Neuroprotective effects of isoquercitrin in diabetic neuropathy via Wnt/β-catenin signaling pathway inhibition

Diabetic neuropathy is a peripheral nervous system disorder affecting both somatic and autonomic components of nervous system. A growing body of evidence have depicted that high glucose levels can induce activation of the Wnt/beta-catenin pathway, however there are no studies targeting this pathway in DN. The intent of the present study was to investigate the effects of isoquercitrin (ISQ), a Wnt/beta-catenin signaling pathway inhibitor, in diabetic neuropathy. Streptozotocin (50 mg/kg, i.p.) was used to induce diabetes in rats. 6-week diabetic rats were treated intrathecally with ISQ at 10 and 30 mu M doses for 3 days. Furthermore, to confirm the results of the intrathecal study, a 2-week intraperitoneal treatment of ISQ was given to diabetic rats. After 6 weeks, diabetic rats developed neuropathy which was evident from reduced thermal and mechanical hyperalgesia thresholds and significant deterioration in motor nerve conduction velocity (MNCV), nerve blood flow (NBF). Sciatic nerves of diabetic neuropathy rats showed increased expression of Wnt pathway proteins namely beta-catenin, c-myc and MMP2. Treatment with ISQ, both intrathecally (10 and 30 mu M) and intraperitoneally (10 mg/kg), significantly ameliorated the alterations in behavioral pain thresholds and improved functional parameters in diabetic rats. Moreover, ISQ also downregulated the expression of Wnt/beta-catenin pathway proteins significantly in diabetic rats as compared to vehicle-treated diabetic rats. Results of the present study suggest the neuroprotective potential of ISQ in the treatment of DN via inhibition of Wnt/beta-catenin signaling pathway.