Pulchinenoside B4 Attenuates Gouty Arthritis by Regulating NLRP3 Inflammasome and Macrophage Polarization: A Transcriptomics-Based Analysis

Gouty arthritis (GA) is an inflammatory disorder characterized by the deposition of monosodium urate (MSU) crystals in joint tissues. Pulchinenoside B4 (B4) exhibits broad-spectrum anti-inflammatory properties, yet its specific role and underlying mechanism in GA pathogenesis remain undefined. This study aims to integrate transcriptomic analysis with in vivo and in vitro experiments to thoroughly investigate the therapeutic efficacy of B4 in GA and its underlying molecular mechanisms. In an MSU-induced mouse model of GA, treatment with B4 significantly ameliorated ankle edema and suppressed inflammatory cell infiltration. Transcriptome sequencing analysis identified key differentially expressed long non-coding RNAs (lncRNAs) including Nod1, Rbck1, and Pycard. Mechanistic investigations further focused on the NOD-like receptor signaling pathway modulated by B4, the NF-κB signaling cascade, and the polarization state of macrophages. Experimental validation via qPCR, Western blot, and immunofluorescence assays confirmed that B4 significantly suppressed the expression and activation of key components of the NLRP3 inflammasome (such as ASC, Caspase-1, IL-1β) in both in vivo and in vitro models. Flow cytometry and immunofluorescence analyses further demonstrated that B4 potently inhibited MSU-induced macrophage polarization toward the pro-inflammatory M1 phenotype. Collectively, this study elucidates that B4 effectively ameliorates MSU-induced inflammatory responses in GA via a dual mechanism: suppressing NLRP3 inflammasome activation and blocking M1 macrophage polarization. These findings highlight B4 as a highly promising candidate for the therapeutic management of GA.