Uncovering the therapeutic potential of Si-Miao-Yong-An decoction in abdominal aortic aneurysm: An integrative study combining network pharmacology, machine learning, molecular docking and dynamics simulation

Abdominal aortic aneurysm (AAA) is a progressive and life-threatening vascular disorder characterized by abnormal dilation of the abdominal aorta and a high risk of rupture. Current pharmacological interventions remain limited in efficacy, highlighting the need for alternative therapeutic strategies. Si-Miao-Yong-An Decoction (SMYAD), a classical formula in traditional Chinese medicine, has demonstrated anti-inflammatory and vascular-protective effects, yet its underlying mechanisms in AAA treatment remain unclear. This study employed an integrative approach combining network pharmacology, machine learning, and molecular modeling to elucidate the pharmacological basis of SMYAD against AAA. A total of 106 bioactive compounds and 235 putative targets were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. These were cross-referenced with disease-associated and differentially expressed genes from GEO datasets, identifying 15 targets potentially involved in AAA pathogenesis. Functional enrichment analyses revealed their involvement in the interleukin-17 and tumor necrosis factor signaling pathways. Integrated PPI network analysis and 3 machine learning algorithms jointly identified 6 hub genes (IL6, PTGS2, IL1B, FOS, MAOA, and COL1A1) as central to AAA pathology. Gene expression profiling and ROC curve analysis further supported the diagnostic relevance of these targets. Five key compounds—quercetin, luteolin, kaempferol, isorhamnetin, and stigmasterol—exhibited strong binding affinities with the identified hub targets. Molecular docking and dynamics simulations confirmed stable interactions between the selected compounds and their targets. Overall, this study provides mechanistic insights into the multi-target actions of SMYAD in AAA and offers theoretical support for its potential clinical application.