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Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review)

  • Authors:
    • Wenjie Hu
    • Rui Li
    • Zhongming Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Chengdu Xindu District Second People's Hospital, Chengdu, Sichuan 610501, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 46
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    Published online on: November 20, 2025
       https://doi.org/10.3892/mmr.2025.13756
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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology remains incompletely understood. As the proposal and progress of the ‘mucosal origin hypothesis’, the role of the ‘gut‑joint axis’ mechanism in the pathological process of RA is gradually being revealed. Changes in the intestinal microbiota, damage to the mucosal barrier, mucosal immune dysfunction and disorders of microbial‑derived metabolites all regulate the occurrence and development of RA. Natural compounds, bioactive entities isolated from natural sources, have demonstrated distinct therapeutic advantages across a broad spectrum of diseases. The intestine may be the key for these compounds to exert their therapeutic effects on diseases. The present review summarized the ‘gut‑joint axis’ in RA and the natural compounds that exert therapeutic effects via this pathway. It emphasized that improving intestinal microecology may be a potential treatment method for RA, and natural compounds are expected to become promising treatment strategies for RA in this way. However, there are still numerous problems that need to be urgently solved to complete the clinical transformation of these natural compounds.2
View Figures

Figure 1

The ‘gut-joint axis’ mechanism in RA.
Changes in the gut, such as the microbiota and mucosal
permeability, may be potential mechanisms that promote the
occurrence and progression of RA. RA, rheumatoid arthritis.

Figure 2

Natural compounds for the treatment
of RA based on the ‘gut-joint axis’. RA, rheumatoid arthritis; TPG,
total polysaccharide and glycoside; THH, Tripterygium
hypoglaucum (Levl.) Hutch.
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Copy and paste a formatted citation
Spandidos Publications style
Hu W, Li R and Zhang Z: Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review). Mol Med Rep 33: 46, 2026.
APA
Hu, W., Li, R., & Zhang, Z. (2026). Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review). Molecular Medicine Reports, 33, 46. https://doi.org/10.3892/mmr.2025.13756
MLA
Hu, W., Li, R., Zhang, Z."Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review)". Molecular Medicine Reports 33.1 (2026): 46.
Chicago
Hu, W., Li, R., Zhang, Z."Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review)". Molecular Medicine Reports 33, no. 1 (2026): 46. https://doi.org/10.3892/mmr.2025.13756
Copy and paste a formatted citation
x
Spandidos Publications style
Hu W, Li R and Zhang Z: Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review). Mol Med Rep 33: 46, 2026.
APA
Hu, W., Li, R., & Zhang, Z. (2026). Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review). Molecular Medicine Reports, 33, 46. https://doi.org/10.3892/mmr.2025.13756
MLA
Hu, W., Li, R., Zhang, Z."Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review)". Molecular Medicine Reports 33.1 (2026): 46.
Chicago
Hu, W., Li, R., Zhang, Z."Natural compounds for the treatment of rheumatoid arthritis based on the ‘gut‑joint axis’ (Review)". Molecular Medicine Reports 33, no. 1 (2026): 46. https://doi.org/10.3892/mmr.2025.13756
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