Chronic diabetes complication cataracts

The roots of S. oblonga have been extensively used for the treatment of diabetes in the Ayurvedic system of traditional Indian medicine. From the ethyl acetate soluble portion of the methanolic extract from the roots of S. oblonga Matsuda et al. isolated compound (14), a friedelane-type triterpene [42]. The methanolic extract and the ethyl acetate soluble portions were found to show inhibitory activity on aldose reductase, which is related to chronic diabetes complications such as peripheral neuropathy, retinopathy and cataracts. Compound (14) was assayed for aldose reductase rat lens inhibitory activity. It showed inhibition percentages of 21.8 % at a concentration of 30 pM and 48.2 % at a concentration of 100 pM. The activity of (14) and other terpenoids isolated from this plant could prove to be the reason for the popular use of the plant in the Ayurvedic system for the treatment of diabetes. 

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). 

The Amadori sugar-amino acid residue adducts in proteins are produced with prolonged hyperglycemia and undergo progressive nonenzymatic reactions involving dehydration, condensation, and cyclization. These compounds are collectively known as advanced glycosylation end products and are involved in the chronic complications of diabetes mellitus (cataracts and nephropathy) (Chapter 22). 

Insulin therapy has been dramatically effective in eliminating keto-acidotic coma as a cause of death in diabetics. However, while prolonging life, insulin therapy does not prevent the occurrence of disabling complications of chronic diabetes, such as neuropathy, nephropathy, retinopathy and cataracts [ 13-Insulin therapy is only partially effective in normalizing glucose levels, and the occurrence of diabetic complications appears to be related to the severity and duration of diabetic hyperglycaemia. 

Chronic Complications - A great deal of interest has been generated in recent years, regarding the possibility that polyol accumulation may be fundamental to the development of diabetic complications in certain tissues. While sorbitol accumulation in the lens has long been implicated as being causally related to diabetic cataract formation , more recent work has provided compelling evidence that a similar situation may exist for the development of diabetic neuropathy " and macroangio-pathy. ... 

Substituted spiro[imidazolidine-4,4 (T/0quinazoline]-2,2, 5(3 /0-triones (713) (Scheme 109) have been prepared and tested as aldose reductase inhibitors, which are of therapeutic interest in counteracting chronic complications of diabetes (retinopathy, neuropathy, nephropathy, cataracts). The spiro derivatives (713) were prepared from 1-carbamoylisatins (711) and S-ethylisothiouronium bromide with subsequent treatment of the 4-(2-ethyl-2-isothioureido)carbonyl-3,4-dihydro-4-hyd-roxy-2(l/f)quinazolinone (712) with acid <91CPB1694>. 

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