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Furthermore, RA imposes a substantial economic burden on healthcare systems globally. Current clinical treatments primarily consist of non\u2010steroidal anti\u2010inflammatory drugs, glucocorticoids, and disease\u2010modifying antirheumatic drugs, which effectively control symptoms and delay joint damage. However, achieving a complete cure remains a considerable challenge. Consequently, therapeutic strategies aimed at joint protection and the prevention of systemic complications have become central to research efforts. Spermidine (SPD), a naturally occurring polyamine in the human body, has garnered significant attention due to its multifaceted effects as anti\u2010aging, cardiovascular protection, neuroregulation, and anti\u2010inflammation. Notably, SPD has shown significant therapeutic effects in mouse models of various inflammatory diseases, including inflammatory bowel disease, psoriasis, osteoarthritis and RA. The exploration of the role of SPD in RA may provide new targets and effective therapeutic approaches for the treatment of RA. This review provided a comprehensive overview of the potential mechanisms of SPD in the pathological progression of RA, including the inhibition of inflammatory cytokines expression, reduction of oxidative stress, modulation of immune cell functions, and maintenance of bone metabolism homeostasis. Through these mechanisms, SPD shows potential as a promising novel candidate for RA therapy. However, its precise efficacy and safety must be validated through large\u2010scale clinical trials. This article aimed to provide theoretical insights and future research directions for understanding the pathological mechanisms of RA and developing novel therapeutic agents.<\/jats:p>","DOI":"10.1111\/1756-185x.70610","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T12:01:21Z","timestamp":1774008081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic Potential of Spermidine in Rheumatoid Arthritis: Mechanisms and Future Directions"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5817-8131","authenticated-orcid":false,"given":"Yi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University  Changsha 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