ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1615519
Xuetongsu Attenuates Synovial Inflammation in Rheumatoid Arthritis by Inhibiting the IL-23/IL-17/NF-κB Inflammatory Axis
Provisionally accepted
- Hunan University of Chinese Medicine, Changsha, China
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Persistent synovial hyperplasia, a hallmark of rheumatoid arthritis (RA), can lead to joint deformities. During the pathogenesis of RA, the expression of IL-23 promotes Th17 cell proliferation and IL-17 production, which in turn upregulates TNF-α, IL-1β, and RANKL in RA fibroblast-like synovial cells (RAFLS), forming the IL-23/IL-17/NF-κB inflammatory signaling axis, which further exacerbates synovial inflammation and joint destruction. Therefore, inhibiting the IL-23/IL-17/NF-κB inflammatory signaling axis may help alleviate synovial inflammation and could be a promising approach for treating RA. In our previous studies, we found a natural antiinflammatory active component, Xuetongsu, which is the active ingredient in the Chinese Tujia ethnomedicine Xuetong, and it has shown significant effects in inhibiting the inflammatory proliferation of RAFLS. In this study, we will establish RAFLS models and adjuvant-induced arthritis (AIA) animal models, with silencing or overexpression of IL-23, to investigate whether Xuetongsu can target and inhibit the IL-23 protein, thereby impairing the IL-23/IL-17/NF-κB inflammatory signaling axis.The findings indicated that Xuetongsu exerted no notable influence on downstream molecular pathways such as IL-17 and NF-κB in RAFLS cells with silenced IL-23.However, in RAFLS cells with overexpressed IL-23 and in the RA rats model, Xuetongsu exhibited a clear inhibitory effect on the downstream factors, which demonstrated a certain dose-dependent relationship. These findings suggest that XTS targets IL-23 to inhibit the IL-23/IL-17/NF-κB axis, offering new insights into RA treatment. This study provides the first evidence that the natural product XTS exerts anti-inflammatory effects in RA by specifically targeting IL-23. Our findings reveal its molecular mechanism and establish a novel paradigm for developing IL-23-targeted RA therapies, advancing traditional medicine modernization.
Keywords: Rheumatoid arthritis, Xuetongsu, Synovial inflammation, IL-23, IL-23/IL-17/NF-κB inflammatory signaling axis, RAFLS cell
Received: 21 Apr 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Chen, Deng, Zheng, Li, Yang, Huang, Yuan, Wang, Wang and Yu. 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:
Wei Wang, Hunan University of Chinese Medicine, Changsha, China
Huanghe Yu, Hunan University of Chinese Medicine, Changsha, China
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