Beta-sitosterol mitigates type 2 diabetes-induced cognitive deficits: a behavioral and molecular investigation in Swiss albino mice.

This study examines the long-term effects of diabetes, focusing on its association with cognitive impairment, and investigates the neuroprotective potential of β-sitosterol (BST) against cognitive deficits induced by type 2 diabetes mellitus (T2DM). T2DM was induced in Swiss albino mice using a cafeteria (CAF) diet for four weeks followed by a single dose of streptozotocin (STZ) (45 mg/kg, i.p.). Weekly assessments of body weight and blood glucose levels were conducted, along with behavioral evaluations using the radial arm maze (RAM), nest building test, and novel object recognition test (NORT) to assess spatial learning and memory. Additionally, lipid profile (TC, TG, LDL, HDL), biochemical markers (GSH, CAT, MDA), molecular markers (IL-1β, TNF-α, IL-10, Akt, Gsk-3β), and histopathological analyses were performed. Treatment with β-sitosterol (10 mg/kg and 20 mg/kg, p.o.) and metformin (200 mg/kg, i.p.) significantly improved cognition, as observed in behavioral tasks, by restoring antioxidant levels, increasing the anti-inflammatory marker IL-10 and neuroprotective Akt, and reducing MDA, IL-1β, TNF-α, and Gsk-3β compared to the T2DM group. β-sitosterol also ameliorated glucose and lipid metabolism abnormalities in T2DM mice. These findings suggest that the cognitive benefits of β-sitosterol and its combination therapy may be attributed to its neuroprotective effects, which are likely mediated through its antioxidant and anti-inflammatory activities.