The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites

Abstract

Small molecule, dietary antioxidants exert a remarkably broad range of bioactivities, and many of these can be explained by the influence of antioxidants on the redox homeostasis. Such compounds help to modulate the levels of harmful reactive oxygen/nitrogen species, and therefore participate in the regulation of various redox signaling pathways. However, upon ingestion, antioxidants usually undergo extensive metabolism that can generate a wide range of bioactive metabolites. This makes it difficult, but otherwise a need, to identify the ones responsible for the different activities of antioxidants. By better understanding their ways of action, the use of antioxidants in therapy can be improved. This review provides a summary on the role of the in vivo metabolic changes and the oxidized metabolites on the mechanisms behind the bioactivity of antioxidants. A special attention is given to metabolites described as products of biomimetic oxidative chemical reactions, which can be considered as models of free radical scavenging. During such reactions a wide variety of metabolites are formed, and they can exert completely different specific bioactivities as compared to their parent antioxidants. This implies that exploring the free radical scavenging‐related metabolite fingerprint of each antioxidant molecule, collectively defined here as the scavengome, will lead to a deeper understanding of the bioactivity of these compounds. Furthermore, this paper aims to be a working tool for systematic studies on oxidized metabolic fingerprints of antioxidants, which will certainly reveal an often‐neglected segment of chemical space that is a treasury of bioactive compounds.

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“…This is based on the notion that i) scavenging reactive oxygen or nitrogen species (ROS or RNS, respectively, collectively referred to as RONS) with antioxidants frequently results in chemically stable, bioactive, oxidized metabolites, ii) such metabolites may have a dramatically altered bioactivity compared to their parent compound, and iii) this altered bioactivity is due to new chemical information directly translated from oxidative stress. Therefore, this chemical metabolite space, that we defined as the scavengome, should be particularly rich in bioactive compounds [ 5 ].…”