Background:Beta-amyloid(Aβ)deposition,associated neuronal apoptosis and neuroinflammation are considered as important factors leading to cognitive deficits in Alzheimers disease(AD). Icariside Ⅱ(ICS Ⅱ),an active flavonoid compound derived from Epimedium brevicum Maxim,has been extensively used to treat erectile dysfunction,osteoporosis and dementia. Recently, ICS Ⅱ attracts great interest due to its broad-spectrum anti-cancer property. ICS Ⅱ shows an anti-inflammatory potential both in cancer treatment and cerebral ischemia-reperfusion. It is not yet clear whether the anti-inflammatory effect of ICS Ⅱ could delay progression of AD. Therefore, the current study aimed to investigate the effects of ICS Ⅱ on the behavioral deficits,Aβ levels, neuroinflammatory responses and apoptosis in Aβ25-35 treated rats. Methods:Rats subjected to bilateral hippocampal injection of Aβ25-35 or normal saline were administered with ICS Ⅱ 20 mg·kg-1 or vehicle once a day for consecutive 15 days. Leing and memory function was evaluated using Morris water maze. The neuronal morphology in hippocampus was examined by HE staining and Nissl staining, respectively. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay. The activation of microglia and astrocytes were analyzed by immunohistochemistry. The expression of interleukin-1β(IL-1β),cyclooxygenase-2(COX-2),tumor necrosis factor-α(TNF-α)and inducible nitric oxide synthase(iNOS)were detected by quantitative real-time polymerase chain reaction(qRT-PCR)and West blot. The expression of caspase-3,Bax and Bcl-2 and the content of beta-amyloid were measured by West blot. Results:Rats treated with Aβ25-35 displayed cognitive impairment,neuronal damage,along with the increase of Aβ,inflammation and apoptosis in the hippocampus. However,treatment with ICS Ⅱ 20 mg·kg-1 could improve the cognitive deficits,ameliorate neuronal death,and reduce the levels of Aβin the hippocampus. Furthermore,ICSⅡ could suppress microglial and astrocytic activation,inhibit expression of IL-1b,TNF-a,COX-2, and iNOS mRNA and protein,and attenuate the Aβinduced Bax/Bcl-2 ratio elevation and caspase-3 activation. Conclusions:These findingssuggest that ICS Ⅱ couldreverse Aβ-induced cognitive deficits,possibly via the inhibition of neuroinflammation and apoptosis,which suggested a potential protective effect of ICS Ⅱ on AD.