Article

Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway

Authors: Yong Zheng1,2, Yan Deng1, Jian-mei Gao1,2, Chun Lv2, Ling-hu Lang1, Jing-shan Shi2, Chang-yin Yu3, Qi-hai Gong1,2
1 Department of Clinical Pharmacotherapeutics of School of Pharmacy, Zunyi Medical University, Zunyi 563000, China
2 Department of Pharmacology, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China
3 Department of Neurology, the Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China
Correspondence to: Chang-yin Yu: yuchangyin6812@126.com, Qi-hai Gong: gqh@zmu.edu.cn,
DOI: 10.1038/s41401-019-0300-2
Received: 15 May 2019
Accepted: 16 August 2019
Advance online: 25 September 2019

Abstract

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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-κB 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 IκB-α degradation and NF-κB 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

Keywords: icariside II; dexamethasone; astrocytes; nuclear factor-kappa B; beta secretase 1; β-amyloid; neuroinflammation; Alzheimer’s disease

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