Panax Notoginseng Saponins Protect H9c2 Cells From Hypoxia-reoxygenation Injury Through the Forkhead Box O3a Hypoxia-inducible Factor-1 Alpha Cell Signaling Pathway

J Cardiovasc Pharmacol. 2021 Aug 5;78(5):e681-e689. doi: 10.1097/FJC.0000000000001120.

Abstract

Panax notoginseng saponins (PNS) are commonly used in the treatment of cardiovascular diseases. Whether PNS can protect myocardial ischemia-reperfusion injury by regulating the forkhead box O3a hypoxia-inducible factor-1 alpha (FOXO3a/HIF-1α) cell signaling pathway remains unclear. The purpose of this study was to investigate the protective effect of PNS on H9c2 cardiomyocytes through the FOXO3a/HIF-1α cell signaling pathway. Hypoxia and reoxygenation of H9C2 cells were used to mimic MIRI in vitro, and the cells were treated with PNS, 2-methoxyestradiol (2ME2), and LY294002." Cell proliferation, lactate dehydrogenase, and malonaldehyde were used to evaluate the degree of cell injury. The level of reactive oxygen species was detected with a fluorescence microscope. The apoptosis rate was detected by flow cytometry. The expression of autophagy-related proteins and apoptosis-related proteins was detected by western blot assay. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway. Furthermore, the protective effects of PNS were abolished by HIF-1α inhibitor 2ME2 and PI3K/Akt inhibitor LY294002. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cardiovascular Agents / isolation & purification
  • Cardiovascular Agents / pharmacology*
  • Cell Line
  • Forkhead Box Protein O3 / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Membrane Proteins / metabolism
  • Mitochondrial Proteins / metabolism
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Panax notoginseng* / chemistry
  • Phosphatidylinositol 3-Kinase / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Signal Transduction

Substances

  • BNIP3 protein, rat
  • Cardiovascular Agents
  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins
  • Mitochondrial Proteins
  • Plant Extracts
  • Reactive Oxygen Species
  • Saponins
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt