Emodin alleviates bleomycin-induced pulmonary fibrosis in rats

Toxicol Lett. 2016 Nov 16;262:161-172. doi: 10.1016/j.toxlet.2016.10.004. Epub 2016 Oct 4.


Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the underlying mechanism remains largely unknown. This study aimed to further investigate the effects of emodin on the inflammation and fibrosis of BLM-induced pulmonary fibrosis and the mechanism involved in rats. Our results showed that emodin improved pulmonary function, reduced weight loss and prevented death in BLM-treated rats. Emodin significantly relieved lung edema and fibrotic changes, decreased collagen deposition, and suppressed the infiltration of myofibroblasts [characterized by expression of α-smooth muscle actin (α-SMA)] and inflammatory cells (mainly macrophages and lymphocytes). Moreover, emodin reduced levels of TNF-α, IL-6, TGF-β1 and heat shock protein (HSP)-47 in the lungs of BLM-treated rats. In vitro, emodin profoundly inhibited TGF-β1-induced α-SMA, collagen IV and fibronectin expression in human embryo lung fibroblasts (HELFs). Emodin also inhibited TGF-β1-induced Smad2/3 and STAT3 activation, indicating that Smad2/3 and STAT3 inactivation mediates emodin-induced effects on TGF-β1-induced myofibroblast differentiation. These results suggest that emodin can exert its anti-fibrotic effect via suppression of TGF-β1 signaling and subsequently inhibition of inflammation, HSP-47 expression, myofibroblast differentiation and extracellular matrix (ECM) deposition.

Keywords: Emodin; Extracellular matrix deposition; Heat shock protein-47; Inflammation; Myofibroblast differentiation; Pulmonary fibrosis.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Bleomycin / antagonists & inhibitors*
  • Bleomycin / toxicity*
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Differentiation / drug effects
  • Cell Line
  • Cytokines / metabolism
  • Emodin / therapeutic use*
  • Enzyme Inhibitors / therapeutic use*
  • Extracellular Matrix / drug effects
  • HSP47 Heat-Shock Proteins / antagonists & inhibitors
  • HSP47 Heat-Shock Proteins / biosynthesis
  • Humans
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Male
  • Myofibroblasts / drug effects
  • Myofibroblasts / metabolism
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Function Tests
  • Weight Loss / drug effects


  • Antibiotics, Antineoplastic
  • Cytokines
  • Enzyme Inhibitors
  • HSP47 Heat-Shock Proteins
  • Bleomycin
  • Emodin