Pharmacokinetics and bioavailability of quercetin glycosides in humans.

Due to its potentially beneficial impact on human health, the polyphenol quercetin has come into the focus of medicinal interest. However, data on the bioavailability of quercetin after oral intake are scarce and contradictory. Previous investigations indicate that the disposition of quercetin may depend on the sugar moiety of the glycoside or the plant matrix. To determine the influence of the sugar moiety or matrix on the absorption of quercetin, two isolated quercetin glycosides and two plant extracts were administered to 12 healthy volunteers in a four-way crossover study. Each subject received an onion supplement or quercetin-4'-O-glucoside (both equivalent to 100 mg quercetin), as well as quercetin-3-O-rutinoside and buckwheat tea (both equivalent to 200 mg quercetin). Samples were analyzed by HPLC with a 12-channel coulometric array detector. In human plasma, only quercetin glucuronides, but no free quercetin, could be detected. There was no significant difference in the bioavailability and pharmacokinetic parameters between the onion supplement and quercetin-4'-O-glucoside. Peak plasma concentrations were 2.3 +/- 1.5 microg x mL(-1) and 2.1 +/- 1.6 microg x mL(-1) (mean +/- SD) and were reached after 0.7 +/- 0.2 hours and 0.7 +/- 0.3 hours, respectively. After administration of buckwheat tea and rutin, however, peak plasma levels were--despite the higher dose-only 0.6 +/- 0.7 microg x mL(-1) and 0.3 +/- 0.3 microg x mL(-1), respectively. Peak concentrations were reached 4.3 +/- 1.8 hours after administration of buckwheat tea and 7.0 +/- 2.9 hours after ingestion of rutin. The terminal elimination half-life was about 11 hours for all treatments. Thus, the disposition of quercetin in humans primarily depends on the sugar moiety. To a minor extent, the plant matrix influences both the rate and extent of absorption in the case of buckwheat tea administration compared with the isolated compound. The site of absorption seems to be different for quercetin-4'-O-glucoside and quercetin-3-O-rutinoside. The significance of specific carriers on the absorption of quercetin glycosides, as well as specific intestinal beta-glucosidases, needs to be further evaluated.

Degradation of quercetin-3-glucoside in gnotobiotic rats associated with human intestinal bacteria.

AIM: The two bacterial species, Eubacterium ramulus and Enterococcus casseliflavus, which had previously been isolated from human faeces using the flavonoid quercetin-3-glucoside as the growth substrate, were tested for their ability to utilize this compound in vivo. METHODS AND RESULTS: Germ-free rats were associated with Eu. ramulus and subsequently with Ent. casseliflavus and vice versa. Identification and enumeration of the bacterial cell counts in faeces and intestinal contents were performed by whole cell fluorescence in situ hybridization. Eubacterium ramulus and Ent. casseliflavus occurred in caecal and colonic contents at cell counts of up to 10(10) g(-1) dry weight. In the jejunum, only Ent. casseliflavus was found (10(9) g(-1) dry weight). Upon oral administration of 32 micromol quercetin-3-glucoside, quercetin was detected in the faeces and urine of germ-free rats (2.2 x 10(-1)-8.1 x 10(-1) micromol 24-h(-1) faeces collection and 1.0 x 10(-2)-2.8 x 10(-1) micromol 24-h(-1) urine collection, respectively) and of rats monoassociated with Ent. casseliflavus (7.9 x 10(-1)-2.7 micromol 24-h(-1) faeces and 1.0 x 10(-1)-5.9 x 10(-1) micromol 24-h(-1) urine, respectively). In contrast, the faeces and urine of rats associated with Eu. ramulus contained 3,4-dihydroxyphenylacetic acid (4.7 x 10(-2)-3.6 micromol 24-h(-1) faeces and 2.4 x 10(-2)-1.0 micromol 24-h(-1) urine, respectively) but only low, or undetectable, concentrations of faecal quercetin (up to 9.3 x 10(-2) micromol 24-h(-1) faeces; detection limit 2.5 x 10(-2) micromol). Urinary quercetin concentrations varied markedly from undetectable amounts up to 1.0 micromol 24-h(-1) urine (detection limit 1.0 x 10(-2) micromol). Isorhamnetin was found in the urine of all animals independent of their bacterial status. There were no significant differences between the groups (2.0 x 10(-2)-2.8 x 10(-1) micromol 24-h(-1) urine). In complete intestinal tissues of animals, associated with both species, quercetin-3-glucoside and its metabolites were detected by a more sensitive and selective method at concentrations that were two to three orders of magnitude lower than in faeces or urine. CONCLUSIONS: These results indicate that Eu. ramulus may be a key organism for the bacterial transformation of flavonoids in the gut.

Flavonols and flavones of parsley cell suspension culture change the antioxidative capacity of plasma in rats.

The flavonoid aglycones from an illuminated parsley (Petroselinum crispum (Mill.) Nym.) cell suspension culture were identified and quantified as the flavones apigenin, luteolin and chrysoeriol and the flavonols kaempferol, quercetin and isorhamnetin. Flavonoid extracts from these cultures were purified by solid phase extraction from RP C-18 phase and given by gavage to rats. Only extract from illuminated culture increased the antioxidative capacity (AOC) of blood plasma temporarily with maximum values after 1 h. It is concluded that the course of AOC reflects changes in the plasma content of flavonoids.

Distribution pattern of a flavonoid extract in the gastrointestinal lumen and wall of rats.

Purified flavonoid extract from illuminated parsley (Petroselinum crispum (Mill.) Nym.) cell culture was administered by gavage to Wistar rats. The dose corresponded to 6.9 mg flavonoids on aglycone base/kg body mass. Segments of the gastrointestinal wall from stomach to colon, their luminal contents, and liver and kidneys were collected at time intervals between 1 and 12 h and investigated by HPLC of the respective extracts for flavonoids. The spreading of the flavonoids was accompanied by partial deglycosylation that began already in the stomach where at first quercetin and later apigenin, chrysoeriol and isorhamnetin aglycones were detected. We got evidence of flavonoid absorption by the stomach that does not require the liberation of aglycones. Due to obvious differences in metabolization and absorption rates the composition and the content of flavonoids changes in the gastrointestinal segments and their contents with time. Flavonoids could be detected neither within the gastrointestinal lumen after 12 h nor in the kidneys at any time. But traces of flavonoids were found in the livers at 1.5 and 12 h.