Objective To systematically identify the candidate core herb combination and potential therapeutic targets for ischemic stroke by integrating patent mining, spatiotemporal multi-omics analysis, and computational simulation, and elucidate the scientific connotation of the traditional Chinese medicine therapeutic principle of “Tongfu Xingshen” based on the patent database of traditional Chinese medicine compound prescriptions. Methods The China National Intellectual Property Administration patent database was searched. Cluster analysis was used to screen the candidate core herb combination. Network pharmacology, molecular docking, and molecular dynamics simulations were then performed to identify and evaluate candidate therapeutic targets of traditional Chinese medicine compound prescriptions for ischemic stroke. Single-cell RNA sequencing, spatial transcriptomics, and CellOracle-based in silico knockdown analysis were further integrated to perform multidimensional association analysis. Results A candidate core herb combination consisting of Yuanzhi (Polygalae Radix), Shichangpu (Acori Tatarinowii Rhizoma), Dahuang (Rhei Radix et Rhizoma), and Yujin (Curcumae Radix) was identified. Nine representative active components, including 1-hydroxyacoronene, aristolone, calamendiol, β-asarone, α-asarone, kaempferol, thymol, eugenol, and caffeic acid, and six candidate therapeutic targets, including tumor necrosis factor (TNF), interleukin-6 (IL-6), protein kinase B1 (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), and prostaglandin-endoperoxide synthase 2 (PTGS2), were obtained. Molecular docking and molecular dynamics simulations suggested that some representative active components exhibited certain binding tendencies with the candidate target proteins. Among them, the kaempferol-PTGS2 and kaempferol-EGFR complexes showed a degree of stability under simulation conditions. Single-cell and spatial transcriptomic analyses further showed that the regions with high expression of candidate targets were spatially consistent with the distribution of macrophages, astrocytes, and other cell populations. CellOracle analysis suggested that Jun/Fos, signal transducer and activator of transcription 3 (STAT3), and other related transcription factors may be involved in post-ischemic inflammatory responses, cell-state transitions, and repair-related regulatory processes. Conclusion This study identified a candidate core herb combination consisting of Polygalae Radix, Acori Tatarinowii Rhizoma, Rhei Radix et Rhizoma, and Curcumae Radix from national patent traditional Chinese medicine compound prescriptions, and proposed that PTGS2, IL-6, EGFR, and related targets may serve as important candidate targets in the regulation of the inflammatory microenvironment in ischemic stroke. These findings preliminarily construct a mechanistic evidence chain integrating the core herb combination, core components, candidate targets, and spatiotemporal validation, and provide a reference for the modern mechanism explanation and subsequent experimental verification of the “Tongfu Xingshen” therapeutic principle in ischemic stroke from the perspectives of inflammatory microenvironment regulation, cell-cell communication, and neurovascular remodeling.

ischemic stroke  /  data mining  /  single-cell RNA sequencing  /  spatial transcriptomics  /  in silico knockdown  /  Polygalae Radix  /  Acori Tatarinowii Rhizoma  /  Rhei Radix et Rhizoma  /  Curcumae Radix  /  kaempferol