The flavonoids form a group of approximately nine thousand plant metabolites. Chemically, they can be classified as polyphenols or phenolics. Subgroups of flavonoids include flavones, flavonols, flavanols, flavanones, chalcones, aurones, isoflavones, anthocyanins, and proanthocyanidins. Subgroup representatives vary structurally by their oxygenation, methylation, prenylation, and glycosylation pattern. Their name is derived from ‘flavus’ (Greek, meaning ‘yellow’), indicating that many representatives are yellow plant pigments. Physiologically, flavonoids play roles in allelopathy, attraction of pollinators, protection against damage from sunlight, protection against herbivores and microbes, and in plant growth and development. Many health effects of fruits, vegetables, and dietary supplements (nutraceuticals) have been attributed to the presence of flavonoids. Flavonoids exhibit antioxidant, anti‐inflammatory, anticancer, antiobesity, cardioprotective, and neuroprotective activities. Modulation of cell signalling pathways rather than antioxidant activity may explain the health‐promoting effects of flavonoids in vivo. Most flavonoids are poorly absorbed, extensively metabolised and primarily excreted as glucuronides and sulfates.

Key Concepts:

  • Flavonoids are synthesised by virtually all green plants except algae. They are biosynthesised from phenylalanine and three molecules of malonic acid to form chalconaringenin, from which virtually all other flavonoid skeleta are derived, that is, flavanones, flavones, flavonols, aurones, isoflavones, anthocyanins, and proanthocyanidins.

  • In plants, flavonoids are important for growth and development, attraction of pollinator animals, nitrogen‐fixation in leguminous plants, and for protection against damage by herbivores, microbes, UV and reactive oxygen species.

  • Flavonoids ingested by animals and humans are mainly in the form of glycosides which are hydrolysed in the intestines. The resulting free forms (aglycones) can be degraded to phenolic acids or conjugated with glucuronic acid, sulfate, and methyl groups by the intestinal microflora and the liver.

  • Plasma and intracellular concentrations of flavonoids are low because of poor absorption, extensive metabolism and quick excretion from the body. Isoflavones are the most bioavailable flavonoids in humans.

  • Flavonoids, as aglycones or conjugate metabolites, may confer health benefits related to cancer, inflammatory disease, cardiovascular disease, neurological disorders, metabolic syndrome, obesity and osteoporosis. Epidemiological studies show that consumption of flavonoid‐rich foods is associated with reduced risk of developing cancer and cardiovascular disease.

  • Modulation of cell signalling pathways via NF‐κB, Nrf2 and protein kinases, rather than antioxidant activity, may mediate most of the biological activities of flavonoids in vivo. The direct antioxidant activity of flavonoids has not been established in humans.

  • Flavonoids may interfere in the absorption and metabolism of drugs and nutrients but they themselves are of low or negligible toxicity at the concentrations found in foods.

  • Clinical studies are needed to better understand the pharmacokinetics and health‐promoting effects and side effects, if any, of flavonoids when used as dietary supplements or as pure compounds in pharmacological doses.

Keywords: flavonoids; biosynthesis; bioavailability; antioxidant; inflammation; cardiovascular disease; neurological disorders; metabolic syndrome; osteoporosis; cell signalling

Figure 1.

Enzymes involved in the biosynthesis of flavonoids: 1, phenylalanine ammonia lyase (PAL); 2, cinnamate‐4‐hydroxylase (C4H); 3, 4‐coumarate:CoA ligase (4CL); 4, chalcone synthase (CHS); 5, chalcone reductase (CHR); 6, aureusidin synthase (AS); 7 chalcone isomerase (CHI); 8, flavone synthases I and II (FNS); 9, flavanone 3‐hydroxylase (F3H); 10, flavonol synthase (FLS); 11, dihydroflavonol 4‐reductase (DFR); 12, leucoanthocyanidin reductase (LAR); 13, anthocyanidin synthase (ANS); 14, anthocyanidin reductase (ANR); 15, unknown condensing enzyme(s) (CON); 16, 2‐hydroxyflavanone synthase (IFS); 17, 2‐hydroxyisoflavanone dehydratase (IFD); 18, isoflavone 2′‐hydroxylase; 19, isoflavone reductase (IFR); 20, pterocarpan synthase (PTS). Adapted from Dao et al., ; Dewick, ; He et al., ; Pang et al., ; Xie et al., .

Figure 2.

Metabolism of flavonoids by mammalian and bacterial enzymes. Biotransformations in panels (a) and (e) are typically mediated by hepatic phase I and II enzymes. Panels (b), (c), (d) and (e) show biotransformations carried out by intestinal bacteria. Adapted from Del Rio et al., ; Legette et al., ; Setchell and Clerici, ; Yuan et al., .

Figure 3.

Redox cycling of flavonoids. Oxidation of catecholic flavonoids leads to ortho‐quinone formation. The quinones are redox active and promote generation of reactive oxygen species (ROS) via redox cycling thereby leading to deoxyribonucleic acid (DNA) damage and oxidative modification of proteins. Quinones are also potent electrophiles that can covalently modify DNA and other endogenous nucleophiles, such as glutathione and proteins. The reactivity of both, the ROS and the quinone, towards thiols may modulate redox homoeostasis and signalling, thereby changing the balance between health promoting and adverse effects of redox‐active flavonoids.

Figure 4.

Modulation of the Keap1‐Nrf2 signalling pathway by flavonoids. Flavonoids activate the Keap1‐Nrf2 signalling pathway (green arrows) through phosphorylation of Nrf2 by upstream kinases, oxidation of cysteine thiols or direct binding of electrophiles to cysteine thiols of Keap1 (Fraga and Oteiza, ; Mann et al., ; Surh et al., ).

Figure 5.

Modulation of NF‐κB‐mediated signalling pathways by flavonoids. Flavonoids exert their anti‐inflammatory activity by interfering with multiple steps of the NF‐κB activation process (Banerjee et al., ; Fraga and Oteiza, ; Surh et al., ). EGCG inhibits the activity of IKK or suppresses the activation of IKK and the degradation of IκBα. Epicatechin and catechin inhibit the phosphorylation of IKKβ, the subsequent degradation of IκBα and the binding of NF‐κB to its DNA consensus sequence. Quercetin inhibits the degradation of IκBα and the nuclear translocation of p50 and p65 subunits of NF‐κB. Genistein could interfere in the binding of NF‐κB to DNA. Epicatechin and B dimers can interact with the DNA‐binding site in the NF‐κB proteins, preventing the interaction of NF‐κB with κB DNA binding sites, thus inhibiting gene transcription. Catechins inhibit the proteolytic activity of the 26S proteosome that inhibits IκB degradation.



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Miranda, Cristobal L, Maier, Claudia S, and Stevens, Jan F(Jun 2012) Flavonoids. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003068.pub2]