VA exhibited reduction in AChE, TNF-α, and corticosterone with improved antioxidants to contribute neuroprotection and could be an effective therapeutic agent for treating neurodegenerative disorders.

Context: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties. Objective: This study evaluates the protective effect of HSP on L-methionine-induced hyperhomocysteinemia (HHcy) in rats. Materials and methods: Male Wistar rats were randomly divided into seven groups as DMSO, L-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by oral administration of L-methionine (1.7 g/kg) for 32 days. From the 14 th day of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to L-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28 th -32 nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done. Results: HSP (100 mg/kg) treatment in L-methionine-treated rats exhibited significant (p < 0.001) dosedependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 ± 2.36 versus 10.73 ± 1.26 lmoles/mg), brain lipid peroxidation (15.25 ± 1.65 versus 6.18 ± 0.74 nM/mg), serum homocysteine (Hcy) (22.37 ± 0.30 versus 11.01 ± 1.01 lg/mL) and serum cholesterol (182.7 ± 2.15 versus 101.5 ± 2.76 mg/dL) and increased brain antioxidant levels. HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing the effect of L-methionine on acetylcholine-induced endothelialdependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations. Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.ARTICLE HISTORY

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