Effects of emodin, a plant-derived anthraquinone, on TGF-β1-induced cardiac fibroblast activation and function

J Cell Physiol. 2021 Nov;236(11):7440-7449. doi: 10.1002/jcp.30416. Epub 2021 May 27.


Cardiac fibrosis accompanies a number of pathological conditions and results in altered myocardial structure, biomechanical properties and function. The signaling networks leading to fibrosis are complex, contributing to the general lack of progress in identifying effective therapeutic approaches to prevent or reverse this condition. Several studies have shown protective effects of emodin, a plant-derived anthraquinone, in animal models of fibrosis. A number of questions remain regarding the mechanisms whereby emodin impacts fibrosis. Transforming growth factor beta 1 (TGF-β1) is a potent stimulus of fibrosis and fibroblast activation. In the present study, experiments were performed to evaluate the effects of emodin on activation and function of cardiac fibroblasts following treatment with TGF-β1. We demonstrate that emodin attenuates TGF-β1-induced fibroblast activation and collagen accumulation in vitro. Emodin also inhibits activation of several canonical (SMAD2/3) and noncanonical (Erk1/2) TGF-β signaling pathways, while activating the p38 pathway. These results suggest that emodin may provide an effective therapeutic agent for fibrosis that functions via specific TGF-β signaling pathways.

Keywords: TGF-β; emodin; fibroblast; fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Collagen / metabolism
  • Emodin / pharmacology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Myocardium / cytology
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Smad2 Protein
  • Smad2 protein, rat
  • Smad3 Protein
  • Smad3 protein, rat
  • Transforming Growth Factor beta1
  • Collagen
  • Mapk1 protein, rat
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Emodin