Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aβ) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD. Here, we investigated the effects of a polyphenolic extract of Arabidopsis thaliana (a plant belonging to the Brassicaceae family) on inflammatory response induced by Aβ. BV2 murine microglia cells treated with both Aβ25–35 peptide and extract showed a lower pro-inflammatory (IL-6, IL-1β, TNF-α) and a higher anti-inflammatory (IL-4, IL-10, IL-13) cytokine production compared to cells treated with Aβ only. The activation of the Nrf2-antioxidant response element signaling pathway in treated cells resulted in the upregulation of heme oxygenase-1 mRNA and in an increase of NAD(P)H:quinone oxidoreductase 1 activity. To establish whether the extract is also effective against Aβ-induced neurotoxicity in vivo, we evaluated its effect on the impaired climbing ability of AD Drosophila flies expressing human Aβ1–42. Arabidopsis extract significantly restored the locomotor activity of these flies, thus confirming its neuroprotective effects also in vivo. These results point to a protective effect of the Arabidopsis extract in AD, and prompt its use as a model in studying the impact of complex mixtures derived from plant-based food on neurodegenerative diseases.
Highlights
Natural polyphenols, a vast group of compounds present in plant-based food, confers protection against cancer, cardiovascular, metabolic and neurodegenerative diseases [1,2,3,4].The interest in polyphenols as possible therapeutic agents in neurodegenerative diseases stems from the well-documented evidence of their antioxidant effects both in vitro and in vivo, as largely studied in Alzheimer’s disease (AD) [5]
Our data support the evidence that an Arabidopsis thaliana extract rich in phenolic compounds exert anti-inflammatory activity through the activation of the Nrf2 pathway
This evidence further underlines the importance of correct nutrition as pointed out by epidemiological studies indicating that a diet rich in fruits, vegetables and spices may afford protection against neurodegeneration
Summary
A vast group of compounds present in plant-based food, confers protection against cancer, cardiovascular, metabolic and neurodegenerative diseases [1,2,3,4].The interest in polyphenols as possible therapeutic agents in neurodegenerative diseases stems from the well-documented evidence of their antioxidant effects both in vitro and in vivo, as largely studied in Alzheimer’s disease (AD) [5]. Polyphenols may counteract neurodegenerative diseases with different mechanisms at various levels They exert antioxidant activity by inducing the expression of antioxidant enzymes, as well as inhibiting the expression of pro-oxidant enzymes [9,10,11]. Polyphenols may modulate Aβ production and aggregation by stimulating α-secretase and by inhibiting β- and γ-secretase, and by competitively interacting with aromatic residues preventing the π–π interaction, blocking the amyloid self-assembly process [14,15]. Some phenolics, such as quercetin and myricetin, are able to inhibit the β-secretase enzyme interfering with the Aβ generation cascade, whereas other phenolics, such as epigallocatechin gallate, curcumin, trans-resveratrol, or oleuropein, are able to inhibit amyloid aggregation and fibrillogenesis [16]. A polyphenol rich extract of Hypericum was suggested to positively affect Aβ clearance by activation of ABC transporters in the blood-brain-barrier [17,18,19]
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