Ginkgo biloba extract-761 protects myocardium by regulating Akt/Nrf2 signal pathway

Drug Des Devel Ther. 2019 Feb 13;13:647-655. doi: 10.2147/DDDT.S191537. eCollection 2019.

Abstract

Objective: The aim of this study was to investigate the protective effect and mechanism of Ginkgo biloba extract-761 (EGb 761) in the rat with myocardial ischemia-reperfusion injury (MIRI).

Materials and methods: Forty Sprague Dawley rats were randomly divided into following four groups: sham group, I/R group and EGb 761 groups (20 and 40 mg/kg). MIRI model was established after 14 days of administration. The myocardial infarct size and myocardial histology were measured and compared. Meanwhile, the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), TNF-α, IL-6, IL-1β, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bcl-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2.

Results: The levels of infarct size, CK-MB, LDH, TnT, TNF-α, IL-6 and IL-1β in the EGb 761 groups were significantly lower than those in the ischemia/reperfusion (I/R) group. The content of MDA was lower in the myocardium, whereas the activities of SOD and GSH-Px were higher than those in the I/R group. The expressions of Caspase-3 and Bax in the EGb 761 groups were significantly lower than those in the I/R group, whereas the expressions of Bcl-2, p-Akt and HO-1 and nuclear protein Nrf2 in the EGb 761 groups were higher than those in the I/R group.

Conclusion: EGb 761 might inhibit the apoptosis of myocardial cells and protect the myocardium by activating the Akt/Nrf2 pathway, increasing the expression of HO-1, decreasing oxidative stress and repressing inflammatory reaction.

Keywords: Ginkgo biloba extract; myocardial ischemia-reperfusion injury; oxidative stress; superoxide dismutase.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Ginkgo biloba
  • Heart / drug effects*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Plant Extracts
  • Ginkgo biloba extract
  • Proto-Oncogene Proteins c-akt