Sunflower Receptacle Extract Alleviates Acute Gouty Arthritis via HMGB1-TLR4-NLRP3 Inflammatory Pathway.

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.