Flavonoid

Flavonoids are a group of phytochemicals, which make up a large part of the flower pigments. They are derived from the chemical backbone of the flavan (2- Phenylchroman ) from and consist of two aromatic rings connected by a tetrahydropyran ring. In nature, there are approximately 8000 compounds, the diversity created by different oxidation states in the oxygen- containing ring, different substitutions on the aromatic rings and the attachment of sugars ( glycoside formation). The pathway involves the Shikimisäureweg.

Flavonoids are universally present in plants, and thus also in the human diet. They are presented as particularly antioxidant properties. A number of flavonoid-containing plants are used medicinally.

The flavonoids were in the 1930s, discovered by Nobel laureate Albert Szent- Györgyi of Nagyrapolt and initially referred to as vitamin P. The "P" in vitamin P stands for " permeability factor ".

Name

Some plants like the dyer's oak (Quercus tinctoria ), the Färberwau ( Reseda lutea) or the dyer mulberry tree ( Maclura tinctoria ) were used in the past to yellowing. After they had identified their ingredients, called this group of dyes flavones, after the Latin word flavus for yellow. When it was recognized that a lot of the ingredients were similarly constructed, many of which are differently colored or colorless, called the group of substances flavonoids.

Occurrence

Flavonoids are widely used universally in the plant kingdom and occur in both seed plants and in mosses and ferns. Only a few microorganisms, the formation of flavonoids known, such as the watering can mold Aspergillus candidus. Animals can not form flavonoids. The occurrence in some species, such as the wings of some butterflies is due to the inclusion of plant flavonoids in the diet and their incorporation into the body. For other details, the flavonoids are limited to the plants.

Structure, diversity and subgroups

The basic structure of flavonoids consists of two aromatic rings are linked by a C3 - bridge. A ring generally points to the substitution pattern of the phloroglucinol, indicating its Acetogeninherkunft. B ring and the C 3- bridge derived from the Shikimisäureweg, ring B is usually from 4 ' hydroxylated, often in the 3' or 3 'and 5'. The C3 - bridge ( except chalcones) to an O - heterocyclic ring closed ( ring C) in the vast majority of flavonoids. The basic structure of flavonoids is thus the flavan (2- Phenylchroman ). Ring B is rarely moved to the position 3 ( Isoflavan derived therefrom isoflavones ) or 4 ( Neoflavan ).

Overall, more than 8000 different flavonoids have already been described (in 2006 ). The design, especially the degree of oxidation at the C3 - bridge is used for classification of flavonoids in the different subgroups.

The flavonoids are divided according to the degree of oxidation of the C3 bridge into different groups. Six major subgroups are found in most higher plants: chalcones, flavones, flavonols, Flavandiole, anthocyanidins and condensed tannins. The aurones are very widespread, but not ubiquitous. Limited to a few groups such as the isoflavones (primarily in Fabaceae ), and 3- deoxy- anthocyanidins, which are formed, for example as a precursor of Phlobaphene of Vitis vinifera, Arachis hypogaea and Pinus sylvestris.

The structural diversity of flavonoids is due to the variety of substitution patterns on the rings A and B, and the fact that the flavonoids usually not free, but are present as glycosides. There are proven over 80 different sugars. 179 different glycosides have been described for the quercetin.

Biosynthesis

Starting point for the biosynthesis of flavonoids, the aromatic amino acid phenylalanine, which is formed over the Shikimisäureweg. Phenylalanine is converted by the phenylalanine ammonia-lyase (PAL) to trans-cinnamic acid. This is in turn hydroxylated by cinnamate 4-hydroxylase with p - coumaric acid. This approach is common to all phenylpropanoids. The p- coumaric acid is activated to cinnamoyl -coenzyme A.

In the next step, the second aromatic ring is formed: the enzyme chalcone synthase ( CHS) is out of the cinnamoyl -CoA and three molecules of malonyl -coenzyme A, which originate from the Fettsäuresyntheseweg, the chalcone. Chalcone is by the action of chalcone isomerase ( CHI ) and the flavanone in equilibrium. This takes place the ring closure of the third ring.

The three key enzymes (PAL, CHS and CHI) and some enzymes of further synthesis steps are as enzyme complexes. Probably there is the complex on the cytosolic side of the endoplasmic reticulum.

The different paths lead to the flavones, flavonols, isoflavones and anthocyanidins from flavanone.

The biosynthesis of flavonoids is induced by light, storage occurs mainly in the vacuole.

Most of the enzymes for the biosynthesis of flavonoid derived from three classes of enzymes that are found in all organisms: oxoglutarate -dependent dioxygenases, NADPH-dependent reductase and the cytochrome P450 hydroxylases. The two key enzymes CHS and CHI belonging to other families. CHI is likely to be both in terms of sequence, such as a three-dimensional structure unique to plants. CHS in turn belongs to the superfamily of plant polyketide synthases.

Importance

The various flavonoids in the plants meet a variety of functions.

Flavonoids are the most important group among the flower pigments and are used the attraction of pollinators. The anthocyanidins provide a variety of colors ranging from orange to red to blue. In all anthocyanidinhaltigen flowers also flavones and / or flavonols are included, which serve to stabilize the anthocyanidins, but also cause a shift in flower color in the blue region at higher concentrations. Yellow flower color is rarely caused by flavonoids. Flavonols as Gossypetin and quercetagetin are responsible for the yellow flower color in Gossypium hirsutum, Primula vulgaris and some composite flowers such as Chrysanthemum segetum. Chalcones and aurones cause the yellow flower color in some other composites such as coreopsis and Dahlia and in nine other plant families. Often come in composite flowers yellow flavonoids together with the equally yellow carotenoids ago. White flower color is conditioned to 95% by flavonoids: flavones such as luteolin and apigenin, and kaempferol flavonols such as quercetin and, where flavonols absorb some more in the long wavelength range.

The condensed tannins interact with the glycoproteins in the saliva of herbivores and astringent. They decrease the digestibility of the plants and thus deter many potential herbivores.

Other flavonoids act as a defense mechanism against herbivores ( repellent). For specialized insects such flavonoids are in turn feeding stimulants. Especially flavone and flavonol glycosides, such as based on rutin, quercitrin and isoquercitrin, are toxic to insects while they are non-toxic to higher animals. The growth of various caterpillars reduced dramatically in the presence of, for example Isoquercitrin in the diet, 10% of the control groups. These flavonoids are mainly found in herbaceous plants and are expected to replace the condensed tannins here of woody plants.

Particularly flavones and flavonols act as protection against UV radiation and short-wavelength light. They are deposited in the free form of plants to extreme environments such as in arid or alpine areas of the leaf surface, often in the form of flour-like coverings. This will help prevent photo-oxidative destruction of membranes and photosynthetic pigments. Because of their lipophilicity, they also reduce the colonization of the leaf surface with microorganisms. However, the flavonoids also have direct antiviral, antibacterial and antifungal activity.

Certain Pflanzenflavonoide play a role in the regulation of gene expression of the nodule bacterium Rhizobium.

Highly methoxylated flavonoids commonly found in bud exudates and other lipophilic secretions. They act fungicidal, as well as the Nobiletin in citrus leaves.

Flavonoids serve as a structural motif for the development of selective GABAA receptor ligands.

Flavonoids in food and medicine

Food

Man takes on flavonoids with the food in larger quantities. Around two- thirds of the approximately one gram of comprehensive phenolic substances that man takes to himself, are flavonoids. " It is believed that, thanks to its antioxidant effect, which in some cases is stronger in vitro than that of known antioxidants such as vitamin E, have a significant impact on human health. "

Epidemiological studies showed a lower risk for various diseases at higher Flavonoidaufnahme, including about mortality from cardiovascular disease. Flavonoids contribute to the arachidonic acid metabolism and hence on the blood coagulation. For cancer, the epidemiological studies showed no association, with the exception of lung cancer, the risk is reduced primarily by Flavonoidaufnahme about apples.

For some compounds of mutagenicity or genotoxicity has been demonstrated in in vitro tests. But there is no evidence of toxicity in humans, animal studies showed no carcinogenic effects of flavonoids.

Certain flavonoids lead to a strong inhibition of the cytochrome P450-dependent monooxygenases ( phase I enzymes ), others to activation. There may be a dose- dependent activation of phase II enzymes. All this can lead to interactions with drugs, such as grapefruit.

Medical Terms

A number of flavonoid-containing medicinal drugs are used therapeutically, in addition some pure substances. They are used as means veins due to their vascular protective, ödemprotektiven effect, inotropic as cardiovascular agents because of their positive, antihypertensive effect, as diuretics, anticonvulsants than with gastrointestinal complaints as well as liver therapeutics. Their effect is mainly attributed to their antioxidant properties and inhibition of enzymes.

Epidemiological, as well as most in vivo studies indicate that flavonoids have a beneficial effect on various cardiovascular diseases. Traditionally, these effects were attributed only to their antioxidant activities. However, there is in addition to the direct binding of reactive oxygen species ( ROS), a number of other effects at pharmacologically achievable concentrations, the positive effect of the flavonoids, such as the cardiovascular Taxifolin may be responsible. These include in particular the inhibition of ROS - forming enzymes, inhibition of platelet function, inhibition of leukocyte activation and vasodilator properties.

Among the many effects of flavonoids have been identified in in vitro and in vivo experiments, are the most important:

• Anti-allergic and anti-inflammatory effect
• Antiviral and antimicrobial effect
• Antioxidant effect
• Antiproliferative and anticarcinogenic effect

Flavonoids act through multiple mechanisms of action. The focus is on the interaction with DNA and enzymes, activation of cells, their role as scavengers, as well as the influence of different signal transduction pathways in the cells (NF -kB, MAPK). Flavonoids inhibit over thirty enzymes in the human body. Activate a variety of cell types of the immune system. The two last properties are responsible for example for anti-inflammatory effects of flavonoids.

The following flavonoids are used as pure substances vein means:

• Citrusbioflavonoide, hesperidin
• Diosmin
• Rutin and Hydroxymethylrutinoside

Among the herbal drugs outweigh those containing flavonol glycosides and Glykosylflavone. Important medicinal drugs that contain greater amounts of flavonoids are:

• Arnica flowers ( Arnica )
• Birch leaves ( silver birch, downy birch )
• Buckwheat herb ( Fagopyrum esculentum)
• Ginkgo Leaves (Ginkgo )
• Goldenrod ( Solidago from virgaurea, Solidago gigantea and Solidago canadensis)
• Elderflower ( Black Elderberry )
• Hop cones ( Real Hop )
• Chamomile flower ( camomile)
• Katzenpfötchenblüten ( Ordinary Mountain Everlasting )
• Larch extract ( taxifolin )
• Meadowsweet and blossoms ( meadowsweet )
• Milk thistle ( Silybum marianum )
• Passion flower ( Passiflora incarnata from )
• Bitter orange peel ( Bitter Orange )
• Calendula flower (marigold)
• Roman chamomile
• Red vine (Vitis vinifera )
• Safflower ( safflower)
• Pansy ( Viola arvensis and Viola tricolor)
• Licorice root ( licorice )
• Hawthorn leaves with flowers ( several hawthorn species)