Hongjingtian injection protects against myocardial ischemia reperfusion-induced apoptosis by blocking ROS induced autophagic- flux

Biomed Pharmacother. 2021 Mar:135:111205. doi: 10.1016/j.biopha.2020.111205. Epub 2021 Jan 1.

Abstract

Background: Hongjingtian injection (HJT) has been widely used in the clinic to treat coronary heart disease in China. However, the underlying mechanisms of therapies still need to be illustrated. The present study aims to determine whether HJT protects against myocardial ischemia reperfusion injury via Reactive Oxygen Species (ROS)-induced autophagic flux and apoptosis and, if so, to explore the underlying mechanisms.

Methods: In vivo myocardial protection and autophagy regulation of HJT in myocardial ischemia reperfusion injury in C57BL/6 J and CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice were investigated. In vitro, the effects of HJT on apoptosis, autophagic flux, oxidative stress and mitochondrial function were observed in H2O2-induced H9c2 cells. In addition, apoptosis-related proteins and autophagy-related proteins were assessed to explore the underlying mechanisms.

Results: HJT significantly decreased the infarct area and cell apoptosis after myocardial ischemia reperfusion injury in C57BL/6 J mice. Autophagic flux was reduced by HJT treatment after myocardial ischemia reperfusion injury in CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice. HJT inhibited H2O2-induced cell apoptosis by significantly decreasing the levels of cleaved caspase 3 and increasing the Bcl-2/Bax ratio. HJT inhibited autophagic flux after H2O2 stimulation by significantly decreasing LC3-Ⅱ and p-AMPK expression and increasing p-mTOR. HJT inhibited ROS production and improved mitochondrial function in H2O2-induced cells by significantly increasing the mitochondrial membrane potential, intracellular ATP contents and oxygen consumption.

Conclusion: The beneficial effects of HJT in treating myocardial ischemia reperfusion are partially due to improved mitochondrial function and regulated autophagy to inhibit cell apoptosis through the AMPK/mTOR pathway.

Keywords: Apoptosis; Autophagic flux; Hongjingtian injection; Myocardial ischemia reperfusion injury; Reactive oxygen species.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Cell Line
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxidative Stress / drug effects*
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Drugs, Chinese Herbal
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • hongjingtian
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases