3,6'-disinapoyl sucrose attenuates Aβ1-42 - induced neurotoxicity in Caenorhabditis elegans by enhancing antioxidation and regulating autophagy

Abstract

The aggregation of β-amyloid (Aβ) has the neurotoxicity, which is thought to play critical role in the pathogenesis of Alzheimer's disease (AD). Inhibiting Aβ deposition and neurotoxicity has been considered as an important strategy for AD treatment. 3,6'-Disinapoyl sucrose (DISS), one of the oligosaccharide esters derived from traditional Chinese medicine Polygalae Radix, possesses antioxidative activity, neuroprotective effect and anti-depressive activity. This study was to explore whether DISS could attenuate the pathological changes of Aβ_1-42 transgenic Caenorhabditis elegans (C. elegans). The results showed that DISS (5 and 50 μM) treatment significantly prolonged the life span, increased the number of egg-laying, reduced paralysis rate, decreased the levels of lipofuscin and ROS and attenuated Aβ deposition in Aβ_1-42 transgenic C. elegans. Gene analysis showed that DISS could up-regulate the mRNA expression of sod-3, gst-4, daf-16, bec-1 and lgg-1, while down-regulate the mRNA expression of daf-2 and daf-15 in Aβ_1-42 transgenic C. elegans. These results suggested that DISS has the protective effect against Aβ_1-42 -induced pathological damages and prolongs the life span of C. elegans, which may be related to the reduction of Aβ deposition and neurotoxicity by regulating expression of genes related to antioxidation and autophagy.

Keywords: Caenorhabditis elegans; 3,6'-disinapoyl sucrose; Alzheimer's disease; autophagy; oxidative stress; β-amyloid.

FIGURE 1

Effects of DISS on life span, egg‐laying and paralysis of Aβ_1‐42 transgenic Caenorhabditis elegans CL2006. (A) The life span of C. elegans. 200 nematodes in each group were treated with or without DISS, and dead nematodes were counted every 2 days. The curve of life span was made by combining the data of three experiments. (B) The number of egg‐laying of C. elegans. Data represent means ± SD, the eggs of 6 nematodes each group were counted. ^## p < 0.01 vs. C. elegans N2 group; **p < 0.01 vs. Aβ_1‐42 transgenic C. elegans CL2006 group. (C) the paralysis rate of C. elegans. 150 nematodes in each group were incubated with or without DISS, and the paralysed nematodes were recorded every 2 days. The curve of paralysis was made by combining the data of three experiments

FIGURE 2

DISS reduced ROS production and lipofuscin accumulation in Aβ_1‐42 transgenic Caenorhabditis elegans CL2006. (A) The representative picture of ROS and lipofuscin. Synchronized nematodes were treated with or without DISS for 10 days. (B and C) Quantitative analysis of the ROS and lipofuscin fluorescence intensity, respectively. Data represent means ± SD, and obtained from 6 nematodes in each group. ^## p < 0.01 vs. C. elegans N2 group; *p < 0.05, **p < 0.01 vs. Aβ_1‐42 transgenic C. elegans CL2006

FIGURE 3

DISS reduced Aβ deposition in Aβ_1‐42 transgenic Caenorhabditis elegans CL2006. (A) The representative picture of Aβ deposition. Synchronized nematodes were treated with or without DISS for 10 days. Yellow arrow represents Aβ deposition. (B) Quantitative analysis of the fluorescence intensity. Data represent means ± SD, and obtained from 6 nematodes in each group. ^## p < 0.01 vs. C. elegans N2 group; *p < 0.05, **p < 0.01 vs. Aβ_1‐42 transgenic C. elegans CL2006

FIGURE 4

DISS regulated the expression of related gene mRNA in Aβ_1‐42 transgenic Caenorhabditis elegans CL2006. (A) The expression of skn‐1, sod‐3, gst‐4, daf‐2 and daf‐16 mRNA in C. elegans CL2006. (B) The expression of autophagy‐related genes lgg‐1,bec‐1 and daf‐15 mRNA in C. elegans CL2006. Synchronized nematodes were treated with or without DISS for 10 days. Data represent means ± SD, and obtained from three experiments. *p < 0.05, **p < 0.01. vs. Aβ_1‐42 transgenic C. elegans CL2006

FIGURE 5

Sketch map of the protection of DISS against pathological alterations in Aβ_1‐42 transgenic Caenorhabditis elegans CL2006