Paeoniflorin elevates the expression of SOCS3 in macrophages to prevent MIA-induced osteoarthritis in mice

Osteoarthritis (OA) is a degenerative joint disease that occurs frequently in middle-aged and elderly individuals, limiting joint function and causing disability with severe pain. However, available treatment options for inhibiting inflammation, preventing cartilage degradation, and relieving pain remain limited. Paeoniflorin, a monoterpene glycoside isolated from the Chinese medicine Paeonia lactiflora exhibits anti-inflammatory and immunomodulatory effects. In the present study, we investigated the efficacy and possible mechanisms of paeoniflorin in attenuating pain, inflammation, and cartilage degradation in a mouse model of OA. The analgesic effect of paeoniflorin was assessed by measuring mechanical allodynia with von Frey hairs. H&E staining was used to evaluate the structural integrity and inflammation of joint tissues. RAW264.7 cells were used to investigate the effects of paeoniflorin on related signaling pathways and on lipopolysaccharide (LPS)-induced inflammation by Western blotting. Paeoniflorin relieved mechanical allodynia and reduced cartilage degeneration in vivo. Moreover, paeoniflorin upregulated Gas6 expression, activated the Axl receptor, upregulated suppressor of cytokine signaling 3 (SOCS3) expression, inhibited MMP-9 expression, and decreased p38 phosphorylation in the joints. Cell experiments revealed that paeoniflorin regulated the Gas6-TAM pathway via the ERK signaling pathway and decreased MMP-9 expression and M1 polarization. Collectively, paeoniflorin may inhibit joint inflammation and relieve pain by upregulating the Gas6-TAM pathway and promoting macrophage M2 polarization, suggesting that it may serve as a potential therapeutic agent for osteoarthritis.