Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease.It is known that aucubin(AU)exerts anti-in-flammatory activity,but its effects and mechanisms in RA are unclear.This study investigated the anti-inflammatory effects and mech-anisms of AU in vivo and in vitro.Human fibroblast-like synoviocyte cells from patients with RA(HFLS-RA),RAW264.7 cells,and MC3T3-E1 cells were used to evaluate the effects of AU on migration,invasion,apoptosis,osteoclast differentiation and production.Immunofluorescence was used to observe nuclear translocation of nuclear factor(NF)-κB,the double luciferase reporter gene method was used to observe NF-κB-p65 activity in AU-treated MC3T3-E1 cells.RT-qPCR was used to measure expression of bone metabol-ism and inflammation-related genes,and western blot was used to measure bone metabolism and NF-KB protein expression levels.Col-lagen-induced arthritis(CIA)rat model was used for pharmacodynamics study.Arthritis indexes were measured in the ankle and knee,histological staining and Micro-computed tomography were performed on the ankle joints.Also,inflammatory factor gene expression and the levels of NF-κB-related proteins were detected as in vitro.AU effectively inhibited HFLS-RA cell migration and invasion,pro-moted apoptosis,and inhibited RAW264.7 cell differentiation into osteoclasts,as well as inhibited NF-κB-p65 activity in MC3T3-E1 cells.Notably,AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors,effectively inhibited the expression of p-Iκκαβ,p-IKBα,and p-p65 proteins.In vivo,AU relieved joint inflammation,reduced related inflammatory factors,and inhibited NF-KB signaling.It could be used to treat RA-related synovial inflammation and bone de-struction through the NF-κB pathway.

ZHANG Yan;TANG Li-Dong;WANG Jian-Ying;WANG Hao;CHEN Xiao-Yun;ZHANG Lei;YUAN Ying

School of Traditional Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Innovation Center of TCM Health Service,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Key Laboratory of Formulated Chinese Medicines,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Longhua Hospital affiliated to Shanghai University of TCM,Rheumatoid Department,Shanghai 200232,China

中国天然药物

[1]ZHANG Yan;TANG Li-Dong;WANG Jian-Ying;WANG Hao;CHEN Xiao-Yun;ZHANG Lei;YUAN Ying-.Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis)[J].中国天然药物,2022(06):458-472

aucubin,HFLS,metabol

Anti,inflammatory,effects,cellular,animal,models,rheumatoid,arthritis,Rheumatoid,chronic,autoimmune,disease,It,known,that,AU,exerts,anti,activity,but,its,mechanisms,are,unclear,This,study,investigated,vivo,vitro,Human,fibroblast,like,synoviocyte,cells,from,patients,RAW264,MC3T3,E1,were,used,evaluate,migration,invasion,apoptosis,differentiation,production,Immunofluorescence,was,observe,nuclear,translocation,double,luciferase,reporter,method,p65,treated,qPCR,expression,bone,inflammation,related,genes,western,blot,metabolism,levels,Col,lagen,induced,CIA,pharmacodynamics,Arthritis,indexes,measured,ankle,knee,histological,staining,Micro,computed,tomography,performed,joints,Also,proteins,detected,effectively,inhibited,moted,into,osteoclasts,well,Notably,significantly,reduced,three,factors,IKB,In,relieved,signaling,could,be,synovial,struction,through,pathway

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