A novel rhamnogalacturonan from Polygonum aviculare ameliorates kidney disease

Polygonum aviculare L. a traditional Chinese medicinal herb, is widely used to treat urinary stones. In this work, a novel rhamnogalacturonan I , PAPN1, was isolated from the plant, and its anti-nephrolithiatic effects were assessed through integrated multi-omics approaches. In vivo, oral administration of PAPN1 significantly reduced renal calcium oxalate crystal deposition and improved renal function parameters. 16S rRNA gene sequencing and serum metabolomics profiling revealed that PAPN1 reshaped the gut microbiota composition, markedly increasing taurine levels. Bulk and single-cell RNA sequencing showed that PAPN1 suppressed the TNF expression in macrophages, thereby attenuating inflammatory responses and crystal adhesion. Collectively, PAPN1 modulates the gut microbiota to enhance taurine production, which inhibits the TNF expression in kidneys, alleviating local inflammation and crystal retention to exert anti-nephrolithiatic effects. This study highlights the therapeutic potential of PAPN1 as a natural anti-inflammatory agent and elucidates the critical role of the gut-kidney axis in nephrolithiasis prevention.