The present study was designed to explore the mechanism of
hesperidin action via the
nitric oxide pathway in the protection against ischemic reperfusion cerebral injury-induced memory dysfunction. Male Wistar rats (200-220 g) were subjected to bilateral carotid artery occlusion for 30 min followed by 24 h reperfusion.
Hesperidin (50 and 100 mg/kg, po) pretreatment was given for 7 days before animals were subjected to cerebral I/R injury. Various behavioral tests (rotarod performance and memory retention), biochemical parameters (lipid peroxidation,
nitrite concentration,
glutathione levels,
superoxide dismutase activity and
catalase activity), mitochondrial complex
enzyme dysfunctions (complex I, II, III and IV) and histopathological alterations were subsequently assessed in hippocampus. Seven days of
hesperidin (50 and 100 mg/kg) treatment significantly improved neurobehavioral alterations (delayed fall off time and increased memory retention), oxidative defense and mitochondrial complex
enzyme activities in hippocampus compared to control (I/R) animals. In addition,
hesperidin treatment significantly attenuated histopathological alterations compared to control (I/R) animals.
L-arginine (100 mg/kg) pretreatment attenuated the protective effect of the lower dose of
hesperidin on memory behavior, biochemical and
mitochondrial dysfunction compared with
hesperidin alone. However,
L-NAME pretreatment significantly potentiated the protective effect of
hesperidin. The present study suggests that the
L-arginine-NO signaling pathway is involved in the protective effect of
hesperidin against cerebral I/R-induced memory dysfunction and biochemical alterations in rats.