Kuo I fan, Chen Jie, Chang Thomas K H
Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada.
Can J Physiol Pharmacol. 2004 Jan;82(1):57-64. doi: 10.1139/y03-133.
The present study investigated the in vitro effect of Ginkgo biloba extracts and some of the individual constituents (ginkgolides, bilobalide, and flavonols such as kaempferol, quercetin, isorhamnetin, and their glycosides) on CYP1A-mediated 7-ethoxyresorufin O-dealkylation in hepatic microsomes isolated from rats induced with beta-naphthoflavone. G. biloba extract competitively inhibited CYP1A activity, with an apparent Ki value of 1.6 +/- 0.4 microg/mL (mean +/- SE). At the concentrations present in the G. biloba extracts, ginkgolides A, B, C, and J and bilobalide did not affect CYP1A activity, whereas kaempferol (IC50 = 0.006 +/- 0.001 microg/mL, mean +/- SE), isorhamnetin (0.007 +/- 0.001 microg/mL), and quercetin (0.050 +/- 0.003 microg/mL) decreased this activity. The monoglycosides (1 and 10 microg/mL) and diglycosides (10 microg/mL) of kaempferol and quercetin but not those of isorhamnetin also inhibited CYP1A activity. The order of inhibitory potency was kaempferol approximately equal to isorhamnetin > quercetin, and for each of these flavonols the order of potency was aglycone >> monoglycoside > diglycoside. In summary, G. biloba extract competitively inhibited rat hepatic microsomal CYP1A activity, but the effect was not due to ginkgolides A, B, C, or J, bilobalide, kaempferol, quercetin, isorhamnetin, or the respective flavonol monoglycosides or diglycosides.
本研究调查了银杏叶提取物及其某些单一成分（银杏内酯、白果内酯以及黄酮醇如槲皮素、山奈酚、异鼠李素及其糖苷）对从经β-萘黄酮诱导的大鼠分离的肝微粒体中CYP1A介导的7-乙氧基异吩恶唑酮O-脱烷基作用的体外影响。银杏叶提取物竞争性抑制CYP1A活性，表观Ki值为1.6±0.4μg/mL（平均值±标准误）。在银杏叶提取物中的浓度下，银杏内酯A、B、C和J以及白果内酯不影响CYP1A活性，而槲皮素（IC50 = 0.006±0.001μg/mL，平均值±标准误）、异鼠李素（0.007±0.001μg/mL）和山奈酚（0.050±0.003μg/mL）降低了该活性。槲皮素和山奈酚的单糖苷（1和10μg/mL）以及二糖苷（10μg/mL）但不是异鼠李素的单糖苷和二糖苷也抑制CYP1A活性。抑制效力顺序为槲皮素≈异鼠李素＞山奈酚，对于这些黄酮醇中的每一种，效力顺序为苷元＞＞单糖苷＞二糖苷。总之，银杏叶提取物竞争性抑制大鼠肝微粒体CYP1A活性，但该作用并非由于银杏内酯A、B、C或J、白果内酯、槲皮素、山奈酚、异鼠李素或相应的黄酮醇单糖苷或二糖苷。
