Hydroxysafflor Yellow A Induces Apoptosis and Inhibits Inflammatory Cytokine Expression in Rheumatoid Arthritis Synovial Fibroblasts Through the MEK‐ERK Pathway

OBJECTIVE: The objective of this study was to investigate whether hydroxysafflor yellow A (HSYA) affects the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA). Synovial fibroblast hyperplasia is a key pathological feature of RA, and its inhibition may slow disease progression. Although HSYA has attracted significant interest, its effects on RA are not yet fully understood. Thus, we performed a series of experiments to examine the impact of HSYA on FLSs. METHODS: To investigate the effects of HSYA on FLSs, we exposed FLSs to Interleukin-1 beta (IL-1β) and assessed their proliferation via CCK8, scratch, transwell, TUNEL, and flow cytometry assays. Inflammatory cytokine levels were determined by ELISA. The involvement of the MEK-ERK signaling pathway was validated via RT-qPCR and immunofluorescence analyses. RESULTS: Treatment with HSYA significantly inhibited FLSs proliferation, while promoting their apoptosis. Moreover, HSYA altered the expression of the inflammatory cytokines IL-6, IL-10, and TNF-α in FLSs. The anti-inflammatory and anti-proliferative effects of HSYA on FLSs were mediated, at least in part, through the inhibition of the ERK signaling pathway. CONCLUSION: Our findings demonstrate that HSYA induces apoptosis, inhibits proliferation, and suppresses the production of inflammatory cytokines in FLSs via the ERK/MEK signaling pathway. These findings suggest that HSYA has potential therapeutic value in the treatment of RA and warrants further investigation.