Pinelliae Rhizoma, a Toxic Chinese Herb, Can Significantly Inhibit CYP3A Activity in Rats

Molecules

Jinjun Wu¹  Zaixing Cheng²  Shugui He¹  Jian Shi¹  Shuqiang Liu¹  Guiyu Zhang¹  Lijun Zhu¹  Liang Liu³  Zhongqiu Liu¹  Na Lin¹  Linlin Lu¹ 

[1] International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; E-Mails:;College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China; E-Mail:;State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; E-Mail:

关键词: Pinelliae Rhizoma;    CYP3A;    testosterone;    buspirone;    drug–drug interactions;   

DOI  :  10.3390/molecules20010792

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
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