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

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

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

Molecules. 2019 Jul 24;24(15):2687.

PMID: 31344860

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP52286596	Ginsenoside Re		52286-59-6	Price

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