Network Pharmacology Identifies AKT1 and TP53 as Core TargetsMediating Yang-Invigorating Herbs in Cold-Coagulation ACS

INTRODUCTION: This study clarified the multitarget mechanisms of TCM formulas for treating ACS with CCHV pattern, providing a scientific basis for climate-adaptive prevention and treatment strategies for cardiovascular diseases. METHODS: Literature mining screened clinically effective TCM formulas. Meridian tropism was analyzed via TCMICS; active compounds were retrieved from TCMSP. GEO transcriptomic data and disease targets from GeneCards, OMIM, and PharmGKB were integrated to construct herbcompound- target and PPI networks, followed by GO and KEGG enrichment analyses. Molecular docking, 100-ns MD simulations, and ADME analysis verified the pharmacokinetics of drug formulations, supplemented by cell experiment validation of key interactions. RESULTS: A core formula consisting of Fuzi, Ganjiang, Wutou, Shujiao, Renshen, and Gancao was identified. Key bioactive compounds (e.g., quercetin, kaempferol) targeted TP53, AKT1, and MAPK1, modulating glycolipid metabolism, inflammation, and oxidative stress. They exhibited strong binding to AKT1 (binding free energies -16.89 and -21.26 kcal·mol⁻¹), forming stable complexes. They also possessed favorable pharmacological properties, inhibited cold - induced cardiomyocyte apoptosis, and showed a correlation with AKT1 and TP53 in WB experiments. DISCUSSION: Core TCM drugs demonstrate that they target AKT1 and TP53 via quercetin and kaempferol, regulating metabolism, inflammation, and oxidative stress. CONCLUSION: This provides a multitarget mechanism basis for treating ACS with CCHV patterns.