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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1435274

Morinda officinalis iridoid glycosides, as an inhibitor of GSK-3β, alleviates rheumatoid arthritis through inhibition of NF-κB and JAK2/STAT3 pathway

Provisionally accepted
Yi Shen Yi Shen 1Ronghua Bao Ronghua Bao 1Xinyuan Ye Xinyuan Ye 1Heming Li Heming Li 1Yiqi Sun Yiqi Sun 1Qiuru Ren Qiuru Ren 1Jinman Du Jinman Du 1Tianwen Ye Tianwen Ye 2Quanlong Zhang Quanlong Zhang 1Qiming Zhao Qiming Zhao 1Ting Han Ting Han 3*Luping Qin Luping Qin 1*Qiao-YAN Zhang Qiao-YAN Zhang 1*
  • 1 Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 2 Department of Orthopedic Surgery, Shanghai Changzheng Hospital, Huangpu, Shanghai Municipality, China
  • 3 Second Military Medical University, Shanghai, China

The final, formatted version of the article will be published soon.

    Morinda officinalis iridoid glycosides (MOIG) showed potential benefits in the treatment of rheumatoid arthritis (RA), but their exact mechanism has yet to be explored. In this study, we evaluated the effects of MOIG on RA, and explored the potential targets and molecular mechanism of MOIG in RA. The results showed that MOIG significantly alleviated the paw swelling and synovial hyperplasia in type II collagen-induced arthritis (CIA) rats. Moreover, MOIG suppressed proliferation, migration and invasion, the secretion of inflammatory factors, and the expression of adhesion related proteins in tumor necrosis factor (TNF)-α-stimulated fibroblast-like synoviocytes (FLSs). MOIG also inhibited the activation of Janus activating kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB) signaling pathway in FLSs. Interestingly, the plant metabolites in MOIG had a good affinity with glycogen synthase kinase-3β (GSK-3β), and inhibition of GSK-3β attenuated the effects of MOIG on FLSs.Knockdown GSK-3β gene could inhibit the paw swelling and inflammatory indicators, decrease the arthritis score and synovial hyperplasia, reduce the phosphorylation of p65 and STAT3 in AA mice, thereby suppressing the NF-κB and STAT3 signaling activation, and MOIG treatment had no significant effects on adjuvant induced arthritis (AA) mice with si-GSK-3β. The results suggested that MOIG alleviates joint inflammation in RA through inhibition NF-κB and JAK2/STAT3 pathway via suppression of GSK-3β in FLSs, which provides supports for MOIG as a promising therapeutic agent of RA.

    Keywords: Morinda officinalis iridoid glycosides, Rheumatoid arthritis, Fibroblast-like synoviocytes, Type II collagen-induced arthritis, adjuvant induced arthritis

    Received: 24 May 2024; Accepted: 26 Sep 2024.

    Copyright: © 2024 Shen, Bao, Ye, Li, Sun, Ren, Du, Ye, Zhang, Zhao, Han, Qin and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ting Han, Second Military Medical University, Shanghai, China
    Luping Qin, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang Province, China
    Qiao-YAN Zhang, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.