Pinelliae rhizoma, a toxic chinese herb, can significantly inhibit CYP3A activity in rats.

Jinjun Wu,Zaixing Cheng,Jian Shi,Lijun Zhu,Linlin Lu,Liang Liu,Na Lin,Shugui He,Shuqiang Liu,Zhongqiu Liu,Guiyu Zhang

doi:10.3390/molecules20010792

Abstract

Raw Pinelliae Rhizoma (RPR) is a representative toxic herb that is widely used for eliminating phlegm or treating cough and vomiting. Given its irritant toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP) and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA), are more commonly applied and administered concomitantly with other chemical drugs, such as cough medications. This study aimed to investigate the effects of RPR, PRP, and PRPZA on CYP3A activity. Testosterone (Tes) and buspirone (BP) were used as specific probe substrates ex vivo and in vivo, respectively. CYP3A activity was determined by the metabolite formation ratios from the substrates. Ex vivo results show that the metabolite formation ratios from Tes significantly decreased, indicating that RPR, PRP, and PRPZA could inhibit CYP3A activity in rats. CYP3A protein and mRNA levels were determined to explore the underlying mechanism. These levels showed marked and consistent down-regulation with CYP3A activity. A significant decrease in metabolite formation ratios from BP was also found in PRPZA group in vivo, implying that PRPZA could inhibit CYP3A activity. Conclusively, co-administration of PR with other CYP3A-metabolizing drugs may cause drug–drug interactions. Clinical use of PR-related formulae should be monitored carefully to avoid adverse interactions.

Highlights

Pinelliae Rhizoma (PR), the tuber of Pinellia ternate (Thunb.) Breit, is a commonly used Chinese herb with high bioactivity against cough and vomiting, or for eliminating the stagnation of phlegm [1,2,3].PR is distributed in China, Korea, and Japan
The results show that Raw Pinelliae Rhizoma (RPR), PRP, and Praeparatum cum Zingibere et Alumine (PRPZA) significantly down-regulated the cytochrome P450 isoenzyme 3A (CYP3A) protein and CYP3A1/2 mRNA expression levels
This study is the first to investigate the influence of RPR, as well as its processed products PRP and PRPZA, on CYP3A ex vivo and in vivo, which assessed the safety of co-administration of PR with other CYP3A-metabolizing drugs from the perspective of CYPs

Summary

Introduction

Pinelliae Rhizoma (PR), the tuber of Pinellia ternate (Thunb.) Breit, is a commonly used Chinese herb with high bioactivity against cough and vomiting, or for eliminating the stagnation of phlegm [1,2,3]. PR is distributed in China, Korea, and Japan. It has been used as an essential drug in Chinese clinics for thousands of years. PR is a representative toxic herbal medicine, which can cause irritant toxicity to oral, throat, and gastrointestinal mucosa [4,5,6]. PR is commonly used in its preparation forms in Chinese clinics.

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