Luteolin and quercetin from tongguan capsules alleviate myocardial infarction: A network pharmacology and in vitro study.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Tongguan Capsule (TGC), a traditional Chinese medicine formulation, has been used for treating cardiovascular diseases, but its active components and mechanisms remain incompletely understood.In this study, we systematically identified the key active components of TGC and validated their cardioprotective effects through an integrated strategy combining network pharmacology, molecular docking, molecular dynamics simulations, and in vitro biological experiments, enabling a stepwise workflow from computational prediction to experimental validation.Network pharmacology analysis revealed that luteolin and quercetin are the core active components of TGC against MI. The core targets included Akt1, IL-6, Caspase3, VEGFA, and MMP9. GO and KEGG enrichment analyses indicated that these components primarily act through biological processes including oxidative stress, inflammation, and apoptosis, with the PI3K/Akt and MAPK signaling pathways being the main enriched pathways.Molecular docking and molecular dynamics simulations demonstrated strong binding affinities between the two compounds and their core targets, particularly Caspase3. In vitro experiments using H₂O₂-induced HL-1 cardiomyocytes showed that treatment with luteolin (10 μM) and quercetin (20 μM) significantly reduced the phosphorylation levels of ERK, P38, and Akt. Furthermore, the treatment decreased the protein expression ratios of Bax/Bcl-2 and Cleaved Caspase3/Caspase3, as well as the levels of MMP9 and NLRP3. The mRNA expression levels of ANP, BNP, β-MHC, TNF-α, IL-6, collagen I, and collagen III were also downregulated. Collectively, these findings demonstrate that luteolin and quercetin - two active components derived from TGC - alleviate myocardial infarction by mitigating oxidative stress, inhibiting apoptosis and inflammation, and reducing fibrosis. This study combines network pharmacology, molecular docking, molecular dynamics simulations and in vitro experimental techniques to elucidate the cardioprotective mechanisms of the two compounds.