scholarly journals Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2306
Author(s):  
Violetta Mohos ◽  
Eszter Fliszár-Nyúl ◽  
Orsolya Ungvári ◽  
Katalin Kuffa ◽  
Paul W. Needs ◽  
...  

Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact with several proteins of pharmacokinetic importance. However, the interactions of its metabolites with biotransformation enzymes and drug transporters have barely been examined. In this study, the inhibitory effects of quercetin and its most relevant methyl, sulfate, and glucuronide metabolites were tested on cytochrome P450 (CYP) (2C19, 3A4, and 2D6) enzymes as well as on organic anion-transporting polypeptides (OATPs) (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) and ATP (adenosine triphosphate) Binding Cassette (ABC) (BCRP and MRP2) transporters. Quercetin and its metabolites (quercetin-3′-sulfate, quercetin-3-glucuronide, isorhamnetin, and isorhamnetin-3-glucuronide) showed weak inhibitory effects on CYP2C19 and 3A4, while they did not affect CYP2D6 activity. Some of the flavonoids caused weak inhibition of OATP1A2 and MRP2. However, most of the compounds tested proved to be strong inhibitors of OATP1B1, OATP1B3, OATP2B1, and BCRP. Our data demonstrate that not only quercetin but some of its conjugates, can also interact with CYP enzymes and drug transporters. Therefore, high intake of quercetin may interfere with the pharmacokinetics of drugs.

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3062 ◽  
Author(s):  
Yuichi Uwai

Drug transporters mediate the absorption, tissue distribution, and excretion of drugs. The cDNAs of P-glycoprotein, multidrug resistance proteins (MRPs/ABCC), breast cancer resistance protein (BCRP/ABCG2), peptide transporters (PEPTs/SLC15), proton-coupled folate transporters (PCFT/SLC46A1), organic anion transporting polypeptides (OATPs/SLCO), organic anion transporters (OATs/SLC22), organic cation transporters (OCTs/SLC22), and multidrug and toxin extrusions (MATEs/SLC47) have been isolated, and their functions have been elucidated. Enantioselectivity has been demonstrated in the pharmacokinetics and efficacy of drugs, and is important for elucidating the relationship with recognition of drugs by drug transporters from a chiral aspect. Enantioselectivity in the transport of drugs by drug transporters and the inhibitory effects of drugs on drug transporters has been summarized in this review.


2012 ◽  
Vol 33 (4) ◽  
pp. 235-242 ◽  
Author(s):  
Izumi Yamasaki ◽  
Masayoshi Yamada ◽  
Nobuo Uotsu ◽  
Sachiyuki Teramoto ◽  
Risa Takayanagi ◽  
...  

2020 ◽  
Vol 58 (1) ◽  
pp. 247-252
Author(s):  
Xunge Zhang ◽  
Ping Feng ◽  
Xinfu Gao ◽  
Bin Wang ◽  
Chunxia Gou ◽  
...  

Xenobiotica ◽  
2017 ◽  
Vol 47 (10) ◽  
pp. 849-855 ◽  
Author(s):  
Jixiao Lang ◽  
Wei Li ◽  
Jingming Zhao ◽  
Kaiyou Wang ◽  
Dexi Chen

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