Exploring the Mechanism of Shexiang Baoxin Pill in the Treatment of Ischemic Stroke: A Study Integrating Network Pharmacology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation

Ischemic stroke (IS) is a major global cause of mortality and long-term disability and is closely associated with cardiovascular disease (CVD). Its pathogenesis overlaps with cardiovascular disorders, particularly atherosclerosis and immune-inflammatory dysregulation. Shexiang Baoxin Pill (SBP), a traditional Chinese medicine used for coronary heart disease and angina pectoris, has been reported to improve microcirculation and alleviate inflammation; however, the mechanisms of SBP against IS remain unclear. Here, an integrated strategy combining network pharmacology, machine learning, molecular docking, and molecular dynamics simulation was applied to explore the potential mechanisms of SBP in IS. In total, 126 bioactive compounds and 796 potential targets of SBP were identified. Intersection analysis with IS-related differentially expressed genes from GEO datasets identified six candidate targets: CXCL8, IL1B, JUN, NR4A2, PTGS2, and TNF. Functional enrichment analysis suggested that these targets were mainly involved in cardiovascular and cerebrovascular processes, including inflammatory responses, immune regulation, and apoptosis. Combined protein-protein interaction network analysis and machine learning further identified TNF and JUN as hub genes related to IS. Molecular docking and molecular dynamics simulations suggested stable binding between representative active ingredients (e.g., bufalin and bufotalin) and the two hub targets, and the TNF-compound complexes remained structurally stable during the simulation. Collectively, this computational study suggests that SBP may exert therapeutic effects in IS through a multicomponent and multitarget regulatory network involving inflammation- and immunity-related pathways. These findings provide preliminary molecular evidence and a basis for further experimental validation of the cerebrovascular protective effects of SBP.