Puerariae lobatae Radix ameliorates chronic kidney disease by reshaping gut microbiota and downregulating Wnt/β‑catenin signaling

Mol Med Rep. 2024 Jul;30(1):117. doi: 10.3892/mmr.2024.13241. Epub 2024 May 17.

Abstract

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present 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, The medium and high doses of PLR significantly alleviated CKD‑associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/β‑catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt‑induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/β‑catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

Keywords: Puerariae lobatae Radix; Wnt/β‑catenin pathway; chronic kidney disease; fecal microbiota transplantation; gut microbiota; high salt diet.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Dysbiosis / drug therapy
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome* / drug effects
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pueraria* / chemistry
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / metabolism
  • Wnt Signaling Pathway* / drug effects

Substances

  • plant extract, Puerariae Radix

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant nos. 82173304 and 82370782) and the Natural Science Foundation of Guangdong (grant no. 2023A1515012565).