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

Author

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

Subjects
Pinelliae Rhizoma, CYP3A, testosterone, buspirone, drug–drug interactions, Organic chemistry, QD241-441
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.

Published
2015
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2. Pinelliae Rhizoma, a Toxic Chinese Herb, Can Significantly Inhibit CYP3A Activity in Rats

Author

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

Subjects
CYP3A, Metabolite, Pinellia, Pinelliae Rhizoma, Pharmaceutical Science, Pharmacology, Article, Analytical Chemistry, Buspirone, lcsh:QD241-441, chemistry.chemical_compound, lcsh:Organic chemistry, In vivo, Drug Discovery, medicine, Animals, Cytochrome P-450 CYP3A, RNA, Messenger, Physical and Theoretical Chemistry, buspirone, biology, Organic Chemistry, biology.organism_classification, Rats, Isoenzymes, Plants, Toxic, chemistry, Chemistry (miscellaneous), Toxicity, testosterone, Microsome, Microsomes, Liver, Molecular Medicine, drug–drug interactions, Ex vivo, medicine.drug
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.

Published
2015

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