摘要Objective:The objective of this study was to explore the therapeutic effects of kaempferol(Kae)on rheumatoid arthritis(RA)and to elucidate the underlying mechanisms.Methods:The collagen-induced arthritis(CIA)model was established using collagen Ⅱ to induce RA.Mice were treated with Kae at a dose of 25 or 50 mg/kg/day via gavage.Pathological changes in the ankle joint were analyzed.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of inflammatory factors.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was used to assess the expression of genes associated with the balance of regulatory T(Treg)/T helper 17(Th 17)cells.Flow cytometry was utilized to determine the Treg/Th17 ratio.Furthermore,these techniques were employed to evaluate the impact of miR-34a and Foxp3 dysregulation on cellular functions in RA under the influence of Kae.Dual luciferase reporter assay was conducted to analyze the binding of miR-34a to Foxp3.Results:Treatment with Kae led to a downregulation of receptor-related orphan receptor gamma t(RORγt)and IL-17 expression,and an upregulation of Foxp3,IL-10,and TGF-β expression in CIA mice.Kae intervention inhibited the production of proinflammatory cytokines and increased the production of anti-inflammatory cytokines.Furthermore,Kae treatment suppressed the expression of miR-34a,which was identified as a target of miR-34a.Finally,Kae regulated Treg/Th 17 balance-related genes and cellular inflammation through the miR-34a/Foxp3 axis.Conclusion:The study demonstrated that Kae effectively ameliorates CIA in mice by modulating the Treg/Th17 balance and related genes via the miR-34a/Foxp3 axis.These findings suggest that Kae may serve as a promising therapeutic agent for the treatment of RA and for restoring immune homeostasis.