Quasi-vitamins: Flavonoids Domina Petric, MD

There are seven general classes of flavonoids, classified by their common ring substituents. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Flavonols are the most abundant flavonoids in human diets. These derivatives (R3 hydroxy, R4 keto) include quercetin, kaempferol, isorhamnetic and myricetin. Flavonols are the most abundant flavonoids in human diets. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Flavonols Flavonols are found in a variety of fruits and vegetables, often as glycosides. Relatively high amounts (15-40 mg/100 g) are found in broccoli, kale, leeks and onions. Flavanols are also found in red wine, tea and fruit juices. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Green tea and dark chocolate are rich in catechins (40-65 mg/100 g). Flavanols These derivatives (R3 hydroxy) include catechin, epicatechin, epigallocatechin and their gallate derivatives. Flavanols are found in apples, apricots and red grapes (2-20 mg/100 g). Green tea and dark chocolate are rich in catechins (40-65 mg/100 g). 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Flavones This group of some 300 compounds retains the basic flavane nucleus structure. Flavones include apigenin and luteolin in very high concentrations (>600 mg/100 g) in parsley, and in lower but significant amounts in cereal grains, celery and citrus rinds (which contain polymethoxylated forms). 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Proanthocyanidins These derivatives are polymeric flavanols, also called condensed tannins. Proanthocyanidins are present in all plants. These polyphenols have strong antioxidant properties in vitro. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Anthocyanins These derivatives (R3 and R4 reduced) exist as glycosides, their aglycone chromophores being referred to as anthocyanidins. The most common anthocyanins are cyanidin, delphinidin, malvinidin, pelargonidin, peonidin, petunidin and malvidin. Most are red or blue pigments. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Anthocyanins The richest sources (600 mg/100 g) are raspberries, black berries and blue berries. Cherries, radishes, red cabbage, red skinned potato, red onions, and red wine are also good sources (50-150 mg/100 g). 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Anthocyanins have antioxidant properties. Unlike other flavonoids, anthocyanins are relatively unstable to cooking and high-temperature food processing. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Flavanones These derivatives (R4 keto, C ring otherwise reduced) are found primarily in citrus fruit (15-50 mg/100 g) where they are also present as O- and C-glycosides and methoxylated derivatives. Flavanones include eriocitrin, neoericitrin, hesperidin, neohesperidin, naringin, narirutin, didymin and poncirin. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Isoflavones These derivatives (B aromatic ring linked at R3) are contained only in legumes, mostly as glycosides. Isoflavones include daidzein, genistein, and glycitein, which are also referred to as phytoestrogens due to the affinities of their 7- and 4′-hydroxyl groups to binding mammalian estrogen receptors. Soy products can contain 25-200 mg/100 g. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Flavonoid utilization The hydroxyl groups of these polyphenols enable them to form glycosidic linkages with sugars. Most flavonoids occur naturally as glycosides. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Flavonoid utilization Flavonoid glycosides appear to be hydrolyzed by glycosidases in saliva, the brush border of the intestines and the intestinal microflora. Hindgut bacteria can also degrade the flavanoid by cleaving the heterocyclic ring, leading to the formation of various phenolic acids and their lactones, some of which may be absorbed from the colon. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Flavonoid utilization Upon absorption, flavonoids are conjugated as glucuronides or sulfates in the liver and are degraded to a variety of phenolic compounds that are rapidly excreted. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Health effects 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Antioxidant activity Flavonoids are able to chelate divalent metal cations (Cu2+, Fe2+), thus serving antioxidant functions by removing those catalysts of lipid peroxidation reactions. The flavonol quercetin (multiple phenolic hydroxyl groups, carbonyl group at C-4, free C-3 and C-5 hydroxyl groups) can scavenge superoxide radical ions, hydroxyl radicals and fatty acyl peroxyl radicals. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Antioxidant activity Flavonols and some proanthocyanins have been shown to inhibit macrophage-mediated LDL oxidation in vitro, probably by protecting LDL-α-tocopherol from oxidation or by reacting with the tocopheroxyl radical to regenerate α-tocopherol. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Enzyme modulation Flavonoids have been found to interact with all classes of enzymes and to selectively affect the activities of some. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Enzyme modulation Induction of phase II enzymes: epoxide reductase, UDP-glucoronosyltansferase, glutathione-S-transferase, NAD(P)H:quinone oxidoreductase, by affecting their transcription through binding to promoter regions of their respective genes. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Enzyme modulation Inhibition of other enzymes: aldose reductase, phosphodiesterase, O-methyltransferase, and several serine- and threoninekinases, by direct binding to the respective protein. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Tea flavanols: Induce phase II enzymes. Inhibit redox-sensitive transcription factors: NFkB, AP-1. Inhibit prooxidative enzymes: lipooxygenases, cyclooxygenases, nitric oxide synthase, xanthine oxidase. Induce phase II enzymes. Induce antioxidant enzymes: glutathione S-transferases, superoxide dismutases. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Enzyme modulation Flavanones have been shown to induce phase II enzymes and to exert anti-inflammatory effects. Naringin has been implicated in the effect of grapefruit juice in inhibiting cytrochrome P450-dependent drug metabolism. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chronic diseases Some epidemiologic studies have demonstrated associations of diets high in flavonoids (mainly quercetin) with reduced risks of cardiovascular diseases (21-53% reductions in prevalence) and cancers of the lung and rectum (44-47% reductions in prevalence). 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chronic diseases Cardioprotective effects have been attributed to: vasodilatory effects and blood pressure reduction antioxidant protection of LDLs against lipid peroxidation inhibition of platelet aggregation reduced inflammation 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chronic diseases Quercetin has been found to inhibit the activation of c-Jun N-terminal kinase in the modulation of angiotensin-induced hypertrophy of vascular smooth muscle cells. Various proanthocyanins have been shown to inhibit platelet activation and expression of interleukin-2, to lower serum levels of glucose, triglyceride and cholesterol. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chronic diseases Various flavones have been found to inhibit cell proliferation and angiogenesis in vitro and to inhibit phorbol ester-induced skin cancer in the mouse model. These effects may involve inhibition of protein kinase C, stimulation of DNA repair mechanisms and altered carcinogen metabolism. Some proanthocyanins have been shown to induce apoptosis. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Antiestrogenic effects of soy isoflavones Isoflavones bind to estrogen receptors α and ß, thus affecting the estrogen-synthetic activity of 17ß-steroid oxidoreductase, as well as estrogen-dependent signal transduction pathways. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Antiestrogenic effects of soy isoflavones The consumption of soy isoflavones has been associated with higher bone mineral density in a limited number of epidemiological studies. Soy isoflavones might be useful in improving bone mineralization for the prevention of osteoporosis. 13.11.2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 13.11.2018