Nutr Res Pract.  2020 Feb;14(1):3-11. 10.4162/nrp.2020.14.1.3.

Neuroprotective effects of urolithin A on Hâ‚‚Oâ‚‚-induced oxidative stress-mediated apoptosis in SK-N-MC cells

Affiliations
  • 1Research Institute, Seoul Medical Center, Seoul 02053, Korea. nostoi72@naver.com
  • 2Department of Neurosurgery, Seoul Medical Center, 156 Shinnea-ro, Seoul 02053, Korea.

Abstract

BACKGROUND/OBJECTIVES
Oxidative stress causes cell damage and death, which contribute to the pathogenesis of neurodegenerative diseases. Urolithin A (UA), a gut microbial-derived metabolite of ellagitannins and ellagic acid, has high bioavailability and various health benefits such as antioxidant and anti-inflammatory effects. However, it is unknown whether it has protective effects against oxidative stress-induced cell death. We investigated whether UA ameliorates Hâ‚‚Oâ‚‚-induced neuronal cell death.
MATERIALS/METHODS
We induced oxidative damage with 300 µM Hâ‚‚Oâ‚‚ after UA pretreatment at concentrations of 1.25, 2.5, and 5 µM in SK-N-MC cells. Cytotoxicity and cell viability were determined using the CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using a 2,7-dichlorofluorescein diacetate assay. Hoechst 33342 staining was used to characterize morphological changes in apoptotic cells. The expressions of apoptosis proteins were measured using Western blotting.
RESULTS
UA significantly increased cell viability and decreased intracellular ROS production in a dose-dependent manner in SK-N-MC cells. It also decreased the Bax/Bcl-2 ratio and the expressions of cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved PARP. In addition, it suppressed the phosphorylation of the p38 mitogen-activated protein kinase (MAPK) pathway.
CONCLUSIONS
UA attenuates oxidative stress-induced apoptosis via inhibiting the mitochondrial-related apoptosis pathway and modulating the p38 MAPK pathway, suggesting that it may be an effective neuroprotective agent.

Keyword

Neurodegenerative diseases; metabolite; reactive oxygen species; apoptosis; p38MAPK

MeSH Terms

Apoptosis*
Biological Availability
Blotting, Western
Caspase 3
Caspase 9
Cell Death
Cell Survival
Cytochromes c
Ellagic Acid
Hydrolyzable Tannins
Insurance Benefits
Neurodegenerative Diseases
Neurons
Neuroprotective Agents*
Oxidative Stress
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Protein Kinases
Reactive Oxygen Species
Sincalide
Caspase 3
Caspase 9
Cytochromes c
Ellagic Acid
Hydrolyzable Tannins
Neuroprotective Agents
Protein Kinases
Reactive Oxygen Species
Sincalide
p38 Mitogen-Activated Protein Kinases
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