Sal B Alleviates Myocardial Ischemic Injury by Inhibiting TLR4 and the Priming Phase of NLRP3 Inflammasome

Molecules. 2019 Dec 3;24(23):4416. doi: 10.3390/molecules24234416.

Abstract

Salvianolic acid B is one of the main water-soluble components of Salvia miltiorrhiza Bge. Many reports have shown that it has significant anti-myocardial ischemia effect. However, the underlying mechanism remains unclear. Our present study demonstrated that Sal B could alleviate myocardial ischemic injury by inhibiting the priming phase of NLRP3 inflammasome. In vivo, serum c-troponin I (cTn), lactate dehydrogenase (LDH) levels, the cardiac function and infract size were examined. We found that Sal B could notably reduce the myocardial ischemic injury caused by ligation of the left anterior descending coronary artery. In vitro, Sal B down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated H9C2 cells. Furthermore, Sal B reduced the expression levels of IL-1β and NLRP3 inflammasome in a dose-dependent manner. In short, our study provided evidence that Sal B could attenuate myocardial ischemic injury via inhibition of TLR4/NF-κB/NLRP3 signaling pathway. And in an upstream level, MD-2 may be the potential target.

Keywords: NF-κB; NLRP3 inflammasome; Sal B; TLR4; priming phase.

MeSH terms

  • Animals
  • Benzofurans / administration & dosage*
  • Benzofurans / chemistry
  • Benzofurans / pharmacology
  • Cell Line
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Lipopolysaccharides / adverse effects*
  • Lymphocyte Antigen 96 / antagonists & inhibitors
  • Lymphocyte Antigen 96 / chemistry
  • Male
  • Models, Molecular
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / etiology
  • Myocardial Ischemia / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Rats
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Benzofurans
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • salvianolic acid B