Emblica officinalis Corrects Functional, Biochemical and Molecular Deficits in Experimental Diabetic Neuropathy by Targeting the Oxido‐nitrosative Stress Mediated Inflammatory Cascade

Abstract

Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. Diabetic neuropathic pain is amongst the most difficult types of pain to treat mainly due to the lack of understanding of its etiology and inadequate relief with available drug therapy. The present study targeted oxidative stress mediated nerve damage in diabetic rats using an aqueous extract of Emblica officinalis, a potent natural antioxidant. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test (thermal hyperalgesia) and decreased paw withdrawal threshold in both Randall-Selitto (mechanical hyperalgesia) and von-Frey hair test (mechanical allodynia). A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress, nitrite levels and cytokines (TNF-α, IL-1β and TGF-β1) both in the serum and sciatic nerve of diabetic rats. Treatment with the Emblica officinalis aqueous extract (250, 500 and 1000 mg/kg/day) significantly attenuated all the behavioral, biochemical and molecular alterations in a dose-dependent manner. The major finding of the study is that insulin alone corrected the hyperglycemia and partially reversed the pain response in diabetic rats. However, combination with Emblica officinalis extract not only attenuated the diabetic condition but also reversed neuropathic pain through modulation of oxidative-nitrosative stress in diabetic rats.