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.