Flavonoids aid in delaying the progression of diabetic neuropathy in type-2 diabetic rats

Diabetic neuropathy (DN), is a debilitating condition primarily synonymous with type-2 diabetes, which heightens the nociceptive response. This study examines the effects of hesperidin, a bioflavonoid, in combination with a flavonoid-rich methanolic extract of Emblica officinalis fruit (MEEF). A modified diet (high fat and fructose) was fed to male Wistar rats for a 14-day duration, along with a sub-diabetogenic dose of streptozotocin for DN induction. Diabetic rats were then dosed with MEEF, hesperidin (high 50% & low 25% dose), combination (low dose hesperidin + MEEF) and metformin (standard). Assessment of parameters such as serum glucose levels, antioxidant status, lipid profile, & TNF-α & IL-6 was conducted. Low-dose flavonoid treatment (hesperidin/ MEEF), known for its antioxidant effects, successfully reduced neuropathy-like symptoms (hyperalgesia) in diabetic subjects. This was shown by increased tail flick response times in hot plate and tail immersion tests compared to diabetic controls and metformin. Restoration of defensive antioxidative enzymes (superoxide dismutase and catalase) in treatment groups was observed, along with an improvement in lipid peroxidation. At the molecular level, the treatment also regulated IL-6 and TNF-α, which aided in recovery by neuroprotection. The findings indicated that combination therapy of hesperidin and MEEF evidently aided in alleviating neuropathic pain induced by hyperglycemia by delaying its progression.