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Its pathogenesis overlaps with cardiovascular disorders, particularly atherosclerosis and immune\u2013inflammatory 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\u2010related 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\u2013protein 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\u2010compound 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\u2010 and immunity\u2010related pathways. These findings provide preliminary molecular evidence and a basis for further experimental validation of the cerebrovascular protective effects of SBP.<\/jats:p>","DOI":"10.1155\/bmri\/9932683","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:08:56Z","timestamp":1780553336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["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"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0956-8417","authenticated-orcid":false,"given":"Jingju","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3955-5117","authenticated-orcid":false,"given":"Yukun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3345-5334","authenticated-orcid":false,"given":"Xinyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0125-1415","authenticated-orcid":false,"given":"Xue","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.08.015"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001123"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.025250"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.010"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-24-00924"},{"key":"e_1_2_13_7_2","first-page":"1389","article-title":"Current Status and Progress of Mechanical Thrombectomy for Intracranial Distal Medium Vessel Occlusion","volume":"34","author":"Cheng K.","year":"2025","journal-title":"Journal of Interventional Radiology"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.2478\/jtim-2024-0014"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.26599\/1671-5411.2023.09.008"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD010315.pub4"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.189"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30017-X"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1578783"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107953"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1038906"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119341"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01161"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2101026"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117567"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.665456"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-024-01444-z"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1839-4_12"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1996.tb02080.x"},{"key":"e_1_2_13_24_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012487302797"},{"key":"e_1_2_13_25_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010933404324"},{"key":"e_1_2_13_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_13_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2025.108352"},{"key":"e_1_2_13_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_13_29_2","first-page":"5174","article-title":"Mining Potential Anti-inflammatory Targets and Key Active Components of Tiannanxing (Arisaema erubescens) for Treating Maj or Depressive Disorder Based on Machine Learning and Molecular Dynamics Simulation","volume":"55","author":"Zheng Y. 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