Effect of You-Gui Yin on the Activities of Seven Cytochrome P450 Isozymes in Rats.

Fan He,Weidong Chen,Shizhong Hong,Ting Jiang,Lei Wang,Li Liu

doi:10.1155/2020/9784946

Abstract

You-Gui Yin (YGY) is a traditional Chinese medicine (TCM) decoction composed of eight Chinese herbs. The interaction between TCM and Western medicine has attracted much attention nowadays. It is therefore necessary to study the clinical application of YGY in combination with Western medicine from the perspective of metabolic enzymes. This study aims to investigate the effect of YGY on the activities of seven CYP450 isozymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) in rats. Twenty-four Sprague-Dawley (SD) rats were randomly divided into four groups: high, middle, and low-dose YGY-treated groups and the control group. They were given 13.78, 20.67, and 31 g/kg/d YGY decoction by oral administration and normal saline (10 mL/kg), respectively, for 14 days. Half an hour after the last administration, a mixed probe substrate (1 mg/kg) was administered by tail vein injection. Then, blood was taken from the venous plexus at different time points. The protein expression level of the CYP450 enzymes in the control and treatment groups was determined by western blot. The effect of YGY on the activity of CYP isoenzymes was studied by comparing the plasma pharmacokinetics between the control and treatment groups. Compared with the control group, YGY at a high (31 g/kg) dosage could decrease AUC(0–t), AUC(0–∞) and Cmax of diclofenac, omeprazole, and midazolam by at least 35.4%, while increase CL by at least 88.9%; this revealed that YGY could induce CYP2C9, CYP2C19, and CYP3A4. The results show that when we use You-Gui Yin decoction in combination with other drugs, especially drugs metabolized by CYP2C9, CYP2C19, and CYP3A4 enzymes, the interaction between drugs needs special attention.

Highlights

Introduction e combination of traditionalChinese medicine (TCM) and Western drugs is becoming common in clinical applications leading to herb-drug interactions (HDIs) [1]. e HDIs may enhance or weaken the efficacy of the herbs
Compared with the control group, YGY at a high (31 g/kg) dosage could decrease AUC(0–t), AUC(0–∞) and Cmax of diclofenac, omeprazole, and midazolam by at least 35.4%, while increase CL by at least 88.9%; this revealed that YGY could induce CYP2C9, CYP2C19, and CYP3A4. e results show that when we use You-Gui Yin decoction in combination with other drugs, especially drugs metabolized by CYP2C9, CYP2C19, and CYP3A4 enzymes, the interaction between drugs needs special attention
Studying the effect of drugs on CYP activity is helpful for the rational selection of therapeutic drugs and avoiding the occurrence of toxic reactions [9]. e cocktail probe drug method agrees with the overall dialectical view of traditional Chinese medicine (TCM) in evaluating the properties of metabolites, drug interactions, phenotypic analysis of drug metabolism, and evaluation of clinical administration schemes of TCM in the liver CYP450 enzyme system. erefore, its application value in the modernization of TCM cannot be ignored

Summary

Introduction

Introduction e combination of traditionalChinese medicine (TCM) and Western drugs is becoming common in clinical applications leading to herb-drug interactions (HDIs) [1]. e HDIs may enhance or weaken the efficacy of the herbs. Chinese medicine (TCM) and Western drugs is becoming common in clinical applications leading to herb-drug interactions (HDIs) [1]. It is referred to as the cocktail probe substrate method which is a kind of application that simultaneously gives a variety of relatively low doses of probe drugs. It can use modern instrumental analysis technology to determine the metabolic rate or metabolic typing index of the probe drugs in biological samples to obtain multiple CYP450 isoenzyme phenotypes’ information. E cocktail probe drug method agrees with the overall dialectical view of TCM in evaluating the properties of metabolites, drug interactions, phenotypic analysis of drug metabolism, and evaluation of clinical administration schemes of TCM in the liver CYP450 enzyme system. Accurate and high throughput methods can evaluate CYP450 enzyme activity [12]

Methods

Results

Discussion

Conclusion