Triptolide alleviates isoprenaline-induced cardiac remodeling in rats via TGF-β1/Smad3 and p38 MAPK signaling pathway

Pharmazie. 2015 Apr;70(4):244-50.


Triptolide (TPL) is a diterpene triepoxide with potent immunosuppressive and anti-inflammatory properties. It is the main effective component of the traditional Chinese herb Tripterygium wilfordii Hook F and has been used in China for centuries to treat immune-related disorders. The present study was conducted to investigate the effects of TPL on cardiac remodeling in rats. Age matched male Wistar rats were used in this study. Cardiac remodeling rat model was established by hypodermic injection of isoprenaline for ten days. The rats were treated with TPL (20 or 100 μg/kg/d) for six consecutive weeks. At the end of the study, the cardiac function, collagen volume fraction, perivascular collagen area and hydroxyproline concentration were studied. Echocardiography, Masson staining, immunohistochemistry, western blot and real-time polymerase chain reaction were performed. The protein and mRNA expression of transforming growth factor-β1 (TGF-β1), drosophila mothers against decapentaplegic protein 3 (Smad3) and p38 mitogen activated protein kinase (p38 MAPK) were analyzed. The results indicated that TPL treatment significantly reduced the collagen volume fraction, perivascular collagen area, ventricular weight/body weight ratio and hydroxyproline concentration in myocardial tissue compared with the model group. In addition, it also improved the cardiac function. TPL attenuated cardiac remodeling in rats by down-regulating the p38 MAPK and TGF-β1/Smad3 signaling pathways. TPL treatment significantly attenuated cardiac fibrosis and improved cardiac function through suppressing the p38 MAPK and TGF-β1/Smad3 signaling pathway in isoprenaline-induced cardiac remodeling rats. Our findings suggested that TPL might be a novel complementary medicine in the treatment of chronic heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Pressure / drug effects
  • Cardiotonic Agents / antagonists & inhibitors*
  • Diterpenes / adverse effects
  • Diterpenes / pharmacology*
  • Epoxy Compounds / adverse effects
  • Epoxy Compounds / pharmacology
  • Fibrosis / prevention & control
  • Hydroxyproline / metabolism
  • Isoproterenol / antagonists & inhibitors*
  • Male
  • Myocardium / pathology
  • Organ Size / drug effects
  • Phenanthrenes / adverse effects
  • Phenanthrenes / pharmacology*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Smad3 Protein / physiology*
  • Transforming Growth Factor beta1 / physiology*
  • Ventricular Remodeling / drug effects*
  • p38 Mitogen-Activated Protein Kinases / physiology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cardiotonic Agents
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • Smad3 Protein
  • Smad3 protein, rat
  • Transforming Growth Factor beta1
  • triptolide
  • p38 Mitogen-Activated Protein Kinases
  • Isoproterenol
  • Hydroxyproline