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作 者:ZHANG Yan TANG Li-Dong WANG Jian-Ying WANG Hao CHEN Xiao-Yun ZHANG Lei YUAN Ying
机构地区:[1]School of Traditional Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [2]Shanghai Innovation Center of TCM Health Service,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [3]Shanghai Key Laboratory of Formulated Chinese Medicines,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [4]Shanghai Longhua Hospital affiliated to Shanghai University of TCM,Rheumatoid Department,Shanghai 200232,China
出 处:《Chinese Journal of Natural Medicines》2022年第6期458-472,共15页中国天然药物(英文版)
基 金:This work was supported by the Natural Science Foundation of China(No.81773922);Shanghai Natural Science Foundation(No.19ZR1452000).
摘 要:Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease.It is known that aucubin(AU)exerts anti-inflammatory activity,but its effects and mechanisms in RA are unclear.This study investigated the anti-inflammatory effects and mechanisms 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)-/cB,the double luciferase reporter gene method was used to observe NF-/cB-p65 activity in AU-treated MC3T3-E1 cells.RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes,and western blot was used to measure bone metabolism and NF-a:B protein expression levels.Collagen-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-/cB-related proteins were detected as in vitro.AU effectively inhibited HFLS-RA cell migration and invasion,promoted apoptosis,and inhibited RAW264.7 cell differentiation into osteoclasts,as well as inhibited NF-/cB-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-lKKafi,p-lA:Ba,and p-p65 proteins.In vivo,AU relieved joint inflammation,reduced related inflammatory factors,and inhibited NF-/cB signaling.It could be used to treat RA-related synovial inflammation and bone destruction through the NF-/cB pathway.
关 键 词:AUCUBIN Collagen-induced arthritis Synovial inflammation Bone erosion NF-/cB signaling pathway
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