Objective  Based on the integrated strategy of ultra-performance liquid chroma-tography-orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) multicomponent analysis and network pharmacology, to systematically elaborate the "multi-component-multi-target-multi-pathway" synergistic mechanism of Gualou Xiebai decoction (GLXB) in the treatment of myocardial infarction.

Methods  Qualitative analysis of chemical components in GLXB was conducted using UPLC-Orbitrap-MS/MS technology, and therapeutic potential targets were predicted using bioinformatics tools such as SwissTargetPrediction. Subsequently, a "component-target-pathway" network and a protein-protein interaction network were constructed. Further molecular docking validation was performed using AutoDock Tools 1.5.6 software to evaluate the binding activity between core components and key targets with a binding energy of ≤ -5.0 kcal/mol as the standard.

Results  Five core active components were screened out, including 9S,13R-12-oxophytodienoic acid, tributyl citrate, palmitic acid, L-prolyl-L-leucine, and hexanoylglycine, which were found to target key protein nodes such as mitogen activated protein kinase 3 (MAPK3), mitogen activated protein kinase 1 (MAPK1), heat shock protein 90AA1 (HSP90AA1), estrogen receptor 1 (ESR1), and cysteine-aspartic protease 3 (CASP3). Among them, L-prolyl-L-leucine exhibited the lowest binding energies with MAPK3 and MAPK1 (-9.6 kcal/mol and -8.9 kcal/mol, respectively), suggesting that they may be the core "component-target" pairs responsible for the cardioprotective effect of GLXB.

Conclusion  GLXB exerts cardioprotective effects by regulating the MAPK signaling pathway, nuclear receptor-mediated transcriptional regulation, and inflammatory response networks, thereby improving myocardial energy metabolism, inhibiting oxidative stress-induced damage, and alleviating excessive inflammatory responses.

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