Abstract TP423: Hesperidin in Citrus Fruits Juice Improves Brain Ischemia-Induced Cognitive Impairment

Abstract

Introduction: We recently reported that drinking Citrus iyo juice (CI) inhibited more effectively vascular remodeling in inflammation-induced vascular injury mouse model than Citrus unshiu juice (CU) (PLoS One. 2015). These results led us to explore the possibility that citrus fruits juice drinking could attenuate cognitive decline in transient cerebral ischemia model, focusing on the effects of flavanone, hesperidin, which is more abundantly contained in CI compared with CU and has antioxidant activity. Methods: Eight-week-old male C57BL/6 mice were administrated 10 % CI or CU in drinking water or 100 mg/kg/day hesperidin orally by gavage. Two weeks after administration, brain ischemia was induced by bilateral common carotid artery occlusion (BCCAO) for 18 minutes. The Y maze task was performed 2 weeks after BCCAO operation. After cognitive task, cerebral blood flow (CBF) was measured by a laser speckle flowmetry. Cerebral superoxide anion production 24 hours after BCCAO was measured by dihydroethidium (DHE) staining. mRNA levels were measured by quantitative real-time RT-PCR. Results: Administration of CI, CU or hesperidin did not influence systolic blood pressure, bodyweight and brain weight. Cognitive function was impaired with the increase in superoxide anion production after BCCAO. The cognitive impairment was more effectively attenuated by the administration of CI with the significant increase in CBF than sham group. Interestingly, we also observed that the treatment with hesperidin significantly prevented cognitive decline after BCCAO. Superoxide anion production determined by DHE was attenuated by CI or hesperidin, not by CU. The increases in mRNA levels of tumor necrosis factor (TNF)-α in the brain of the brain 24 hours after BCCAO was prevented by hesperidin. Two weeks after BCCAO, expression of mRNA of NADPH oxidase subunits in the brain tended to decrease in treatment with hesperidin. AT1, AT2 and Mas receptor mRNA expression in the brain did not differ among three groups. Conclusion: These results suggest that the intake of hesperidin in citrus fruits juice should prevent cognitive decline after brain ischemia at least in part due to reduction of oxidative stress, inflammatory cytokine and an increase in CBF.