Microbial Metabolism. Part 6. Metabolites of 3- and 7-Hydroxyflavones

Abstract

Flavonoids and their glycosides form a large group of polyphenolic compounds which are widely distributed in plants. 2,3) Animals depend on plants for flavonoids as they are unable to biosynthesize them.4) The exception was the detection of flavonoids in butterfly wings with the likely source being the plant food of the larva.5) Flavonoids add colour, 6) flavour and processing characteristics to many foods (fruits and vegetables) and drinks (tea, wine). 7) So far, over 4000 flavonoid derivatives have been identified and numerous beneficial health effects including, anti-inflammatory, [8][9][10] antiviral 11) and anti-cancer 8,12,13) properties have been reported. Some epidemiological studies have also demonstrated that the intake of flavonoids reduced the risk of cardiovascular diseases. 8,[14][15][16] Most of the pharmacological activities could be attributed to their ability to inhibit certain enzymes and to their oxygen free radical scavenging and iron chelating capabilities.17) The antioxidant properties are suggested to be due to the number and arrangement of their phenolic hydroxyl groups.18) It has been shown that 3-hydroxy-, 7-hydroxy-and 5-hydroxyflavones have hypochlorite scavenging activity with 3-hydroxyflavone showing the greatest effect.19) Depending on the concentration and the reaction conditions, flavonoids could act as antioxidants as well as prooxidants. 17)Toxicity of some flavonoids has been attributed to their prooxidant behavior. Hence, careful examination of flavonoids for their behavior in varying reaction conditions has to be carried out before being considered for therapeutic uses. 17)Although in vitro experiments have shown that flavonoids possess a wide range of biological activities, their overall function in vivo has to be clarified. It has been observed that only aglycones and flavonoid glucosides are absorbed in the small intestine.18) They are then metabolized rapidly to methylated, glucuronidated or sulphated metabolites in the jejunal and ileal parts of the small intestine. After metabolism in the intestine, the flavonoids are further metabolized in the liver to yield various conjugated forms. The reactions include methylation, sulphation and glucuronidation. Conjugation is essentially a detoxification process in which the compounds are made to eliminate by way of bile and urine by increasing their hydrophilic character.20) The unabsorbed flavonoids undergo further metabolism by the bacterial enzymes in the colon.21) Using animal models, human trials and in vitro fermentation experiments, it was shown that the intestinal microorganisms are greatly responsible for catabolism and scission of the flavonoid. Scission of the flavonoid structure depends on their hydroxylation pattern.21) Absence of hydroxyl groups in the B-ring for example, prevents ring scission. In vitro metabolism studies of flavonoids using rat liver microsomes showed that the B-ring is the main structural moiety that undergoes biotransformation. B-rings with a single hydroxyl group at C-4Ј or none at all get hy...

Microbial Metabolism of Biologically Active Secondary Metabolites from Nerium oleander L.

“…The sugar part was further confirmed by comparing the 13 C-NMR resonances with those reported for the corresponding carbons in a similar O-b-D-4-Omethylglucopyranoside. 39) The remaining signals of the NMR spectra confirmed the structure of the aglycone moiety. The assignment of signals of compound 7 was based on COSY, HMQC and HMBC spectra.…”

“…These proton signals were easily linked to the new carbon signals at d 98. 4 38,39) and shown in Table 2. Further evidence came from the 3 3.44 3H, s CH 3 1.02 (d, 6) sylation was deduced from the H-1Љ/C-7 correlation observed in the HMBC spectrum.…”

Microbial Metabolism Part 9. Structure and Antioxidant Significance of the Metabolites of 5,7-Dihydroxyflavone (Chrysin), and 5- and 6-Hydroxyflavones

“…Metabolites, 4, 6-8, 11, 12, 14 and 15 being known compounds were identified by comparison with published data as, 4Ј-hydroxychrysin (apigenin), 19,20) chrysin 7-sulfate, 21) 4Ј-hydroxy-3Ј-methoxychrysin (chrysoeriol), 19,20) 3Ј,4Ј-dihydroxychrysin (luteolin), 19,20) luteolin 3Ј-sulfate, 5,4Ј-dihydroxyflavone, 19,20) (Ϯ)-6-hydroxyflavanone, 22) and flavone 3- 23) respectively. (Ϯ)-6-hydroxyflavanone (14) indicated a non-stereoselective process of hydroxylation of the olefinic bond in the starting material (3).…”

“…Similar results were obtained with our previous microbial conversion of the flavonoids 3-hydroxyflavone and 7-hydroxyflavone. 23) However, conjugation seems to be the preferred reaction in most of these conversions. Oxygenation and conjugation products obtained with compounds, 1-3 together with many other similar microbial metabolites of flavonoids reported, are paralleled in mammals [27][28][29] indicating the use of microbes to mimic mammalian metabolism.…”

Selection of filamentous fungi of the Beauveria genus able to metabolize quercetin like mammalian cells

“…As reported by different authors, conjugations are the most common final step reactions in mammalian metabolism of intact flavonoids. After absorbed and metabolized in the intestine, they are further metabolized in the liver to yield various conjugated forms (6,10,11,18). Several flavonoids such as quercetin, naringin, and (18) also detected 14 different phase II mono and mixed conjugates of quercetin in various biological systems such as rat liver microsomes, human hepatic microsomes, rat small intestine, human small intestine, rat plasma and human plasma.…”