N-acetyldopamine dimer inhibits neuroinflammation through the TLR4/NF-κB and NLRP3/Caspase-1 pathways

查看全文 作　　者：Lijun [1]Huang;Leiqiang [1]Gong;Xueyan [1]Huo;Lirong [1]Lei;Qi [1]Zhang;Yunjie [1]Hu;Qixuan [1]Kuang;Yu [1]Gui;Yifei [2]Dai;Yucheng [3]Gu;Yun [1]Deng;Dong [1]Wang;Dale [1]Guo

机构地区：[1]State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;[2]Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing 100084,China;[3]Syngenta Jealott’s Hill International Research Centre,Berkshire RG426EY,UK

出　　处：《Acta Biochimica et Biophysica Sinica》索引2023年第55卷第1期,共11页

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.82172723,81673460,and U19A2011);the Science and Technology Plan of Inner Mongolia Autonomous Region(No.201802115);the Department of Science and Technology of Sichuan Province(No.2021ZYD0079);the Chengdu University of Traditional Chinese Medicine(Nos.CZYJC1905,2020XSGG016,2020JCRC006,SKL2021-19,and SKL2021-42);the Experimental Formulary Sichuan Youth Science and technology Innovation research team(No.2020JDTD0022);the National Interdisciplinary Innovation Team of Traditional Chinese Medicine(No.ZYYCXTD-D-202209). 摘　　要：Neuroinflammation mediated by microglia is an important pathophysiological mechanism in neurodegenerative diseases.However,there is a lack of effective drugs to treat neuroinflammation.N-acetyldopamine dimer(NADD)is a natural compound from the traditional Chinese medicine Isaria cicada.In our previous study,we found that NADD can attenuate DSS-induced ulcerative colitis by suppressing the NF-κB and MAPK pathways.Does NADD inhibit neuroinflammation,and what is the target of NADD?To answer this question,lipopolysaccharide(LPS)-stimulated BV-2 microglia was used as a cell model to investigate the effect of NADD on neuroinflammation.Nitric oxide(NO)detection,reactive oxygen species(ROS)detection and enzyme-linked immunosorbent assay(ELISA)results show that NADD attenuates inflammatory signals and proinflammatory cytokines in LPS-stimulated BV-2 microglia,including NO,ROS,tumor necrosis factor(TNF)-α,interleukin(IL)-1βand interleukin-6(IL-6).Western blot analysis show that NADD inhibits the protein levels of Toll-like receptor 4(TLR4),nuclear factor kappa-B(NF-κB),NOD-like receptor thermal protein domain associated protein 3(NLRP3),ASC and cysteinyl aspartate specific proteinase(Caspase)-1,indicating that NADD may inhibit neuroinflammation through the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathways.In addition,surface plasmon resonance assays and molecular docking demonstrate that NADD binds with TLR4 directly.Our study reveals a new role of NADD in inhibiting the TLR4/NF-κB and NLRP3/Caspase-1 pathways,and shows that TLR4-MD2 is the direct target of NADD,which may provide a potential therapeutic candidate for the treatment of neuroinflammation. 关键词：N-acetyldopamine dimer NEUROINFLAMMATION TLR4/NF-κB pathway NLRP3/Caspase-1 pathway surface plasmon resonance assay

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N-acetyldopamine dimer inhibits neuroinflammation through the TLR4/NF-κB and NLRP3/Caspase-1 pathways

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