β-amyloid (Aβ) is one of the inducing factors of astrocytes activation and neuroinflammation,and it is also a crucial factor for the development of Alzheimer’s disease (AD).Icariside Ⅱ (ICS Ⅱ) is an active component isolated from a traditional Chinese herb Epimedium,which has shown to attnuate lipopolysaccharide (LPS)-induced neuroinflammation through regulation of NF-KB signaling pathway.In this study we investigated the effects of ICS Ⅱ on LPS-induced astrocytes activation and Aβ accumulation.Primary rat astrocytes were pretreated with ICS Ⅱ (5,10,and 20 μM) or dexamethasone (DXMS,1 μM) for 1 h,thereafter,treated with LPS for another 24 h.We found that ICS Ⅱ pretreatment dose dependently mitigated the levels of tumor necrosis factor-alpha (TNF-α),interleukin-1 beta (IL-1β),inducible nitric oxide synthase (iNOS),cyclooxygenase-2 (COX-2) in the astrocytes.Moreover,ICS Ⅱ not only exerted the inhibitory effect on LPS-induced IKB-α degradation and NF-KB activation,but also decreased the levels of Aβ1-40,Aβ1-42,amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes.Interestingly,molecular docking revealed that ICS Ⅱ might directly bind to BACE1.It is concluded that ICS Ⅱ has potential value as a new therapeutic agent to treat neuroinflammation-related diseases,such as AD.