Puerariae Lobatae Radix Alleviates High Salt Diet Induced Chronic Kidney Disease by Repairing Intestinal Epithelial Barrier and Down-Regulating Fibrotic Signaling

Chronic kidney disease (CKD) progression can be accelerated by excessive sodium consumption. Gut microbiota dysfunction is a key factor affecting high salt related kidney disease susceptibility. Puerariae Lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote gut microbiota homeostasis, however, its role in renoprotection remains unknown. This study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8-week 2% NaCl-feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, PLR significantly alleviated CKD-associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by down-regulating inflammatory response and the canonical Wnt / β-catenin pathway. Further, we found PLR rescued gut microbiota dysbiosis and protected high salt-induced gut barrier dysfunction. We found enrichment of Akkermansia and Bifidobacterium after PLR intervention, the relative abundance of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that microbiota from mice treated with PLR could ameliorated kidney tissue injury and intestinal barrier damage. Thus, the positive effect of PLR on CKD was at least partially exerted through gut microbiota reestablishment and down-regulation of the Wnt / β-catenin pathway. Our study provides evidence for new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.