Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H(2)O(2)-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H(2)O(2))-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H(2)O(2). First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H(2)O(2)-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H(2)O(2). Mechanistically, MT dramatically suppressed H(2)O(2)-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H(2)O(2)-induced neurotoxicity. These results indicate that MT has protective effects against H(2)O(2)-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.