Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions.

Diabetic neuropathy (DN) is one of the most common long-term complications of diabetes mellitus and clinically can be characterized by an elevated nociceptive response with electrophysiological conduction abnormalities. The present investigation was designed to evaluate the neuroprotective effect of hesperidin against STZ induced diabetic neuropathic pain in laboratory rats. DN was induced in Sprague-Dawley rats (150-200 g) by intraperitoneal administration of streptozotocin (STZ) (55 mg/kg, p.o.). Rats were divided into various groups, namely, STZ control (vehicle), hesperidin (25, 50, and 100 mg/kg, p.o.), insulin (10 IU/kg, s.c.), and combination of hesperidin (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for 4 weeks. Various behavioral (allodynia and hyperalgesia), biochemical parameters [oxido-nitosative stress, Na-K-ATPase, aldose reductase (AR)], and molecular changes (TNF-α and IL-1β) along with hemodynamic changes were determined. Rats treated with hesperidin (50 and 100 mg/kg, p.o., 4 weeks) significantly reduced (p < 0.05) hyperglycemia and its metabolic abnormalities induced by intraperitoneal administration of STZ. The decreased nociceptive threshold, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV), serum insulin as well as Na-K-ATPase activity were significantly increase (p < 0.05) by hesperidin (50 and 100 mg/kg, p.o.) treatment. It significantly attenuated (p < 0.05) elevated glycated hemoglobin, AR activity, oxido-nitrosative stress, neural calcium, and pro-inflammatory cytokines (TNF-α and IL-1β) levels. Histological aberration induced after STZ administration was restored by administration of hesperidin (50 and 100 mg/kg, p.o.) In combination with insulin, hesperidin not only attenuated the diabetic condition but also reversed neuropathic pain via control over hyperglycemia as well as hyperlipidemia to down-regulate generation of free radical, release of pro-inflammatory cytokines as well as elevation in membrane bound enzyme.