Abstract P332: Hesperidin in Citrus Fruit Juice Plays a Role in Preventing Cognitive Impairment Induced by Ischemic Brain Damage

Abstract

Recently we reported that drinking Citrus iyo juice (CI) inhibited more effectively vascular remodeling in the inflammation-induced vascular injury mouse model than Citrus unshiu juice (CU). These results led us to explore the possibility that citrus fruits juice drinking could attenuate cognitive decline in transient cerebral ischemia mouse model, focusing on the effects of flavanone, hesperidin, which is more abundantly contained in CI compared with CU and has antioxidant activity. 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. Morphological changes in the hippocampus were examined. Administration of CI, CU or hesperidin did not influence systolic blood pressure, body weight and brain weight. Cognitive function was significantly impaired (sham, 71% (16 of 23) vs BCCAO, 55% (14 of 27) in Y maze) with the increase in superoxide anion production after BCCAO. The cognitive impairment was more effectively attenuated by the administration of CI than CU (CI, 66% (13 of 23); CU, 61% (17 of 27)) with the significant increase in CBF. Interestingly, we also observed that the treatment with hesperidin significantly prevented cognitive decline (67% (13 of 21)) after BCCAO. The increase in superoxide anion production 24 hours after BCCAO (expressed as fold-increase compared to sham) was attenuated by CI or hesperidin, not by CU (BCCAO, 4.0; CI, 1.2; hesperidin, 1.1; CU, 3.0). The fold-increase in TNF-α mRNA in the hippocampus 24 hours after BCCAO was prevented by hesperidin (BCCAO 5.0; hesperidin, 2.8). Cell number in CA1 region of hippocampus decreased in BCCAO-operated mice. Hesperidin treatment attenuated this decrease (sham, 163±5; BCCAO, 136±4; hesperidin, 154±4). 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.