Mechanism of Portulaca oleracea acidic polysaccharide in ameliorating renal injury in hyperuricemia mice by regulating the CMPK2/NLRP3 pathway.

Abstract

Portulaca oleracea acidic polysaccharide (POPW-A) demonstrates significant efficacy in anti-inflammatory and immune-enhancing properties. Intervention with POPW-A reduced blood uric acid levels and significantly up-regulated uric acid transporter expression in hyperuricemic (HUA) model mice. Additionally, it suppressed the activation of the NLRP3 inflammasome by down-regulating AIF-1 and CMPK2 protein expression, thereby alleviating renal inflammation. The polysaccharide components of POPW-A were screened after purifying. Among them, the POPW-Ab component effectively enhanced the expression of uric acid transport proteins and suppressed the activation of the NLRP3 inflammasome. Structural analysis confirmed that POPW-Ab is a pectin polysaccharide composed primarily of a homogalacturonan (HG) domain with a backbone of →4)-α-D-GalpA-(1→, along with a minor rhamnogalacturonan-I (RG-I) domain containing side chains of →5)-α-L-Araf-(1→. After silencing the CMPK2 gene in model cells, the protective effects of POPW-Ab were counteracted. Conversely, overexpression of the CMPK2 gene restored the intervention efficacy of POPW-Ab. Therefore, POPW-Ab is likely the fundamental material basis for the bioactivity of Portulaca oleracea polysaccharides. The underlying mechanism involves targeted down-regulation of CMPK2 gene expression, thereby inhibiting NLRP3 inflammasome activation and subsequent release of pro-inflammatory cytokines. These findings suggest that POPW-Ab holds promise as a potential therapeutic agent for HUA and its associated renal complications.