Chethan S, Dharmesh Shylaja M, Malleshi Nagappa G
Department of Grain Science and Technology, Central Food Technological Research Institute, Mysore, Karnataka 570020, India.
Bioorg Med Chem. 2008 Dec 1;16(23):10085-90. doi: 10.1016/j.bmc.2008.10.003. Epub 2008 Oct 5.
Retinopathy is a major cause of blindness in the Western world, while cataract is one of the three major causes of blindness worldwide. Diabetes is one of the major risk factor in retinopathy and cataract. The prevalence of blindness in India is 15 per 1000 while cataract alone accounts for 80% of this blindness. Diabetes induced cataract is characterized by an accumulation of sorbitol which is mediated by the action of a key enzyme aldose reductase (AR). Non-enzymatic glycation (binding of glucose to protein molecule) induced during diabetes appear to be the key factor for AR mediated sugar-induced cataract. Finger millet polyphenols (FMP) being a major anti-diabetic and antioxidant component, we have evaluated them for AR inhibiting activity. Phenolic constituents in FMP such as gallic, protocatechuic, p-hydroxy benzoic, p-coumaric, vanillic, syringic, ferulic, trans-cinnamic acids and the quercetin inhibited cataract eye lens effectively, the latter was more potent with an IC(50) of 14.8nM. Structure function analysis revealed that phenolics with OH group at 4th position was important for aldose reductase inhibitory property. Also the presence of neighboring O-methyl group in phenolics denatured the AR activity. Finger millet seed coat polyphenols (SCP) has been found to inhibit AR reversibly by non-competitive inhibition. Results thus, provide a stronger evidence for the potentials of FMP in inhibiting cataractogenesis in humans.
视网膜病变是西方世界失明的主要原因之一，而白内障是全球三大失明原因之一。糖尿病是视网膜病变和白内障的主要危险因素之一。印度的失明患病率为每1000人中有15人，而仅白内障就占这种失明情况的80%。糖尿病性白内障的特征是山梨醇的积累，这是由关键酶醛糖还原酶（AR）的作用介导的。糖尿病期间诱导的非酶糖基化（葡萄糖与蛋白质分子的结合）似乎是AR介导的糖诱导性白内障的关键因素。作为主要的抗糖尿病和抗氧化成分，我们评估了黍米多酚（FMP）的AR抑制活性。FMP中的酚类成分，如没食子酸、原儿茶酸、对羟基苯甲酸、对香豆酸、香草酸、丁香酸、阿魏酸、反式肉桂酸和槲皮素，能有效抑制白内障晶状体，后者更有效，IC(50)为14.8nM。结构功能分析表明，在第4位带有OH基团的酚类物质对醛糖还原酶抑制特性很重要。此外，酚类物质中相邻的O-甲基的存在使AR活性变性。已发现黍米种皮多酚（SCP）通过非竞争性抑制可逆地抑制AR。因此，结果为FMP在抑制人类白内障发生方面的潜力提供了更有力的证据。
