LncRNA transcriptomics elucidates the suppression of gouty arthritis-associated pyroptosis by Pulchinenoside B4 through NLRP3 inflammasome modulation.

Gouty Arthritis (GA) is a prevalent inflammatory condition characterized by pain resulting from the deposition of monosodium urate (MSU) crystals in the joints and surrounding tissues. Pulchinenoside B4 (P-B4) is a natural compound known for its beneficial effects, including heat-clearing, detoxification, blood-cooling, and diarrhea-stopping properties. This study aims to investigate the protective effects of P-B4 on MSU-crystal-induced GA and to elucidate its underlying molecular mechanisms. Long non-coding RNA (lncRNA) sequencing was performed to identify differentially expressed genes (DEGs). Subsequently, RT-qPCR, Western blotting, ELISA, immunofluorescence (IF), transmission electron microscopy (TEM), and other experimental validation methods were employed to confirm key DEGs and target proteins. P-B4 significantly improved ankle swelling and inflammatory cell infiltration in MSU-induced GA mice. LncRNA transcriptome analysis and molecular docking results revealed that DEGs enriched in the NOD-like receptor signaling pathway include lncRNA ENSMUST00000230571, lncRNA MSTRG.119080.1 and lncRNA ENSMUST00000197982. P-B4 exhibited superior binding activity with GSDMD, Caspase-1 and IL-6 proteins. Both in vitro and in vivo experiments demonstrated that P-B4 significantly inhibited the expression of messenger RNAs and proteins such as NLRP3, ASC, caspase-1, and GSDMD-N, reduced the levels of inflammatory factors and decreased the production of ASC specks in both a BMDM inflammation model and a mouse model of acute gouty arthritis. The underlying mechanism may involve the regulation of the NLRP3 inflammasome-mediated pyroptosis. P-B4 could modulate Gsdmd, Caspase-1 and IL-6 proteins expression through upstream therapeutic targets of lncRNA ENSMUST00000230571, lncRNA MSTRG.119080.1 and lncRNA ENSMUST00000197982.