Abstract
BACKGROUND: Diabetic neuropathy is a neurodegenerative complication of diabetes mellitus that occurs due to various factors, with oxidative stress, neuroinflammation and neurotrophic signalling impairment being the major causes. AIM: To evaluate the neuroprotective effects of a polyherbal extract (PHE) prepared from Citrullus colocynthis, Curcuma longa, and Myristica fragrans in diabetic rats. METHODS: Type 2 diabetes was induced in rats with a single intraperitoneal injection of streptozotocin, and those with fasting blood glucose levels of > 250 mg/dL were included for further studies. The animals were categorised into five groups: Control, diabetic, diabetic + PHE, control + PHE and diabetic + metformin. These treatments were administered orally for 8 weeks. Behavioral tests comprised the hot plate, tail-flick, acetone drop and rotarod tests. Serum glucose, insulin, glycosylated haemoglobin and lipid profile analyses were performed, along with oxidative stress (malondialdehyde, reduced glutathione, superoxide dismutase, catalase and glutathione-S-transferase) and pro-inflammatory (tumour necrosis factor-α and interleukin-6) markers. Neurotrophic factors were measured, and the pancreas, liver and sciatic nerve were histologically examined. RESULTS: This study demonstrated that PHE exerts a significant metabolic regulatory effect in streptozotocin-induced diabetic rat models. PHE treatment led to a marked reduction of 30.17% in fasting blood glucose levels, indicating potent antihyperglycemic activity, and also restored the lipid profile, enhanced antioxidant defenses, and reduced neuroinflammation. Serum insulin levels were significantly increased in diabetic rats receiving PHE, suggesting potential stimulation or preservation of pancreatic β-cells. Furthermore, behavioral impairments and histological damage were notably reversed following PHE administration. CONCLUSION: The PHE derived from Curcuma longa, Myristica fragrans, and Citrullus colocynthis mitigates diabetic neuropathy through synergistic chemical-biological interactions targeting key mediators of oxidative stress and inflammation. These findings support the need for comprehensive evaluation of this formulation as a potential therapeutic candidate. This study enhances the current understanding of integrative approaches for managing chronic diabetic complications and provides further evidence supporting the therapeutic potential of plant-based compounds.