Flavonoides.
General chemical structure, biological function
Flavonoids are widely distributed secondary plant constituents with great structural variety and multifarious pharmacological properties.
The yellow (flavus = yellow) colour of many flavonoids has given this group of substances its name. Although purple in colour, the anthocyanidins (anthos = flower, cyanos = blue) also belong to this group of substances.
Because of identical biogenetic precursors, all flavonoids share the characteristic feature of a C15 carbon skeleton, a diphenyl-1,3-propane or 2-phenylbenzopyrane basic structure with a broad spectrum of variations as a result of:
- varying degrees of oxidation of the central C ring (flavone, flavonol, flavanone, flavononol, catechin, anthocyanidin, leucoanthocyanidin).
- major variations in the number and arrangement of OH, O and C alkyl substituents in rings A and B.
- different types, quantities and positions of the sugar residues (glycosides)
- the position of ring B (isoflavone)
Flavonoids are thought to fulfil directly biological functions in the actual plants, such as:
- producing pigmentation in flowers to attract insects
- protecting the plants from attack by insects, viruses and fungi
- regulate growth
- participating in the oxido-reduction systems of the cell metabolism
Effects and use
Technological applications of flavonoid drugs include dyeing wool (e.g. dyer's greenweed) and they are used in the conservation of fats and fruit juices by virtue of their antioxidative properties.
The structural diversity of the flavonoids is also reflected in a multitude of pharmacological effects. At one time, it was thought that a deficiency of citrus flavonoids - rutin, quercetin, taxifolin and others - increased the brittleness of the capillary blood vessels and they were therefore jointly referred to as "vitamin P" (permeability). The more accurate name now used for these substances is bioflavonoids.
Nowadays, water-soluble rutin preparations (e.g. Troxerutin) are used to treat diseases with low capillary resistance (hypertension, arteriosclerosis, diabetes).
The antiphlogistic and anti-edematous effects of rutin, quercetin, apigenin and others are primarily attributable to their influence on the prostaglandin cascade.
Procyanidins from hawthorn (crategus), arnica and ginkgo have vasodilative and cardiotonic (positively inotropic) effects. They are frequently used in diuretic teas made from birch leaves (betula), restharrow (ononis), golden rod (solidago) and ortosiphon leaves.
The antihepatotoxic effect of highly concentrated milk thistle seed extracts (silymarin; silybin, silychristin, silydianin) is used to treat liver diseases.
Red clover has been gaining significance in treating the symptoms of menopause in recent years, due to the oestrogenic effect of its isoflavones.
The antioxidative properties of highly hydroxylated flavonoids as radical scavengers in green tea and wine leaves, for example, are playing an increasingly important role in the food supplements market since they have been found to exert a favourable cancer chemopreventive effect in terms of nutritional physiology.
Analysis
The heterogeneity of the flavonoids found in a drug is such that most of the assays described in the Ph. Eur. and other pharmacopoeias refer to quantitation of the total content. Drugs containing predominantly hydrolysable flavonoid-O-glycosides are first subjected to acid hydrolysis; the flavon aglycones are extracted into ethyl acetate, a complexing agent, such as AlCl3, is added and the complex undergoes photometric quantitation. The results are then calculated according to a specific reference substance (e.g. hyperoside, rutoside or isoquercitrin).
Drugs containing predominantly C-glycosides (passionflower, hawthorn leaves) are extracted and boric acid / oxilic acid reagent, for example, is added directly before undergoing photometric analysis and the results are calculated according to the reference substance, e.g. vitexin or hyperoside.
Procyanidins from hawthorn berries undergo acid hydrolysis to produce red anthocyanins, which are extracted with butanol and quantified as cyanidin chloride.
Anthocyanins from bilberries and red wine leaves can undergo photometric quantitation immediately following extraction.
One technique that is becoming increasingly important is selective quantitative analysis by means of HPLC to determine apigenin and apigenin-7-glucoside in camomile, for example, as well as epicatechin, epicatechin gallate, epigallocatechin and epigallocatechin gallate in black and green teas in accordance with ISO/WDCD14502-2, hesperidin in citrus fruits, orientin in passionflower, quercitrin, quercetin and rutin in St. John's wort.
A few specific flavonoids also play a significant role as analytical markers for plant-based drugs. These include tiliroside, taxifolin, vitexin, vitexin rhamnoside, luteolin, luteolin glucoroside and luteolin glucoside.
An obsolete photometric assay of the total silymarin content in milk thistle seeds has also been superseded by HPLC quantitation of silybin, silychristin and silydianin in the Ph. Eur.
PhytoLab
PhytoLab is Europe's leading external testing laboratory for the analysis of plant constituents and the registration of plant-based medicinal products.
Officially recognized in accordance with § 14 of the German Drug Law (AMG), PhytoLab is also accredited in accordance with ISO 17025 and GLP principles 2 and 7 by the Governmental Recognition Office for Foodstuffs Monitoring (SAL) and, as such, fulfils the requirements of Council Directive 93/99/EEC.
