rhodanine and isoliquiritigenin

The effects of a stable prostacyclin analog, Iloprost, and aldose reductase inhibitors (ONO-2235 and isoliquiritigenin) were studied to elucidate the role of cAMP in diabetic neuropathy in relation to polyol metabolism. In in vivo experiments, the cAMP and myoinositol contents in sciatic nerves and motor nerve conduction velocity were significantly reduced in diabetic rats. Iloprost significantly restored the reduced cAMP content in sciatic nerves and improved motor nerve conduction velocity in diabetic rats. However, the contents of sorbitol or myoinositol in sciatic nerves were not affected by Iloprost in diabetic rats. On the other hand, aldose reductase inhibitors significantly reduced the sorbitol content and increased the cAMP and myoinositol contents in the sciatic nerves of diabetic rats. The motor nerve conduction velocity was also slightly but significantly improved by treatment with aldose reductase inhibitors. There was a negative correlation between cAMP and sorbitol in the sciatic nerves of diabetic rats treated with aldose reductase inhibitors and a positive correlation between cAMP and motor nerve conduction velocity. In in vitro experiments, Iloprost significantly increased cAMP, but did not affect the sorbitol content in sciatic nerves. Aldose reductase inhibitors inhibited sorbitol accumulation and increased cAMP in sciatic nerves. Our data suggest that polyol pathway activation somehow results in cAMP reduction in sciatic nerves and that the reduction of cAMP in peripheral nerves may be closely related to the pathogenesis of diabetic neuropathy.

Topics: Aldehyde Reductase; Animals; Blood Glucose; Chalcone; Chalcones; Cyclic AMP; Cyclic GMP; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Iloprost; Inositol; Male; Neural Conduction; Rats; Rats, Inbred WKY; Rhodanine; Sciatic Nerve; Sorbitol; Thiazolidines

The effects of aldose reductase inhibitors (ARIs) on the synthesis of prostacyclin (PGI2) by aortic rings from diabetic rats were examined. The ARIs studied were ONO-2235 and isoliquiritigenin, a new compound extracted from glycyrrhizae radix. The content of sorbitol in the sciatic nerve of diabetic rats induced by streptozotocin was significantly increased as compared with that of controls. This increase was significantly inhibited by the administration of an ARI. On the other hand, there was a marked decrease in the synthesis of PGI2 by the diabetic rats compared with the control rats. The decrease in PGI2 synthesis was significantly reversed by the administration of an ARI. Furthermore, the synthesis of PGI2 by the aortic rings was inversely correlated with the content of sorbitol in sciatic nerves. Those observations suggest that an ARI may have a beneficial effect on the vascular synthesis of PGI2 in diabetes mellitus.

Topics: Aldehyde Reductase; Animals; Aorta, Thoracic; Blood Glucose; Chalcone; Chalcones; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Epoprostenol; Male; Rats; Rats, Inbred Strains; Rhodanine; Sciatic Nerve; Sorbitol; Streptozocin; Sugar Alcohols; Thiazolidines