The quantitative disposition of 3-O-methyl-(+)-[U-¹⁴C]catechin in man following oral administration

Abstract

Three young male volunteers excreted 51.5, 33.6 and 55.9% of a single 2 g oral dose of radiolabelled 3-O-methyl-(+)-catechin in urine within 120 h of administration. Excretion of the unchanged compound, however, accounted for only 0.7, 0.1 and 0.2% of the dose. The major urinary metabolites were glucuronides of 3,3'-O-dimethyl-(+)-catechin (15.8% dose) and a glucuronide and a sulphate of 3-O-methyl-(+)-catechin (11.4% and 10.6% dose, respectively). No evidence for demethylation was obtained. 3-O-Methyl-(+)-catechin was detected and measured in plasma by h.p.l.c. 0.5-12 h after administration. Peak levels (11-18 micrograms/ml) were attained within two hours of administration and the half-life of removal from plasma was approx. 140 min. Metabolism of 3-O-methyl-(+)-catechin in man was found to vary significantly from other species, as methylated metabolites (3'-O-methyl ethers) in man represented only about 53% of the urinary metabolites, whereas in the mouse, rat and marmoset, 3'-O-methylation was almost quantitative (Hackett and Griffiths 1981). The glucuronic acid conjugates of 3-O-methyl-(+)-catechin detected in man also differed from those previously reported in the rat. Additionally, sulphate conjugation of 3-O-methyl-(+)-catechin was observed in man although not in other species. 3-O-Methyl-(+)-catechin, unlike (+)-catechin, did not undergo ring fission.

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

“…27) Both flavones yielded the conjugated products, 4, 5, 7, 8 and 9. The formation of hydroxylation and conjugation products in this study are paralleled in mammals [32][33][34] indicating the use of microbes to mimic mammalian metabolism. Microbes usually form glucosides rather than glucuronides as occurs in mammals.…”

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

“…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. Conjugation is the most common final step in mammalian metabolism of intact flavonoids.…”

“…Hence, in competition, the former is expected to play an insignificant role as far as antioxidant activity is concerned. 29) However, in the light of new data it has been pointed out that even though flavonoids and their in vivo metabolites may not act as antioxidants, they are present in sufficient amounts in vivo to have pharmacological activity at receptors, transcription factors and enzymes. 29) The formation of conjugated products may be viewed as a safety mechanism which prevents the accumulation of flavonoids to levels harmful to the body 15) by aiding in rapid elimination and retaining the amounts necessary to have beneficial effects.…”

The identification of flavonoids as glycosides in human plasma

“…Diosmetin was detected by liquid chromatography-mass spectrometry at peak levels of 400 ng/ml in plasma after 1 h, decreasing to 50 ng/ml at 48 h. Evidence exists that catechin is absorbed by the human gut [21] and other investigations [22] and measured the supplement in the plasma by HPLC with UV detection at 280 nm. Peak levels of 11-18 |J.g/ml were found within 2 h of administration.…”