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Effect of ginseng extracts on the gene expression of hepatic drug-metabolizing enzymes in rats Yu, Chia-Ting

Abstract

The present study was conducted to investigate the effect of Panax ginseng and Panax quinquefolius extracts of known ginsenoside composition on rat hepatic cytochrome P450 (CYP) and microsomal epoxide hydrolase (mEH) gene expression. Adult male Sprague-Dawley rats (250-300 g) were administered by oral gavage Panax ginseng extract (30 or 100 mg/kg single dose), Panax quinquefolius extract (100 or 400 mg/kg once daily for 21 consecutive days), or an equivalent volume (2 ml/kg) of 0.9% NaCl (vehicle control). All the rats were terminated one day after the last dose. The administration of Panax ginseng extract or Panax quinquefolius extract did not affect: 1) body weight gain, 2) absolute or relative liver weight; 3) absolute or relative testes weight; 4) hepatic microsomal total CYP content; 5) hepatic CYP2B1, CYP3A23, CYP2C11, CYP1A2 and mEH mRNA expression, as determined by validated real-time PCR assays; 6) hepatic microsomal 7-benzyloxyresorufin O-dealkylation and 7- ethoxyresorufin O-dealkylation activities; or 7) hepatic CYP2C11 and mEH protein expression. However, results from the positive control experiments indicated that: 1) phenobarbital (80 mg/kg i.p. once daily for 4 consecutive days) increased hepatic CYP2B1 mRNA (47-fold), microsomal 7-benzyloxyresorufin O-dealkylation activity (37- fold), and hepatic mEH mRNA (17-fold) and protein (2-fold); 2) dexamethasone (100 mg/kg i.p. once daily for 3 consecutive days) increased hepatic CYP3A23 mRNA (75- fold); and 3) (3-naphthoflavone (40 mg/kg i.p. once daily for 3 consecutive days) decreased hepatic CYP2C11 protein (85%) and increased hepatic CYP1A2 mRNA (20- fold) and microsomal 7-ethoxyresorufin O-dealkylation activity (19-fold). Therefore, the lack of an effect by the ginseng extracts on CYP and mEH expression was not due to the assay conditions. In another control experiment, the administration of albendazole (20 mg/kg once daily for 3 consecutive days) by oral gavage increased hepatic microsomal 7-ethoxyresorufin O-dealkylation activity by 21-fold, indicating that the lack of an effect by the ginseng extracts was not a consequence of improper technique in drug administration by oral gavage. In conclusion, Panax ginseng and Panax quinquefolius extracts, at the dosage regimens used in the present study, did not influence hepatic CYP2B1, CYP3A23, CYP2C11, CYP1A2, or mEH gene expression in adult male rats.

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