Melatonin was found to be a potent free radical scavenger in 1993. Since then over 800 publications have directly or indirectly confirmed this observation. Melatonin scavenges a variety of reactive oxygen and nitrogen species including hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide and peroxynitrite anion. Based on the analyses of structure-activity relationships, the indole moiety of the melatonin molecule is the reactive center of interaction with oxidants due to its high resonance stability and very low activation energy barrier towards the free radical reactions. However, the methoxy and amide side chains also contribute significantly to melatonin's antioxidant capacity. The N-C=O structure in the C3 amide side chain is the functional group. The carbonyl group in the structure of N-C=O is key for melatonin to scavenge the second reactive species and the nitrogen in the N-C=O structure is necessary for melatonin to form the new five membered ring after melatonin's interaction with a reactive species. The methoxy group in C5 appears to keep melatonin from exhibiting prooxidative activity. If the methoxy group is replaced by a hydroxyl group, under some in vitro conditions, the antioxidant capacity of this molecule may be enhanced. However, the cost of this change are decreased lipophility and increased prooxidative potential. Therefore, in in vivo studies the antioxidant efficacy of melatonin appears to be superior to its hydroxylated counterpart. The mechanisms of melatonin's interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through an radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4 and C7 and nitrosation. Melatonin also has the ability to repair damaged biomolecules as shown by the fact that it converts the guanosine radical to guanosine by electron transfer. Unlike the classical antioxidants, melatonin is devoid of prooxidative activity and all known intermediates generated by the interaction of melatonin with reactive species are also free radical scavengers. This phenomenon is defined as the free radical scavenging cascade reaction of the melatonin family. Due to this cascade, one melatonin molecule has the potential to scavenge up to 4 or more reactive species. This makes melatonin very effective as an antioxidant. Under in vivo conditions, melatonin is often several times more potent than vitamin C and E in protecting tissues from oxidative injury when compared at an equivalent dosage (micromol/kg). Future research in the field of melatonin as a free radical scavenger might be focused on: 1), signal transduction and antioxidant enzyme gene expression induced by melatonin and its metabolites, 2), melatonin levels in tissues and in cells, 3), melatonin structure modifications, 4), melatonin and its metabolites in plants and, 5), clinical trials using melatonin to treat free radical related diseases such as Alzheimer's, Parkinson's, s...

Melatonin has been shown to be an effective antioxidant in a number of experimental models both in vitro and in vivo. Considering the data available, it is now clear that the indoleamine is involved in antioxidative mechanisms more complex than originally envisaged. These range from the direct radical scavenging of a variety of radicals and reactive species to the control and/or modulation of a number of processes which may trigger a redox imbalance between antioxidant and prooxidant species. This review focuses on the direct radical scavenging activity of melatonin and provides a summary of the mechanisms of the reactions between the indoleamine and reactive species in pure chemical solutions. These actions likely account for at least some of the protective actions of melatonin under conditions of high oxidative stress.

Sicilian cultivars of prickly pear (Opuntia ficus indica) produce yellow, red, and white fruits, due to the combination of two betalain pigments, the purple-red betanin and the yellow-orange indicaxanthin. The betalain distribution in the three cultivars and the antioxidant activities of methanolic extracts from edible pulp were investigated. In addition, the reducing capacity of purified betanin and indicaxanthin was measured. According to a spectrophotometric analysis, the yellow cultivar exhibited the highest amount of betalains, followed by the red and white ones. Indicaxanthin accounted for about 99% of betalains in the white fruit, while the ratio of betanin to indicaxanthin varied from 1:8 (w:w) in the yellow fruit to 2:1 (w:w) in the red one. Polyphenol pigments were negligible components only in the red fruit. When measured as 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) equivalents per gram of pulp, the methanolic fruit extracts showed a marked antioxidant activity. Vitamin C did not account for more than 40% of the measured activity. In addition, the extracts dose-dependently inhibited the organic hydroperoxide-stimulated red cell membrane lipid oxidation, as well as the metal-dependent and -independent low-density lipoprotein oxidation. The extract from the white fruit showed the highest protection in all models of lipid oxidation. Purified betanin and indicaxanthin were more effective than Trolox at scavenging the [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] diammonium salt cation radical. Cyclic voltammetric measurements show two anodic waves for betanin and indicaxanthin, and differential pulse voltammetry shows three anodic waves for betanin, with calculated peak potentials of 404, 616, and 998 mV, and two anodic waves for indicaxanthin, with peak potentials of 611 and 895 mV. Betanin underwent complex formation through chelation with Cu 2+ , whereas indicaxanthin was not modified. These findings suggest that the above betalains contribute to the antioxidant activity of prickly pear fruits.KEYWORDS: Betalains; natural antioxidants; low-density lipoprotein; prickly pear; betanin; indicaxanthin INTRODUCTIONEvidence continues to emerge suggesting that components of fruits and vegetables may be protective against oxidative damage (1-3). In addition to antioxidant vitamins and minerals, polyphenols and other non-nutrient compounds of vegetables and fruits have been recognized as potential factors which can be beneficial to human health (4-6). The prickly pear (Opuntia ficus indica) is a member of the Cactaceae family and is widely distributed in Mexico, much of Latin America, South Africa, and the Mediterranean area. The nutritional properties of the fresh stems (cladodes) have long been known, and prickly pear is used also in traditional medicine for its hypoglycemic and hypolipidemic actions (7-9). In the industrialized countries of the Mediterranean area, cladodes are not a usual nutritional source for humans, but the fruits are largely consumed. Sicily ranks second am...

Our results show that cactus pear fruit is a source of bioavailable betalains and suggest that indicaxanthin and betanin may be involved in the observed protection of LDL against ex vivo-induced oxidative modifications.