Higenamine protects neuronal cells from oxygen-glucose deprivation/reoxygenation-induced injury.

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.

• Authors: Yi Zhang, Jingjing Zhang, Chuntao Wu, Sheng Guo, Jing Su, Wendong Zhao, Hongxia Xing
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 3 Pg. 3757-3764 (03 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30270549 (Publication Type: Journal Article)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Alkaloids
• Antioxidants
• Bax protein, rat
• Bcl2 protein, rat
• Chromones
• Morpholines
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Tetrahydroisoquinolines
• bcl-2-Associated X Protein
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Malondialdehyde
• Heme Oxygenase-1
• Proto-Oncogene Proteins c-akt
• Casp3 protein, rat
• Caspase 3
• Glucose
• Oxygen
• higenamine

Topics

• Alkaloids (pharmacology)
• Animals
• Animals, Newborn
• Antioxidants (pharmacology)
• Caspase 3 (genetics, metabolism)
• Cell Survival (drug effects)
• Chromones (pharmacology)
• Gene Expression Regulation
• Glucose (deficiency, pharmacology)
• Heme Oxygenase-1 (genetics, metabolism)
• Hippocampus (cytology, metabolism)
• Male
• Malondialdehyde (antagonists & inhibitors, metabolism)
• Models, Biological
• Morpholines (pharmacology)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Neurons (cytology, drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxygen (pharmacology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Primary Cell Culture
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Reperfusion Injury (prevention & control)
• Signal Transduction
• Tetrahydroisoquinolines (pharmacology)
• bcl-2-Associated X Protein (genetics, metabolism)