Ginsenoside Rd Protects SH-SY5Y Cells against 1-Methyl-4-phenylpyridinium Induced Injury.

Yang Liu,Jun Zhao,Dong-Yun Feng,Zheng Dong,Rui Wu,Ming Shi,Gang Zhao,Ren-Yu Zhang

doi:10.3390/ijms160714395

Yang Liu, Jun Zhao + Show 6 more

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https://doi.org/10.3390/ijms160714395

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Abstract

Ginsenoside Rd (GSRd), one of the main active monomer compounds from the medical plant Panax ginseng, has been shown to promote neuronal survival in models of ischemic cerebral damage. As an extending study, here we examined whether GSRd could exert a beneficial effect in an experimental Parkinson disease (PD) model in vitro, in which SH-SY5Y cells were injured by 1-methyl-4-phenylpyridinium (MPP+), an active metabolic product of the classical Parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results, from the addition of different concentrations of GSRd (1, 10 and 50 μM), showed that GSRd at 1 and 10 μM could significantly attenuate MPP+-induced cell death. This protective effect may be ascribed to its ability to reduce intracellular reactive oxygen species levels, enhance antioxidant enzymatic activities, preserve the activity of respiratory complex I, stabilize the mitochondrial membrane potential and increase intracellular ATP levels. Additionally, the PI3K/Akt survival-signaling pathway was also involved in the protective effect of GSRd. Finally, using a mouse PD model in vivo, we also found that GSRd obviously reversed the loss of tyrosine hydroxylase-positive cells in substanitia nigra induced by MPTP. Thus, our findings demonstrated that GSRd showed a significant neuro-protective effect against experimental PD models, which may involve its antioxidant effects and mitochondrial function preservation.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the aging population
150 μM MPP+ for 72 h, cell viability indicated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was reduced by >40%, and lactate dehydrogenase (LDH)
MPP+ is a specific antagonist against mitochondrial respiratory complex I, so we investigated the effect of Ginsenoside Rd (GSRd) on mitochondrial depolarization

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the aging population. The underlying mechanism that induces DA neurons death is still obscure, mitochondrial dysfunction, oxidative stress, reticulum stress, and glial related inflammation are widely accepted to be among the common pathogenesis [1,2,3,4]. Because of their high activity in dopamine metabolism and abundance in lipid component and iron, DA neurons are especially susceptible to these events. The safety of GSRd has been assessed in stroke patients in clinical investigations [11] These aforementioned results suggest that GSRd may protect against acute neuronal injuries. We investigated the effects of GSRd on an experimental PD model in vitro, in which human neuroblastoma SH-SY5Y cells, a commonly used neuronal cell line, injured by a classical Parkinsonian toxin1-methyl-4-phenylpyridinium (MPP+), and a mouse PD model in vivo, in which mice were received with 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)

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