Ergosterol peroxide from Cordyceps cicadae ameliorates TGF-β1-induced activation of kidney fibroblasts

Phytomedicine. 2014 Feb 15;21(3):372-8. doi: 10.1016/j.phymed.2013.08.022. Epub 2013 Oct 3.

Abstract

Chronic kidney disease is a growing public health problem with an urgent need for new pharmacological agents. Ergosterol peroxide (EP) is the major sterol produced by Cordyceps cicadae Shing (C. cicadae), a widely used traditional Chinese medicine. C. cicadae has been used to treat many kinds of diseases and has a potential benefit on renoprotection. This study aimed to investigate the anti-fibrotic effects of EP as well as the underlying mechanisms. A normal rat kidney fibroblast cell line (NRK-49F) was stimulated to undergo fibroblast activation by transforming growth factor-β1 (TGF-β1) and EP treatment was applied to explore its potential anti-fibrotic effects. Cell proliferation was investigated using MTT analysis. Fibrosis-associated protein expression was analyzed using immunohistochemistry and/or Western blotting. EP treatment attenuated TGF-β1-induced renal fibroblast proliferation, expression of cytoskeleton protein and CTGF, as well as ECM production. Additionally, EP blocked TGF-β1-stimulated phosphorylation of ERK1/2, p38 and JNK pathway. Moreover, the TGF-β1-induced expression of fibronectin was attenuated by either inhibition of MAPKs or by EP treatment. In conclusion, our findings demonstrate that EP is able to suppress TGF-β1-induced fibroblasts activation in NRK-49F. This new information provides a line of theoretical evidence supporting the use of C. cicadae in the intervention of kidney disease and suggests that EP has the potential to be developed as a therapeutic agent to prevent renal fibrosis.

Keywords: Chronic kidney disease; Cordyceps cicadae; Ergosterol peroxide; Fibroblast-to-myofibroblast transdifferentiaton; TGF-β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation
  • Cells, Cultured
  • Cordyceps / chemistry*
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Ergosterol / analogs & derivatives*
  • Ergosterol / pharmacology
  • Ergosterol / therapeutic use
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibronectins / metabolism
  • Fibrosis
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Rats
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Drugs, Chinese Herbal
  • Fibronectins
  • Transforming Growth Factor beta1
  • Mitogen-Activated Protein Kinases
  • ergosterol-5,8-peroxide
  • Ergosterol