Read this article to learn about Flavonoids. After reading this article you will learn about: 1. Chemistry of Flavonoids 2. Biosynthesis of Flavonoids 3. Dietary Source 4. Extraction 5. Pharmacokinetic Study 6. Pharmacological Importance.
Contents
Chemistry of Flavonoids:
The chemistry of flavonoids is complex and at first glance can be overwhelming. In plants, flavonoids can occur with or without sugar moieties attached. The biochemical activities of flavonoids and their metabolites depend on their chemical structure and the relative orientation of various moieties on the molecule.
An overview of the chemistry of the various classifications of plant flavonoids will be given in this review well as examples for each: including flavonols, flavones, flavanones, catechins (orflavanols), anthocyanidins, iso-flavones, dihydroflavonols, and chalcones.
Structure and Classification of Flavonoids:
Flavonoids are low molecular weight polyphenolic substances based on the flavan nucleus. Fig 23.1 shows the generic structure of flavonoid and the numbering system used to distinguish the carbon positions around the molecule.
The three phenolic rings are referred to as the A, B, and C (or pyrane) rings, the flavonoid aglycone consists of a benzene ring (A) condensed with a six membered ring (C) which in the 2-position carries a phenyl ring (B) as a substituent. Six-member ring condensed with the benzene ring is either a pyrone or its dihydro derivative.
The position of the benzenoid substituent divides the flavonoid class into flavonoids (2-position) and iso-flavonoids (3-position). Flavonols differ from flavonones by hydroxyl group at 3-position and C2-C3 double bonds. Flavonoids are often hydroxylated in position 3, 5, 7, 2′, 3′, 4′, 5′. Methyl ethers and acetyl esters of the alcohol group are known to occur in nature.
When glycosides of flavonoids are formed, the glycosidic linkage is normally located in positions 3 or 7 and the carbohydrate can be L-rhamnose, D-glucose, glucorhamnose, galactose or arabinose (Middleton, 1984). The skeleton (Fig. 23.1) representing as the C6-C3-C6 system of flavonoids.
The chemical structure (Fig 23.2) and nomenclature and classification of flavonoids include flavonols, flavones, flavanones, catechins (or flavanols), anthocyanidins, iso-flavones, dihydro-flavonols, and chalcones are described in table 23.1.
Biosynthesis of Flavonoids:
The biosynthesis of flavonoid is important for understanding their diversity arid to the design of sound analytical procedures. The flavonoid molecule are biosynthesized by their precursor i.e. three molecules of acetic acid and phenyl propane moiety.
It involves the interaction of at least five different pathways, namely the glycolytic pathway, the pentose phosphate pathway, the shikimate pathway that synthesizes phenylalanine, the general phenylpropanoid metabolism that produces activated cinnamic acid derivatives (4-coumaroyl- CoA) and also the plant structural component lignin and finally the diverse specific flavonoid pathways.
In this scheme flavonoids are biosynthesized via a condensation of the shikimic acid and acyipolymalonate pathways.
A cinnamic acid derivative (phenyl propane), synthesized from shikimic acid, acts as the starting compound in a polyketide synthesis, in which an additional three acetate residues are incorporated into the structure and this is followed by ring closure.
Through subsequent hydroxylation’s and reductions, plants are then able to biosynthesized different classes of flavonoids like flavonols, flavones, flavanones, catechins (or flavanols), anthocyanidins, iso-flavones, dihydro- flavonols, and chalcones.
Dietary Source of Flavonoids:
Flavonoids are characteristic constituents of green plants with the possible exception of algae and hornworts. They occur virtually in all parts of the plant but the quantitative distribution varies between different organs of the plant and within different populations of the same plant species (Kevin and Michael, 1997).
This variability is largely controlled by genetics but other factors include maturity, climate, and position on the tree, rootstock and agricultural practices. Dietary flavonoids consist mainly of anthocyanidins, flavonols, flavones, catechins and flavanones (Hertog, 1996; March- and et al., 2000; Hertog et al., 1993; Justesen et al., 1997; Kuhnau, 1976; Hollman et al., 1999; Holden et al., 1987; Mangels, 1993).
Accurate data on population-wide intakes of flavonoids are not available but important dietary sources of flavonoids are:
Extraction of Flavonoids from Plants:
The pharmacological activities of medicinal plants are closely related to types of natural compounds those are present in bioactive plant material. Each of natural chemical compounds may have preferred effective method of extraction which facilitates getting the chemicals compounds out of the plants and into the herbal remedy that is being prepared.
For extraction of flavonoids from plant material, freeze-dried plant sample mixed with 70% HPLC grade methanol and shake for 15 min at room temperature.
After centrifugation (3,000 rpm, 5 min), the supernatant is filter on 90 mm filter paper. The pellet is then re-extracted with 70% methanol and finally rinsed with 100% methanol. All three supernatants are pooled together before removal of the methanol under vacuum with a Rota-evaporator at 70°C.
When the methanol has evaporated, the extract is concentrated and purified using an activated Sep-Pack C18 column (Sep-Pak -> RC Cartridge, Water) and eluted with HPLC grade methanol before being stored at 4°C prior to analysis (Nicolas et al., 2005).
Pharmacokinetic Study of Flavonoids:
The single most important group of phenolics is the flavonoids. They are highly diverse, in both their chemical structure and proposed biological functions. Their metabolic pathways are particularly complex with, in many cases, multiple alternative metabolic fates. Profiling of the components of a pathway over time provides a dynamic view of the metabolic events occurring in the plant (Kevin and Michael, 1997).
The extent of absorption of flavonoids is an important unsolved problem because of the limited data available about them, particularly in humans.
Animal studies show that flavonoids present in foods are to be considered non-absorbable because they are bound to sugars as β-glycosides (with the exception of catechins). In fact, only free flavonoids, without a sugar molecule (so-called aglycones), are thought to be able to pass through the gut wall.
The hydrolysis of the glycosidic bonds occurs only in the colon by micro-organisms that at the same time degrade dietary flavonoids. This is because no enzymes capable of splitting the bond are present or secreted into the gut. After absorption, the subsequent metabolism of flavonoids is quite well known from animal studies, while less data for humans are available.
The liver is main and primary responsible site for the metabolism of absorbed flavonoids. The intestinal wall and kidney are the secondary sites of the metabolism of the absorbed flavonoids.
However, this depends on the flavonoids: those found in citrus fruits are poorly metabolized by the intestinal micro flora, quercetin is not absorbed in humans, rutin is poorly absorbed, whereas pro-cyanidolignanes are readily absorbed in mice.
Many flavonoids are metabolized by intestinal bacteria and these flavonoids are converted to hormone-like compounds with weak estrogenic and antifecondative activities.
The possibility of an enterohepatic cycle has been postulated: micro-organisms in the colon can hydrolyse glucuronides and sulphates, which then presumably enables absorption of the liberated aglycones.
Flavonoids, once absorbed, influence many biological functions including protein Synthesis, cell proliferation differentiation and angio- genesis, making them beneficial in a various human disorders (Giulia et al., 1999).
Pharmacological Importance of Flavonoids:
The use of flavonoids are in the treatment of disease is to large extent is much older than the science of chemistry. Flavonoids have been used in folk as well as modern medicine around the world. Therefore, it seems that these compounds are important not only for plants, but also for animals including humans (Giulia et al., 1999).
The important role of flavonoids in diet and medicine is becoming more and more recognized. From past two decades many researcher has much concentrated on the study of antibacterial, antifungal and antiviral activities of different flavonoids. 