Plantamajoside protects H9c2 cells against hypoxia/reoxygenation-induced injury through regulating the akt/Nrf2/HO-1 and NF-κB signaling pathways

J Recept Signal Transduct Res. 2022 Apr;42(2):125-132. doi: 10.1080/10799893.2020.1859534. Epub 2020 Dec 22.

Abstract

Myocardial ischemia/reperfusion (I/R) injury has been found to be associated with oxidative stress. Plantamajoside (PMS) is a major compound of Plantago asiatica that was reported to possess cardioprotective and antioxidant effects. The current study was designed to investigate the effect of PMS on myocardial I/R injury. Rat cardiomyocytes H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to establish in vitro model of myocardial I/R injury. MTT assay proved that H9c2 cells viability was significant reduced under H/R treatment, while the reduction was ameliorated by PMS. H/R-induced ROS production in H9c2 cells was suppressed by PMS. The decreased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the H/R group were effectively elevated by PMS. In addition, treatment with PMS attenuated H/R-stimulated production of TNF-α, IL-6 and IL-1β in H9c2 cells. Besides, PMS significantly suppressed bax expression and caspase 3 activity, as well as increased bcl-2 expression in H/R-stimulated H9c2 cells. Furthermore, we also found that PMS significantly enhanced the activation of Akt/Nrf2/HO-1 signaling pathway and suppressed the activation of NF-κB signaling pathway in H/R-stimulated H9c2 cells. These results provided substantial evidence that PMS protected against myocardial I/R injury via attenuating oxidative stress, inflammatory response and apoptosis. The protective effects of PMS were attributed to the Akt/Nrf2/HO-1 and NF-κB signaling pathways.

Keywords: Akt/Nrf2/HO-1 pathway; Myocardial ischemia/reperfusion (I/R) injury; NF-κB pathway; inflammation; oxidative stress; plantamajoside (PMS).

MeSH terms

  • Animals
  • Apoptosis
  • Catechols
  • Cell Hypoxia
  • Glucosides
  • Hypoxia / metabolism
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocytes, Cardiac / metabolism
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Signal Transduction

Substances

  • Catechols
  • Glucosides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • plantamajoside
  • Proto-Oncogene Proteins c-akt