Based on the TLR4/NLRP3 Pathway and Its Impact on the Formation of NETs to Explore the Mechanism of Ginsenoside Rg₁...

This study investigated whether ginsenoside Rg₁ (G-Rg₁) alleviated acute gouty arthritis (AGA) in rats by modulating the TLR4/NLRP3 pathway and neutrophil extracellular trap (NET) formation. Rats were orally administered G-Rg₁ or colchicine (Col) for 7 days, and monosodium urate (MSU) was injected into the ankle joints on day 5 to induce AGA. Joint swelling, histopathology (HE staining), and serum markers (MPO, NE, MPO-DNA, IL-6, IL-1β; ELISA) were assessed at the baseline and 6-36 h post-modeling. Western blot and immunofluorescence analyzed the NET-related and TLR4/NLRP3 pathway proteins in synovial tissue. G-Rg₁ significantly reduced ankle swelling and synovial inflammation compared with the AGA group, lowered the serum IL-6, IL-1β, MPO, NE, and MPO-DNA levels, and suppressed NET-associated protein expression. Mechanistically, G-Rg₁ downregulated TLR4/NLRP3 pathway activation in synovial tissue. These findings suggest that G-Rg₁ mitigates AGA by inhibiting TLR4/NLRP3 signaling, thereby reducing inflammatory cytokine release and NET formation.