Astragaloside IV attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-κB signaling pathway

Phytother Res. 2015 Apr;29(4):599-606. doi: 10.1002/ptr.5297. Epub 2015 Jan 21.


Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF-κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B-cell lymphoma-2 associated X protein and caspase-3 expressions and increased B-cell lymphoma-2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF-κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats.

Keywords: TLR4/NF-κB signaling pathway; apoptosis; astragaloside IV; inflammatory response; myocardial ischemia/reperfusion.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Down-Regulation
  • Male
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • NF-kappa B / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / pharmacology*
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / metabolism*
  • Triterpenes / pharmacology*
  • bcl-2-Associated X Protein / metabolism


  • Anti-Inflammatory Agents
  • Bax protein, rat
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Saponins
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Triterpenes
  • bcl-2-Associated X Protein
  • astragaloside A
  • Casp3 protein, rat
  • Caspase 3