Molecular mechanism of Pyrrosia lingua in the treatment of nephrolithiasis: Network pharmacology analysis and in vivo experimental verification

Evidence exists reporting that Pyrrosia lingua (PL, Xinhui Pharmaceutical, Polypodiaceae) alleviates nephrolithiasis in rat models. The precipitation of calcium oxalate may result in kidney stones, and the intestinal microbiota is critical for oxalate metabolism. Therefore, we attempt to delineate the molecular mechanism underlying the effect of PL on nephrolithiasis and its association with gut microbiota.Following differential flora analysis in gutMEGA, the network relationship of PL and nephrolithiasis was analyzed based on the TCMSP, DisGeNET and STRING databases. Moreover, the kidney stone model rats were fed with different doses of PL powder and PL extract. In addition, metabolomics technology was employed to identify the active ingredients in PL extract and the microbial metabolites in rat feces.The effect of PL on the nephrolithiasis was based on quercetin and kaempferol by mediating the toll-like receptor signaling pathway and regulating the expression levels of interleukin 6, tumor necrosis factor, mitogen activated protein kinase 8, and secreted phosphoprotein 1. PL significantly reduced the levels of urine oxalic acid, urine calcium, and osteopontin (OPN) levels in rat models of nephrolithiasis. Notably, PL extract decreased these two indicators to lower levels. Furthermore, contents of Oxalobacter formigenes, Bacteriodetes, Bifidobacterium and Fecalibacterium were obviously reduced after treatment with PL extract.PL powder and its active extracts reduce the oxalate level in urine by regulating oxalate metabolism, thus ameliorating the damage of kidney tissues and preventing kidney stone formation. This study suggests the use of PL and its extracts as an alternative source of promising agents that might directly or indirectly inhibit the progression of kidney stone diseases.