Anthocyanidin attenuates myocardial ischemia induced injury via inhibition of ROS‐JNK‐Bcl‐2 pathway: New mechanism of anthocyanidin action

Abstract

Despite treatment options available to date, myocardial ischemia (MI) remains the leading cause of death worldwide. Studies are focused on finding effective therapeutic strategies against MI injury. Growing interest has been developed in natural compounds possessing medicinal properties with scarcer side effects. Here, we have evaluated the cardioprotective potential of anthocyanidin against MI injury and explored its underlying protective mechanism. Left anterior descending coronary artery was ligated to induce MI in mice. Neonatal mice cardiomyocytes were treated with H2O2 to induce oxidative stress (a major contributor to MI injury) in vitro. Anthocyanidin pretreatment significantly reduced the infarct size, preserved the cell viability, and protected against ischemia‐induced cardiac injury in treatment groups compared with the H2O2‐treated group in vitro. Measurement of reactive oxygen species (ROS) validated the strong antioxidant potential of anthocyanidin, as significant reduction in oxidative stress was observed in anthocyanidin‐pretreated groups. Mechanistically, pretreatment with anthocyanidin significantly subdued the activation of JNK (to p‐JNK) and elevated Bcl‐2 levels. Both in vivo and in vitro findings suggest that anthocyanidin can induce a state of myocardial resistance against ischemic insult. We have provided the experimental evidence for inhibition of ROS/p‐JNK/Bcl‐2 pathway being the underlying mechanism of action of anthocyanidin. Our results support the use of anthocyanidin as therapeutic strategy against MI injury.

[8]‐Gingerol exerts anti‐myocardial ischemic effects in rats via modulation of the MAPK signaling pathway and L‐type Ca2+ channels

“…If MI does occur, the oxidative stress reaction would be accelerated, thus, causing a large accumulation of oxygen free radicals, ROS production, and Ca 2+ overload, which would lead to aggravated myocardial injury and even cause cardiocyte apoptosis. 14 , 43 SOD, CAT, and GSH, as important antioxidant enzymes, can effectively eliminate oxygen free radicals and prevent ROS generation so as to protect myocardial tissue. In addition, excessive production of oxygen free radicals can cause lipid peroxidation and further myocardial injury.…”

“…Evidence has been found that the stress‐activated JNK (p‐JNK) mediates phosphorylation of Bcl‐2 under ischemic conditions, which leads to irreversible cardiac injury. 14 Based on these studies, it appears that the level of ROS production and relative activity of MAPK pathway will determine whether cells survive or not. Therefore, this pathway may be a potential target for the therapy of MI disease by inhibition of oxidative stress and apoptosis.…”

“…Bcl‐2 family proteins contain anti‐apoptotic genes Bcl‐2 and apoptosis‐stimulating protein Bax. Evidence has been found that the stress‐activated JNK (p‐JNK) mediates phosphorylation of Bcl‐2 under ischemic conditions, which leads to irreversible cardiac injury 14 . Based on these studies, it appears that the level of ROS production and relative activity of MAPK pathway will determine whether cells survive or not.…”

Pharmacology of Catechins in Ischemia-Reperfusion Injury of the Heart

“…It can be modulated also by exogenously administered cardioprotective compounds, including natural phenolic compounds [135,136]. As for the role of JNK/p38-MAPK in cardioprotective action of catechins, it has been documented that EGCG infused to the perfusion medium before regional I/R (35 min/2 h) in isolated rat hearts reversed I/Renhanced p38 phosphorylation and reduced IS [89].…”

“…In myocardial I/R, the JNK pathway is activated mainly during the reperfusion period and was also reported to participate in ischemic preconditioning (for review see: [ 133 , 134 ]). It can be modulated also by exogenously administered cardioprotective compounds, including natural phenolic compounds [ 135 , 136 ]. As for the role of JNK/p38-MAPK in cardioprotective action of catechins, it has been documented that EGCG infused to the perfusion medium before regional I/R (35 min/2 h) in isolated rat hearts reversed I/R-enhanced p38 phosphorylation and reduced IS [ 89 ].…”