Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/I?B/NF-?B/BACE1 signaling pathway.
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ABSTRACT: ?-amyloid (A?) 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-?B signaling pathway. In this study we investigated the effects of ICS II on LPS-induced astrocytes activation and A? accumulation. Primary rat astrocytes were pretreated with ICS II (5, 10, and 20??M) or dexamethasone (DXMS, 1??M) 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-?), interleukin-1 beta (IL-1?), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in the astrocytes. Moreover, ICS II not only exerted the inhibitory effect on LPS-induced I?B-? degradation and NF-?B activation, but also decreased the levels of A?1-40, A?1-42, 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.
SUBMITTER: Zheng Y
PROVIDER: S-EPMC7470889 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
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