Bioprospection of Natural Sources of Polyphenols with Therapeutic Potential for Redox-Related Diseases
Regina Menezes,
Alexandre Foito,
Carolina Jardim,
Inês Costa,
Gonçalo Garcia,
Rita Rosado-Ramos,
Sabine Freitag,
Colin James Alexander,
Tiago Fleming Outeiro,
Derek Stewart,
Cláudia N. Santos
Affiliations
Regina Menezes
CEDOC, Chronic Diseases Research Centre, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
Alexandre Foito
Environmental and Biochemical Science Group, The James Hutton Institute, Dundee DD2 5DA, UK
Carolina Jardim
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal
Inês Costa
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal
Gonçalo Garcia
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal
Rita Rosado-Ramos
CEDOC, Chronic Diseases Research Centre, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
Sabine Freitag
Environmental and Biochemical Science Group, The James Hutton Institute, Dundee DD2 5DA, UK
Colin James Alexander
Biomathematics and Statistics Scotland, Invergowrie, Dundee DD2 5DA, UK
Tiago Fleming Outeiro
Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettinge, 37073 Göttingen, Germany
Derek Stewart
Environmental and Biochemical Science Group, The James Hutton Institute, Dundee DD2 5DA, UK
Cláudia N. Santos
CEDOC, Chronic Diseases Research Centre, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
Plants are a reservoir of high-value molecules with underexplored biomedical applications. With the aim of identifying novel health-promoting attributes in underexplored natural sources, we scrutinized the diversity of (poly)phenols present within the berries of selected germplasm from cultivated, wild, and underutilized Rubus species. Our strategy combined the application of metabolomics, statistical analysis, and evaluation of (poly)phenols’ bioactivity using a yeast-based discovery platform. We identified species as sources of (poly)phenols interfering with pathological processes associated with redox-related diseases, particularly, amyotrophic lateral sclerosis, cancer, and inflammation. In silico prediction of putative bioactives suggested cyanidin–hexoside as an anti-inflammatory molecule which was validated in yeast and mammalian cells. Moreover, cellular assays revealed that the cyanidin moiety was responsible for the anti-inflammatory properties of cyanidin–hexoside. Our findings unveiled novel (poly)phenolic bioactivities and illustrated the power of our integrative approach for the identification of dietary (poly)phenols with potential biomedical applications.