Bioprospection of Natural Sources of Polyphenols with Therapeutic Potential for Redox-Related Diseases

Abstract

Funding: iNOVA4Health-UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged. This work was supported by Fundação para a Ciência e Tecnologia (IF/01097/2013 to C.N.S.), by The Scottish Government Rural and Environment Science and Analytical Services Division (A.F. and D.S.), and BacHBerry FP7-KBBE-2013-613793 (R.M., A.F., C.J., I.C., G.G., R.R.-R., J.P., A.M., C.D., D.S. and C.N.S.). T.F.O. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), and is currently supported by the DFG under Germany’s Excellence Strategy—EXC 2067/1-390729940.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.publishersversionpublishe