Bioavailability of [2-¹⁴C]Quercetin-4′-glucoside in Rats

Abstract

[2-(14)C]quercetin-4'-glucoside (4 mg/kg body weight) was fed by gavage to rats housed in metabolic cages, and over an ensuing 72 h period, radiolabeled products in body tissues, plasma, feces, and urine were monitored by high-performance liquid chromatography with online radioactivity and MS2 detection. One and 6 h after ingestion, while in the small intestine, the flavonol glucoside was converted to glucuronide and methylated and sulfated derivatives of quercetin, but only trace amounts of these metabolites were excreted in urine. On entering the cecum and the colon, the flavonol metabolites declined as they were converted to phenolic acids, principally 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid, by the colonic microflora. Feces contained mainly 3-hydroxyphenylacetic acid. Urine collected 0-12 and 0-24 h after ingestion contained radiolabeled hippuric acid and 3-hydroxyphenylacetic acid. 14C-Hippuric acid declined markedly in the 24-48 and 48-72 h urine samples, and there was a concomitant increase in labeled benzoic acid. There was minimal accumulation of radioactivity in plasma, despite a 69% recovery of label in urine over the 72 h period, and likewise, very little radioactivity was detected in body tissues out with the gastrointestinal tract. This is reflected in the fact that 72 h after ingestion 96% of the ingested radioactivity was recovered in feces, urine, and the cage washes, which comprise a mixture of urine and feces. The study reveals that as it passes through the gastrointestinal tract, almost all of the of [2-(14)C]quercetin-4'-glucoside is converted to phenolic acids, compounds not monitored in previous flavonol bioavailability studies with model animal systems, some of which have used exceedingly high doses of the aglycone quercetin (500 mg/kg body weight), which is not a normal dietary component.

Microsomal Quercetin Glucuronidation in Rat Small Intestine Depends on Age and Segment

“…We and others have reported that glucuronidation in the small intestine plays a key role in quercetin metabolism in rats (Graf et al, 2006;Mullen et al, 2008). Our results further confirm the importance of this organ for first-pass metabolism of flavonoids through glucuronidation.…”

“…Prolonged quercetin feeding to F344 rats resulted in mainly mono-, di-, or mixed glucuronides or quercetin in intestinal tissue (Graf et al, 2006). In Sprague-Dawley rats, the primary metabolites of quercetin 4Ј-glucoside in intestinal tissue were also glucuronides (Mullen et al, 2008). We also found that SI microsomal quercetin CL int was similar to that of the liver of F344 rats of our previous study (Bolling et al, 2010).…”

Relative bioavailability of the flavonoids quercetin, hesperetin and naringenin given simultaneously through diet

“…The low urinary recovery (1.5%) of the ingested quercetin leaves a large amount of the ingested dose unaccounted for compared with hesperetin and naringenin. The most likely fate of the absorbed quercetin is excretion via bile (Matsukawa et al, 2009) and further degradation to low-molecular-weight phenolic acids that were not analysed in the current and most previous flavonol bioavailability studies (Mullen et al, 2006(Mullen et al, , 2008. Only small amounts of the 3 0 -methylated form of quercetin, isorhamnetin, were present in the 'juice mix' (1.8 mg/500 ml 'juice mix'), and of this only 4.1 ± 3.3% of isorhamnetin was excreted in urine after 48 h, excluding extensive methylation of quercetin.…”

Metabolite Identification of Myricetin in Rats Using HPLC Coupled with ESI-MS

“…[18,19] of myricetin. And its reported fragmentation patterns [20] have been detected in the M2 mass spectra. Therefore, M2 was tentatively identified as 3,4,5-trihydroxyphenylacetic acid that could only be found in feces.…”