Inhibitory effects of flavonoids on P-glycoprotein in vitro and in vivo: Food/herb-drug interactions and structure-activity relationships

Toxicology and Applied Pharmacology
Jie BaiYan Li

Abstract

Flavonoids are a class of polyphenol antioxygen, despite various known biological activities and therapeutic potential, scattered but not much is known about their interactions with drug transporters. P-glycoprotein (P-gp) as a cellular defense mechanism by effluxing its substrates has been widely investigated. The aim of this study was to investigate the inhibitory effects of 75 flavonoids on P-gp in vitro and in vivo and to illuminate the structure-activity relationships of flavonoids with P-gp. Five flavonoids, including tangeretin, sinensetin, isosinensetin, sciadopitysin and oroxylin A exhibited significant inhibition on P-gp in MDR1-MDCKIIcells, which reduced the P-gp-mediated efflux of paraquat and taxol and consequently increased their cell toxicity. In addition, co-administration of digoxin with five flavonoids increased the AUC0-t of digoxin in different extents in rats, from 19.84% to 81.51%. Molecular docking assays elucidated the inhibitory effect of flavonoids might be related to Pi interactions, but not hydrogen bonds. The pharmacophore model suggested the hydrophobic groups in B benzene ring may play a vital role in the potency of flavonoids inhibition on P-gp. Taken together, our findings would provide the basi...Continue Reading

References

Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F ThiebautM C Willingham
May 20, 1999·Annual Review of Pharmacology and Toxicology·S V AmbudkarM M Gottesman
Aug 5, 2000·The Journal of Nutrition·A Scalbert, G Williamson
Oct 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·R Krishna, L D Mayer
Feb 17, 2001·Clinical Pharmacology and Therapeutics·D DürrK Fattinger
Jun 5, 2002·Annual Review of Biochemistry·P Borst, R Oude Elferink
Jul 10, 2003·Reproductive Toxicology·Thomas StrohekerMarie-Chantal Canivenc-Lavier
Jul 2, 2004·Clinical Pharmacology and Therapeutics·Reinhard DingWalter E Haefeli
Jan 11, 2005·The American Journal of Clinical Nutrition·Augustin ScalbertMike Saltmarsh
Jan 25, 2005·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yit Hong LoonKah Hay Yuen
May 14, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Manthena V S Varma, Ramesh Panchagnula
Feb 4, 2006·Life Sciences·Marilyn E Morris, Shuzhong Zhang
Mar 4, 2006·Clinical Pharmacology and Therapeutics·Julie GrenierMurray P Ducharme
Oct 4, 2006·Free Radical Biology & Medicine·R J Dinis-OliveiraF Carvalho
Oct 29, 2008·European Journal of Pharmacology·Tomohiro NabekuraShuji Kitagawa
Dec 2, 2009·Methods in Molecular Biology·Jean-Pierre Gillet, Michael M Gottesman
Sep 15, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jingwei ZhangGuangji Wang
Dec 2, 2010·Current Pharmaceutical Biotechnology·Chung-Pu WuSuresh V Ambudkar
Jan 11, 2011·Molecular Pharmaceutics·Lars HerfindalStein O Døskeland
Feb 16, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stewart T DunnCharles W Locuson
Jul 7, 2011·PLoS Computational Biology·Elena DolghihMatthew P Jacobson
Dec 12, 2012·Toxicology Letters·Renata SilvaFernando Remião
Aug 13, 2013·Nutrition Research Reviews·Jara Pérez-JiménezFulgencio Saura-Calixto
Oct 10, 2013·Journal of Applied Toxicology : JAT·V Vilas-BoasF Remião
Nov 2, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Ning-Ning WangJin-Hua Wang
Dec 18, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Scott J BrantleyMary F Paine
Jan 15, 2015·Anti-cancer Agents in Medicinal Chemistry·Subburayan Karthikeyan, Sugeerappa Laxmanappa Hoti
Feb 3, 2015·The American Journal of Chinese Medicine·Byul-Bora ChoiGyoo-Cheon Kim
May 9, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Gholamreza KhamisipourMohammad Hojjat-Farsangi
Feb 9, 2017·Archives of Toxicology·Thomas Efferth, Manfred Volm

❮ Previous
Next ❯

Citations

Feb 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wafaa M ElkadyMichael Wink
Dec 2, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yingying ZhaoYong Lai
Sep 26, 2019·Chemico-biological Interactions·Clarissa Feltrin, Cláudia Maria Oliveira Simões
Feb 6, 2020·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jinyun DongJiang-Jiang Qin
Feb 26, 2021·Frontiers in Pharmacology·Lee Han JieKhairana Husain
Mar 23, 2021·Advances in Pharmacological and Pharmaceutical Sciences·El-Shaimaa A ArafaManal A Buabeid
Jul 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·M GanesanN Rajendra Prasad

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.