Antioxidant actions, of flavonoids

L. Anila and N.R. Vijayalakshmi, Antioxidant action of flavonoids from Mangifera indica and Emblicas officinalis in hypercholesterolemic rats. Food Chem. 83 (2003) 569-574. 

C) The antioxidant actions of flavonoids appear to participate in their antithrombotic action. Flavonoids bind to platelet membranes and scavenge platelet-generated lipid peroxides and free radicals, restoring the biosynthesis and the action of endothelial prostacyclin and nitric oxide (NO), respectively [49,88]. 

Galleano, M. Verstraeten, S.V. Oteiza, P.L Fraga, C.G. 2010. Antioxidant actions of flavonoids Thermodynamic and kinetic analysis. Arch. Biochem. Biophys. 501 23-30. 

The antioxidant actions of flavonoids appear to be involved in their observed antithrombotic action [50-52]. The antithrombotic and vasoprotective actions of quercetin, rutin, and other flavonoids have been attributed to their ability to bind to platelet membranes and scavenge free radicals [50]. In this manner, flavonoids restore the biosynthesis and action of endothelial prostacyclin and endothelialderived relaxing factor (EDRF), both of which are known to be inhibited by free radicals [50, 53, 54]. However, some flavonoids may inhibit arachidonic acid metabolism and platelet function by flavonoid-enzyme interactions rather than by antioxidant effects [55]. In addition to their antiaggregatory effects, flavonoids appear to increase vasodilation by inducing vascular smooth muscle relaxation, which may be mediated by inhibition of protein kinase C, PDFs, or by decreased cellular uptake of calcium [56]. 

Nagata H, Takekoshi S, Takagi T, Honma T, Watanabe K. Antioxidative action of flavonoids, quercetin and catechin, mediated by the activation of glutathione peroxidase. Tokai J Exp Clin Med 1999 24 1-11. 

People in France eat a lot of fatty foods but suffer less from fatal heart strokes than people in the northern regions of Europe or in North America, where wine is not consumed on a regular basis ( French paradox ). There is an increased favorable effect from red wine. The unique cardioprotective properties of red wine are due to the action of flavonoids, which are minimal in white wine. The best-researched flavonoids are resveratrol and quercetin, which confer antioxidant properties more potent than a-tocopherol. 

Fig. 1. Schematic diagram showing the different mechanisms of action proposed for the antiulcer action of flavonoids. 1. Blockade of add secretion by decreasing histamine production or inhibiting the proton pump. 2. Bactericidal effect on H. pylori. 3. Antioxidative activity by scavenging free radicals and preventing ROM formation. 4. Potentiation of the mucosal protective factors. PAF platelet activating factor ROM reactive oxygen metabolites H2 histamine receptor 2 M muscarinic receptor G gastrin receptor.

Little information about the mechanism of action of flavonoids is anticipated from in vivo studies. The mechanism of catechin and morin seems to be related to an increase of the activity of detoxifying enzymes like glutathione-S-transferase and NADPH quinone reductase [198, 211]. Similarly, EGCG effect at the colonic level is associated to an increase in tissue superoxide dismutase levels, suggesting that it may act through a potentiation of the antioxidative defense [210]. 

H. Ohshima, Y. Yoshie, S. Auriol and I. Gilibert, Antioxidant and pro-oxidant actions of flavonoids effects on DNA damage induced by nitric oxide, per-oxynitrite and nitroxyl anion, Free Radic. Biol. Med., 25 (1998) 1057-1065. M.K. Johnson and G. Loo, Effects of egpigallocatechin gallate and quercetin on oxidative damage to cellular DNA, Mutat. Res., 459 (2000) 211-218. 

While the positive health benefits associated with the consumption of a flavonoid-rich diet cannot be attributed to any one factor, the antioxidant properties of certain flavonoids have been the focus of considerable attention [8]. The antioxidant actions of chocolate flavonoids were first studied inhibiting LDL-oxidation [9,10]. As a consequence of the availability of purified procyanidins from cocoa (dimer-decamer), this particular family of... 

Flavonoids are widely distributed in fruits and vegetables and are very common nutritional supplements as antioxidants. The results on antioxidant activities of simple catechols provide a useful basis for evaluating results for the many, more complex natural compounds containing the catechol structure, such as the flavonoids, steroidal catechols and hormonal catecholamines. There are several reviews on the antioxidant properties of flavonoids and several reports on experimental " and theoretical evidence linking their antioxidant properties to the catechol moiety usually found in their structure. The basic flavonoid structure (29) is shown in Chart 1, with a few selected examples (30-36) from different groups to illustrate some of the relationships between their detailed structures and related antioxidant properties. Efforts to elucidate these relationships are hampered by their very low solubility in non-polar solvents, and the tendency of some researchers to employ metal ions as initiators of oxidation in aqueous media so that one cannot distinguish between their action as chain-breaking... 

Natural phenolic antioxidants inhibit biological oxidation by a complex multi-step mechanism that remains unclear. Unfortunately, many contemporary studies tend to use non-specific indicators of oxidation and antioxidation. A better understanding of the mechanism of action of flavonoids requires not only well-designed studies in vitro, but also demonstrations of their effectiveness in vivo. The development of reliable biomarkers that can be better related to degenerative disease presents one of the most difficult challenges in this field (Chapter 13). 

There has been considerable interest in recent years in the cytoprotective and neuroprotective effeets of flavonoids, especially in the context of their modes of action as antioxidants. The eleetron-donating properties of flavonoids are well defined to explain their antioxidant properties in vitro [10-14]. Structurally important features defining the reduction potential of flavonoids are the hydroxy-lation pattern, a 3, 4 -dihydroxy eatechol structure in the B-ring, the planarity of the molecule, and the presenee of 2,3 unsaturation in conjugation with a 4-oxo-function in the C-ring. Many studies have described the antioxidant efficacy of flavonoids and demonstrated that these polyphenols can inhibit the oxidation of lipids [12,15,16] and other biomolecules such as proteins and DNA [17-19] in... 

In contrast to many studies that identify beneficial effects of dietary flavonoids against cellular Hpid oxidation, the action of flavonoids on bovine leukemia virus-transformed lamb fibroblasts (line FLK) and HL-60 cells was accompanied by lipid peroxidation [90]. Their toxicity was partly prevented by iron chelator desferrioxamine and antioxidant AA iphenyl-p-phenylene diamine, a result that pointed to the involvement of oxidative stress in their cytotoxicity. Interestingly, the toxicity of quercetin was partly prevented by nontoxic concentrations of other flavonoids examined, thus suggesting potential neutralization of quercetin cytotoxicity by intake of flavonoid mixtures. In another study, supplementation of rat hepatocyte cultures with the flavonoid myricetin led to the formation of phenoxyl radical intermediates, as detected in intact cells by electron paramagnetic resonance (EPR) spectroscopy [220]. These phenoxyl radicals corresponded to one-electron oxidation products of... 

Quercetin displays potent antithrombotic effects It inhibits thrombin and ADP-induced platelet aggregation in vitro, and this may be through inhibition of phospholipase C activity rather than through inhibition of thromboxane synthesis. Flavo-noid binding to platelet membranes may inhibit the interaction of activated platelets with vascular endothelium. In addition, quercetin elicits coronary vasorelaxation that is endothelium independent. The antioxidant activity of flavonoids may also prevent the damaging action of lipid peroxides generated by activated platelets on endothelial nitric oxide and prostacyclin, which both inhibit platelet aggregation and have vasodilatory activity. 

Cyanidin is the most common anthocyanin in foods. In addition, anthocyanins are stabilized by the formation of complexes with other flavonoids (co-pigmentation). In the United States, the daily anthocyanin consumption is estimated at about 200 mg. Several promising studies have reported that consumption of anthocyanin-rich foods is associated with reductions of the risks of cancers - and atherosclerosis and with preventive effects against age-related neuronal and behavioral declines. These beneficial effects of anthocyanins might be related to their reported biological actions such as modulators of immune response and as antioxidants. Knowledge of anthocyanin bioavailability and metabolism is thus essential to better understand their positive health effects. 

Phytochemicals or phytonutrients are bioactive substances that can be found in foods derived from plants and are not essential for life the human body is not able to produce them. Recently, some of their characteristics, mainly their antioxidant capacity, have given rise to research related to their protective properties on health and the mechanisms of action involved. Flavonoids are a diverse group of phenolic phytochemicals (Fig. 6.1) that are natural pigments. One function of flavonoids is to protect plants from oxidative stress, such as ultraviolet rays, environmental pollution, and chemical substances. Other relevant biological roles of these pigments are discussed in other chapters of this book. 

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