Network-based analysis identifies shared mechanisms between ischemic stroke and myocardial infarction and therapeutic...

Ischemic stroke (IS) and myocardial infarction (MI) share overlapping etiology and pathology, highlighting the need for dual-effective therapies. Buyang Huanwu Decoction (BHD) has shown efficacy against both diseases individually, but its core ingredients and dual therapeutic mechanisms remain unclear.

Using network-based analysis, we identified shared targets and convergent pathways for IS and MI, prioritized BHD ingredients by network proximity, and performed functional enrichment analyses. Molecular docking validated interactions between the key target GSK-3β and core ingredients, and surface plasmon resonance (SPR) experimentally determined the binding affinity of the top-ranked ingredient, Myricanone, to GSK-3β.

Thirteen shared core targets were identified, with the "Lipid and atherosclerosis" pathway as the principal common mechanism. Ten key BHD ingredients with predicted dual therapeutic effects were prioritized. Among the shared targets, GSK3B emerged as a central node. Molecular docking showed stable binding of all core ingredients to GSK-3β, with Myricanone exhibiting the strongest affinity (-9 kcal/mol), which was confirmed by SPR (KD = 55.1 µM).

These findings elucidate the shared mechanisms of BHD against IS and MI, supporting its potential as a multi-target phytotherapeutic strategy for ischemic cardio-cerebrovascular disorders.