Journal Article

Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells

Liu, Meichen, Wang, Jiawen, Liu, Ying, Zhao, Daqing, Yu, Shiting, Qiao, Juhui, Wang, Siming, Zhao, Wenxue, Bai, Xueyuan

2019

Overview

Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis represents the effective strategies in combating AD. Ginsenoside Re (Re) has pharmacological effects against Aβ-induced neurotoxicity. However, its molecular mechanism remains elusive. The present study evaluated the effect of Re against Aβ-induced cytotoxicity and apoptosis in SH-SY5Y cells, and investigated the underlying mechanism. We demonstrate that Re inhibits the Aβ-triggered mitochondrial apoptotic pathway, as indicated by maintenance of mitochondrial functional, elevated Bcl-2/Bax ratio, reduced cytochrome c release, and inactivation of caspase-3/9. Re attenuated Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, and JNK activation. ROS-scavenging abrogated the ability of Re to alter ASK-1 activation. Simultaneously, inhibition of JNK abolished Re-induced Bax downregulation in Aβ-challenged SH-SY5Y cells. In addition, Re enhanced activation of the nuclear factor-E2-related factor 2 (Nrf2) in Aβ-induced SH-SY5Y cells. Knockdown of Nrf2 by small interfering RNA targeting Nrf2 abolished the protective effect of Re. Our findings indicate that Re could be a potential therapeutic approach for the treatment of AD.

• Publisher: MDPI AG,MDPI
• Subject: Alzheimer's disease / Amyloid beta-Peptides - metabolism / Antioxidants / Antioxidants - chemistry / Antioxidants - pharmacology / Apoptosis / Apoptosis - drug effects / Cell Line, Tumor / Cell Survival - drug effects / Cytotoxicity / ginsenoside Re / Ginsenosides - chemistry / Ginsenosides - pharmacology / Humans / Hypotheses / JNK Mitogen-Activated Protein Kinases - metabolism / Kinases / MAP Kinase Kinase Kinase 5 - metabolism / Mitochondria / Mitochondria - drug effects / Mitochondria - metabolism / Molecular Structure / Nervous system / Neuroprotective Agents - chemistry / Neuroprotective Agents - pharmacology / NF-E2-Related Factor 2 - metabolism / Oxidative stress / Oxidative Stress - drug effects / Pathogenesis / Pathology / Phosphorylation / Physiology / Proteins / Reactive oxygen species / Reactive Oxygen Species - metabolism / Signal Transduction - drug effects / β-amyloid