Exploration on Medication Patterns and Mechanisms of National Patented Traditional Chinese Medicine Compound Prescriptions for Ischemic Stroke Based on Data Mining and In Silico Knockdown
This study systematically interrogated the China National Intellectual Property Administration patent database to identify candidate core herb combinations and therapeutic targets for ischemic stroke (IS), integrating cluster analysis, network pharmacology, molecular docking, molecular dynamics simulations, single-cell RNA sequencing, spatial transcriptomics, and CellOracle-based in silico knockdown. A core herb combination of Polygalae Radix, Acori Tatarinowii Rhizoma, Rhei Radix et Rhizoma, and Curcumae Radix was identified, yielding nine representative active components (1-hydroxyacoronene, aristolone, calamendiol, β-asarone, α-asarone, kaempferol, thymol, eugenol, caffeic acid) and six candidate targets (TNF, IL-6, AKT1, EGFR, MAPK1, PTGS2). Molecular docking and dynamics simulations indicated binding tendencies, with kaempferol-PTGS2 and kaempferol-EGFR complexes showing stability under simulated conditions. Single-cell and spatial transcriptomics revealed spatial concordance between high candidate target expression regions and macrophage/astrocyte distribution. CellOracle predicted that Jun/Fos and STAT3 transcription factors may regulate post-ischemic inflammatory responses and cell state transitions. The study constructs a mechanistic evidence chain linking core herbs, active components, candidate targets, and spatiotemporal validation, offering a modern biological interpretation of the 'Tongfu Xingshen' therapeutic principle. However, findings remain computational and require experimental validation; limitations include single-timepoint single-cell data (24 h post-MCAO), reliance on public databases, and lack of in vivo/in vitro efficacy experiments.