FLAVONOIDS AND THEIR HEALTH BENEFITS

FLAVONOIDS AND THEIR HEALTH BENEFITS

 Flavonoids are low molecular weight bioactive polyphenols which play a vital role in photosynthesising cells. They are a large family of over 5,000 hydroxylated polyphenolic compounds that carry out important functions in plants. The original "flavonoid" research apparently began in 1936, when Hungarian scientist Albert Szent-Gyorgi was uncovering a synergy between pure vitamin C and as yet unidentified co-factors from the peels of lemons, which he first called "citrin," and, later, "vitamin P". Flavonoids are secondary metabolites characterised by flavan nucleus and C6-C8-C6 carbon-skeleton. These are group of structurally related compounds with a chromane-type skeleton having phenyl substituent in C2-C3 position. The basic structural feature of flavonoid is 2-phenyl-benzo-γ-pyrane nucleus consisting of two benzene rings (A and B) linked through a heterocyclic pyran ring (C) as shown in fig (I). Flavonoids are one of the largest groups of secondary metabolites and widely distributed in leaves, seeds, bark and flowers of plants with more than 4000 different structures which are classified according to their chemical structures as follows; flavones, flavonols, flavanones, dihydroflavonols, isoflavones, anthocyanins, catechins and calchones. Flavonoids which are part of human diet are thought to have positive effects on human health such as reducing risk of cardiovascular diseases and cancer. Most of the beneficial effects of flavonoids are attributed to their antioxidant and chelating abilities. Flavonoids are structurally related compounds with a chromane-type skeleton with a phenyl substituent in the C2 or C3 position . They are consisting of phenylpropane (C6-C3) unit derived from shikimic acid pathway and C6 unit derived from polyketide pathway biosynthetically.

Chemical structure of Flavonoids

 

Figure 1: diphenylpropane, a basic structure of flavonoids

 

Chemically flavonoids are based upon a fifteen-carbon skeleton consisting of two benzene rings (A and B as shown in Figure 1) linked via a heterocyclic pyrane ring (C). They can be divided into a variety of classes such as flavones (e.g., flavone, apigenin, and luteolin), flavonols (e.g.,

quercetin, kaempferol, myricetin, and fisetin), flavanones (e.g., flavanone, hesperetin, and naringenin), and others. Their general structures are shown in Table 1. The various classes of flavonoidsdiffer in the level of oxidationandpattern of substitution of the C ring, while individual compounds within a class differ in the pattern of substitution of the A and B rings.

Flavonoids occur as aglycones, glycosides, and methylated derivatives. The basic flavonoid structure is aglycone (Figure 1). Six-member ring condensed with the benzene ring is either a 𝛼-pyrone (flavonols and flavanones) or its dihydroderivative (flavonols and flavanones). The position of the benzenoid substituent divides the flavonoid class into flavonoids (2-position) and isoflavonoids (3-position). Flavonols differ from flavanones by hydroxyl group at the 3- position and a C2–C3 double bond. Flavonoids are often hydroxylatedinpositions 3, 5, 7, 2, 3󸀠, 4󸀠, and5󸀠.Methyl ethers and acetyl esters of the alcohol group are known to occur in nature. When glycosides 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.

 

Classes of flavonoids

Flavonoids are classified into eight classes based on differences in their arrangement of hydroxyl, methoxy and glycosidic side groups and in the conjuction between A and B rings. A variation in C ring provides division of subclasses. According to their molecular structure, they are divided into eight classes, namely: Flavone, Flavonones, Flavonol, Isoflavone , Anthocyanidin, Catechin, Dihydroflavonol and Chalcone.

Metabolism of flavonoids

The absorption of the dietary flavonoids liberated from the food by chewing will depend on its physicochemical properties such as molecular size, configuration, lipophilicity, solubility, and pKa. The flavonoid can be absorbed from the small intestine or has to go to the colon before absorption. It may depend upon structure of flavonoid, that is, whether it is glycoside or aglycone. Most flavonoids, except for the subclass of catechins, are present in plants bound to sugars as b-glycosides. Aglycans can be easily absorbed by the small intestine, while flavonoid glycosides have to be converted into aglycan form. The hydrophilic flavonoid glucoside such as quercetin are transported across the small intestine by the intestinal

Na+-dependent glucose cotransporter (SGLT1). An alternative mechanism suggests that flavonoid glucosides are hydrolyzed by lactase phloridzin hydrolase (LPH), a 𝛽-glucosidase on the outside of the brush bordermembrane of the small intestine. Subsequently, the liberated aglycone can be absorbed across the small intestine. The substrate specificity of this LPH enzyme varies significantly in a broad range of glycosides (glucosides, galactosides, arabinosides, xylosides, and rhamnosides) of flavonoids. The glycosides which are not substrates for these enzymes are transported toward the colon where bacteria have ability to hydrolyze flavonoid glycosides, but simultaneously they will also degrade the liberated flavonoid aglycones . Since absorption capacity of the colon is far less than that of the small intestine, only trivial absorption of these glycosides is to be expected. After absorption, the flavonoids are conjugated in the liver by glucuronidation, sulfation, or methylation or metabolized to smaller phenolic compounds. Due to these conjugation reactions, no free flavonoid aglycones can be found in plasma or urine, except for catechins. Depending on the food source bioavailability of certain flavonoids differs markedly; for example, the absorption of quercetinfrom onions is fourfold greater than that from apple or tea. The flavonoids secreted with bile in intestine and those that cannot be absorbed fromthe small intestine are degraded in the colon by intestinal microflora which also break down the flavonoid ring structure (Figure 3). Oligomeric flavonoids may be hydrolyzed tomonomers and dimers under influence of acidic conditions in the stomach. Larger molecules reach the colon where they are degraded by bacteria. The sugar moiety of flavonoid glycosides is an important determinant of their bioavailability. Dimerization has been shown to reduce bioavailability. Among all the subclasses of flavonoids, isoflavones exhibit the highest bioavailability. After ingestion of green tea, flavonoid content is absorbed rapidly as shown by their elevated levels in plasma and urine. They enter the systemic circulation soon after ingestion and cause a significant increase in plasma antioxidant status.

Health benefits of Flavonoids

Flavonoids act as antioxidants by suppressing reactive oxygen specie (ROS) formation either by inhibition of enzymes or by chelating trace elements involved in free radical generation. Flavonoids inhibits the enzymes involved in ROS generation, that is, microsomal monooxigenase, glutathione s-transferase, mitochondrial succinoxidase, NADH oxidase etc. they also inhibits lipid peroxidation. Other health benefits of flavonoids include, anti-inflammation, antibacterial, anticancer antiviral.