Background: Despite significant advances in therapeutic approaches, the overall prognosis of acute myocardial infarction (AMI) patients remains poor. Poria cocos, a traditional edible medicinal fungus, contains Pachymic acid A (PAA), a triterpenoid compound recognized for its potent anti-inflammatory properties across various inflammatory conditions. Therefore, we investigated the effects of PAA in a murine AMI model and explored its underlying mechanisms.

Methods: AMI was induced in mice by tying the left anterior descending (LAD) coronary artery, and the model mice were treated with different concentrations of PAA. Histological staining was employed to assess cardiac tissue injury. Oxidative stress markers and inflammatory cytokines in myocardial tissues were quantified using Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). and biochemical assays. Apoptotic cardiomyocytes were identified via the Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay. Immunoblotting was conducted to quantify autophagy-associated proteins (Microtubule-associated protein 1A/1B light chain 3 (LC3) II/LC3I, Beclin1, p62) and the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway.

Results: PAA treatment significantly reduced myocardial injury and fibrosis in AMI mice. It suppressed the expression levels of pro-inflammatory cytokines Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-6, and IL-1β, decreased malondialdehyde (MDA), and icreased glutathione peroxidase (GSH-Px) activity (p < 0.05). Furthermore, PAA attenuated cardiomyocyte apoptosis and enhanced autophagy, as evidenced by elevated LC3II/LC3I and Beclin1 expression and reduced p62 levels. The AMPK pathway was found to be activated due to increased p-AMPK/AMPK ratios and reduced p-mTOR/mTOR expression (p < 0.05).

Conclusion: PAA may reduce AMI-induced cardiac injury by activating AMPK signaling and promoting autophagy, thereby reducing inflammation, oxidative stress, and apoptosis in myocardial tissue.