Absorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter

Day, Andrea J.; Gee, Jennifer M.; DuPont, M.Susan; Johnson, Ian T.; Williamson, Gary

doi:10.1016/s0006-2952(03)00039-x

Cited by 295 publications

(213 citation statements)

References 33 publications

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“…The most likely explanation is preferential absorption of kaempferol-3-glucoside present in the endive soup at 14% of total kaempferol. Quercetin glucosides are preferentially absorbed from the small intestine by mechanisms that almost certainly involve active transport (eg via SGLT1; Gee et al, 2000) and deglycosylation processes (eg lactase phlorizin hydrolase and cytosolic b-glucosidase; Day et al, 2000bDay et al, , 2003Nemeth et al, 2003). Kaempferol glucosides are almost certainly absorbed from the small intestine via similar processes due to the high degree of structural similarity between kaempferol glucosides and quercetin glucosides.…”

Section: Discussionmentioning

confidence: 99%

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

et al. 2004

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Objective: To determine the absorption, excretion and metabolism of kaempferol in humans. Design: A pharmacokinetic study of kaempferol from endive over 24 h. Subjects: Four healthy males and four healthy females. Results: Kaempferol, from a relatively low dose (9 mg), was absorbed from endive with a mean maximum plasma concentration of 0.1 mM, at a time of 5.8 h, indicating absorption from the distal section of the small intestine and/or the colon. Although a 7.5-fold interindividual variation between the highest and lowest maximum plasma concentration was observed, most individuals showed remarkably consistent pharmacokinetic profiles. This contrasts with profiles for other flavonoids that are absorbed predominantly from the large intestine (eg rutin). An average of 1.9% of the kaempferol dose was excreted in 24 h. Most subjects also showed an early absorption peak, probably corresponding to kaempferol-3-glucoside, present at a level of 14% in the endive. Kaempferol-3-glucuronide was the major compound detected in plasma and urine. Quercetin was not detected in plasma or urine indicating a lack of phase I hydroxylation of kaempferol. Conclusions: Kaempferol is absorbed more efficiently than quercetin in humans even at low oral doses. The predominant form in plasma is a 3-glucuronide conjugate, and interindividual variation in absorption and excretion is low, suggesting that urinary kaempferol could be used as a biomarker for exposure. Sponsorship: Biotechnology and Biological Sciences Research council for core strategic funding and the University of Leeds for a departmental fellowship (AJD).

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Section: Discussionmentioning

confidence: 99%

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

et al. 2004

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“…Thus far, the most widely accepted hypothesis involves lactase phlorizin hydrolase (LPH) as the major step [8,9,10] , and sodiumdependent glucose transporter 1 (SGLT1) as a second step. LPH is an extracellular enzyme localized on the outer surface of the small intestinal brushborder membrane (BBM) [10,11] .…”

Section: Absorption Of Iqmentioning

confidence: 99%

“…The deglycosylation of IQ leads to a higher concentration of the aglycone at the apical enterocyte membrane, thereby increasing the rate of absorption [9] . A small amount of IQ is transported by the SGLT1 [8] present in the BBM of the small intestine, thereby transporting the intact glycoside into the cell [14] . In enterocytes, cytosolic βglycosidase hydrolyzes the intact IQ, which is then transported via the SGLT1 route, into the quercetin aglycone.…”

Section: Absorption Of Iqmentioning

confidence: 99%

“…A fatenriched diet enhances quercetin3Oglucoside bioavailability, which might be owing to improved solubility and enhanced absorption of the lipophilic quercetin aglycone via lipid micelles, as well as delayed elimination of quercetin from the plasma owing to a prolonged enter ohepatic circulation [12] . It is important to note that follow ing the enzymatic hydrolysis by hesperidinase, rutin is mainly bioconverted into Q3G [4,7,8,1012] , thereby increasing the absorption [15] and bioavailability [16] .…”

Section: Absorption Of Iqmentioning

confidence: 99%

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Review of anticancer mechanisms of isoquercitin

Orfali¹,

Duarte²,

Bonadio³

et al. 2016

WJCO

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This review was based on a literature search of PubMed and Scielo databases using the keywords "quercetin, rutin, isoquercitrin, isoquercitin (IQ), quercetin-3-glucoside, bioavailability, flavonols and favonoids, and cancer" and combinations of all the words. We collected relevant scientific publications from 1990 to 2015 about the absorption, bioavailability, chemoprevention activity, and treatment effects as well as the underlying anticancer mechanisms of isoquercitin. Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom. The subclass of flavonols receives special attention owing to their health benefits. The main components of this class are quercetin, rutin, and IQ, which is a flavonoid and although mostly found as a glycoside, is an aglycone (lacks a glycoside side chain). This compound presents similar therapeutic profiles to quercetin but with superior bioavailability, resulting in increased efficacy compared to the aglycone form. IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant, antiproliferative, anti-inflammatory, anti-hypertensive, and anti-diabetic. The protective effects of IQ in cancer may be due to actions on lipid peroxidation. In addition, the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway, mixed-lineage protein kinase 3, mitogen-activated protein kinase, apoptotic pathways, as well proinflammatory protein signaling. This review contributed to clarifying the mechanisms of absorption, metabolism, and actions of IQ and isoquercitrin in cancer.

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“…LPH is expressed at very low levels in Caco-2 cells (Chantret et al, 1994;Day et al, 2003) and therefore lack of hydrolysis and basolateral transfer of kaempferol-3-glucoside were anticipated. Furthermore, kaempferol-3-glucoside was transported from the basolateral to apical side of the Caco-2 cells, suggesting that efflux transporters are involved.…”

Section: Transport Studymentioning

confidence: 99%

Transport oftrans-tiliroside (kaempferol-3-β-D-(6″-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestine

2015

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Abstract1. Absorption and metabolism of tiliroside (kaempferol 3--D-(6''-p-coumaroyl)-glucopyranoside) and its related compounds kaempferol, kaempferol-3-glucoside and p-coumaric acid were investigated in the small intestinal Caco-2 cell model. Apparent permeation (P app ) was determined as 0.62  10 -6 cm/s, 3.1 10 -6 cm/s, 0 and 22.8 10 -6 cm/s respectively.2. Mechanistic study showed that the transportation of tiliroside, kaempferol-3-glucoside and p-coumaric acid in Caco-2 model were transporter(s) involved, while transportation of kaempferol was solely by passive diffusion mechanism.3. Efflux transporters, multi-drug-resistance-associated protein-2 (MRP2), was shown to play a role in limiting the uptake of tiliroside. Inhibitors of MRP2, (MK571 and rifampicin) and co-incubation with kaempferol (10 M), increased transfer from the apical to the basolateral side by three-five fold.4. Metabolites of kaempferol-3-glucoside and p-coumaric acid were not detected in the current Caco-2 model, while tiliroside was metabolised to a limited extent, with two tiliroside mono-glucuronides identified; and kaempferol was metabolised to a higher extent, with three mono-glucuronides and two mono-sulfates identified.3 5. In conclusion, tiliroside was metabolised and transported across Caco-2 cell membrane to a limited extent. Transportation could be increased by applying MRP2 inhibitors or co-incubation with kaempferol. It is proposed that tiliroside can be absorbed by human; future pharmacokinetics studies are warranted in order to determine the usefulness of tiliroside as a bioactive agent.

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Absorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter

Cited by 295 publications

References 33 publications

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

Review of anticancer mechanisms of isoquercitin

Transport oftrans-tiliroside (kaempferol-3-β-D-(6″-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestine

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