Inhibition of aldose reductase from cataracted eye lenses by finger millet (Eleusine coracana) polyphenols

Abstract

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.