Maitra I, Marcocci L, Droy-Lefaix M T, Packer L
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Biochem Pharmacol. 1995 May 26;49(11):1649-55. doi: 10.1016/0006-2952(95)00089-i.
Antioxidant mechanisms have been proposed to underlie the beneficial pharmacological effects of EGb 761, an extract from Ginkgo biloba leaves used for treating peripheral vascular diseases and cerebrovascular insufficiency in the elderly. In vitro evidence has been reported that EGb 761 scavenges various reactive oxygen species, i.e. nitric oxide, and the superoxide, hydroxyl, and oxoferryl radicals. However, the ability of EGb 761 to scavenge peroxyl radicals (reactive species mainly involved in the propagation step of lipid peroxidation) has not been investigated. To characterize further the antioxidant action of EGb 761, we measured the protective effects of EGb 761 during: (1) the oxidation of B-phycoerythrin by peroxyl radicals generated in aqueous solution by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH); and (2) the reaction of luminol or cis-parinaric acid with peroxyl radicals generated from 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN) in liposomes or in human low density lipoprotein (LDL), respectively. To evaluate the peroxyl radical scavenging activity of EGb 761 in a more physiologically relevant model of damage to lipid-containing systems, we also analyzed the effect of the extract on the oxidation of human LDL exposed to the azo-initiators in terms of: (1) accumulation of cholesterol linoleate ester hydroperoxides, (2) depletion of alpha-tocopherol and beta-carotene, and (3) changes in intrinsic tryptophan fluorescence. EGb 761 afforded protection against oxidative damage in all the systems we analyzed; thus, it is an efficient scavenger of peroxyl radicals. This result extends the oxygen radical scavenging properties of the extract and supports the hypothesis of an antioxidant therapeutic action of EGb 761.
抗氧化机制被认为是银杏叶提取物EGb 761有益药理作用的基础,EGb 761用于治疗老年人外周血管疾病和脑血管功能不全。体外证据表明,EGb 761能清除多种活性氧,即一氧化氮、超氧阴离子、羟基自由基和氧亚铁自由基。然而,EGb 761清除过氧自由基(主要参与脂质过氧化传播步骤的活性物质)的能力尚未得到研究。为了进一步表征EGb 761的抗氧化作用,我们测量了EGb 761在以下过程中的保护作用:(1)2,2'-偶氮二(2-脒基丙烷)盐酸盐(AAPH)在水溶液中产生的过氧自由基氧化B-藻红蛋白;(2)鲁米诺或顺式紫黄质酸分别与2,2'-偶氮二(2,4-二甲基戊腈)(AMVN)在脂质体或人低密度脂蛋白(LDL)中产生的过氧自由基反应。为了在更具生理相关性的含脂质系统损伤模型中评估EGb 761的过氧自由基清除活性,我们还从以下方面分析了该提取物对暴露于偶氮引发剂的人LDL氧化的影响:(1)胆固醇亚油酸酯氢过氧化物的积累,(2)α-生育酚和β-胡萝卜素的消耗,以及(3)内在色氨酸荧光的变化。在我们分析的所有系统中,EGb 761都能提供抗氧化损伤保护;因此,它是一种有效的过氧自由基清除剂。这一结果扩展了该提取物清除氧自由基的特性,并支持了EGb 761具有抗氧化治疗作用的假说。