Protective effects of Gingko biloba extract 761 on myocardial infarction via improving the viability of implanted mesenchymal stem cells in the rat heart

Mol Med Rep. 2014 Apr;9(4):1112-20. doi: 10.3892/mmr.2014.1959. Epub 2014 Feb 18.

Abstract

When introduced into the infarcted heart, bone marrow‑derived mesenchymal stem cells (MSCs) prevent the heart from deleterious remodeling and improve its recovery. The aim of the present study was to investigate the effects of Ginkgo biloba extract (EGb) 761 on the infarcted myocardium microenvironment following MSC transplantation. The established rat myocardial infarction (MI) model, with implanted PKH‑26 marked MSCs (1x105 cells), were randomly divided into two groups: The control group (injected with normal saline) and the EGb 761 treatment group (injected with 100 mg/kg/day EGb 761). The following indices for cardiac function, including the extent of inflammation, oxidative stress, MSC apoptosis and MSC differentiation were measured 1, 2 and 7 days after treatment. The anti‑inflammatory effect of EGb 761 was observed by histological examination. Compared with the respective control group, the malondialdehyde content significantly decreased and the superoxide dismutase, catalase and glutathione peroxidase activity significantly increased in the EGb761‑treated groups. In addition, the apoptotic index gradually decreased (P<0.05) with the extension of MI time in the EGb761-treated groups compared to the respective control groups, suggesting that EGb761 exhbits anti-oxidative effects. In addition, the level of the Fas protein was positively correlated with the implanted MSC apoptotic ratio. Following 7 days of MSC transplantation with EGb 761 treatment, the expression of cTnI in PKH26‑labeled MSCs was observed in the transplanted myocardium. Cardiac function, including the ejection fraction, left ventricular end‑systolic pressure and dp/dtmax significantly increased, and the left ventricular end diastolic diameters, left ventricular end‑diastolic volumes and left ventricular end‑diastolic pressure significantly decreased (P<0.05, vs. the control group). The results demonstrated that EGb 761 is important in improving cardiac function and the infarcted myocardium microenvironment. The present study indicated that the protective effects of EGb 761 on the infarcted myocardium may be mediated by improving the viability and the differentiation of the implanted MSCs into cardiomyocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Blotting, Western
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Electrocardiography
  • Ginkgo biloba
  • Inflammation / pathology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / physiopathology
  • Myocardium / pathology
  • Organic Chemicals / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Ultrasonography
  • fas Receptor / metabolism

Substances

  • Biomarkers
  • Cardiotonic Agents
  • Fas protein, rat
  • Organic Chemicals
  • PKH 26
  • Plant Extracts
  • fas Receptor
  • Ginkgo biloba extract