Ferroptosis is a form of cell death primed by iron and lipid hydroperoxides and prevented by GPx4. Ferrostatin-1 (fer-1) inhibits ferroptosis much more efficiently than phenolic antioxidants. Previous studies on the antioxidant efficiency of fer-1 adopted kinetic tests where a diazo compound generates the hydroperoxyl radical scavenged by the antioxidant. However, this reaction, accounting for a chain breaking effect, is only minimally useful for the description of the inhibition of ferrous iron and lipid hydroperoxide dependent peroxidation. Scavenging lipid hydroperoxyl radicals, indeed, generates lipid hydroperoxides from which ferrous iron initiates a new peroxidative chain reaction. We show that when fer-1 inhibits peroxidation, initiated by iron and traces of lipid hydroperoxides in liposomes, the pattern of oxidized species produced from traces of pre-existing hydroperoxides is practically identical to that observed following exhaustive peroxidation in the absence of the antioxidant. This supported the notion that the anti-ferroptotic activity of fer-1 is actually due to the scavenging of initiating alkoxyl radicals produced, together with other rearrangement products, by ferrous iron from lipid hydroperoxides. Notably, fer-1 is not consumed while inhibiting iron dependent lipid peroxidation. The emerging concept is that it is ferrous iron itself that reduces fer-1 radical. This was supported by electroanalytical evidence that fer-1 forms a complex with iron and further confirmed in cells by fluorescence of calcein, indicating a decrease of labile iron in the presence of fer-1. The notion of such as pseudo-catalytic cycle of the ferrostatin-iron complex was also investigated by means of quantum mechanics calculations, which confirmed the reduction of an alkoxyl radical model by fer-1 and the reduction of fer-1 radical by ferrous iron. In summary, GPx4 and fer-1 in the presence of ferrous iron, produces, by distinct mechanism, the most relevant anti-ferroptotic effect, i.e the disappearance of initiating lipid hydroperoxides.

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Highly reactive radicals, ROO(*), were generated from 2, 2'-azobis[2-(2-imidazolin-2-yl)propane] and linoleic acid. The ROO(*) scavenging capacity of some Italian red wines was evaluated following the changes in oxygen consumption. Under the experimental conditions the time course of oxygen consumption shows two typical behaviors: trolox-like (class I) and gallic acid-like (class II). Usually the time course of wine was similar to that of gallic acid. The rate of oxygen consumption was found to decrease exponentially with the amount of wine or gallic acid added to the test solution. On this basis the capacity of red wines to scavenge peroxy radicals was expressed as content of gallic acid (S(GA)). The S(GA) values were found to be correlated to the amount of total proanthocyanidins and total polyphenols of some Italian red wines (p < 0.01). The proanthocyanidins extracted from seeds were shown to make a major contribution to the peroxy radical scavenging capacity of red wines, whereas, interestingly, the chemical class of the low molecular weight tannins reactive to vanillin did not correlate with the S(GA) values.

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Eight varieties of Cichorium genus vegetables (five heavily red colored, one red spotted, and two fully green) were investigated for their phenolic content (by HPLC and UV-vis spectrophotometry) and for their antioxidant activity. In particular, the capacity (that is, the amount of trapped peroxyl radicals) and the efficiency (that is, the amount of antioxidant necessary to halve the steady-state concentration of peroxyl radicals) were measured. All of the studied chicories are characterized by the presence of a large amount of hydroxybenzoic and hydroxycinnamic acids, whereas the red color is due to cyanidin glycosides. The presence of these phenolics in red chicories confers to them an exceptionally high peroxyl radical scavenging activity in terms of both capacity and efficiency, particularly in their early stage of growth, and makes this popular and low-cost foods comparable or superior to many foods having well-known antioxidant properties such as red wine, blueberry, and tomato.

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Forty-one samples of apples (peel plus pulp), obtained from eight cultivars, were examined for concentration of some important phytochemicals and for antioxidant activity expressed as peroxyl radical trapping efficiency. Five major polyphenolic groups plus ascorbate were identified and quantified by HPLC in the apple varieties. Oligomeric and polymeric proanthocyanidins were found to be about two-thirds of total polyphenols. The antioxidant efficiency of the apple extracts and of representative pure compounds for each group of phytochemicals was measured in a micellar system mimicking lipid peroxidation in human plasma. Although the amount of polyphenols measured by HPLC is similar to that measured by standard methods, the antioxidant efficiency calculated on the basis of the contribution of the pure compounds was lower than the antioxidant efficiency of the apple extracts. The higher efficiency of apples appears to be strictly related to the overwhelming presence of oligomeric proanthocyanidins.

Some wild Mediterranean plants used as traditional food are an extraordinary source of antioxidants. We tested some properties of 10 of these herbaceous plants, used in Liguria (Northwest Italy) to prepare a traditional dish known as "prebuggiun." A total of 9 of them were found to have a polyphenol content and antioxidant properties similar or better than those of red chicory and blueberry, which are, in the case of vegetables and fruits, among the richest of antioxidants. Practical Application: In this article, we reported a study on wild plants growing in the Mediterranean area. These herbs have been neglected and this study aimed to revalue these plants because they are an extraordinary source of antioxidants. The increasing demand for natural antioxidants (additives in the food industry too) justifies the search for new sources of natural antioxidants. The revaluation of these plants will be interesting for: (1) consumer health, rediscovering a vegetable source of high antioxidant power; (2) possibility of producing new commercial products, such as food supplements of high quality and low cost; (3) pharmacological applications.