Gypenoside Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting Cardiomyocytes Apoptosis via Inhibition of CHOP Pathway and Activation of PI3K/Akt Pathway In Vivo and In Vitro

Cell Physiol Biochem. 2016;39(1):123-36. doi: 10.1159/000445611. Epub 2016 Jun 20.

Abstract

Background/aims: Ischemia-reperfusion (I/R) injury is believed to be the major cause for detriments in coronary heart diseases, but few effective therapies for prevention or treatment of I/R injury are available. Gypenoside (GP) is the predominant effective component of Gynostemma pentaphyllum and possesses capacities against inflammation and oxidation. In the present study, the role of GP in ameliorating myocardial I/R injury was investigated.

Methods: effect GP on the cardiac structure of I/R injured rats was assessed by H&E and TTC staining. Then the influence of GP on the cardiac function of rat model was determined by measuring hemodynamics parameters, levels of lactate dehydrogenase (LDH) and creatine kinase (CK). Thereafter, effect of GP on apoptotic process was evaluated with both rat and cell models. The production of molecules related to ER stress and apoptosis was quantified for revelation of pathways involved in the myocardial protective effect of GP.

Results: Impairments in cardiac structure due to I/R injury was ameliorated by GP treatment. And it was evidently demonstrated that administration of GP not only effectively decreased the apoptotic rates in both rat and cell models but also markedly improved the cardiac function of I/R injured rats. In addition, results of western blotting revealed that the GP inhibited ER-stress and apoptosis through the blockade of CHOP pathway and activation of PI3K/Akt pathway.

Conclusion: the current study showed the potential of GP to alleviate myocardial I/R injury and preliminarily uncovered the underling mechanism driving this treatment.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Blotting, Western
  • Cardiotonic Agents / pharmacology
  • Cell Line
  • Endoplasmic Reticulum Stress / drug effects
  • Flow Cytometry
  • Gynostemma / chemistry
  • Male
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Transcription Factor CHOP / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Cardiotonic Agents
  • Ddit3 protein, rat
  • Plant Extracts
  • gypenoside
  • Transcription Factor CHOP
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt