Antioxidant Quercetin 3-<i>O</i>-Glycosylated Plant Flavonols Contribute to Transthyretin Stabilization
Lidia Ciccone,
Nicolò Tonali,
Carole Fruchart-Gaillard,
Lucia Barlettani,
Armando Rossello,
Alessandra Braca,
Elisabetta Orlandini,
Susanna Nencetti
Affiliations
Lidia Ciccone
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Nicolò Tonali
Centre National de la Recherche Scientifique (CNRS), Biomolécules: Conception, Isolement et Synthèse (BioCIS), Université Paris-Saclay, 92290 Chatenay-Malabry, France
Carole Fruchart-Gaillard
Département Médicaments et Technologies pour la Santé (DMTS), Service d’Ingénierie Moléculaire pour la Santé (SIMoS), Commissariat à l’Énergie Atomique et aux Énergies Alternatives (CEA), Institut National de Recherche pour l’Agricolture, l’Alimentation et l’Environment (INRAE), Université Paris Saclay, 91191 Gif-Sur-Yvette, France
Lucia Barlettani
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Armando Rossello
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Alessandra Braca
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Elisabetta Orlandini
Research Center “E. Piaggio”, Università di Pisa, 56122 Pisa, Italy
Susanna Nencetti
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Plants are rich in secondary metabolites, which are often useful as a relevant source of nutraceuticals. Quercetin (QUE) is a flavonol aglycone able to bind Transthyretin (TTR), a plasma protein that under pathological conditions can lose its native structure leading to fibrils formation and amyloid diseases onset. Here, the dual nature of five quercetin 3-O-glycosylated flavonol derivatives, isolated from different plant species, such as possible binders of TTR and antioxidants, was investigated. The crystal structure of 3-O-β-D-galactopyranoside in complex with TTR was solved, suggesting that not only quercetin but also its metabolites can contribute to stabilizing the TTR tetramer.
