Poricoic acid a inhibits mitochondrial dysfunction in myocardial infarction by activating SIRT3.

Abstract

Acute myocardial infarction (MI) is the most severe clinical manifestation of ischemic heart disease. Despite this, the mechanisms that disrupt mitochondrial homeostasis and contribute to cardiomyocyte loss during MI are poorly understood, emphasizing the urgent need for new therapeutic interventions. Poricoic acid A (PAA), the principal active component of pachymaria, possesses a range of pharmacological effects. However, the specific role and mechanisms by which PAA addresses mitochondrial dysfunction in MI remain unclear. This study aims to elucidate the impact of PAA on MI and uncover its potential regulatory mechanisms. We developed MI cell models using mouse primary cardiomyocytes incubated in a Forma Steri-Cult chamber containing 1% oxygen, 94% nitrogen, and 5% carbon dioxide. Our results demonstrate that PAA significantly improves cardiomyocyte injury in hypoxia-induced mouse primary cardiomyocytes. Furthermore, PAA activates the AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1-alpha/Sirtuin 3 (AMPK/PGC-1α/SIRT3) signaling pathway in hypoxia-induced mouse primary cardiomyocytes. PAA enhances the oxidative stress response in hypoxia-induced mouse primary cardiomyocytes by activating SIRT3. Additionally, it improves mitochondrial dysfunction in these cardiomyocytes and reduces apoptosis by activating SIRT3. In summary, PAA inhibits mitochondrial dysfunction associated with MI by activating SIRT3, indicating its promise as a therapeutic agent for MI.