Cucurbitacin B inhibits Th17 cell differentiation via the suppression of the JAK/STAT pathway and alleviates collagen-induced arthritis in mice

  • Int J Immunopathol Pharmacol. 2025 Jan-Dec:39:3946320251348715. doi: 10.1177/03946320251348715.
Shu-Ping Kung  1  2 ,  Hira Umbreen  2 ,  Jou-Hsuan Wang  3 ,  Chih-Ming Tsia  4 ,  Tim Chi-Chen Lin  1  5  6  7  8 ,  Yu-Ting Chen  9
Affiliations
  • 1. Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taiwan, China, R.O.C.
  • 2. Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan, China, R.O.C.
  • 3. Department of Physical Medicine and Rehabilitation, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, China, R.O.C.
  • 4. Division of Infectious Diseases, Department of Pediatrics, University of California, La Jolla, CA, USA, R.O.C.
  • 5. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, China, R.O.C.
  • 6. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, China, R.O.C.
  • 7. Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, China, R.O.C.
  • 8. The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, China, R.O.C.
  • 9. Graduate Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan, China, R.O.C.
PMID: 40518910 DOI: 10.1177/03946320251348715
Abstract

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited treatment options and associated side effects or resistance. This study aims to investigate the therapeutic potential of the natural compound cucurbitacin B (CuB) in RA treatment.

Methods: We utilized a collagen-induced arthritis (CIA) mouse model to evaluate the effects of CuB. Arthritis scores, histological damage, and pro-inflammatory cytokine expression (TNF-α, IL-17A) were assessed. In addition, network pharmacology analysis was performed to explore CuB's molecular mechanisms, focusing on Th17 cell differentiation, IL-17 signaling, and the JAK-STAT pathway.

Results: CuB significantly reduced arthritis severity, decreased histological damage, and lowered the expression of pro-inflammatory cytokines in CIA mice. CuB was found to inhibit STAT3 phosphorylation and reduce the proportion of Th17 cells in the spleen, indicating its potential anti-inflammatory effects.

Conclusion: These findings suggest that cucurbitacin B may serve as a promising novel therapeutic agent for rheumatoid arthritis by targeting key inflammatory pathways.

Keywords
JAK/STAT pathway; Th17 cell differentiation; anti-inflammatory therapy; cucurbitacin B; rheumatoid arthritis (RA).
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