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Cardamonin attenuates cerebral ischemia/reperfusion injury by activating the HIF-1α/VEGFA pathway
Hongzao Ni1, Jinxiao Li2, Jinyu Zheng1
1Department of Neurosurgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, The Second People's Hospital of Huai'an, Huai'an, China.
Insights
Cardamonin protects brain cells from ischemic stroke by activating the Hypoxia-inducible factor-1 alpha (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway. This natural compound reduces cell damage and brain injury, offering a potential therapeutic strategy.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Ischemic stroke is a leading cause of death and disability worldwide.
- Cardamonin, a natural chalcone, exhibits known neuroprotective properties.
- The precise mechanism of cardamonin's action in ischemic stroke remains to be fully elucidated.
Purpose of the Study:
- To investigate the therapeutic functions of cardamonin in ischemic stroke.
- To elucidate the underlying mechanism of action of cardamonin in stroke models.
- To explore the role of the Hypoxia-inducible factor-1 alpha (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling pathway.
Main Methods:
- Established in vitro (Oxygen-glucose deprivation and reperfusion - OGD/R) and in vivo (middle cerebral artery occlusion - MCAO) models of ischemic stroke.
- Assessed cell viability, permeability, and apoptosis in human brain microvascular endothelial cells (HBMECs).
- Measured protein levels of HIF-1α and VEGFA using Western blotting; evaluated brain injury markers in mice.
Main Results:
- Cardamonin significantly alleviated OGD/R-induced HBMEC damage, including reduced viability, increased permeability, and apoptosis.
- Cardamonin promoted the activation of the HIF-1α/VEGFA signaling pathway in both cellular and animal models.
- Inhibition of the HIF-1α/VEGFA pathway reversed the protective effects of cardamonin, confirming pathway involvement.
Conclusions:
- Cardamonin demonstrates significant neuroprotective effects against ischemic stroke-induced damage.
- The mechanism involves the activation of the HIF-1α/VEGFA signaling pathway.
- Cardamonin represents a promising therapeutic agent for ischemic stroke treatment.
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.
