Pulchinenoside B4 attenuates gouty arthritis by regulating NLRP3 inflammasome and macrophage polarization: a transcriptomics-based analysis

Abstract

Gouty arthritis (GA) is an inflammatory disorder characterized by the deposition of monosodium urate (MSU) crystals in joint tissues. Pulchinenoside B4 (B4) has broad-spectrum anti-inflammatory properties, but its role and potential mechanism in the pathogenesis of GA are still unclear. The purpose of this study is to comprehensively elucidate the therapeutic effect and mechanism of B4 on GA by integrating transcriptome analysis and in vitro and in vivo experiments. In the MSU-induced mouse GA model, B4 treatment significantly improved ankle edema and reduced inflammatory cell infiltration. Through the analysis of transcriptome sequencing results, we identified multiple differentially expressed long non-coding RNAs (lncRNAs), such as Nod1, Rbck1 and Pycard. In the in-depth exploration of the mechanism, we focused on the NOD-like receptor signaling pathway, NF-κB signaling cascade, and B4-regulated macrophage polarization. In vitro and in vivo models, we confirmed that B4 significantly inhibited the expression and activation of key components of NLRP3 inflammasome (such as ASC, Caspase-1 and IL-1β) by qPCR, Western blot and immunofluorescence. Flow cytometry and immunofluorescence analysis further showed that B4 could prevent MSU-induced macrophage polarization to pro-inflammatory M1 phenotype. Based on these results, this study elucidated the mechanism of B4 improving MSU-induced GA inflammatory response by inhibiting NLRP3 inflammasome activation and blocking M1 macrophage polarization. These results suggest that B4 has great potential as a candidate drug for the treatment of GA.