(Poly)phenol metabolites from Arbutus unedo leaves protect yeast from oxidative injury by activation of antioxidant and protein clearance pathways

Oxidative stress is a key process in several diseases and a growing body of preclinical/clinical evidence has pushed forward the health benefits of (poly)phenols. The protective potential of Corema album and Arbutus unedo (Poly)phenol Digested Metabolites (PDM), generated after in vitro digestion was evaluated. Chemical alterations caused by the digestion led to alterations of compounds reactivity. A. unedo leaf PDM arose as the fraction conferring the highest protective activity to the wild type and oxidative stress-sensitive yap1 yeast strains challenged with H₂O₂. Our mechanistic studies disclosed the effect of A. unedo leaf PDM on cell redox homeostasis and mitochondrial function, and identified HAP4, SOD1, SOD2, GSH1 and GLR1 as mediators of cellular protection. Also, RPN4- and ATG8-associated protein clearance pathways were revealed as putative targets. Overall, these data suggest the nutraceutical potential of A. unedo leaf PDM as a functional food for human health.