The neuroprotective role of eucalyptol in a type-2 diabetes induced neuropathy rat model

Type 2 diabetes mellitus is a chronic metabolic condition that may cause diabetic neuropathy, a debilitating complication driven by chronic hyperglycemia, lipid imbalance, oxidative stress and persistent inflammation. In this study, we investigated the neuroprotective potential of eucalyptol in a streptozotocin-induced rat model of diabetic neuropathy. We found that eucalyptol treatment significantly reduced thermal and mechanical hypersensitivity, lowered blood glucose and glycated hemoglobin, improved insulin levels and favorably regulated lipid profiles by decreasing total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C). Antioxidant defenses were strengthened, as evidenced by elevated superoxide dismutase, catalase and glutathione-S-transferase activities, alongside reduced malondialdehyde levels. Eucalyptol also exhibited anti-inflammatory effects by inhibiting nuclear factor kappa B (NF-κB) activation and lowering tumor necrosis factor-αlpha (TNF-α) and interleukin-6 (IL-6) expression. Histopathological analysis revealed preserved neuronal cytoarchitecture and reduced degeneration in the brain, along with regeneration of β-cells and restoration of islet morphology in the pancreas. Restoration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), both key neurotrophins supporting neuronal growth and survival, reflected enhanced neuronal survival and regeneration, further supported by electron microscopic evidence of sciatic nerve repair and remyelination. Collectively, we conclude that eucalyptol provided neuroprotection via glucose-lowering, antioxidant, anti-inflammatory and neurotrophic actions, highlighting its therapeutic potential.