Your new experience awaits. Try the new design now and help us make it even better

REVIEW article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1651763

This article is part of the Research TopicSentinels of the Immune System: Tissue-Resident Macrophages in the Battle Against Infection and AutoimmunityView all 5 articles

Modulating M1/M2 Macrophage Polarization with plant metabolites: A Therapeutic Strategy for Rheumatoid Arthritis

Provisionally accepted
  • 1Heilongjiang University of Chinese Medicine, Harbin, China
  • 2Lanzhou University First Hospital, Lanzhou, China
  • 3First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China

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

Rheumatoid arthritis (RA) is a systemic autoimmune disorder marked by persistent synovitis and the degradation of joint cartilage and surrounding bone due to inflammation. A variety of immune cells, particularly macrophages, are involved in the initiation and maintenance of inflammation in RA, along with leukocyte adhesion and migration, matrix breakdown, and neovascularization. Environmental and internal stimuli drive macrophages to polarize into two major phenotypes: M1, which exerts strong bactericidal effects and contributes to chronic inflammation and tissue injury, and M2, which inhibits inflammation and facilitates tissue repair. The dysregulation of M1/M2 macrophage polarization is a key contributor to the pathogenesis and disease progression of RA. Plant metabolites are typically characterized by multi-component, multi-target, and multi-pathway actions, and their underlying mechanisms may include regulation of immune function, especially the balance of macrophage polarization. Current evidence indicates that such metabolites may provide certain therapeutic benefits and a relatively manageable safety profile in the management of RA and related disorders. In this review, we summarize the potential mechanisms by which various plant metabolites modulate macrophage function and polarization under inflammatory conditions, providing evidence for their clinical application in RA treatment and offering new insights into precision therapy for RA.

Keywords: Plant metabolite, Macrophage polarization, Rheumatoid arthritis, Mechanism, TraditionalChinese Medicine

Received: 22 Jun 2025; Accepted: 10 Oct 2025.

Copyright: © 2025 Yang, Wang, Kong, Pan, Yang, Zhang and Li. 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: Zeguang Li, hljzy_lzg@163.com

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.