersomes and liver microsomes were used to study the metabolic profiles of kurarinone and its inhibitory actions against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes. 100 μM of kurarinone strongly inhibited more than 90% of UGT1A1, UGT1A6, CYP1A2, and CYP2C9. CYP1A2 and CYP2D6 played important roles in catalyzing the biotransformation of kurarinone. Moreover, metabolism of kurarinone considerably differs among species, and metabolic characteristics were similar between monkey and human. Kurarinone demonstrated moderate permeability at values of pH 4.0 and 7.4. Our findings offer a clearer idea to understand the pharmacological and toxicological mechanisms of kurarinone.