Influences of Corydalis decumbens on the Activities of CYP450 Enzymes in Rats with a Cocktail Approach.

Chen Cheng,Wei Sun,Wanshu Li,Lejing Lian,Jianchang Qian,Zhe Wang,Chengke Huang,Yaoyao Dong,Mengchun Chen

doi:10.1155/2019/9614781

Abstract

Corydalis decumbens, a Traditional Chinese Medicine, has been widely used for the alternative and/or complementary therapy of hypertension, arrhythmias rheumatoid arthritis, sciatica, stroke, hemiplegia, paraplegia, and vascular embolism. The aim of this study was to determinate the potential effects of Corydalis decumbens on the five cytochrome P450 (CYP) enzyme activities (CYP1A2, CYP3A4, CYP2C9, CYP2C19, and CYP2D6) by cocktail approach. To evaluate whether concurrent use of Corydalis decumbens interferes with the effect of several prescription drugs, saline (control group) or Corydalis decumbens (XTW group) were administrated via gavage for 7 successive days. A probe cocktail solution (phenacetin, omeprazole, metoprolol, tolbutamide, and midazolam) was given 24 h after the last dose of saline or Corydalis decumbens. A specific and sensitive UHPLC–MS/MS method was validated for the determination of five substrates and their metabolites in control group and XTW group. Our results indicated that Corydalis decumbens could have inductive effects of CYP2C19 and inhibit the activities of CYP1A2 and CYP3A4. However, Corydalis decumbens had no significant influence on CYP2C9 and CYP2D6. The herb-drug interaction should require more attention by careful monitoring and appropriate drug dosing adjustments to the concurrent use of western medications which were metabolized by CYP1A2, CYP2C19, and CYP3A4 in human—Corydalis decumbens, Cytochrome P450, Cocktail, Pharmacokinetics, herb–drug interactions.

Highlights

Herbal medicine was gradually being used as an alternative and/or complementary treatment for serious diseases [1]
Our results indicated that the activities of CYP1A2 and CYP3A4 might be inhibited by Corydalis decumbens
There were no significant differences in pharmacokinetics dates of tolbutamide and metoprolol between two different groups, which demonstrated that the activities of CYP2C9 and CYP2D6 were not obviously influenced by Corydalis decumbens

Summary

Introduction

Herbal medicine was gradually being used as an alternative and/or complementary treatment for serious diseases [1]. Corydalis decumbens (Thunb.) Pers, a herbal medicine, was named “Xiatianwu” in China. A Traditional Chinese Medicine (TCM), has been widely used for the treatment of hypertension, hemiplegia or cerebral embolism hemiplegia, paralytic stroke, rheumatic arthritis, and sciatica [2]. Earlier clinical and/or preclinical studies have demonstrated that Corydalis decumbens (tablet/injection) has exerted the benefit effect on hypertension [3], rheumatoid arthritis [4], sciatica [5], trigeminal neuralgia [6], inhibiting platelet aggregation [7], and memory [8]. Besides clinical doctor’s recommendations, many patients take western medication in combination with Corydalis decumbens or other herbal medicine which they think is safe and often not inform self-medication to their primary physician [9,10,11,12]. In order to avoid clinically insufficient benefits and/or unacceptable risks, it is important to discover and identify harmful combination interactions

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