Synergistic Impact of Mangiferin with Metformin and Gliclazide on Diabetic Neuropathic Pain

Diabetic neuropathy is one of the microvascular complications of diabetes mellitus. It is characterized by neuronal damage resulting in neuropathic pain. Hence, we studied the impact of mangiferin combined with therapeutically used oral hypoglycemic drugs metformin and gliclazide to check for synergistic effects on diabetic neuropathy. Hyperanalgesia and mechanical allodynia are two commonly used experimental models of neuropathic pain. Sprague Dawley male rats were given a high-fat diet for 12 weeks followed by a low dose of streptozotocin to induce type 2 diabetes. Mangiferin, metformin, and gliclazide individually and in combination were given in different doses and checked for pain perception both in thermal and mechanical allodynia and evaluated the neuronal damage due to hyperglycemia by measuring the markers of oxidative stress and inflammation. The results from hyperanalgesia and allodynic experiments reveal that pain perception is delayed in rats treated with a combination of mangiferin with metformin and gliclazide than the individual drugs. The possible synergistic impact was noted in the antioxidant enzyme levels in the brain tissue and substantiated that combination drugs have better influence than the individual drug-treated rats. These results testify that the naturally occurring mangiferin in combination with the commonly used oral hypoglycemic drugs helps to alleviate the symptoms of diabetic complications.