Ginsenoside Rh1 Exerts Neuroprotective Effects by Activating the PI3K/Akt Pathway in Amyloid-β Induced SH-SY5Y Cells

Miey Park,So-Hyeun Kim,Hae-Jeung Lee

doi:10.3390/app11125654

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of β-amyloid plaques and hyperphosphorylated tau proteins in the brain. Cell signaling pathways such as PI3K/Akt are known to play an essential role in regulating cell survival, motility, transcription, metabolism, and progression of the cell cycle. Recent studies demonstrated that the disruption of these signaling pathways in neurodegenerative disorders leads to oxidative stress and cell death. Targeting these altered signaling pathways could be considered as the therapeutic approach for neurodegenerative disorders. Ginsenoside Rh1 is known to provide beneficial effects in various diseases such as cancer, diabetes, and inflammation. In this study, human neuroblastoma SH-SY5Y cells were treated with the β-amyloid oligomers alone or in combination with ginsenoside Rh1. We observed that ginsenoside Rh1 was able to attenuate β-amyloid induced oxidative stress and cell death by activating the PI3K/Akt signaling pathway. Based on these findings, we suggest that ginsenoside Rh1 might be an efficacious therapeutic agent for AD.

Highlights

Dementia can be caused by a wide variety of conditions and a chronic disease with a significant emotional and physical burden [1]
Our study reported for the first time that ginsenoside Rh1 significantly attenuates Aβ oligomers-induced oxidative stress and cell death in SH-SY5Y cells
We further demonstrated that ginsenoside Rh1 protects against Aβ oligomers-induced cell death by activating the phosphatidylinositol 3-kinase (PI3K)/Akt/Glycogen synthase kinase-3 (GSK-3) pathway

Summary

Introduction

Dementia can be caused by a wide variety of conditions and a chronic disease with a significant emotional and physical burden [1]. Alzheimer’s disease is characterized by the accumulation of insoluble β-amyloid plaques formed due to an improper cleavage of amyloid precursor protein (APP) in addition to the formation of neurofibrillary tangles formed due to the hyper-phosphorylation of micro-tubular protein tau [5,6]. Both of them are involved in neuronal cell death, a prominent feature of AD [7]. Recent studies demonstrated that inhibition of P13K/Akt by the β-amyloid could cause oxidative stress and neuronal cell death [8,9]

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