Catalpol alleviates myocardial ischemia reperfusion injury by activating the Nrf2/HO-1 signaling pathway

Microvasc Res. 2022 Mar:140:104302. doi: 10.1016/j.mvr.2021.104302. Epub 2021 Dec 15.

Abstract

Purpose: Myocardial ischemia/reperfusion injury (MI/RI) is a major problem in the clinical treatment of ischemic cardiomyopathy, and its specific underlying mechanisms are complicated and still unclear. A number of studies have indicated that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxidase-1(HO-1) signaling pathway might serve as an important target for the management of MI/RI. Catalpol is a kind of iridoid glucoside that has been found to exhibit diverse anti-inflammatory and antioxidant properties. This study was aimed at investigating the role of Catalpol in targeting MI/RI and its related mechanisms in an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro and a preclinical ischemia/reperfusion (I/R) model.

Methods: This study using both in vitro and in vivo models investigated the possible role and underlying mechanisms used by Catalpol for modulating of MI/RI. The potential effects of Catalpol on the viability of cardiomyocytes were measured by cell counting kit-8 (CCK-8) assays. The phenotypes of myocardial injury, oxidative stress and inflammation markers were measured by western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) etc. Nrf2/HO-1 signaling pathway was detected by immunofluorescence and western blot analysis.

Results: We found that Catalpol significantly suppressed the process of MI/RI and protected OGD/R-treated cardiomyocytes by inhibiting the various markers of inflammation and suppressing oxidative stress. Additionally, mechanistically it was also demonstrated that Catalpol could effectively activate Nrf2/HO-1 signaling pathway to suppress the damage caused by inflammation and oxidative stress in MI/RI.

Conclusion: In summary, the findings suggest that Catalpol exerted significant cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/HO-1 signaling pathway.

Keywords: Apoptosis; Catalpol; Inflammation; Myocardial ischemia/reperfusion injury; Nrf2/HO-1 signaling pathway; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Cell Hypoxia
  • Cell Line
  • Disease Models, Animal
  • Glucose / deficiency
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Inflammation Mediators / metabolism
  • Iridoid Glucosides / pharmacology*
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Reperfusion Injury / enzymology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / pathology
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Inflammation Mediators
  • Iridoid Glucosides
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Nfe2l2 protein, mouse
  • catalpol
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Glucose