Antioxidant Flavonoids:
Structure, Function and Clinical Usage

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   Alternative Medicine Review 1996 (Jul);   1 (2):   103–111 ~ FULL TEXT

Alan L. Miller, ND

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Flavonoids occur in most plant species, and account for a significant percentage of the chemical constituents of some; e.g. dried green tea leaves contain approximately 30% flavonoids by weight. Flavonoids have been shown to have antibacterial, anti-inflammatory, antiallergic, antimutagenic, antiviral, antineoplastic, anti-thrombotic, and vasodilatory activity. The potent antioxidant activity of flavonoids—their ability to scavenge hydroxyl radicals, superoxide anions, and lipid peroxy radicals—may be the most important function of flavonoids, and underlies many of the above actions in the body. Oxidative damage is implicated in most disease processes, and epidemiological, clinical, and laboratory research on flavonoids and other antioxidants suggest their use in the prevention and treatment of a number of these. Catechin and its derivatives, oligomeric proanthocyanidins, quercetin and quercetin chalcone, Ginkgo flavone glycosides, silymarin, and others can be utilized in preventative and treatment protocols for cardiovascular disease, cancer, inflammatory conditions, asthma, periodontal disease, liver disease, cataracts and macular degeneration.

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Introduction

Flavonoids, or bioflavonoids, are a ubiquitous group of polyphenolic substances which are present in most plants, concentrating in seeds, fruit skin or peel, bark, and flowers. A great number of plant medicines contain flavonoids, which have been reported by many authors as having antibacterial, anti-inflammatory, antiallergic, antimutagenic, antiviral, antineoplastic, anti-thrombotic, and vasodilatory actions. The structural components common to these molecules include two benzene rings on either side of a 3-carbon ring (see Figure 1). Multiple combinations of hydroxyl groups, sugars, oxygens, and methyl groups attached to these structures create the various classes of flavonoids: flavanols, flavanones, flavones, flavan-3-ols (catechins), anthocyanins, and isoflavones. Flavonoids have been shown in a number of studies to be potent antioxidants, capable of scavenging hydroxyl radicals, superoxide anions, and lipid peroxy radicals.

Free radicals, including the superoxide radical (O2?-), hydroxyl radical (.OH), hydrogen peroxide (H2O2) , and lipid peroxide radicals have been implicated in a number of disease processes, including asthma, [1,2] cancer, [3] cardiovascular disease, [4,5] cataracts, [6,7] diabetes, [8,9] gastrointestinal inflammatory diseases, [10,11] liver disease, [12] macular degeneration, [13,14] periodontal disease, [15] and other inflammatory processes. These radical oxygen species (ROS) are produced as a normal consequence of biochemical processes in the body and as a result of increased exposure to environmental and/or dietary xenobiotics. ROS are also beneficial components of the immune response, hepatic cytochrome P450-mediated detoxification, and regulation of smooth muscle tone. [1] It is an imbalance in these oxidant versus antioxidant processes (oxidative stress) that is thought to cause the subsequent cellular damage which leads to the disease processes named above. The body’s antioxidant systems, including superoxide dismutase, catalase, and glutathione, should keep the oxidative processes in check; however, deficiencies of nutritional antioxidants (flavonoids; vitamins A, C, E; the minerals selenium and zinc; coenzyme Q10, lipoic acid; and L-cysteine), and/or an overwhelming oxidant stress can overload this system. [16]

The mechanism of free-radical damage includes ROS-induced peroxidation of polyunsaturated fatty acids in the cell membrane lipid bilayer, which causes a chain reaction of lipid peroxidation, thus damaging the cellular membrane and causing further oxidation of membrane lipids and proteins. Subsequently, cell contents, including DNA, are damaged. It is this free radical-induced damage which is thought to precede these overt disease processes. [17,18] Epidemiological Studies Two recent epidemiological studies reveal an inverse correlation between dietary flavonoid intake and coronary heart disease mortality. A Finnish study of 5133 men and women found that those with the highest intake of flavonoids (mostly from onions and apples) had a reduced risk for coronary disease. [19] A Dutch study (The Zutphen Elderly Study) of 805 men also noted an inverse relationship between dietary flavonoid intake and heart disease, with the majority of dietary flavonoids coming from tea, onions, and apples. [5]

LDL Cholesterol Oxidation Oxidation of low-density lipoproteins (LDL) is considered by many sources to be a very important component of the development of atherosclerotic lesions. [4,5,17,19-22] Circulating monocytes scavenge oxygenmodified LDL molecules with a very high affinity —up to ten times greater than “native LDL.” [4] These monocytes/macrophages penetrate into the subendothelial space and become the first stage of atherogenesis, the socalled “fatty streak.” Antioxidants which interrupt this process can be very helpful in the process of preventing and/or treating cardiovascular disease.

A number of flavonoids, including quercetin, morin, gossypetin, chrysin, myricetin, rutin, catechin and its derivatives, and the oligomeric proanthocyanidins (OPCs), have been shown in in vitro studies to inhibit the oxidation of LDL. [18,20-24 ] Oxidation of LDL is used as a model of the anti-lipid peroxidation activity of flavonoids, as the LDL molecule has an outer phospholipid layer similar to cell membranes. The mechanism by which flavonoids inhibit LDL is not totally known, but it is thought that they reduce free radical formation, protect LDL-a-tocopherol or regenerate oxidized LDL-a-tocopherol, and/or sequester metal ions which participate in oxidation reactions. [18,22]

Alternative Medicine Review 1996 (Jul); 1 (2): 103–111

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