Inhibition of hydroxycinnamic acid sulfation by flavonoids and their conjugated metabolites

Wong, Chi Chun; Williamson, Gary

doi:10.1002/biof.1127

Cited by 19 publications

(22 citation statements)

References 21 publications

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“…The nature of the substitution of (-)-epicatechin was different in the two models: whereas sulfation was favored in vivo with 73% of metabolites sulfated, methylation was the main conjugation in vitro with 77.4% of metabolites methylated. Fifteen percent of metabolites were glucuronidated in vivo, whereas such substitution could not be detected in the Caco-2 cell model, suggesting the absence of some specific uridine 59-diphospho-glucuronosyltransferase (UGT) isoforms in this model as anticipated by Vaidyanathan and Walle (2001) and Wong and Williamson (2013).…”

Section: Discussionmentioning

confidence: 98%

“…With the use of a multilumen perfusion catheter in humans, it was recently demonstrated that nature and substitution position of (-)-epicatechin conjugation are major determinants of the metabolic fate in the body, influencing whether the compound is effluxed into the lumen or absorbed into the blood (Actis- Goretta et al, 2013). Previous in vitro studies using Caco-2 cell monolayers as intestinal barrier model highlighted the effect of coadministration of different flavonoids on the apical and basolateral efflux of hesperetin and hydroxycinnamic acid (Brand et al, 2010;Wong and Williamson, 2013). The objective of our study was to investigate the extent of competition of (-)-epicatechin with other polyphenols to better understand its absorption and metabolism.…”

Section: Discussionmentioning

confidence: 99%

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Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

Sanchez-Bridge¹,

Lévêques²,

Li³

et al. 2014

Drug Metab Dispos

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Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (-)-epicatechin may reduce the risk of cardiovascular diseases. The interaction of (-)-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (-)-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 39-O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of (-)-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 39-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 39-Omethyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this (-)-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of (-)-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting (-)-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

Sanchez-Bridge¹,

Lévêques²,

Li³

et al. 2014

Drug Metab Dispos

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“…Inhibition of sulfotransferase activity in human intestinal S9 -= - [134] a↓, the respective conjugate(s) have a lower activity than the aglycone; =, the respective conjugates have an equal activity to the aglycone; A > B, conjugate A is more active than conjugate B.…”

Section: Quercetinmentioning

confidence: 98%

“…Methylation, sulfation and glucuronidation are reported to reduce the activity of quercetin to inhibit sulfotransferases in human liver S9, while methylation does not affect the activity of quercetin to inhibit sulfotransferases in human intestinal S9. The activity of quercetin to inhibit sulfotransferases in HepG2 cells is reported to be reduced by sulfation and abolished by glucuronidation, which is likely to be due to the very low cellular uptake of the glucuronides [134].…”

Section: Inhibition Of Sulfotransferasesmentioning

confidence: 99%

“…Flavonoids are known inhibitors of sulfotransferases [21,[133][134][135], and conjugation is reported to reduce the activity of quercetin to inhibit sulfotransferases (see Table 7.6). Methylation, sulfation and glucuronidation are reported to reduce the activity of quercetin to inhibit sulfotransferases in human liver S9, while methylation does not affect the activity of quercetin to inhibit sulfotransferases in human intestinal S9.…”

Section: Inhibition Of Sulfotransferasesmentioning

confidence: 99%

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The influence of phase II conjugation on the biological activity of flavonoids

Beekmann¹

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Application of a skin and liver Chip2 microphysiological model to investigate the route‐dependent toxicokinetics and toxicodynamics of consumer‐relevant doses of genistein

Tao,

Brandmair,

Gerlach

et al. 2023

J of Applied Toxicology

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The HUMMIC skin–liver Chip2 microphysiological system using EpiDerm™ and HepaRG and stellate liver spheroids was used to evaluate the route‐specific metabolism and toxicodynamic effects of genistein. Human‐relevant exposure levels were compared: 60 nM representing the plasma concentration expected after topical application of a cosmetic product and 1 μM representing measured plasma concentrations after ingesting soya products. Genistein was applied as single and repeated topical and/or systemic doses. The kinetics of genistein and its metabolites were measured over 5 days. Toxicodynamic effects were measured using transcriptional analyses of skin and liver organoids harvested on Days 2 and 5. Route‐specific differences in genistein's bioavailability were observed, with first‐pass metabolism (sulfation) occurring in the skin after topical application. Only repeated application of 1 μM, resembling daily oral intake of soya products, induced statistically significant changes in gene expression in liver organoids only. This was concomitant with a much higher systemic concentration of genistein which was not reached in any other dosing scenario. This suggests that single or low doses of genistein are rapidly metabolised which limits its toxicodynamic effects on the liver and skin. Therefore, by facilitating longer and/or repeated applications, the Chip2 can support safety assessments by linking relevant gene modulation with systemically available parent or metabolite(s). The rate of metabolism was in accordance with the short half‐life observed in in vivo in humans, thus supporting the relevance of the findings. In conclusion, the skin–liver Chip2 provides route‐specific information on metabolic fate and toxicodynamics that may be relevant to safety assessment.

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Inhibition of hydroxycinnamic acid sulfation by flavonoids and their conjugated metabolites

Abstract: Abstract.Hydroxycinnamic acids and flavonoids are dietary phenolic antioxidants that are abundant in our diet. Hydroxycinnamic acids are highly sulfated in vivo, and sulfotransferases

Cited by 19 publications

References 21 publications

Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

The influence of phase II conjugation on the biological activity of flavonoids

Application of a skin and liver Chip2 microphysiological model to investigate the route‐dependent toxicokinetics and toxicodynamics of consumer‐relevant doses of genistein

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