Hemanth_2016_Pharm.Biol__1

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 14th 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 (28th-32nd 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) dose-dependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 +/- 2.36 versus 10.73 +/- 1.26 mumoles/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 mug/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 endothelial-dependent 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.