Calycosin-7-O-β-D-glucoside attenuates myocardial ischemia-reperfusion injury by activating JAK2/STAT3 signaling pathway via the regulation of IL-10 secretion in mice

Mol Cell Biochem. 2020 Jan;463(1-2):175-187. doi: 10.1007/s11010-019-03639-z. Epub 2019 Nov 11.

Abstract

Calycosin-7-O-β-D-glucoside (CG) is the component of Astragali Radix, and the aim of the present study is to investigate whether CG protects myocardium from I/R-induced damage by the regulation of IL-10/JAK2/STAT3 signaling pathway. H9C2 cells were subjected to I/R treatment and pretreated with 1 μm CG in vitro. In addition, a mouse model of myocardial I/R injury was induced by left anterior descending (LAD) coronary artery ligation and administrated with 30 mg/kg CG by intravenous injection before I/R surgery. In vitro and in vivo results showed that CG up-regulated IL-10 level, activated the JAK2/STAT3 pathway, and protected myocardial cells from I/R-induced apoptosis. The hemodynamic measurement, TTC staining, TUNEL staining, and western blot results in vivo showed that the protective effects of CG on myocardial function and cell apoptosis were all reversed by the IL-10R α neutralizing antibody. CG-induced phosphorylation activation of JAK2/STAT3 signaling pathway was also suppressed by the blocking of IL-10. In summary, these findings suggest that CG might alleviate myocardial I/R injury by activating the JAK2/STAT3 signaling pathway via up-regulation of IL-10 secretion, which provides us insights into the mechanism underlying the protective effect of CG on myocardial I/R injury.

Keywords: Calycosin-7-O-β-D-glucoside; IL-10; JAK2/STAT3 signaling pathway; Myocardial ischemia–reperfusion.

MeSH terms

  • Animals
  • Cell Line
  • Glucosides / pharmacology*
  • Interleukin-10 / metabolism*
  • Isoflavones / pharmacology*
  • Janus Kinase 2 / metabolism*
  • Mice
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / metabolism
  • Myocardial Reperfusion Injury* / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Rats
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Glucosides
  • IL10 protein, mouse
  • Isoflavones
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • calycosin-7-O-beta-D-glucoside
  • Interleukin-10
  • Jak2 protein, mouse
  • Janus Kinase 2