文献类型：期刊文献

英文题名：Oxymatrine hydrazone (OMTH) synthesis and its protective effect for rheumatoid arthritis through downregulation of MEK/NF-κB pathway

作者：Zhang, Guangwen[1];Liu, Baojian[1];Zeng, Zhaoyang[1];Chen, Qinghai[1];Feng, Yiyun[1];Ning, Xueqian[1]

第一作者：张广文

通信作者：Liu, BJ[1]

机构：[1]Gansu Univ Chinese Med, Dept Arthroplasty Surg, Affiliated Hosp, 732 Jiayuguan West Rd, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学第二附属医院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Dept Arthroplasty Surg, Affiliated Hosp, 732 Jiayuguan West Rd, Lanzhou 730000, Gansu, Peoples R China.|[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;[10735]甘肃中医药大学;

年份：2021

卷号：36

期号：12

起止页码：2448

外文期刊名：ENVIRONMENTAL TOXICOLOGY

收录：;EI(收录号：20213510834584);Scopus(收录号：2-s2.0-85113718939);WOS:【SCI-EXPANDED(收录号:WOS:000690798700001)】；

语种：英文

外文关键词：cartilage; cytokines; inflammation; pain; rheumatoid arthritis

摘要：Rheumatoid arthritis (RA) is one of the inflammatory diseases detected in more than 1% of the world population. In the present study, oxymatrine hydrazone (OMTH) was synthesized and investigated for treatment of RA in vitro in TNF-alpha induced fibroblast-like synoviocyte cell model. Cell viability and apoptosis were detected using MTT and flow cytometry assays, respectively. ELISA was used for determination of inflammatory cytokines and western blotting for evaluation of protein expression. Pretreatment of HFLS-RA cells with 0.5, 1.0, 1.5, 2.0, and 2.5 mu M doses of OMTH suppressed TNF-alpha induced promotion of proliferative potential in dose-based manner. The OMTH pretreatment of TNF-alpha exposed HFLS-RA cells significantly increased apoptotic cell proportion. In TNF-alpha exposed HFLS-RA cells OMTH pretreatment elevated Bax and suppressed Bcl-2 expression. Treatment of HFLS-RA cells with OMTH prevented TNF-alpha mediated elevation of IL-1 beta, IL-6 and IL-8. Moreover, OMTH treatment of HFLS-RA cells effectively suppressed TNF-alpha mediated elevated levels of MMP-1 and MMP-13. Pretreatment of HFLS-RA cells with OMTH reversed TNF-alpha mediated promotion of iNOS and COX-2 levels. The MEK/1/2 and p65 phosphorylation in TNF-alpha exposed HFLS-RA cells was reduced by OMTH pre-treatment in dose-based manner. Thus, OMTH successfully inhibited TNF-alpha-mediated increased viability of RA synovial cells and activated apoptosis. Pretreatment of TNF-alpha exposed synovial cells with OMTH targeted phosphorylation of MEK/NF-kappa B. Therefore, OMTH may act as potential therapeutic agent for RA treatment.