Total glucosides of peony induce fibroblast-like synovial apoptosis, and ameliorate cartilage injury via blocking the NF-κB/STAT3 pathway

BACKGROUND: Rheumatoid arthritis (RA) is one of the most common inflammatory arthritis worldwide. Total glucosides of peony (PG) were isolated from Paeonia lactiflora Pall, which were found to have the capacity to intervene in the progression of arthritis via an anti-inflammatory action. This study aimed to explore the protective effect of PG against RA. METHODS: In this study, we further investigated the molecular mechanisms of PG on RA. We constructed RA models by Bovine type II collagen in vitro or complete Freund’s adjuvant (FCA) in vivo. The RA-MH7A cells were cultured and treated with different doses (10, 20, 50 µg/mL) of PG. Cell proliferation, apoptosis, and release of inflammatory cytokines were determined. Furthermore, the effect of PG was also explored in vivo using the collagen-induced arthritis rat model. After 30 days, the rats were sacrificed; histological changes, cytokine level, and protein expression were measured. RESULTS: It was revealed that PG dose-dependently inhibited RA-synovial cell growth and induce apoptosis by regulating relative gene level. Besides, PG downregulated the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β, and upregulated IL-10 level in vitro and in vivo. The regulation contributed to the restoration of cartilage injuries. Furthermore, PG also downregulated the expression of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. CONCLUSIONS: All these results showed that PG inhibits the excessive proliferation of synovial cells, and ameliorates cartilage injury via blocking the NF-κB/STAT3 pathway. Collectively, this study provides novel insights into the mechanism of PG, laying a foundation for the application of PG in RA.