Abstract
Higenamine, a plant-based alkaloid, exhibits various properties, such as antiapoptotic and antioxidative effects. Previous studies proved that higenamine possesses potential therapeutic effects for ischemia/reperfusion (I/R) injuries. However, the role of higenamine in cerebral I/R injury has not been fully evaluated. Therefore, we aimed to investigate the effect of higenamine on cerebral I/R injury and the potential mechanism. Our data showed that higenamine ameliorated oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal cells injury. Induction of reactive oxygen species and malonaldehyde production, and the inhibition of superoxide dismutase and glutathione peroxidase activity caused by OGD/R were attenuated by higenamine. In addition, higenamine inhibited the increases in caspase-3 activity and Bax expression, and inhibited the decrease in Bcl-2 expression. Furthermore, higenamine elevated the expression levels of p-Akt, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitor of PI3K/Akt (LY294002) abolished the protective effects of higenamine on OGD/R-induced neuronal cells. These findings indicated that higenamine protects neuronal cells against OGD/R-induced injury by regulating the Akt and Nrf2/HO-1-signaling pathways. Collectively, higenamine might be considered as new strategy for the prevention and treatment of cerebral I/R injury.
Keywords:
cell apoptosis; cerebral ischemia/reperfusion injury; higenamine; oxidative stress.
© 2018 Wiley Periodicals, Inc.
MeSH terms
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Alkaloids / pharmacology*
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Animals
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Animals, Newborn
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Antioxidants / pharmacology*
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cell Survival / drug effects
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Chromones / pharmacology
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Gene Expression Regulation
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Glucose / deficiency
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Glucose / pharmacology*
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Heme Oxygenase-1 / genetics
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Heme Oxygenase-1 / metabolism
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Hippocampus / cytology
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Hippocampus / metabolism
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Male
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Malondialdehyde / antagonists & inhibitors
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Malondialdehyde / metabolism
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Models, Biological
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Morpholines / pharmacology
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NF-E2-Related Factor 2 / genetics
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NF-E2-Related Factor 2 / metabolism
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Neuroprotective Agents / pharmacology*
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Oxygen / pharmacology*
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Primary Cell Culture
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / antagonists & inhibitors
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Reactive Oxygen Species / metabolism
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Reperfusion Injury / prevention & control
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Signal Transduction
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Tetrahydroisoquinolines / pharmacology*
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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Alkaloids
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Antioxidants
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Bax protein, rat
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Bcl2 protein, rat
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Chromones
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Morpholines
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NF-E2-Related Factor 2
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Neuroprotective Agents
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Nfe2l2 protein, rat
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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Tetrahydroisoquinolines
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bcl-2-Associated X Protein
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Malondialdehyde
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Heme Oxygenase-1
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Proto-Oncogene Proteins c-akt
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Casp3 protein, rat
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Caspase 3
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Glucose
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Oxygen
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higenamine