Abstract
Treatment of rats with a single oral dose (10-30 mg/kg) of a crude Panax ginseng extract of unknown ginsenoside content has been reported to modestly increase hepatic microsomal cytochrome P450-mediated aminopyrine N-demethylation activity. In the present study, we compared the effect of P. ginseng and Panax quinquefolius extracts on rat hepatic CYP2B1, CYP3A23, and CYP1A2 gene expression. Adult male Sprague-Dawley rats (250-275 g) received, by oral gavage or i.p., P. ginseng extract [4% (w/w) total ginsenosides; 30 or 100 mg/kg/day for 1 or 4 days], P. quinquefolius extract [10% (w/w) total ginsenosides; 100 or 400 mg/kg/day for 21 consecutive days), or an equivalent volume (2 ml/kg) of the vehicle (0.9% NaCl or 0.3% carboxymethylcellulose) and were terminated 1 day after the last dose. P. ginseng and P. quinquefolius extracts did not affect body weight gain, absolute or relative liver weight, hepatic CYP2B1, CYP3A23, or CYP1A2 mRNA expression, or microsomal CYP2B-mediated 7-benzyloxyresorufin O-dealkylation (BROD) or CYP1A-mediated 7-ethoxyresorufin O-dealkylation (EROD) activity. In contrast, results from positive control experiments indicated that phenobarbital increased CYP2B1 mRNA and BROD activity, dexamethasone increased CYP3A23 mRNA, and β-naphthoflavone increased CYP1A2 mRNA and EROD activity levels. Treatment of primary cultures of rat hepatocytes with either of the ginseng extracts (0.1-1000 μg/ml for 2 days) also did not affect CYP2B1 or CYP3A23 mRNA expression. Overall, our data indicate that P. ginseng and P. quinquefolius extracts do not increase rat hepatic CYP2B1, CYP3A23, or CYP1A2 gene expression.
Footnotes
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This research was supported by Grant AT-00286 (to T.K.H.C.) from the National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, and a major equipment grant from the Dawson Endowment Fund in Pharmaceutical Sciences (to T.K.H.C.). C.T.Y. was supported in part by a Merck Research Laboratories M.Sc. Traineeship in Drug Metabolism and a Kam Li Ma Graduate Traineeship in Pharmaceutical Sciences. V.T. was supported by a Doctoral Research Award from the Canadian Institutes of Health Research. T.K.H.C. received a Research Career Award in the Health Sciences from the Canadian Institutes of Health Research and the Rx&D Health Research Foundation.
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The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Complementary and Alternative Medicine, National Institutes of Health.
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doi:10.1124/dmd.104.001917.
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ABBREVIATIONS: BNF, β-naphthoflavone; BROD, 7-benzyloxyresorufin O-dealkylation; DEX, dexamethasone; DMSO, dimethyl sulfoxide; EROD, 7-ethoxyresorufin O-dealkylation; P450, cytochrome P450; PB, phenobarbital; PCR, polymerase chain reaction.
- Received August 18, 2004.
- Accepted September 28, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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