LAUSR

Cardamonin is a chalcone with neuroprotective activity. The aim of our study was to explore the functions and mechanism of action of cardamonin in ischemic stroke. Oxygen–glucose deprivation and reperfusion (OGD/R)‐induced human brain microvascular endothelial cells (HBMECs) and middle cerebral artery occlusion (MCAO) mouse model were utilized to mimic ischemic stroke. Cell viability was analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide. Permeability was investigated via fluorescein isothiocyanate‐dextran assay. Apoptosis was detected by TdT‐Mediated dUTP Nick End Labeling staining. Hypoxia‐inducible factor (HIF)‐1α and vascular endothelial growth factor A (VEGFA) protein levels were measured using Western blotting. Brain injury was evaluated by 2,3,5‐triphenyltetrazolium chloride staining, neurological score and brain water content. The 37 overlapping targets of ischemic stroke and cardamonin were predicted to be associated with the HIF‐1/VEGFA signaling. Cardamonin alleviated OGD/R‐induced viability reduction and increase of permeability and apoptosis in HBMECs. Cardamonin increased OGD/R‐induced activation of the HIF‐1α/VEGFA pathway. Inhibition of the HIF‐1α/VEGFA signaling using inhibitor relieved the effect of cardamonin on cell viability, permeability and apoptosis in HBMECs under OGD/R. Cardamonin mitigated brain injury and promoted activation of the HIF‐1α/VEGFA signaling in MCAO‐treated mice. Overall, cardamonin protected against OGD/R‐induced HBMEC damage and MACO‐induced brain injury through activating the HIF‐1α/VEGFA pathway.