0000000000206394
AUTHOR
Siegfried Wolffram
Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans – Implications for the evaluation of transporter-mediated flavonoid–drug interactions
Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration-time curve (AUC0-48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7 ng h/ml, p>0.05; 309.7 versus 212.0 and 280.6 ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0-48h was lowered by 23.9% up to 60.6% in 5 subjects and c…
Modulation of drug transport by selected flavonoids: Involvement of P-gp and OCT?
Flavonoids, as a common component of daily nutrition, are a possible source of interference with absorption processes, due to modulation of transporting proteins. In this study, the influence of selected flavonoids (quercetin, isoquercitrin, spiraeoside, rutin, kaempferol, naringenin, naringin, and kaempferol) on the transport of the P-gp substrate [3H]talinolol across Caco-2 cell monolayers was investigated. To elucidate the mechanism behind the interaction observed in this system the potency of the flavonoids to replace [3H]talinolol from its P-gp binding site as well as their activity to inhibit OCT2-mediated [14C]TEA uptake into LLC-PK(1) cells were measured, as P-gp and OCT have been s…
Inhibition of Folic Acid Uptake by Catechins and Tea Extracts in Caco-2 Cells
In this present study it was aimed to determine whether the catechins contained in green tea and the whole extracts of Camellia sinensis (Theaceae) inhibit the uptake of folic acid by Caco-2 cell monolayers. Our results indicate that (-)-epigallocatechin 3-gallate (EGCG) and (-)-epicatechin 3-gallate (ECG) inhibit cellular folic acid uptake with IC50 values of 34.8 micromol/L and 30.8 micromol/L, respectively. Furthermore, green and black tea extracts were also found to inhibit folic acid uptake with IC50 values of approximately 7.5 and 3.6 mg/mL, respectively. According to these results, simultaneous intake of tea and folic acid may inhibit intestinal folic acid absorption. The consequence…
Effects of the flavonol quercetin and α-linolenic acid on n-3 PUFA status in metabolically healthy men and women: a randomised, double-blinded, placebo-controlled, crossover trial.
AbstractIncreased dietary intake and tissue status of the long-chainn-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion ofα-linolenic acid (ALA) to longer-chainn-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or place…
Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability
Previous in vitro studies using Caco-2 cell monolayers suggested a possible interaction between green and black tea and folic acid at the level of intestinal absorption. The main purpose of the present study was to investigate a possible pharmacokinetic interaction between tea and folic acid in healthy volunteers. In an open-labeled randomized cross-over study, the pharmacokinetic interaction between tea and folic acid (0.4 mg and 5 mg) was investigated in healthy volunteers. Water was used as the reference drink. Subjects ingested 0.4 mg folic acid tablets with water, green or black tea (0.3 g extract/250 ml) or 5 mg folic acid tablets with water or green tea (0.3 g extract/250 ml). Blood …
Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules
The flavonol quercetin, is one of the major flavonoids found in edible plants. The bioavailability of quercetin in humans may be influenced by the food matrix in which it is consumed as well as by its chemical and physical form. The objective of the present study was to investigate the biokinetics of quercetin from quercetin-enriched cereal bars and quercetin powder-filled hard capsules. In a randomised, single-blinded, diet-controlled cross-over study, six healthy women aged 22–28 years took a single oral dose of approximately 130 mg quercetin equivalents from either quercetin-enriched cereal bars (containing 93·3 % quercetin aglycone plus 6·7 % quercetin-4′-glucoside) or quercetin powder-…
Effects of the flavonol quercetin on the bioavailability of simvastatin in pigs
The influence of the dietary flavonol quercetin on the pharmacokinetics of the HMG-CoA reductase inhibitor simvastatin was investigated in pigs. Simvastatin (0.25mg/kg body weight) was orally administered to six pigs either without or with quercetin (10mg/kg). In addition, simvastatin was administered to three pigs that had received a diet supplemented with the flavonol over a period of 1 week. Daily quercetin intake was 10mg/kg in these animals. Co-ingestion of quercetin with the statin did not alter area under the concentration time curve (AUC(0-->infinity)), time to achieve maximum plasma concentration (t(max)) or half-life (t(1/2)) of simvastatin. However, there was a trend towards a re…
Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters.
Psoriasis is a chronic inflammatory skin disease. Its treatment is based on the inhibition of proliferation of epidermal cells and interference in the inflammatory process. A new systemic antipsoriasis drug, which consists of dimethylfumarate and ethylhydrogenfumarate in the form of their calcium, magnesium and zinc salts has been introduced in Europe with successful results. In the present study, a homologous series of mono- and diesters of fumaric acid has been studied with respect to the sites and kinetics of presystemic ester degradation using pancreas extract, intestinal perfusate, intestinal homogenate and liver S9 fraction. In addition, intestinal permeability has been determined usi…
Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial
AbstractThe polyphenol quercetin may prevent CVD due to its antihypertensive and vasorelaxant properties. We investigated the effects of quercetin after regular intake on blood pressure (BP) in overweight-to-obese patients with pre-hypertension and stage I hypertension. In addition, the potential mechanisms responsible for the hypothesised effect of quercetin on BP were explored. Subjects (n 70) were randomised to receive 162 mg/d quercetin from onion skin extract powder or placebo in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 6-week washout period. Before and after the intervention, ambulatory blood pressure (ABP) and office BP were m…
Chronic quercetin feeding decreases plasma concentrations of salicylamide phase II metabolites in pigs following oral administration.
We investigated acute effects and effects after chronic intake of the orally administered flavonol quercetin on pharmacokinetics of salicylamide metabolites (SAM) after oral administration of salicylamide in pigs. Salicylamide (8 mg/kg body weight) was orally administered to seven pigs either without or with quercetin (10 mg/kg body weight). Additionally, salicylamide was administered to five pigs that had received a diet supplemented with the flavonol for 1 week. Daily quercetin intake was 10 mg/kg in these animals. Co-ingestion of quercetin with the drug did not alter area under the concentration-time curve (AUC(0→∞)), time to achieve maximum plasma concentration (t(max)), mean residence …
The Influence of Single-Dose and Short-Term Administration of Quercetin on the Pharmacokinetics of Midazolam in Humans.
Quercetin is a plant flavonol that is available from both daily diet and nutraceuticals. To investigate the effect of acute and short-term intake of high-dose quercetin on CYP3A-mediated metabolism, 10 healthy volunteers received 7.5 mg oral midazolam without, with a single dose of 1500 mg quercetin and after 1-week supplementation with 1500 mg quercetin daily. A substudy was performed in three subjects to explore the impact of repeated quercetin intake on intravenously administered midazolam. Coadministration with a single dose of quercetin did not significantly alter the pharmacokinetics of midazolam and its 1'-hydroxymetabolite, but following short-term quercetin intake, there was a tren…
Effect of alpha-linolenic acid in combination with the flavonol quercetin on markers of cardiovascular disease risk in healthy, non-obese adults: A randomized, double-blinded placebo-controlled crossover trial.
Abstract Objectives Alpha-linolenic acid (ALA) and quercetin are characteristic compounds in plant-based diets. Cardioprotective effects have been described for both substances, although a possible benefit of combining ALA and quercetin has not, to our knowledge, been evaluated yet. The aim of this study was to investigate the potential independent and additive effects of ALA and quercetin on blood pressure (BP) and lipid and glucose metabolism, as well as on biomarkers of inflammation, oxidative stress, and antioxidant status in healthy, non-obese men and women. Another aim was to examine whether chronic supplementation of supranutritional doses of quercetin would result in an accumulation…