7-Hydroxycoumarin modulates the oxidative metabolism, degranulation and microbial killing of human neutrophils.

In the present study, we assessed whether 7-hydroxycoumarin (umbelliferone), 7-hydroxy-4-methylcoumarin, and their acetylated analogs modulate some of the effector functions of human neutrophils and display antioxidant activity. These compounds decreased the ability of neutrophils to generate superoxide anion, release primary granule enzymes, and kill Candida albicans. Cytotoxicity did not mediate their inhibitory effect, at least under the assessed conditions. These coumarins scavenged hypochlorous acid and protected ascorbic acid from electrochemical oxidation in cell-free systems. On the other hand, the four coumarins increased the luminol-enhanced chemiluminescence of human neutrophils stimulated with phorbol-12-myristate-13-acetate and serum-opsonized zymosan. Oxidation of the hydroxylated coumarins by the neutrophil myeloperoxidase produced highly reactive coumarin radical intermediates, which mediated the prooxidant effect observed in the luminol-enhanced chemiluminescence assay. These species also oxidized ascorbic acid and the spin traps α-(4-pyridyl-1-oxide)-N-tert-butylnitrone and 5-dimethyl-1-pyrroline-N-oxide. Therefore, 7-hydroxycoumarin and the derivatives investigated here were able to modulate the effector functions of human neutrophils and scavenge reactive oxidizing species; they also generated reactive coumarin derivatives in the presence of myeloperoxidase. Acetylation of the free hydroxyl group, but not addition of the 4-methyl group, suppressed the biological effects of 7-hydroxycoumarin. These findings help clarify how 7-hydroxycoumarin acts on neutrophils to produce relevant anti-inflammatory effects.

Interaction of Vimang (Mangifera indica L. extract) with Fe(III) improves its antioxidant and cytoprotecting activity.

A standard aqueous stem bark extract from selected species of Mangifera indica L. (Anacardiaceae)--Vimang, whose major polyphenolic component is mangiferin, displays potent in vitro and in vivo antioxidant activity. The present study provides evidence that the Vimang-Fe(III) mixture is more effective at scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, as well as in protecting against t-butyl hydroperoxide-induced mitochondrial lipid peroxidation and hypoxia/reoxygenation-induced hepatocytes injury, compared to Vimang alone. Voltammetric assays demonstrated that Vimang, in line with the high mangiferin content of the extract, behaves electrochemically like mangiferin, as well as interacts with Fe(III) in close similarity with mangiferin's interaction with the cation. These results justify the high efficiency of Vimang as an agent protecting from iron-induced oxidative damage. We propose Vimang as a potential therapy against the deleterious action of reactive oxygen species generated during iron-overload, such as that occurring in diseases like beta-thalassemia, Friedreich's ataxia and haemochromatosis.