New Mechanisms of Action of Natural Antioxidants in Health and Disease II

Epidemiological studies have demonstrated an association between natural antioxidants and human health, suggesting that they are mainly effective in counteracting noncommunicable diseases such as neurodegenerative and cardiovascular diseases, diabetes, and cancer. The mechanisms by which natural antioxidants exert their health protective activity have been extensively revised in recent years. In particular, the classical direct scavenging activity in which natural antioxidants react in one-electron reactions with free radicals has been set aside because kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. One of the most studied mechanisms by which natural antioxidants exert their protective effect is the activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which up-regulates the endogenous antioxidants defense system boosting the expression of antioxidants and detoxifying enzymes . In addition, natural antioxidants exert actions that go beyond their ability to counteract oxidative stress. For many natural antioxidants, the antioxidant effects may be less important for health than other effects including the modulation of different targets such as intracellular signaling cascades, epigenetic mechanisms and the gut microbiota. Moreover, an important issue that must be taken into consideration studying the protective activity of natural antioxidants is their in vivo bioavailability. Natural antioxidants such as polyphenols demonstrate low bioavailability because of different factors: interaction with the food matrix, intestine uptake, microbiota interaction, and endogenous transformation by phase I and phase II metabolism. On the other hand, many of the activities exerted by natural antioxidants may be mediated by their metabolites, which are produced in vivo. This Special Issue, concerned with new mechanisms of action of natural antioxidants in health and disease, contains eighteen contributions: ten research articles and eight reviews, addressing the most recent advances on this topic.