8-Shogaol, a natural compound derived from Zingiber officinale, ameliorates rheumatoid arthritis by targeting TAK1

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by inflammation of the synovial membrane and progressive joint damage [ 1 ]. Without proper treatment, it can lead to permanent joint destruction and reduced life expectancy. Despite advancements in understanding RA pathogenesis and the development of new therapies, many patients still fail to achieve remission and continue to suffer from functional decline [ 2 ]. Fibroblast-like synoviocytes (FLS), which play a central role in RA progression, have emerged as a promising therapeutic target [ 3 ]. To discover compounds that can effectively suppress FLS-driven inflammation, 315 natural extracts were screened for their ability to inhibit IL-17-induced IL-6 production. Among these, Zingiber officinale showed the most promising results. Further investigation identified 8-shogaol as the active compound responsible for this effect. 8-Shogaol significantly reduced inflammation and cell migration triggered by TNF-α, IL-1β, and IL-17 in FLS derived from RA patients as well as in a 3D synovial culture model. Mechanistically, 8-shogaol directly inhibited TAK1, leading to suppression of downstream IKK, Akt, and MAPK signaling pathways. In vivo, treatment with 8-shogaol reduced paw swelling, improved gait, and restored joint structure in adjuvant-induced arthritis (AIA) rats, while also lowering inflammatory markers in the affected joints. Overall, this study identifies 8-shogaol as a novel anti-RA agent that targets TAK1 to alleviate synovial inflammation and joint pathology. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany