Cordyceps cicadae polysaccharides ameliorated renal interstitial fibrosis in diabetic nephropathy rats by repressing inflammation and modulating gut microbiota dysbiosis

Int J Biol Macromol. 2020 Nov 15:163:442-456. doi: 10.1016/j.ijbiomac.2020.06.153. Epub 2020 Jun 24.

Abstract

Diabetic nephropathy (DN), a complication of diabetes mellitus, has been the leading cause of death in people with chronic kidney disease. This study was conducted to examine the potential health benefits of Cordyceps cicadae polysaccharides (CCP) on kidney injury and renal interstitial fibrosis that occur in DN rats. First, a DN model was established using SD rats fed with a high-fat diet for 8 weeks, then injected with STZ (35 mg/kg) intraperitoneally. The rats were then supplemented with CCP (75, 150 and 300 mg/kg) for 4 weeks. The results indicated that CCP improve insulin resistance and glucose tolerance in DN rats. Furthermore, CCP intervention significantly suppressed the inflammation, renal pathological changes and renal dysfunction, slowing down the progression of renal interstitial fibrosis. Moreover, high-throughput pyrosequencing of 16S rRNA suggested that CCP modulated the dysbiosis of gut microbiota by enhancing the relative abundance and proliferation capacity of probiotics. In vitro, CCP can markedly decrease LPS-induced inflammatory cytokine levels and TGF-β1-induced fibroblast activation. In summary, the results provided evidence that CCP exerted a beneficial effect on tubulointerstitial fibrosis in DN rats by possibly suppressing the inflammatory response and modulating gut microbiota dysbiosis, via blocking the TLR4/NF-κB and TGF-β1/Smad signaling pathway.

Keywords: Cordyceps cicadae polysaccharides; Gut microbiota; Renal interstitial fibrosis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Biomarkers
  • Biopsy
  • Cell Line
  • Chemical Phenomena
  • Cordyceps / chemistry*
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / pathology*
  • Disease Models, Animal
  • Dysbiosis* / drug therapy
  • Fibrosis
  • Fungal Polysaccharides / chemistry*
  • Fungal Polysaccharides / pharmacology*
  • Gastrointestinal Microbiome / drug effects*
  • Immunohistochemistry
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / etiology
  • Inflammatory Bowel Diseases / pathology
  • Insulin Resistance
  • Male
  • NF-kappa B / metabolism
  • Rats
  • Smad Proteins / metabolism
  • Spectroscopy, Fourier Transform Infrared
  • Toll-Like Receptor 4 / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Fungal Polysaccharides
  • NF-kappa B
  • Smad Proteins
  • Toll-Like Receptor 4
  • Transforming Growth Factor beta1

Supplementary concepts

  • Cordyceps cicadae