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. 2024 Jan 8;13(1):79.
doi: 10.3390/antiox13010079.

Insights into the Neuroprotective Potential of Epicatechin: Effects against Aβ-Induced Toxicity in Caenorhabditis elegans

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Insights into the Neuroprotective Potential of Epicatechin: Effects against Aβ-Induced Toxicity in Caenorhabditis elegans

Begoña Ayuda-Durán et al. Antioxidants (Basel). .

Abstract

Medical therapies to avoid the progression of Alzheimer's disease (AD) are limited to date. Certain diets have been associated with a lower incidence of neurodegenerative diseases. In particular, the regular intake of foods rich in polyphenols, such as epicatechin (EC), could help prevent or mitigate AD progression. This work aims to explore the neuroprotective effects of EC using different transgenic strains of Caenorhabditis elegans, which express human Aβ1-42 peptides and contribute to elucidating the mechanisms involved in the effects of EC in AD. The performed assays indicate that this flavan-3-ol was able to reduce the signs of β-amyloid accumulation in C. elegans, improving motility and chemotaxis and increasing survival in transgenic strain peptide producers compared to nematodes not treated with EC. The neuroprotective effects exhibited by EC in C. elegans could be explained by the modulation of inflammation and stress-associated genes, as well as autophagy, microgliosis, and heat shock signaling pathways, involving the regulation of cpr-5, epg-8, ced-7, ZC239.12, and hsp-16 genes. Overall, the results obtained in this study support the protective effects of epicatechin against Aβ-induced toxicity.

Keywords: chemotaxis; flavonoids; gene expression; neuroprotection; paralysis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Evolution in the percentage of non-paralyzed worms in the transgenic C. elegans CL4176 strain treated with 150 μM of epicatechin (EC) or without EC (control). Following incubation at 16 °C for 48 h, the expression of β-amyloid peptide (Aβ) was induced by raising the temperature to 25 °C. Twenty-four hours after temperature upshift, worms were scored for paralysis at 120 min intervals. Plots were obtained from the mean of three independent experiments (n = 100 worms/group).
Figure 2
Figure 2
Kaplan–Meier survival curves of CL2006 worms grown at 20 °C in nematode growth medium (NGM) plates supplemented with EC 150 µM or dimethyl sulfoxide (DMSO) (control worms). Plots are representative of three independent experiments (n = 100 worms/experiment).
Figure 3
Figure 3
Chemotaxis behavior in neuronal Aβ-expressing strain CL2355 not treated and treated with EC 150 µM and control strain CL2122. In all cases, the results were obtained from three plates containing 50–70 worms each; three individual experiments were carried out in each case. Data are represented as mean ± SD. Dots represent individual data points. Asterisks indicate significant differences: * p < 0.05 (CL2122 vs. CL2355 untreated) and ** p < 0.01 (CL2355 treated with EC vs. untreated CL2355), ); ns = not significant.
Figure 4
Figure 4
Plots and bars represent the results obtained for the proteasomal activity in transgenic CL2006 worms treated (EC) and not treated (control) with epicatechin 150 µM. The results are expressed as a % of response in relation to the control and presented as mean ± SD (n = 9). Dots represent individual data points; ns = not significant.
Figure 5
Figure 5
Plots and bars representation of the relative mRNA expression levels of vha-5, cpr-5, epg-8, ced-7, ZC239.12, hsp-16.2, and hsp-70 genes in CL4176 C. elegans cultivated in the absence (controls) and presence of EC (150 μM). Analyses were carried out by RT-qPCR using act-1 as an internal control. In all cases, ten independent experiments were performed. The results are presented as the mean values ± SEM. Dots represent individual data points. The differences were considered significant at * p < 0.05 and ** p < 0.01; ns = not significant.

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