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

作　　者：Yong Zheng Yan Deng Jian-mei Gao Chun Lv Ling-hu Lang Jing-shan Shi Chang-yin Yu Qi-hai Gong 

机构地区：[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

出　　处：《Acta Pharmacologica Sinica》2020年第2期154-162,共9页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China(Grant No.81560585);the Program for Excellent Young Talents of Zunyi Medical University(Grant No.15zy-002);the Zunyi Medical University Masters Startup Fund(F-758);The"Hundred"Level of High-Level Innovative Talents in Guizhou Province(Grant No.QKHRCPT 20165684);the Education Department of Guizhou Province of China(Grant No.GNYL(2017)006,YLXKJS-YS-06);Shijingshan's Tutor Studio of Pharmacology[GZS-2016(07)];the Program for Changjiang Scholars and Innovative Research Team in University,China(Grant No.IRT_17R113);the 2011 Collaborative Innovation Center of Guizhou Traditional Chinese Medicine and Ethnic Medicine(No.Qianjiaokeyanfa[2012]311).

摘　　要：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 Aβaccumulation.Primary rat astrocytes were pretreated with ICS II(5,10,and 20μM)or dexamethasone(DXMS,1μM)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-αdegradation 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.

关 键 词：icarisideⅡ DEXAMETHASONE ASTROCYTES nuclear factor-kappa B beta secretase 1 Β-AMYLOID neuroinflammation Alzheimer’s disease 

分 类 号：R285[医药卫生—中药学]