Cardamonin attenuates cerebral ischemia/reperfusion injury by activating the HIF‐1α/VEGFA pathway

Abstract

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.

N6-methyladenosine-modified lncRNA and mRNA modification profiles in cerebral ischemia-reperfusion injury

“…Consistent with the method described previously ( Ni et al, 2022 ), after neurological evaluation, the rats were anesthetized; the whole brain was quickly removed; and the olfactory bulb, cerebellum, and lower brainstem were removed. The brains in each group were removed after being frozen in a freezer at -20°C for 15 min; placed on ice disks from the frontal pole to the occipital pole; centered at the level of the optic chiasm; and subjected to coronal, equal thickness sectioning with a slice thickness of 2 mm.…”

Chlorogenic acid promotes angiogenesis and attenuates apoptosis following cerebral ischaemia-reperfusion injury by regulating the PI3K-Akt signalling

“…The MCAO model was established referring to the previously reported protocols (Ni et al. 2022 ). In brief, a midline incision was created in the anaesthetized mice by 2% isoflurane.…”

The Signaling Pathways and Targets of Natural Compounds from Traditional Chinese Medicine in Treating Ischemic Stroke

“…Mey.) and Cardamonin (a chalcone component extracted from the seeds of Amomum villosum Lour..) activates the HIF-1α/VEGF signaling pathway in rats with ischemia-reperfusion injury, and upregulate the protein expression of HIF-1α and VEGF, thereby increasing cerebral microvascular density and promoting intracerebral revascularization, and promoting angiogenesis, neural repair and functional recovery in MCAO rats [ 118 , 119 ].…”