Chang Thomas K H, Chen Jie, Benetton Salete A
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Drug Metab Dispos. 2002 Apr;30(4):378-84. doi: 10.1124/dmd.30.4.378.
Ginseng extract has been reported to decrease the incidence of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated tumorigenesis in mice. A potential mechanism for this effect by ginseng is inhibition of DMBA-bioactivating cytochrome P450 (P450) enzymes. In the present in vitro study, we examined the effect of a standardized Panax ginseng (or Asian ginseng) extract (G115), a standardized Panax quinquefolius (or North American ginseng) extract (NAGE), and individual ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) on CYP1 catalytic activities, as assessed by 7-ethoxyresorufin O-dealkylation. G115 and NAGE decreased human recombinant CYP1A1, CYP1A2, and CYP1B1 activities in a concentration-dependent manner. Except for the competitive inhibition of CYP1A1 by G115, the mode of inhibition was the mixed-type in the other cases. A striking finding was that NAGE was 45-fold more potent than G115 in inhibiting CYP1A2. Compared with G115, NAGE also preferentially inhibited 7-ethoxyresorufin O-dealkylation activity in human liver microsomes. Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1, either individually or as a mixture and at the levels reflecting those found in an inhibitory concentration (100 microg/ml) of NAGE or G115, did not influence CYP1 activities. However, at a higher ginsenoside concentration (50 microg/ml), Rb1, Rb2, Rc, Rd, and Rf inhibited these activities. Overall, our in vitro findings indicate that standardized NAGE and G115 extracts, which were not treated with calf serum or subjected to acid hydrolysis, inhibited CYP1 catalytic activity in an enzyme-selective and extract-specific manner, but the effects were not due to Rb1, Rb2, Rc, Rd, Re, Rf, or Rg1.
据报道，人参提取物可降低7,12 - 二甲基苯并[a]蒽（DMBA）引发的小鼠肿瘤发生率。人参产生这种作用的一种潜在机制是抑制DMBA生物激活细胞色素P450（P450）酶。在本体外研究中，我们通过7 - 乙氧基异吩恶唑酮O - 脱烷基化评估了标准化的人参（或亚洲人参）提取物（G115）、标准化的西洋参（或北美人参）提取物（NAGE）以及各个人参皂苷（Rb1、Rb2、Rc、Rd、Re、Rf和Rg1）对CYP1催化活性的影响。G115和NAGE以浓度依赖性方式降低人重组CYP1A1、CYP1A2和CYP1B1活性。除G115对CYP1A1的竞争性抑制外，其他情况下的抑制模式均为混合型。一个显著的发现是，NAGE在抑制CYP1A2方面比G115强45倍。与G115相比，NAGE还优先抑制人肝微粒体中的7 - 乙氧基异吩恶唑酮O - 脱烷基化活性。Rb1、Rb2、Rc、Rd、Re、Rf和Rg1，无论是单独还是作为混合物，在反映NAGE或G115抑制浓度（100μg/ml）的水平下，均不影响CYP1活性。然而，在更高的人参皂苷浓度（50μg/ml）下，Rb1、Rb2、Rc、Rd和Rf会抑制这些活性。总体而言，我们的体外研究结果表明，未经小牛血清处理或酸水解的标准化NAGE和G115提取物以酶选择性和提取物特异性方式抑制CYP1催化活性，但这些作用并非由Rb1、Rb2、Rc、Rd、Re、Rf或Rg1引起。
