Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H2O2-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling.

Weishun Tian,Hyun-Jin Tae,In-Shik Kim,Myung-Kon Kim,Dongchoon Ahn,Dae-Woon Kim,Suyoung Heo,Byung-Yong Park

doi:10.3390/ijms22136946

Weishun Tian, Hyun-Jin Tae + Show 6 more

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https://doi.org/10.3390/ijms22136946

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Abstract

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 (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. 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 H2O2-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 H2O2. Mechanistically, MT dramatically suppressed H2O2-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 H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.

Highlights

Introduction published maps and institutional affilNeurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease (AD), are caused mainly by neuronal damage, which is triggered by oxidative stress in many situations [1,2,3,4]
These results indicate that Maclura tricuspidata fruit (MT) is capable of protecting neuroblastoma cells from H2 O2 -induced damage by blocking Mitogenactivated protein kinase (MAPK) and Nuclear factor-κB (NF-κB) signaling
Most natural medicines are rich in antioxidants and have limited side effects. In this case, looking for potential neuroprotective agents from natural products that can reduce neurotoxicity caused by oxidative stress may help prevent and treat neurodegenerative diseases [30]

Summary

Introduction

Neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease (AD), are caused mainly by neuronal damage, which is triggered by oxidative stress in many situations [1,2,3,4]. Endogenous ROS such as hydrogen peroxide (H2 O2 ) has long been considered destructive molecules, which have been implicated in the pathogenesis of neurodegenerative diseases by causing oxidative stress and inducing apoptosis, and promoting the pathological process of neurodegenerative diseases [5]. ROS can inactivate enzymes, oxidize proteins, damage DNA, cause lipid peroxidation, and denature proteins, disrupting cell function and integrity. They bring about neuronal injury, necrosis, and apoptosis, resulting in neurodegenerative diseases and loss of other functions [6,7]. Activating the main antioxidant enzymes in the brain is an important method and mechanism to reduce neuronal iations

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