1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside delays amyloid-β aggregation and reduces amyloid cytotoxicity.

Zohra Dhouafli, Manuela Leri, Monica Bucciantini, Massimo Stefani, Hamza Gadhoumi, Borhane Mahjoub, Hichem Ben Jannet, Jérôme Guillard, Riadh Ksouri, Moufida Saidani Tounsi, Claudio Soto, El Akrem Hayouni

Journal: BioFactors (Oxford, England) 2018;44(3):272-280

PMID: 29582494

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Abstract

Presently, misfolding and aggregation of amyloid-β (Aβ ) are considered early events in Alzheimer's disease (AD) pathogenesis. The use of natural products to inhibit the aggregation process and to protect cells from cytotoxicity of early aggregate grown at the onset of the aggregation path is one of the promising strategies against AD. Recently, we have purified a new powerful antioxidant and inhibitor of Aβ aggregation from the leaves of Lawsonia inermis. The new compound was identified as a new Lawsoniaside; 1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside (THNG). Herein, we show that THNG interferes with Aβ aggregation, inhibits its conformational change to a β-sheet-rich structure, decreases its polymerization into large fibrillar species, reduces oxidative stress, and aggregate cytotoxicity. These results indicate that THNG has great potential as a neuroprotective and therapeutic agent against AD. © 2018 BioFactors, 44(3):272-280, 2018.

Address: Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunis 2092, Tunisia.; Laboratoire des Plantes Aromatiques et Médicinales (LPAM- LR15CBBC06), Centre de Biotechnologie de Borj-Cédria, Hammam-Lif, Tunisia.; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Florence, Italy.; Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.; Laboratoire de Chimie, Institut Supérieur Agronomique de Chott Meriem, Sousse, Tunisia.; Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité (LR11ES39), Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Tunisie.; Institut de Chimie des Milieux et Matériaux de Poitiers, IC2MP, UMR CNRS 7285, Poitiers Cedex 9, France.; Mitchell Center for Alzheimer's disease and related Brain disorders, University of Texas Medical School at Houston, Houston, TX, USA.

DOI: 10.1002/biof.1422

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MeSH Terms: Amyloid beta-Peptides, Benzothiazoles, Calcium, Cell Line, Tumor, Cell Survival, Circular Dichroism, Glucosides, Humans, Lawsonia Plant, Naphthalenes, Neurons, Neuroprotective Agents, Peptide Fragments, Plant Extracts, Protein Aggregates, Protein Conformation, beta-Strand, Reactive Oxygen Species, Spectrometry, Fluorescence, Thiazoles