Interaction of quercetin and its metabolites with warfarin: Displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme

Poór, Miklós; Boda, Gabriella; Needs, Paul W.; Kroon, Paul A.; Lemli, Beáta; Bencsik, Tímea

doi:10.1016/j.biopha.2017.01.092

Cited by 43 publications

(51 citation statements)

References 36 publications

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“…Take 250-500 mg (level unpacked 1/4 tsp) up to twice daily 1 daily (600 mg) NA 1-2 daily (250-500 mg) drugs, primarily due to modulation of biotransformation enzymes and drug transporters (Miron et al, 2017;Srinivas, 2015). It has been reported that quercetin inhibits CYP enzymes (CYP3A4 and CYP2C9), sulfotransferases (SULT1), organic anion transporters (OAT1), organic anion-transporting polypeptides (OATP1A2 and OATP2B1), and ATP-binding cassette transporters (MRP1, P-gp, and BCRP); while it increases the expression of CYP3A4, CYP1A1, and P-gp (Kimura et al, 2010;Miron et al, 2017;Poór et al, 2017). In addition to quercetin, its metabolites (e.g., isorhamnetin, quercetin-3'-O-sulfate, and quercetin glucuronides) can also affect the function of enzymes and transporters, including CYP2C9, CYP3A4, OATs, and GLUT (glucose transporter) (Csepregi et al, 2018;Kimura et al, 2010;Miron et al, 2017;Poór et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that quercetin inhibits CYP enzymes (CYP3A4 and CYP2C9), sulfotransferases (SULT1), organic anion transporters (OAT1), organic anion-transporting polypeptides (OATP1A2 and OATP2B1), and ATP-binding cassette transporters (MRP1, P-gp, and BCRP); while it increases the expression of CYP3A4, CYP1A1, and P-gp (Kimura et al, 2010;Miron et al, 2017;Poór et al, 2017). In addition to quercetin, its metabolites (e.g., isorhamnetin, quercetin-3'-O-sulfate, and quercetin glucuronides) can also affect the function of enzymes and transporters, including CYP2C9, CYP3A4, OATs, and GLUT (glucose transporter) (Csepregi et al, 2018;Kimura et al, 2010;Miron et al, 2017;Poór et al, 2017). As reported in animal and human studies, quercetin significantly affects the pharmacokinetics of several drugs by interacting with CYP3A4, P-gp, and other biotransformation enzymes and transporters (Andres et al, 2018 than the nominal quantity); therefore, they may induce clinically relevant interactions with certain drugs.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its potential pharmacodynamic effects, quercetin can interact with serum albumin (causing displacement of drugs from albumin; Poór et al, 2013), cytochrome P450 (CYP) enzymes (Kimura, Ito, Ohnishi, & Hatano, 2010), and transport proteins (Wang et al, 2013). These effects may be responsible for pharmacokinetic interaction between quercetin and medications (Poór et al, 2017;Srinivas, 2015). When compared with other flavonoids, quercetin is also extensively biotransformed in the human body, forming conjugated (methyl, sulfate, and glucuronide) metabolites (Kelly, 2011;Mullen, Edwards, & Crozier, 2006).…”

mentioning

confidence: 99%

“…When compared with other flavonoids, quercetin is also extensively biotransformed in the human body, forming conjugated (methyl, sulfate, and glucuronide) metabolites (Kelly, 2011;Mullen, Edwards, & Crozier, 2006). Like the parent compound, some quercetin metabolites can also interact with serum albumin, biotransformation enzymes, and drug transporters (Miron, Aprotosoaie, Trifan, & Xiao, 2017;Poór et al, 2017;Poór, Boda, Mohos, et al, 2018). Quercetin supplements received great attention by consumers and patients favoring Complementary and Alternative Medicine because of its potent antioxidant effect (Ozgen, Kilinc, & Selamoğlu, 2016).…”

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confidence: 99%

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Dietary quercetin supplements: Assessment of online product informations and quantitation of quercetin in the products by high‐performance liquid chromatography

Vida

Fittler

Somogyi-Végh

et al. 2019

Phytotherapy Research

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Administration of the increasingly popular dietary supplements containing quercetin may interfere with drug therapy. We intended to evaluate the online availability and quercetin content of the high‐dose mono‐component quercetin products and to review the potential use of quercetin products and their interactions with drugs. We monitored the online access to quercetin‐containing dietary supplements, collected the relevant information from the websites, procured selected products from the vendors, and subjected them to substance analysis. The quercetin content was quantified by an HPLC‐UV method. Twenty‐five websites offered mono‐component quercetin products, and nine products were procured. The quercetin content of eight products differed only ±10% from the nominal dose, whereas one product contained almost 30% more quercetin. Misleading indications such as antitumor and cardiovascular effects were often found on the sellers' websites. Quercetin‐containing dietary supplements are available online with misleading indications. The recommended daily doses are often high (occasionally over 1,000 mg), which may induce clinically relevant interactions with medications. Because high‐quercetin content of dietary supplements was confirmed, health care professionals should be aware of the unregulated internet market of dietary supplements and should consider the interactions of these substances with drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dietary quercetin supplements: Assessment of online product informations and quantitation of quercetin in the products by high‐performance liquid chromatography

Vida

Fittler

Somogyi-Végh

et al. 2019

Phytotherapy Research

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“…As it has been reported, flavonoids and their conjugated metabolites interact with serum albumin [5,43,44] and with several biotransformation enzymes [45][46][47][48]. Flavonoids and their conjugated metabolites reach only nanomolar or low micromolar systemic plasma concentrations [49], in contrast to some of the colonic flavonoid metabolites [27].…”

Section: Discussionmentioning

confidence: 95%

Testing the Pharmacokinetic Interactions of 24 Colonic Flavonoid Metabolites with Human Serum Albumin and Cytochrome P450 Enzymes

et al. 2020

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Flavonoids are abundant polyphenols in nature. They are extensively biotransformed in enterocytes and hepatocytes, where conjugated (methyl, sulfate, and glucuronide) metabolites are formed. However, bacterial microflora in the human intestines also metabolize flavonoids, resulting in the production of smaller phenolic fragments (e.g., hydroxybenzoic, hydroxyacetic and hydroxycinnamic acids, and hydroxybenzenes). Despite the fact that several colonic metabolites appear in the circulation at high concentrations, we have only limited information regarding their pharmacodynamic effects and pharmacokinetic interactions. Therefore, in this in vitro study, we investigated the interactions of 24 microbial flavonoid metabolites with human serum albumin and cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes. Our results demonstrated that some metabolites (e.g., 2,4-dihydroxyacetophenone, pyrogallol, O-desmethylangolensin, and 2-hydroxy-4-methoxybenzoic acid) form stable complexes with albumin. However, the compounds tested did not considerably displace Site I and II marker drugs from albumin. All CYP isoforms examined were significantly inhibited by O-desmethylangolensin; nevertheless, only its effect on CYP2C9 seems to be relevant. Furthermore, resorcinol and phloroglucinol showed strong inhibitory effects on CYP3A4. Our results demonstrate that, besides flavonoid aglycones and their conjugated derivatives, some colonic metabolites are also able to interact with proteins involved in the pharmacokinetics of drugs.

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Natural products‐based antiangiogenic agents: New frontiers in cancer therapy

Azevedo,

Ferreira,

Peña‐Corona

et al. 2024

Food Frontiers

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Angiogenesis, vital for tumor growth and metastasis, is a promising target in cancer therapy. Natural compounds offer potential as antiangiogenic agents with reduced toxicity. This review provides a comprehensive overview of natural product‐based antiangiogenic therapies, focusing on molecular mechanisms and therapeutic potential. A systematic search identified relevant articles from 2019 to 2023. Various natural compounds, including polyphenols, terpenes, alkaloids, cannabinoids, omega‐3 fatty acids, polysaccharides, proteins, and carotenoids, were investigated for their antiangiogenic properties. Challenges such as dose standardization, routes of administration, and potential side effects remain. Further studies, including in‐depth animal models and human epidemiological studies, must elucidate clinical efficacy and safety. Synergistic effects with current antiangiogenic therapies, such as bevacizumab and tyrosine kinase inhibitors, should be explored. Additionally, the potential hormone‐dependent effects of compounds like genistein highlight the need for safety evaluation. In conclusion, natural products hold promise as adjunctive therapies to conventional antineoplastic drugs in modulating angiogenesis in cancer. However, robust clinical trials are needed to validate preclinical findings and ensure safety and efficacy.

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Interaction of quercetin and its metabolites with warfarin: Displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme

Cited by 43 publications

References 36 publications

Dietary quercetin supplements: Assessment of online product informations and quantitation of quercetin in the products by high‐performance liquid chromatography

Dietary quercetin supplements: Assessment of online product informations and quantitation of quercetin in the products by high‐performance liquid chromatography

Testing the Pharmacokinetic Interactions of 24 Colonic Flavonoid Metabolites with Human Serum Albumin and Cytochrome P450 Enzymes

Natural products‐based antiangiogenic agents: New frontiers in cancer therapy

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