Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion

Alzheimer's disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NF kappa B mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.