Inhibitory Effect of Lychee Seed Saponins on Apoptosis Induced by Aβ25-35 through Regulation of the Apoptotic and NF-κB Pathways in PC12 Cells.

Xiuling Wang,Rong Chen,Jianming Wu,Dalian Qin,Hong Zhang,Li Gu,Mao Li,Yong Tang,Haixia Chen,Shousong Cao,Jian Liu

doi:10.3390/nu9040337

Abstract

Neuronal apoptosis plays a critical role in the pathogenesis of Alzheimer’s disease (AD). Previous studies have shown that lychee seed saponins (LSS), isolated and extracted from traditional Chinese medicine lychee seeds, possess many beneficial activities including anti-oxidation, anti-diabetes, anti-AD, etc. In the present study, we established an in vitro neuronal apoptotic model of PC12 cells induced by Aβ25-35 and studied the effect of LSS on apoptosis by the methods of Hoechst 33342/propidium iodide (PI) fluorescence double staining, Annexin V/PI double staining, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). We also investigated the effects of LSS on mitochondria membrane potential, the expressions of Bcl-2 and Bax proteins, and the mRNA expression and the nuclear translocation of NF-κBp65 in PC12 cells. The results showed that LSS markedly inhibited apoptosis, improved the mitochondria membrane potentials, upregulated the expression of Bcl-2 protein, downregulated the expression of Bax protein, and decreased the mRNA expression and nuclear translocation of NF-κBp65 in PC12 cells. The study demonstrated that LSS significantly inhibited apoptosis induced by Aβ25-35 via regulation of the apoptotic and NF-κB pathways in PC12 cells. Therefore, LSS has the potential to be developed as a novel agent or nutrient supplement for the prevention and/or treatment of AD.

Highlights

Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder that is characterized by the abnormal deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) owing to formations of amyloid-β protein (Aβ) and hyperphosphorylation of Tau protein in the brain [1]
We studied the effect of lychee seed saponins (LSS) on apoptosis induced by Aβ25-35 in pheochromocytoma 12 (PC12) cells through Hoechst 33342/propidium iodide (PI) double staining under a fluorescence microscope
The summarized results of the apoptotic ratio of cells are shown in Figure 1B and indicate that Aβ25-35 treatment significantly increased apoptosis compared to control cells treated with vehicle (p < 0.01), but LSS significantly inhibited Aβ25-35 -induced apoptosis compared to vehicle treatment (p < 0.01) in PC12 cells

Summary

Introduction

Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder that is characterized by the abnormal deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) owing to formations of amyloid-β protein (Aβ) and hyperphosphorylation of Tau protein in the brain [1]. Neuronal apoptosis is influenced by multiple stimuli, such as activation of relevant enzymes [5], reactive oxygen species (ROS) [6], mitochondrial permeability transition [7], tumor necrosis factor-α (TNF-α) [8], Bcl-2, Bax, caspases [9], and so on. As a hallmark in the pathogenesis of AD, can inhibit phosphatidylinositol 3 kinase (PI3K)/Akt to increase the expression of pro-apoptosis genes such as Bcl-2-associated death promoter (BAD), glycogen synthase kinase 3β (GSK-3β), and nuclear factor (NF)-κB, and lead to neuronal apoptosis [10,11]. Distorted expressions of apoptosis-related proteins, including Bak, Bad, Bax, Bcl-2, p53, Par-4, and Fas, as well as the activation of caspases, have been implicated in the pathogenesis of AD [13,14]

Results

Discussion

Conclusion