Zie ook flavonoiden en phenolzuren
Absorption and Metabolism of Polyphenols: Phenolic Acids and Flavonoids
The efficiency of polyphenols absorption depends on their physicochemical properties: the size of the molecule, the presence of functional groups, spherical configuration, lipophilicity, and solubility. The forms soluble in water are better absorbed from the gastrointestinal tract than lipophilic compounds. Polyphenols in the chemically bound forms are subjected to the activity of bowel microflora enzymes and absorbed in the final section of the bowel.
The research by Konishi et al. has demonstrated that the absorption of gallic acid is significantly lower than that of caffeic acid. The absorption of hydroxyaromatic acids, benzoates, phenylacetates and hydroxycinnamates requires breaking down the polyphenol in the gastrointestinal tract to a lower molecular form.
The absorption of both flavonoids and phenolic acids depends on their structure. Quercetin and genistein aglycones are directly absorbed by the intestinal mucosa, and correspondingly metabolized to caffeic acid. Donovan et al. estimated that the absorption of quercetin aglycones in rat small intestine amounts to 67%.
However, in natural products only small amounts of aglycones are present. Flavonoid glycosides are less absorbed due to their hydrophilic nature. Isoflavones are an exception here, since no difference has been determined between aglycones and glycosides. Hydrolysis of flavonoid glycosides can effectively take place in the whole gastrointestinal tract, including the oral cavity. Hollman et al. [49] demonstrated that hydrophilic quercetin glycosides can be transported to the small intestine by intestinal Na+-dependent glucose transporter 1 (SGLT1). Flavonoid glycosides can penetrate enterocytes where they are hydrolised by a broad-specific-β-glucosidase enzyme (BSPβG). In addition, lactase phlorizin hydrolase (LPH) located in the brush border of the mammalian small intestine may participate in flavonoid glycoside hydrolysis. It is known that the sugar moiety of glycosides is a major determinant of their absorption, for example the absorption of pure quercetin-3-β-rutinoside amounts to 20% compared to pure quercetin-4′-β-glucoside. Moreover, food may influence the absorption of these compounds—for example, milk decreases the absorption of flavonols.
Polyphenols ingested with food affect the gastrointestinal tract. Polyphenols with a pyran ring and hydroxyl functional groups increase the solubility of chyme. Quercetin activates fermentation processes, playing a protective role against toxins in food. The metabolism of flavonoids occurs along three paths: oxidation, glucuronisation and sulphonation. Oxidation of flavonoids takes place with the participation of cytochrome P450 enzymes. Many studies have demonstrated the inhibiting influence of flavonoids on CYPs, especially CYP1A1/1A2. The enzymes participate in the oxidation of galangin in the following order: CYP2C9, and then CYP1A2 and CYP1A1. In kaempferide oxidation, CYP1A2 takes part first, and then CYP2C9 and CYP1A1 play a dominant role. Research has shown that CYP1A2 and CYP2E1 participate in the oxidation of numerous isoflavones. Coupled metabolism competes with flavonoid oxidation because after the absorption of polyphenols into enterocytes, the compounds undergo glucuronisation. The generation of glucuronic acid conjugates with quercetin, luteolin, chrysin and diosmetin occurs with the participation of UDP-glucuronosulphotransferase (UGT). The attachment of glucuronic acid to a polyphenol molecule depends on the number, as well as on the location of hydroxyl groups. Furthermore, methylation may also take place in enterocytes. In the case of quercetin, the process takes place at the 3′ and 4′ positions of the aromatic ring. Depending on the position where the reactions take place, the antioxidative properties and the biological activity of the compounds may vary.
Quercetin has a high antioxidative potential, while its glucuronides and sulphates are only partially as potent. In studies on human cells, covalent binding of oxidised quercetin to DNA and cellular protein has been determined. The interaction with proteins may influence flavonoid biological activity, but further studies are required to confirm that. Polyphenols bind to blood albumins in the small and large intestines. During the transport to the liver, glucuronide bonds are dissociated and then metabolised to glucuronide and sulphate conjugates, therefore they become more water-soluble. This process prevents the accumulation of polyphenols and their metabolites in the liver. In the liver, catechol-O-methyltransferase is responsible for methylation reactions of flavonoids, while sulphotransferase accounts for their reactions with sulphates.
Catechol-like flavonoid structures are susceptible to ortho-methylation by soluble catechol-O-methyltransferase (COMT). Olthof et al. state that binding with glucuronic and sulphuric acids decreases antioxidative properties of phenolic acids. Quercetin-4′-glucuronide demonstrates a very low antioxidant activity, quercetin-3-glucuronide is quite potent, but less than quercetin. In the case of quercetin-4′-glucoside and quercetin-3-glucoside the situation is similar. From the liver, polyphenols are transported to the blood, where they stay for a time interval different for particular compound. Quercetin is present there for over a dozen hours, and then it is eliminated. Polyphenols are excreted mainly with urine, but they can also be excreted with faeces, and according to King et al., 21% of isoflavones ingested with food are excreted with faeces.
Flavonoids are effectively metabolised by the cells of the gastrointestinal tract, and then excreted with faeces in the form of glucuronides and sulphates. The main product of quercetin excretion is carbon dioxide measured by trapping exhaled air, which indicates that bacteria from the lower part of the intestines constitute one of the steps of flavonoid elimination. Polyphenols, which have not been excreted from the body, are transported back from the blood to tissues and may have biological effects [57]. Fiorani et al. [58] state that quercetin, myricetin and genistein affect red blood cells metabolism. They are accumulated in red blood cells and perform antioxidative functions. In normal diet, flavonoid concentration in the blood serum is lower than 1 µM .
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