Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress

Oxid Med Cell Longev. 2018 Jun 25;2018:4327901. doi: 10.1155/2018/4327901. eCollection 2018.

Abstract

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.

MeSH terms

  • Animals
  • Cell Line
  • Disease Models, Animal
  • Echocardiography
  • Hemodynamics / drug effects
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Iridoid Glucosides / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism*
  • Myocardium / metabolism
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase Type I / metabolism
  • Nitrogen Oxides / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism
  • Thioredoxins / metabolism
  • Ventricular Remodeling / drug effects

Substances

  • Iridoid Glucosides
  • Nitrogen Oxides
  • Reactive Oxygen Species
  • aucubin
  • Thioredoxins
  • Nitric Oxide Synthase Type I
  • NG-Nitroarginine Methyl Ester