Yu Chia-Ting, Chen Jie, Teng Xiao Wei, Tong Vincent, Chang Thomas K H
Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, B. C. V6T 1Z3, Canada.
Drug Metab Dispos. 2005 Jan;33(1):19-22. doi: 10.1124/dmd.104.001917. Epub 2004 Oct 1.
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 beta-naphthoflavone increased CYP1A2 mRNA and EROD activity levels. Treatment of primary cultures of rat hepatocytes with either of the ginseng extracts (0.1-1000 microg/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.
据报道，用单次口服剂量（10 - 30毫克/千克）人参总皂苷含量未知的人参粗提取物处理大鼠，可适度提高肝微粒体细胞色素P450介导的氨基比林N - 脱甲基化活性。在本研究中，我们比较了人参提取物和西洋参提取物对大鼠肝脏CYP2B1、CYP3A23和CYP1A2基因表达的影响。成年雄性Sprague - Dawley大鼠（250 - 275克）通过灌胃或腹腔注射接受人参提取物[总皂苷4%（w/w）；30或100毫克/千克/天，持续1或4天]、西洋参提取物[总皂苷10%（w/w）；100或400毫克/千克/天，连续21天]，或等量体积（2毫升/千克）的赋形剂（0.9%氯化钠或0.3%羧甲基纤维素），并在最后一次给药后1天处死。人参提取物和西洋参提取物不影响体重增加、绝对或相对肝脏重量、肝脏CYP2B1、CYP3A23或CYP1A2 mRNA表达，或微粒体CYP2B介导的7 - 苄氧基试卤灵O - 脱烷基化（BROD）或CYP1A介导的7 - 乙氧基试卤灵O - 脱烷基化（EROD）活性。相比之下，阳性对照实验结果表明，苯巴比妥增加CYP2B1 mRNA和BROD活性，地塞米松增加CYP3A23 mRNA，β - 萘黄酮增加CYP1A2 mRNA和EROD活性水平。用人参提取物之一（0.1 - 1000微克/毫升，处理2天）处理大鼠原代肝细胞培养物，也不影响CYP2B1或CYP3A23 mRNA表达。总体而言，我们的数据表明，人参提取物和西洋参提取物不会增加大鼠肝脏CYP2B1、CYP3A23或CYP1A2基因表达。
