Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula, on the Main CYP450 Activities in Rats Using a Cocktail Method.

Huan-Hua Xu,Cheng-Rong Xiao,Ming Li,Qian-De Liang,Zeng-Chun Ma,Fei-Ran Hao,Hong-Ling Tan,Mei-Xi Wang,Yu-Guang Wang,Si-Jia Ren,Xiang-Lin Tang,Yue Gao

doi:10.1155/2017/2374624

Abstract

The purpose of this work was to study the influences of Realgar-Indigo naturalis (RIF) and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11 enzyme activity significantly. Interestingly, in realgar high dosage group, CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of realgar manifested a good dose-dependent manner. The RIF results indicated that drug coadministrated with RIF may need to be paid attention in relation to drug-drug interactions (DDIs). Realgar, a toxic traditional Chinese medicine (TCM), does have curative effect on acute promyelocytic leukemia (APL). Its toxicity studies should be focused on. We found that, in realgar high dosage group, CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its potential toxicity mechanism.

Highlights

The complexity of medicine suggests that treatment protocols should be carefully designed, and construction of a prescription is an art in fighting disease
This paper aims at elucidating the potential influences of Realgar-Indigo naturalis formula (RIF) and realgar on the activities of four CYP450 isozymes (CYP1A2, CYP2C11, CYP2E1, and CYP3A1/2) in rats
To investigate whether endogenous substances would interfere with the assay, blank plasma, blank plasma extracted by ethylacetate containing internal standard (IS), blank plasma spiked with analytes, and a plasma sample collected at 45 min after administration intravenously of mixed probe drugs to rats were processed according to the procedures described above and analyzed

Summary

Introduction

The complexity of medicine suggests that treatment protocols should be carefully designed, and construction of a prescription is an art in fighting disease. Increasing evidences demonstrate that, in treating diseases, especially cancer [1] and chronic diseases [2], therapeutic regimens containing multiple drugs with distinct but related mechanisms can usually amplify the therapeutic efficacies or reduce adverse effect of each agent, leading to maximal therapeutic efficacy with minimal adverse effects [3]. Traditional Chinese medicine (TCM) formula [4] is a unique medical system assisting the ancient Chinese in dealing with disease for thousands of years. In a formula, there is a component called “emperor” medicine which represents the principal component and exerts the main therapeutic effect, while other medicines serve as adjuvant ones to assist the therapeutic effect or reduce the adverse effect of the “emperor” medicine. In most formulas, essential compounds and precise mechanisms remain undefined, especially the formulas containing toxic elements, such as arsenic and mercury. In western countries, undefined mechanisms and excess toxic substance are the reasons to ban TCM, impeding the modernization of TCM

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