Abstract P447: Hesperidin, Ingredient of Citrus Fruits Juice, Attenuates Cognitive Impairment Induced by Ischemic Brain Damage

Abstract

Objectives: We 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). We aim 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: 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. Cognitive function was determined by Y-maze task 2 weeks after BCCAO (the number of alternations/total arm entry). Cerebral blood flow (CBF) was measured by a laser speckle flowmetry. Cerebral superoxide anion production 24 hours after BCCAO was measured by dihydroethidium staining and depicted as arbitrary unit of intensity vs control. mRNA levels were measured by quantitative real-time RT-PCR. Results: Cognitive function was impaired with the increase in superoxide anion production after BCCAO (71% (16 of 23) vs 55% (14 of 27) in Y maze). The cognitive impairment was more effectively attenuated by the administration of CI with the significant increase in CBF than CU (CI, 66% (13 of 23); CU, 61% (17 of 27)). Interestingly, we observed that the treatment with hesperidin significantly prevented cognitive decline (67% (13 of 21)) after BCCAO with the increase in CBF. Administration of CI, CU or hesperidin did not influence systolic blood pressure, body and brain weight. Superoxide anion production was attenuated by CI or hesperidin, not by CU (BCCAO, 4.0; CI, 1.2; hesperidin, 1.1; CU, 3.0). The increases in mRNA levels of NADPH oxidase subunit such as p22 and p47, and TNFα in the cortex of the brain after BCCAO seemed to be prevented by hesperidin. AT1, AT2, and Mas receptor mRNA levels in the brain cortex did not differ among these groups. Conclusion: Taken together, these results suggest that the intake of hesperidin in CI should prevent cognitive decline after brain ischemia at least in part due to reduction of oxidative stress and an increase in CBF.