神经保护
SH-SY5Y型
安普克
自噬
氧化应激
PI3K/AKT/mTOR通路
药理学
蛋白激酶A
活性氧
西妥因1
化学
细胞凋亡
MAPK/ERK通路
下调和上调
激酶
细胞生物学
神经母细胞瘤
生物化学
生物
细胞培养
遗传学
基因
作者
Ha-Rin Moon,Jung‐Mi Yun
出处
期刊:Journal of Medicinal Food
[Mary Ann Liebert]
日期:2023-09-01
卷期号:26 (9): 641-653
被引量:1
标识
DOI:10.1089/jmf.2023.k.0022
摘要
Oxidative stress is recognized as one of the main reasons for cellular damage and neurodegenerative diseases. Zerumbone is one of the sesquiterpenoid compounds in the essential oil of Zingiber zerumbet Smith. Zerumbone exhibits various physiological activities, such as anticancer, antioxidant, and antibacterial effects. However, studies on the neuroprotective efficacy of zerumbone and the mechanism behind it are lacking. In this study, we explored the neuroprotective efficacy of zerumbone and its mechanism in hydrogen peroxide-treated human neuroblastoma SH-SY5Y cells. H2O2 treatment (400 μM) for 24 h enhanced the generation of intracellular reactive oxygen species (ROS) compared to untreated cells. By contrast, zerumbone treatment significantly suppressed the production of intracellular ROS. Zerumbone significantly inhibited H2O2-induced nitric oxide production and expression of inflammation-related genes. Moreover, zerumbone decreased H2O2-induced mitogen-activated protein kinase (MAPK) protein expression. Various hallmarks of apoptosis in H2O2-treated cells were suppressed in a dose-dependent manner through downregulation of the Bax/Bcl-2 expression ratio by zerumbone. Since activation of AMP-activated kinase (AMPK) is a promising therapeutic target for neurodegenerative diseases, we also investigated the mammalian target of rapamycin (mTOR) as part of the autophagy mechanism in H2O2-treated SH-SY5Y cells. In this study, zerumbone upregulated the expression of Sirtuin 1 (SIRT1) and p-AMPK (which were downregulated by the H2O2 treatment) and downregulated p-mTOR. Altogether, our results propose that inhibition of apoptosis and inflammation by autophagy activation plays an important neuroprotective role in H2O2-treated SH-SY5Y cells. Zerumbone may thus be a potent dietary agent that reduces the onset and progression, as well as prevents neurodegenerative diseases.
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