This study was designed to understand the pivotal anti-
cerebral ischemia/
reperfusion injury (CIRI) targets and pathways of
calycosin through network pharmacology and molecular docking analyses. In this study, bioinformatics tools were employed to characterize and identify the pharmacological functions and mechanisms of
calycosin for CIRI management. The network pharmacology data identified potential, merged CIRI-associated targets of
calycosin including
tumor protein p53 (
TP53), protein kinase B (AKT1),
vascular endothelial growth factor A (VEGFA),
interleukin 6,
tumor necrosis factor (TNF), and
mitogen-activated protein kinase 1 (MAPK1). Molecular docking analysis indicated the binding efficacy of
calycosin with three of the targets, namely TP53, AKT1, and VEGFA. The biological processes of
calycosin for the treatment of CIRI are mainly involved in the improvement of endothelial cell proliferation and growth, inflammatory development, and cellular metabolism. In addition, the anti-CIRI actions of
calycosin were primarily through suppression of the
toll-like receptor, PI3K-AKT, TNF, MAPK, and
VEGF signaling pathways. Taken together, the current bioinformatic findings revealed pivotal targets, biological functions, and pharmacological mechanisms of
calycosin for the treatment of CIRI. In conclusion,
calycosin, a functional
phytoestrogen, can be potentially used for the treatment of CIRI in future clinical trials.