Structural aspects of the inhibitory effect of glabridin on LDL oxidation
Structural aspects of the inhibitory effect of glabridin on LDL oxidation
复制标题
DOI：
10.1016/s0891-5849(98)00006-9
复制
发表时间：
1998-06-01
影响因子：
7.4
通讯作者：
Vaya, J
中科院分区：
文献类型：
--
作者：
Belinky, PA;Aviram, M;Vaya, J
本文研究了甘草异黄酮类化合物光甘草定（glabridin）及其衍生物对铜离子诱导或巨噬细胞介导的低密度脂蛋白（LDL）氧化的抑制作用，探讨了光甘草定分子中不同部分对异黄酮抗氧化活性的贡献。分析了异黄烷衍生物的峰电位（E-1/2）、对DPPH自由基的清除能力以及对重金属的螯合能力，并与它们对LDL氧化的抑制活性进行了比较。在铜离子诱导的LDL氧化中，光甘草定（1）、4 ′-O-甲基光甘草定（2）、hispaglabridin A（3）和hispaglabridin B（4）在环B的2 ′和4 ′位上有两个羟基或在2 ′位上有一个羟基，它们成功地抑制了共轭二烯、硫代巴比妥酸反应物质（TBARS）和脂质过氧化物的形成，并抑制LDL在氧化状态下的电泳迁移率。化合物1-3表现出相似的活性，而化合物4的活性较低。在巨噬细胞介导的LDL氧化中，TEARS形成也被这些葡聚糖（1-4）抑制，其活性顺序与铜离子诱导的LDL氧化中获得的活性顺序相似。另一方面，2 '-O-甲基光甘草定（5），一种合成的化合物，其2'-位羟基被保护，4 '-位羟基是游离的，在两种LDL氧化系统中仅显示出轻微的抑制活性。2 ′，4 ′-O-二甲基光甘草定（6），其2 ′-和4 ′-位的羟基均被保护，无活性。与光甘草定中的酚B环相同的间苯二酚（7）在这些氧化体系中表现出低活性。在杂环C环中含有额外双键的异黄烯glabrene（8）是在两种氧化系统中测试的黄酮衍生物中活性最高的化合物。在pH7.4下测试的化合物1-5（300 μ M）的峰电位相似（425-530 mV），化合物6和8的峰电位分别为1078和80 mV。化合物1、2、3、4、8对DPPH自由基的清除率分别为31%、16%、74%、51%、86%，而化合物5和6对LDL氧化几乎没有抑制作用，但对DPPH自由基的清除率也很低。异黄烷衍生物和异黄烯化合物都不能螯合铁或铜离子。这些结果表明光甘草定对LDL氧化的抗氧化作用似乎主要存在于2'羟基，并且异黄烷的疏水部分对于获得这种作用是必需的。B环上羟基的位置显著影响异黄烷衍生物对LDL氧化的抑制效率，但不影响它们向DPPH提供电子的能力或峰电位值。(C)1998年爱思唯尔科学公司
The inhibitory effects of glabridin, an isoflavan isolated from licorice (Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced by copper ions or mediated by macrophages were studied, in order to evaluate the contribution of the different parts of the isoflavan molecule to its antioxidant activity. The peak potential (E-1/2) of the isoflavan derivatives, their radical scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and their ability to chelate heavy metals were also analyzed and compared to their inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation, glabridin (1), 4'-O-methylglabridin (2), hispaglabridin A (3), and hispaglabridin B (4), which have two hydroxyl groups at positions 2' and 4' or one hydroxyl at position 2' on ring B, successfully inhibited the formation of conjugated dienes, thiobarbituric acid reactive substances (TBARS) and lipid peroxides, and inhibited the electrophoretic mobility of LDL under oxidation. Compounds 1-3 exhibited similar activities, whereas compound 4 was less active. In macrophage-mediated LDL oxidation, the TEARS formation was also inhibited by these isoflavans (1-4) at a similar order of activity to that obtained in copper ion-induced LDL oxidation. On the other hand, 2'-O-methylglabridin (5), a synthesized compound, whose hydroxyl at 2'-position is protected and the hydroxyl at 4'-position is free, showed only minor inhibitory activity in both LDL oxidation systems. 2',4'-O-Dimethylglabridin (6), whose hydroxyls at 2'- and 4'-positions are both protected was inactive. Resorcinol (7), which is identical to the phenolic B ring in glabridin, presented low activity in these oxidation systems. The isoflavene glabrene (8), which contains an additional double bond in the heterocyclic C ring, was the most active compound of the flavonoid derivatives tested in both oxidation systems. The peak potential of compounds 1-5 (300 mu M), tested at pH 7.4, was similar (425-530 mV), and that for compound 6 and 8 was 1078 and 80 mV, respectively. Within 30 min of incubation, compounds 1, 2, 3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%, respectively, of DPPH radical, whereas compounds 5 and 6, which almost did not inhibit LDL oxidation, also failed to scavenge DPPH. None of the isoflavan derivatives nor the isoflavene compound were able to chelate iron, or copper ions. These results suggest that the antioxidant effect of glabridin on LDL oxidation appears to reside mainly in the 2' hydroxyl, and that the hydrophobic moiety of the isoflavan is essential to obtain this effect. It was also shown that the position of the hydroxyl group at B ring significantly affected the inhibitory efficiency of the isoflavan derivatives on LDL oxidation, but did not influence their ability to donate an electron to DPPH or their peak potential values. (C) 1998 Elsevier Science Inc.