Neuroprotective effects of urolithin A on H 2 O 2 -induced oxidative stress-mediated apoptosis in SK-N-MC cells

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 H2O2-induced neuronal cell death. MATERIALS/METHODS:We induced oxidative damage with 300 μM H2O2 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.