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Planta Med 2010; 76(3): 245-250
DOI: 10.1055/s-0029-1186082
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Herb-Drug Interactions: In Vivo and In Vitro Effect of Shenmai Injection, a Herbal Preparation, on the Metabolic Activities of Hepatic Cytochrome P450 3A1/2, 2C6, 1A2, and 2E1 in Rats

Chun-hua Xia1 , 2 [*] , Jian-guo Sun1 [*] , Guang-ji Wang1 , Li-li Shang1 , Xiao-xuan Zhang1 , Rong Zhang1 , Ying Peng1 , Xiao-jin Wang1 , Hai-ping Hao1 , Lin Xie1 , Michael S. Roberts3
  • 1Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
  • 2Clinical Pharmacology Institute, Medical College of Nanchang University, Nanchang, China
  • 3Therapeutics Research Unit, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia
Further Information

Publication History

received February 24, 2009 revised July 29, 2009

accepted August 3, 2009

Publication Date:
11 September 2009 (online)

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Abstract

Shenmai injection (SMI), a mixture of Radix Ginseng and Radix Ophiopogonis, is one of the most popular herbal medicinal products and is widely used for the treatment of coronary atherosclerotic cardiopathy and viral myocarditis. The purpose of this study was to investigate the effect of SMI, in vivo and in vitro, on the metabolic activities of hepatic cytochrome CYP450 3A1/2, 2C6, 2E1, and 1A2 in rats. After a single or multiple pretreatment with SMI, the rats were administrated intravenously a cocktail containing midazolam (1 mg/kg), diclofenac (0.5 mg/kg), theophylline (1 mg/kg), and chlorzoxazone (0.5 mg/kg) as probe substrates of rat CYP450 3A1/2, 2C6, 1A2, and 2E1, respectively. Single and multiple SMI pretreatment to rats resulted in a rise of 33.8 % (p < 0.01) and 25.6 % (p < 0.01) in AUC for midazolam, and an increase in AUC for diclofenac by 14.7 % (p < 0.05) and 31.2 % (p < 0.01), respectively. However, the pharmacokinetics of chlorzoxazone and theophylline in rats was not altered markedly. In rat liver microsomes, linear mixed-type inhibition of SMI against the enzyme activities of CYP3A1/2, CYP2C6, and CYP1A2 was shown with IC50 values of 3.3 %, 2.0 %, and 3.1 % and K i values of 3.8 %, 1.5 %. and 1.9 %, respectively. These in vivo and in vitro results demonstrated that SMI had the potential to inhibit the activities of hepatic CYP3A1/2 and CYP2C6, but might not significantly affect CYP1A2 and CYP2E1-mediated metabolism in rats.

Key words

Shenmai injection - Radix Ginseng (Panax ginseng C. A. Mey. - Araliaceae) - Radix Ophiopogonis (Ophiopogon japonicus Ker‐Gawl. - Liliaceae) - metabolism‐based interactions - CYP450 - pharmacokinetics

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1 These authors contributed equally to this work.

Prof. Guangji Wang

Key Lab of Drug Metabolism and Pharmacokinetics
China Pharmaceutical University

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210009 Nanjing

P. R. China

Phone: + 86 25 83 27 11 28

Fax: + 86 25 83 30 28 27

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