Abstract / Summary
Background/Objectives: Acute gouty arthritis (AGA) is an auto-inflammatory disorder characterized by dysregulated innate immune activation and overactive NOD-like receptor family pyrin domain-containing 3 (NLRP3)/Toll-like receptor 4 (TLR4) inflammatory signaling. While adverse effects limit current therapies, the mechanism by which sunflower receptacle extract (SPE) alleviates gout remains unclear. Methods: This study investigated the anti-inflammatory mechanism of SPE in a male SPF-grade SD rat model of AGA induced by intra-articular monosodium urate crystals. Rats were orally administered SPE or colchicine, and ankle joint swelling, synovial histopathology, serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β), and interleukin-6 (IL-6), and synovial protein expression were assessed. Western blotting was used to assess the expression of the high-mobility group box 1 (HMGB-1), TLR4, and mitogen-activated protein kinase (MAPK) signaling pathways, as well as the activation of NLRP3. Results: Compared to the AGA group, treatment with colchicine and SPE significantly reduced ankle joint swelling, improved inflammatory infiltration in synovial tissue, and lowered serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 (p < 0.05, p < 0.01). They also markedly decreased the expression of HMGB-1 and proteins in the TLR4, nuclear factor-ĸB (NF-ĸB), and MAPK pathways in joint synovial tissue (p < 0.05, p < 0.01, p < 0.001). Conclusions: SPE markedly reduced joint swelling and synovial inflammatory infiltration, lowered serum TNF-α, IL-1β, and IL-6 levels, and decreased synovial expression of HMGB-1, TLR4, MyD88, TRAF6, and NF-ĸB. Moreover, SPE suppressed NLRP3 inflammasome assembly and MAPK pathway activation. These results indicate that SPE mitigates AGA by inhibiting the HMGB-1-TLR4-NLRP3 inflammatory axis.