Gentianella acuta prevents acute myocardial infarction induced by isoproterenol in rats via inhibition of galectin-3/TLR4/MyD88/NF-кB inflammatory signalling

Inflammopharmacology. 2021 Feb;29(1):205-219. doi: 10.1007/s10787-020-00708-4. Epub 2020 Apr 30.

Abstract

Gentianella acuta (G. acuta), as a folk medicine, was used to treat heart disease by the Ewenki people in Inner Mongolia. However, the effect of G. acuta on acute myocardial infarction (AMI) is not clear. To explore the mechanisms of G. acuta on isoproterenol (ISO)-induced AMI, rats were administered G. acuta for 28 days, then injected intraperitoneally with ISO (85 mg/kg) on days 29 and 30. An electrocardiogram helped to evaluate the myocardial injury. Serum lactate dehydrogenase (LDH), creatinine kinase (CK) and aspartate aminotransferase (AST) levels were evaluated, and haematoxylin eosin, Masson's trichrome staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to detect myocardial histological changes. Radioimmunoassay was used to measure serum tumour necrosis factor alpha (TNFα) and interleukin (IL)-6. An enzyme-linked immunosorbent assay kit was used to analyse serum galectin-3 (Gal-3) levels. Immunohistochemistry, Western blotting and reverse transcription polymerase chain reaction were used to examine relevant molecular events. The results revealed that pre-treatment with G. acuta decreased the elevation in the ST segment; reduced serum LDH, CK and AST levels; alleviated cardiac structure disorder; and reduced inflammatory infiltration, abnormal collagen deposition and cardiomyocyte apoptosis that were induced by ISO. Furthermore, pre-treatment with G. acuta inhibited serum Gal-3 levels and Gal-3 expression in heart tissue, and also impeded TLR4/MyD88/NF-кB signalling activation, which ultimately prevented the expression of inflammatory cytokines. The study indicated that pre-treatment with G. acuta protects against ISO-induced AMI, and the protective role may be related to inhibiting Gal-3/TLR4/MyD88/NF-кB inflammatory signalling.

Keywords: Acute myocardial infarction (AMI); Gal-3/TLR4/MyD88/NF-кB inflammatory signalling; Galectin-3 (Gal-3); Gentianella acuta (G. acuta).

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiotonic Agents / isolation & purification
  • Cardiotonic Agents / pharmacology*
  • Cytokines / metabolism
  • Galectin 3 / metabolism
  • Gentianella / chemistry*
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Isoproterenol / toxicity
  • Male
  • Myeloid Differentiation Factor 88 / metabolism
  • Myocardial Infarction / prevention & control*
  • NF-kappa B / metabolism
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism

Substances

  • Cardiotonic Agents
  • Cytokines
  • Galectin 3
  • Lgals3 protein, rat
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Plant Extracts
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Isoproterenol