Shikonin protects H9C2 cardiomyocytes against hypoxia/reoxygenation injury through activation of PI3K/Akt signaling pathway

Biomed Pharmacother. 2018 Aug:104:712-717. doi: 10.1016/j.biopha.2018.04.144. Epub 2018 May 25.

Abstract

Myocardial ischemic/reperfusion (I/R) injury often leads to irreversible myocardial cell death and even heart failure, with limited therapeutic possibilities. In the present study, we evaluated the protective effects of shikonin (SHK) against hypoxia/reoxygenation (H/R)-induced cardiomyocyte damage and explored the underlying mechanisms. H9C2 cardiomyocytes were pretreated with different doses of SHK prior to H/R exposure. We observed that SHK pretreatment significantly increased cell viability, attenuated LDH release, and suppressed cardiomyocyte apoptosis induced by H/R exposure. SHK pretreatment also restored the loss of mitochondrial membrane potential (MMP) and cytochrome c release. In addition, SHK significantly enhanced the phosphorylation of Akt and GSK-3β in H/R-treated H9C2 cells. These protective effects of SHK were partially reversed by LY294002, a specific PI3K/Akt inhibitor. Therefore, our findings suggested that SHK might be a promising agent for myocardial I/R injury, and PI3K/Akt signaling plays a crucial role during this process.

Keywords: H9C2 cells; Hypoxia/reoxygenation injury; Mitochondria-dependent apoptosis; PI3K/Akt signaling; Shikonin; Viability.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiotonic Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Chromones / pharmacology
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Hypoxia / metabolism*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Morpholines / pharmacology
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardium / metabolism
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Naphthoquinones / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Protective Agents / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Signal Transduction / drug effects

Substances

  • Cardiotonic Agents
  • Chromones
  • Morpholines
  • Naphthoquinones
  • Protective Agents
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • shikonin
  • Phosphatidylinositol 3-Kinases
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt