The Neuroprotective Effects of Arecae Pericarpium against Glutamate-Induced HT22 Cell Cytotoxicity

• Published in: Current Issues in Molecular Biology Vol. 44; no. 12; pp. 5902 - 5914
• Main Authors: Jeong, Yun Hee, Oh, You-Chang, Kim, Tae In, Bae, Jong-Sup, Ma, Jin Yeul
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.11.2022; MDPI
• Subjects: Amino acids; Antidepressants; antioxidant; Antioxidants; Apoptosis; Arecae Pericarpium; Development and progression; Glutamate; Nervous system diseases; neuroprotection; nuclear factor erythroid 2-related factor 2; phosphoinositide 3-kinase; protein kinase B; South Korea; Arecae Pericarpium; antioxidant; nuclear factor erythroid 2-related factor 2; neuroprotection; phosphoinositide 3-kinase; protein kinase B
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb44120402

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.