Diabetic neuropathy polyol pathway

In Ayurveda and folklore medicines, cinnamon is used in the treatment of diabetes. Cinnamon is reported to reduce the blood glucose level in non-insulin-dependent diabetics. Therapeutic studies have proved the potential of cinnamaldehyde as an antidiabetic agent. Cinnamaldehyde inhibits aldose reductase, a key enzyme involved in the polyol pathway. This enzyme catalyses the conversion of glucose to sorbitol in insulin-insensitive tissues in diabetic patients. This leads to accumulation of sorbitol in chronic complications of diabetes, such as cataract, neuropathy and retinopathy. Aldose-reductase inhibitors prevent conversion of glucose to sorbitol, thereby preventing several diabetic complications (Lee, 2002). 

Some typical structural templates embedded with the thiazoHdine frame have been reported as potent inhibitors of aldose reductase (AR), an enzyme in the polyol pathway responsible for the conversion of glucose to sorbitol. In this, the accumulation of sorbitol has been attributed to causing cataracts, neuropathy, and retinopathy in diabetic cases [ 157,158]. The planar hydrophobic (aromatic) regions and propensity to charge transfer interactions have been... 

ALDOSE REDUCTASE INHIBITORS (ARI) act at the enzyme aldose reductase, which is the first enzyme in the sorbitol (or polyol) pathway which converts glucose to sorbitol. It is thought that in hyperglycaemic states there may be an accumulation of sorbitol, leading to hyperosmotic pathology. ARI agents are under trial for use in the treatment of peripheral diabetic neuropathies, retinopathy and nephropathies. (These include tolrestat. also alrestatin, sorbinil, zenarestat and zopolrestat)... 

Aldose reductase inhibitors (ARI) reduce the flux of glucose through the polyol pathway thereby inhibiting the accumulation of sorbitol and fructose and preventing NADPH consumption and oxidative stress. Numerous studies of ARI in animal models of diabetic complications have demonstrated the potential of ARI against diabetic neuropathy. However, animal models of neuropathy do not predict outcome in human beings well. 

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