Cardioprotective effects of total flavonoids from Jinhe Yangxin prescription by activating the PI3K/Akt signaling pathway in myocardial ischemia injury

Biomed Pharmacother. 2018 Feb:98:308-317. doi: 10.1016/j.biopha.2017.12.052. Epub 2017 Dec 27.

Abstract

The purpose of the present study was to investigate the cardioprotective effects of total flavonoids of Jinhe yangxin prescription (JHTF) on myocardial ischemia (MI) injury rats induced by Isoproterenol (ISO) and explore the potential mechanisms underlying these effects. 128 male rats were randomized into 8 groups: Control, Model, Positive, JHTF-H (2.64 g/kg/d), JHTF-M (1.32 g/kg/day), JHTF-L (0.66 g/kg/d), LY + JHTF (JHTF-H plus LY294002, an inhibitor of PI3K/Akt) and LY groups. Electrocardiogram, histopathological examination and terminal deoxynucleotidyl transferase dUTP nickend labeling (TUNEL) assay were performed. Heart weight index, markers of cardiac marker enzymes [creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI)], oxidative stress [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and nitric oxide (NO)] and inflammation [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)] were also measured in each group. Proteins involved in PI3K/Akt pathway were detected by Western blot. JHTF decreased the ST elevation induced by MI, decreased serum levels of CK, CK-MB, cTnI, LDH, MDA, IL-6 and TNF-α, and increased serum SOD, GSH-Px and NO activities. Furthermore, JHTF inhibited myocardial apoptosis, which may be related to downregulated caspase-3 and Bax, upregulated Bcl-2, and increased the protein levels of phosphorylated Akt, GSK-3β and endothelial nitric oxide synthase (eNOS). However, all the previously mentioned effects of JHTF were blocked when JHTF was coadministered with LY294002. In conclusion, these observations indicated that JHTF has cardioprotective effects against MI, and these effects seem to be related to the activation of PI3K/Akt signaling pathway in the myocardium.

Keywords: Apoptosis; Flavonoids; Herb pairs; Myocardial ischemia; Oxidative stress; PI3K/Akt.

MeSH terms

  • Animals
  • Cardiotonic Agents / isolation & purification
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Electrocardiography / drug effects
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Male
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / prevention & control
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prescription Drugs / pharmacology
  • Prescription Drugs / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Treatment Outcome

Substances

  • Cardiotonic Agents
  • Drugs, Chinese Herbal
  • Flavonoids
  • Prescription Drugs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt