**Preface to "New Mechanisms of Action of Natural Antioxidants in Health and Disease"**

The current understanding of the complex role of ROS in the organism, and pathological sequelae of oxidative stress, points to the necessity of comprehensive studies of antioxidant reactivities and interactions with cellular constituents. Many of the protective actions of natural antioxidants in health and diseases have been ascribed to their antioxidant properties, but in recent years, many studies have suggested that their classic hydrogen-donating antioxidant activity is unlikely to be the sole explanation for their effects. First of all, natural antioxidants are broadly metabolized in vivo, resulting in significant modifications. Moreover, the concentrations of natural antioxidants and their metabolites in vivo are lower than those usually utilized in vitro. Consequently, natural antioxidants do not exert their biological action in vivo via simply reacting with ROS. Accumulating evidence suggests that the cellular effects of natural antioxidants may be mediated by their interactions with specific proteins that are central to intracellular signaling cascades, modulating the expression and activity of key proteins, influencing epigenetic mechanisms, or modulating gu<sup>t</sup> microbiota. This Special Issue includes 10 peer-reviewed papers, including eight original research papers and two reviews. Together, they represent the most recent advances in the state-of-the-art of new mechanisms of action of natural antioxidants, in both health and disease. The reviews include overviews on the function and mechanisms of cyanidin-3-glucoside and its phenolic metabolites in maintaining intestinal integrity, and on hormetic and mitochondria-related mechanisms of the antioxidant action of phytochemicals. The research papers present data on the antioxidant potential of seaweed extracts, fermented papaya preparation, and peptides from fermented milk. The neuroprotective activities of Rosmarinus officinalis essential oil in a zebrafish model and the neuroprotective effect of three phytochemicals (sulforaphane, epigallocatechin gallate, and plumbagin), alone or in combination, in a 3D neuroblastoma cell culture model, were reported. Moreover, the anti-atherosclerotic effect of Hibiscus leaf polyphenols in vascular smooth muscle cells was investigated. Finally, the skin whitening effect of ectoine was studied in keratinocytes, promoting antioxidant application in the cosmetic field. We would like to thank all the authors for their valuable contributions and all the reviewers for their availability to review the papers and their suggestions to improve scientific quality. Thank you also to the journal's publishing team for their help in disseminating the call for papers and in every step of the publishing process.

> **Silvana Hrelia, Cristina Angeloni**

> > *Special Issue Editors*
