Natural dietary antioxidants, fisetin and hesperidin ameliorate chronic mild hyperhomocysteinemia induced cognitive dysfunction and oxidative stress in Wistar rats

This study was aimed to evaluate the neuroprotective role of fisetin and hesperidin on homocysteine induced cognitive dysfunction, oxidative/nitrative stress,inflammatory and morphological parameters of brain cortex and hippocampus of rats subjected to chronic mild hyperhomocysteinemia. Male wistar rats received DL-homocysteine (0.03 µmoL/g /b.w.) by subcutaneous route twice daily and control and vehicle control ( 0.5 mL/kg and 10 mL/kg, b.w.) once daily from 30th - 62nd postpartum day. Rats received fisetin (25 mg/kg/b.w.), hesperidin (100 mg/kg/b.w.), combination (25 + 100 mg/kg/b.w.) and donepezil (0.1 mg/kg/b.w.) per orally, once daily from 36th - 62nd postpartum day. Results showed that chronic mild hyperhomocysteinemia induced cognitive impairment,increased serum homocysteine, brain acetylcholinesterase, lipid peroxidation,TNF-α, IL-6 and myeloperoxidase levels, decreased brain nitrite, superoxide dismutase, catalase, reduced glutathione, brain-derived neurotrophic factor and mitochondrial respiratory complexes, caused necrotic foci and marked neurodegeneration in cortex and hippocampus regions. Our findings showed that fisetin, hesperidin and combination treatment totally prevented behavioral deficits, increased brain antioxidant and nitrite levels, decreased serum homocysteine, pro-inflammatory biomarkers,lipid peroxidation, cholinergic and mitochondrial dysfunction and histological abberrations.However,fisetin in combination with hesperidin showed b...
Source: PharmaNutrition - Category: Nutrition Source Type: research