Triptolide attenuates pressure overload-induced myocardial remodeling in mice via the inhibition of NLRP3 inflammasome expression

Biochem Biophys Res Commun. 2017 Mar 25;485(1):69-75. doi: 10.1016/j.bbrc.2017.02.021. Epub 2017 Feb 12.


Triptolide is the predominant active component of the Chinese herb Tripterygium wilfordii Hook F (TwHF) that has been widely used to treat several chronic inflammatory diseases due to its immunosuppressive, anti-inflammatory, and anti-proliferative properties. In the present study, we elucidated the cardioprotective effects of triptolide against cardiac dysfunction and myocardial remodeling in chronic pressure-overloaded hearts. Furthermore, the potential mechanisms of triptolide were investigated. For this purpose, C57/BL6 mice were anesthetized and subjected to transverse aortic constriction (TAC) or sham operation. Six weeks after the operation, all mice were randomly divided into 4 groups: sham-operated with vehicle group, TAC with vehicle group, and TAC with triptolide (20 or 100 μg/kg/day intraperitoneal injection) groups. Our data showed that the levels of NLRP3 inflammasome were significantly increased in the TAC group and were associated with increased inflammatory mediators and profibrotic factor production, resulting in myocardial fibrosis, cardiomyocyte hypertrophy, and impaired cardiac function. Triptolide treatment attenuated TAC-induced myocardial remodeling, improved cardiac diastolic and systolic function, inhibited the NLRP3 inflammasome and downstream inflammatory mediators (IL-1β, IL-18, MCP-1, VCAM-1), activated the profibrotic TGF-β1 pathway, and suppressed macrophage infiltration in a dose-dependent manner. Our study demonstrated that the protective effect of triptolide against pressure overload in the heart may act by inhibiting the NLRP3 inflammasome-induced inflammatory response and activating the profibrotic pathway.

Keywords: Hypertension; Inflammation; Myocardial remodeling; NLRP3; Triptolide; Triptolide(PubChem CID: 107985).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / therapeutic use*
  • Diterpenes / chemistry
  • Diterpenes / therapeutic use*
  • Down-Regulation / drug effects*
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / therapeutic use
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / therapeutic use
  • Fibrosis
  • Heart Ventricles / drug effects
  • Heart Ventricles / immunology
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Hypertrophy, Left Ventricular / drug therapy*
  • Hypertrophy, Left Ventricular / genetics
  • Hypertrophy, Left Ventricular / immunology
  • Hypertrophy, Left Ventricular / pathology
  • Immunity, Innate / drug effects
  • Inflammasomes / genetics*
  • Inflammasomes / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / immunology
  • Myocardium / metabolism
  • Myocardium / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • Phenanthrenes / chemistry
  • Phenanthrenes / therapeutic use*
  • Tripterygium / chemistry
  • Ventricular Remodeling / drug effects*


  • Anti-Inflammatory Agents
  • Diterpenes
  • Drugs, Chinese Herbal
  • Epoxy Compounds
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Phenanthrenes
  • triptolide