• Journal of Nutrition and Health
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• v.50 no.5
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• pp.415-425
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• 2017

Purpose: Many studies have suggested that neuronal cells protect against oxidative stress-induced apoptotic cell death by polyphenolic compounds. We investigated the neuroprotective effects and the mechanism of action of Momordica charantia ethanol extract (MCE) against $H_2O_2-induced$ cell death of human neuroblastoma SK-N-MC cells. Methods: The antioxidant activity of MCE was measured by the quantity of total phenolic acid compounds (TPC), quantity of total flavonoid compounds (TFC), and 2,2-Diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging activity. Cytotoxicity and cell viability were determined by CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Antioxidant enzyme (SOD-1,2 and GPx-1) expression was determined by real-time PCR. Mitogen-activated protein kinases (MAPK) pathway and apoptosis signal expression was measured by Western blotting. Results: The TPC and TFC quantities of MCE were 28.51 mg gallic acid equivalents/extract g and 3.95 mg catechin equivalents/extract g, respectively. The $IC_{50}$ value for DPPH radical scavenging activity was $506.95{\mu}g/ml$ for MCE. Pre-treatment with MCE showed protective effects against $H_2O_2-induced$ cell death and inhibited ROS generation by oxidative stress. SOD-1,2 and GPx-1 mRNA expression was recovered by pre-treatment with MCE compared with the presence of $H_2O_2$. Pre-treatment with MCE inhibited phosphorylation of p38 and the JNK pathway and down-regulated cleaved caspase-3 and cleaved PARP by $H_2O_2$. Conclusion: The neuroprotective effects of MCE in terms of recovery of antioxidant enzyme gene expression, down-regulation of MAPK pathways, and inhibition apoptosis is associated with reduced oxidative stress in SK-N-MC cells.

• Journal of Life Science
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• v.31 no.9
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• pp.806-817
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• 2021

Increasing evidence suggests that depression is associated with impairments in neural plasticity. Sirtuin 1 plays an important role in neural plasticity, and the activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling is known to improve neural plasticity. In this study, we aimed to determine whether sirtuin 1 affects dendrite outgrowth and spine formation through mTORC1 signaling. Resveratrol (sirtuin 1 activator; 1 and 10 μM) and sirtinol (sirtuin 1 inhibitor; 1 and 10 μM) were treated in primary cortical culture with and without dexamethasone (500 μM). Levels of sirtuin 1, phospho-extracellular signal regulated protein kinase 1/2 (ERK1/2), phospho-mTORC1, and phospho-p70 ribosomal protein S6 kinase (p70S6K) were evaluated using Western blot analysis. Dendritic outgrowth and spine density were assessed using immunostaining. Resveratrol significantly increased levels of sirtuin 1 expression and phosphorylation of ERK1/2 (a downstream target of sirtuin 1), mTORC1, and p70S6K (a downstream target of mTORC1) in a concentration-dependent manner under dexamethasone conditions. Resveratrol also significantly increased dendritic outgrowth and spine density. Conversely, sirtinol significantly decreased levels of sirtuin 1 expression and phosphorylation of ERK1/2, mTORC1, and p70S6K in a concentration-dependent manner under normal conditions. Moreover, sirtinol significantly decreased dendritic outgrowth and spine density. Consistent with the results of sirtinol, sirtuin 1 knockdown using sirtuin 1 siRNA transfection significantly decreased dendritic outgrowth and spine density as well as phosphorylation levels of ERK1/2 and mTORC1. These data suggest that sirtuin 1 enhances dendritic outgrowth and spine density by activating mTORC1 signaling.