Polyphenols are bioactive substances that participate in the prevention of chronic illnesses. High content has been described in Berberis microphylla G. Forst (calafate), a wild berry extensively distributed in Chilean–Argentine Patagonia. We evaluated its beneficial effect through the study of mouse plasma metabolome changes after chronic consumption of this fruit. Characterized calafate extract was administered in water, for four months, to a group of mice fed with a high-fat diet and compared with a control diet. Metabolome changes were studied using UHPLC-DAD-QTOF-based untargeted metabolomics. The study was complemented by the analysis of protein biomarkers determined using Luminex technology, and quantification of OH radicals by electron paramagnetic resonance spectroscopy. Thirteen features were identified with a maximum annotation level-A, revealing an increase in succinic acid, activation of tricarboxylic acid and reduction of carnitine accumulation. Changes in plasma biomarkers were related to inflammation and cardiovascular disease, with changes in thrombomodulin (−24%), adiponectin (+68%), sE-selectin (−34%), sICAM-1 (−24%) and proMMP-9 (−31%) levels. The production of OH radicals in plasma was reduced after calafate intake (−17%), especially for the group fed with a high-fat diet. These changes could be associated with protection against atherosclerosis due to calafate consumption, which is discussed from a holistic and integrative point of view.
