Neuroprotective Effect of Naringin Against STZ Diabetes-Induced Peripheral Sensory Neuropathy in Rats by Lowering Blood Glucose and Lipid Levels and Suppressing Inflammation and Oxidative Stress

Background: Diabetic neuropathy (DN) is the most prevalent complication of diabetes, impacting up to 60% of people with diabetes. It is characterized by distal symmetrical loss of sensory function in the lower extremities, presenting with spontaneous excruciating neuropathic pain, hyperalgesia, and allodynia that impairs quality of life. The current work aims to evaluate the neuroprotective potential of naringin (a citrus flavonoid) and examine its ability to improve STZ-induced diabetic neuropathic pain by investigating its hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. Methods: out of 40 adult male Sprague-Dawley rats, diabetes was induced in 30 rats by a single injection of STZ (45 mg/kg dissolved in citrate buffer). Ten days after induction of diabetes, rats were divided into four groups (10/group): normal control, diabetic control, naringin-treated diabetic rats, and glimepiride-treated diabetic rats as a positive control group. At the end of the experiment, serum and brain tissue samples will be collected then the hypoglycemic, lipid-lowering, antioxidant, and anti-inflammatory effects of naringin will be assessed and compared with that of glimepiride (a standard antidiabetic drug). Hyperalgesia and the effect of the studied drugs on it will also be evaluated by observing pain related behaviors in diabetic rats using hot plate, tail immersion, and mechanical sensitivity (von Frey) tests. Results: Significant increase in the serum levels of glucose, tri-glyceride (TG), total cholesterol (t‐cholesterol), low‐density lipoprotein‐cholesterol (LDL-C), and nitric oxide (NO), with a concomitant decrease in body weight (BW), plasma insulin and high‐density lipoprotein‐cholesterol (HDL-C) were observed in diabetic rats. Also, the brain level of malondialdehyde (MDA) was increased, while that of reduced glutathione (GSH), glutathione peroxidase (Gpx), superoxide dismutase (SOD), and catalase (CAT) were markedly decreased. Furthermore, diabetic rats showed a marked increase in plasma levels of proinflammatory cytokines including interleukin‐6 (IL-6) and tumor necrosis factor‐α (TNF-α). Moreover, hot plate, tail immersion, and von Frey tests revealed hyperalgesia in diabetic rats. Treatment with naringin and glimepiride reduced pain hypersensitivity, restored body weight and nearly normalized the altered biochemical parameters, more significantly with naringin than with glimepiride. Conclusion: These results may highlight the potential effects of naringin as a therapeutic strategy for diabetes and its complications including peripheral neuropathy.