Abstract: Objective To investigate the protective effects and mechanisms of catechins （Cat） against isoprenaline （ISO）-induced chronic sympathetic stress-related myocardial injury, using network pharmacology, molecular docking, and in vivo and in vitro experiments. Methods Potential targets of Cat were predicted from the BATMAN, DrugBank, TargetNet, TCMSP, and CTD databases. Genes associated with excessive sympathetic nerve activation and myocardial injury were retrieved from the OMIM and GeneCards databases. The overlapping targets between the two datasets were identified as potential therapeutic targets. A protein-protein interaction （PPI） network was constructed using the STRING database and Cytoscape 3.9.1, and core targets were screened out. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to predict relevant signaling pathways. Molecular docking was conducted using AutoDock Vina 1.5.6, and the target-ligand interactions were further validated by visualization with PyMOL. In vivo myocardial injury models were established in mice, and in vitro models were established in AC16 cells, both induced by ISO. The protective effects of Cat and its underlying mechanisms were evaluated by histopathological analysis, TUNEL assay, Annexin Ⅴ-FITC/PI flow cytometry, ELISA, and Western blotting. Results A total of 155 intersecting targets were identified among catechins, sympathetic overactivation, and myocardial injury. KEGG enrichment analysis suggested that the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway might play a key role. Molecular docking results showed that Cat exhibited strong binding affinity to the core targets, namely phosphoinositide-3-kinase catalytic subunit alpha （PIK3CA） and protein kinase B1 （Akt1）. In vivo experiments demonstrated that Cat significantly reversed ISO-induced myocardial fiber disarray, elevated myocardial enzyme levels, and cell apoptosis （P<0.01）. In vitro experiments further confirmed its ability to alleviate ISO-induced myocardial cell apoptosis （P<0.05, P<0.01）. However, after intervention with the PI3K inhibitor LY294002, the anti-apoptotic effect of Cat was markedly attenuated （P<0.05）, suggesting that its action depends on the PI3K/Akt pathway. Conclusion Catechins mitigate sympathetic stress-induced myocardial injury by activating PI3K/Akt signaling and inhibiting cardiomyocyte apoptosis, supporting their potential role in myocardial protection.

Key words: catechins, myocardial injury, PI3K/Akt signaling pathway, network pharmacology