The Neuroprotective Effects of Arecae Pericarpium against Glutamate-Induced HT22 Cell Cytotoxicity.
Yun Hee JeongYou-Chang OhTae-In KimJong Sup BaeJin Yeul MaPublished in: Current issues in molecular biology (2022)
Arecae Pericarpium has been found to exert anti-migraine, antidepressant, and antioxidative effects. However, the mechanisms involved are unclear. This study explored the possibility that Arecae Pericarpium ethanol extract (APE) exerts neuroprotective effects against oxidative stress-induced neuronal cell death. Since glutamate excitotoxicity has been implicated in the pathogenesis and development of several neurodegenerative disorders, we explored the mechanisms of action of APE on oxidative stress-induced by glutamate. Our results revealed that pretreatment with APE prevents glutamate-induced HT22 cell death. APE also reduced both the levels of intracellular reactive oxygen species and the apoptosis of cells, while maintaining glutamate-induced mitochondrial membrane potentials. Western blotting showed that pretreatment with APE facilitates the upregulation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) phosphorylation; the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2); and the production of antioxidant enzymes, including catalase, glutamate-cysteine ligase catalytic subunits, NAD(P)H quinone oxidoreductase 1, and heme oxygenase (HO)-1. The administration of LY294002, a PI3K/Akt inhibitor, attenuated the neuroprotective effects of APE on oxidative stress-induced neuronal cell damage. This allowed us to infer that the protective effects of APE on oxidative damage to cells can be attributed to the PI3K/Akt-mediated Nrf-2/HO-1 signaling pathway.
Keyphrases
- cell cycle arrest
- pi k akt
- oxidative stress
- signaling pathway
- diabetic rats
- cell death
- induced apoptosis
- cell proliferation
- protein kinase
- high glucose
- nuclear factor
- reactive oxygen species
- dna damage
- single cell
- ischemia reperfusion injury
- epithelial mesenchymal transition
- endoplasmic reticulum stress
- drug induced
- toll like receptor
- cerebral ischemia
- south africa
- subarachnoid hemorrhage
- immune response
- major depressive disorder
- endothelial cells
- cell therapy
- mouse model
- bone marrow
- tyrosine kinase
- brain injury
- blood brain barrier
- heat shock