Investigating the Mechanism of Yiqi Huoxue Jieyu Granules Against Ischemic Stroke Through Network Pharmacology, Molecular Docking and Experimental Verification

<b>Background:</b> Ischemic stroke (IS) is a significant cause of global mortality and disability. Yiqi Huoxue Jieyu granules (YHJGs) show therapeutic potential for IS, but their mechanisms remain unclear. This study investigated YHJGs' effects through network pharmacology, molecular docking, and experimental validation. <b>Methods:</b> Active YHJG components and IS targets were identified from TCMSP, GeneCards, and DisGeNET databases. Network analysis and molecular docking (AutoDock Vina) were performed. In vivo studies used 72 male Sprague-Dawley rats (MCAO model) divided into sham, model, nimodipine (10.8 mg/kg), and three YHJG dose groups (0.72, 1.44, 2.88 g/kg). Assessments included neurological scores, TTC staining, histopathology, and molecular analyses (qPCR/Western blot). <b>Results:</b> Network analysis identified 256 shared targets between YHJG and IS, with PI3K-AKT and MAPK as key pathways. Molecular docking showed strong binding between YHJG compounds (e.g., quercetin) and core targets (AKT1, ERK1/2). YHJG treatment significantly improved neurological function (<i>p</i> < 0.01), reduced infarct volume (<i>p</i> < 0.01), and attenuated neuronal damage. The expression of IL-1β, TNF-α, IL-6, AKT1, and pERK1/2/ERK1/2 significantly increased in the MCAO group (<i>p</i> < 0.01), while YHJG treatment significantly reduced their expression (<i>p</i> < 0.01). PPAR-γ expression significantly increased in the YHJG-H group (<i>p</i> < 0.01). <b>Conclusions:</b> The expression of IL-1β, TNF-α, IL-6, AKT1, and pERK1/2/ERK1/2 significantly increased in the MCAO group, while YHJG treatment significantly reduced their expression. PPAR-γ expression significantly increased in the YHJG-H group. YHJGs could treat IS through diverse ingredients, targets, and pathways by inhibiting inflammatory indices and AKT1 expression, and reducing ERK1/2 phosphorylation.