spiraeoside and 3-methylquercetin

Quercetin, a flavonoid present in the human diet, which is found in high levels in onions, apples, tea and wine, has been shown previously to inhibit platelet aggregation and signaling in vitro. Consequently, it has been proposed that quercetin may contribute to the protective effects against cardiovascular disease of a diet rich in fruit and vegetables.. A pilot human dietary intervention study was designed to investigate the relationship between the ingestion of dietary quercetin and platelet function.. Human subjects ingested either 150 mg or 300 mg quercetin-4'-O-beta-D-glucoside supplement to determine the systemic availability of quercetin. Platelets were isolated from subjects to analyse collagen-stimulated cell signaling and aggregation.. Plasma quercetin concentrations peaked at 4.66 microm (+/- 0.77) and 9.72 microm (+/- 1.38) 30 min after ingestion of 150-mg and 300-mg doses of quercetin-4'-O-beta-D-glucoside, respectively, demonstrating that quercetin was bioavailable, with plasma concentrations attained in the range known to affect platelet function in vitro. Platelet aggregation was inhibited 30 and 120 min after ingestion of both doses of quercetin-4'-O-beta-D-glucoside. Correspondingly, collagen-stimulated tyrosine phosphorylation of total platelet proteins was inhibited. This was accompanied by reduced tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase Cgamma2, components of the platelet glycoprotein VI collagen receptor signaling pathway.. This study provides new evidence of the relatively high systemic availability of quercetin in the form of quercetin-4'-O-beta-D-glucoside by supplementation, and implicates quercetin as a dietary inhibitor of platelet cell signaling and thrombus formation.

Topics: Blood Platelets; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Collagen; Cross-Over Studies; Dietary Supplements; Dose-Response Relationship, Drug; Female; Flavonols; Glucosides; Humans; Immunoblotting; Male; Phosphorylation; Platelet Activation; Platelet Aggregation; Quercetin; Signal Transduction; Thrombosis; Time Factors; Tyrosine

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.

Topics: Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Fagopyrum; Female; Flavonols; Glucosides; Half-Life; Humans; Male; Metabolic Clearance Rate; Onions; Plant Extracts; Quercetin; Rutin

The efficiency of intestinal absorption and metabolic conversion of quercetin aglycone and its glucosides, quercetin-4'-O-beta-D-glucoside (Q4'G), quercetin-3-O-beta-D-glucoside (Q3G), and quercetin-3,4'-di-O-beta-D-glucoside (Q3,4'G), was estimated by using Caco-2 cell monolayers as an intestinal epithelial cell model. Aglycone was significantly lost from the apical side, resulting in the appearance of free and conjugated forms of quercetin and those of isorhamnetin in the cellular extracts. In the basolateral solution, the conjugated form of quercetin was predominant and increased with the elapse of incubation. As compared with quercetin aglycone, none of the quercetin glucosides were absorbed efficiently from apical side. However, Q4'G yielded conjugated quercetin and isorhamnetin in basolateral solution at higher amounts than Q3G or Q3,4'G. Lipophilicity of Q4'G was found to be higher than that of Q3G or Q3,4'G. This suggests that lipophilicity contributes to the relatively efficient absorption of Q4'G. It is likely that the occurrence of hydrolysis enhances the efficiency of intestinal absorption and metabolic conversion of dietary quercetin glucosides.

Topics: Caco-2 Cells; Cell Extracts; Cell Polarity; Flavonols; Humans; Intestinal Absorption; Intestinal Mucosa; Quercetin