Isorhynchophylline ameliorates the progression of osteoarthritis by inhibiting the NF-?B pathway

作者全名："Li, Zhenyu; Shi, Huasong; Li, Yanmei; Wang, Wang; Li, Zhexi; Chen, Biao; Nie, Daibang"

作者地址："[Li, Zhenyu; Shi, Huasong; Chen, Biao] Wuhan Univ, Dept Orthoped Surg, Div Joint Surg & Sports Med, Zhongnan Hosp, Wuhan 430071, Peoples R China; [Li, Yanmei; Wang, Wang; Nie, Daibang] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing 400016, Peoples R China; [Li, Yanmei; Wang, Wang; Nie, Daibang] Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immu, Chongqing 400016, Peoples R China; [Li, Zhexi] Xinxiang Med Univ, Affiliated Hosp 1, Dept Cardiol, Weihui 453100, Peoples R China"

通信作者："Nie, DB (通讯作者)，Dept Immunol, 1 Yixueyuan Rd, Yuzhong Dist 400016, Peoples R China.; Chen, B (通讯作者)，Wuhan Univ, Zhongnan Hosp, Dept Orthoped Surg, Wuhan 430071, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000798079300003

JCR分区：Q1

影响因子：5

年份：2022

卷号：924

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Osteoarthritis; Chondrocyte; Isorhynchophylline

摘要："Osteoarthritis (OA), a progressive and degenerative joint disease, is characterized by cartilage degradation, synovitis, subchondral bone remodeling and osteophyte formation. Isorhynchophylline (IRN) is an oxindole alkaloid isolated from the traditional Chinese herb Uncaria rhynchophylla. In this study, we evaluated the protective effects of IRN on human OA chondrocytes. IRN treatment dose-dependently decreased the interleukin-1 beta (IL-1 beta)-induced expressions of nitric oxide (NO; p < 0.001), prostaglandin E2 (PGE2; p < 0.001), tumor necrosis factor alpha (TNF-alpha; p < 0.001), interleukin-6 (IL-6; p < 0.001), cyclooxygenase-2 (COX-2; p < 0.001) and inducible nitric oxide synthase (iNOS; p < 0.001) in chondrocytes. Meanwhile, the production of metalloproteinase 13 (MMP13; p < 0.001) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5; p < 0.001) was inhibited by IRN treatment. Molecular docking studies revealed that IRN directly interacted with the nuclear factor kappa B (NF-kappa B) complex, which was associated with a reduced level of NF-kappa B nuclear translocation and the inhibition of NF-kappa B signaling activity. Furthermore, administration of IRN generated marked in vivo protective effects during OA development. Collectively, our results demonstrate that IRN may exhibit therapeutic benefits against OA, potentially by ameliorating the inflammative and degenerative progression of OA via inhibiting the NF-kappa B pathway."

基金机构：Natural Science Foundation of China [81871779]

基金资助正文：Funding This work was supported by the Natural Science Foundation of China (81871779) .