An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone.

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

doi:10.1155/2020/5267684

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.

Highlights

Introduction e dry root ofSophora flavescens Ait. has been an important species in traditional Chinese medicine since the Qin and Han dynasties
Inhibitory Effects of Kurarinone against UGT and cytochrome P450 (CYP) Activities. 100 μM kurarinone inhibited the activities of UGT1A1, UGT1A6, CYP1A2, and CYP2C9 by more than 90%
Kurarinone was incubated with selective chemical inhibitors of the eight CYP isoforms in HLMs, and the results showed that furafylline (CYP1A2 inhibitor) and quinidine (CYP2D6 inhibitor) remarkably inhibited the formation of P1 compared with other CYP isoform inhibitors (Figure 6)

Summary

Introduction

Introduction e dry root ofSophora flavescens Ait. has been an important species in traditional Chinese medicine since the Qin and Han dynasties. S. flavescens is known to exhibit varied pharmacological properties including antitumor [6, 7], anti-inflammatory [8], and antibacterial [9, 10] activities. Kurarinone exhibits antitumor [12, 13], anti-inflammatory [8], antioveractive bladder [14], antioxidant [15], and antityrosinase [16] activities. It induced remarkable cytotoxicity in primary rat hepatocytes and HL-7702 cells [17, 18]

Methods

Results

Conclusion