title: Efficiency of transcellular transport and efflux of flavonoids with different glycosidic units from flavonoids of Litsea coreana L. in a MDCK epithelial cell monolayer model.
abstract: Although there is strong evidence to suggest that beneficial effects of the flavonoids in human health, the extent to which flavonoids are absorbed and the mechanisms involved are controversial. The objective of this study was to determine the bi-directional permeability and efflux characters of the four main flavonoids with different glycosidic units isolated from flavonoids of Litsea coreana L. and to discuss the transport mechanisms using the epithelial cell model MDCK. The transport of the four main flavonoid glycosides at concentration of 40, 80, 160 μM was concentration-dependent in both apical to basolateral and the reverse direction. Contemporary, the influx and efflux of the flavonoid glycosides were temperature-dependent and pH-dependent at concentration of 80 μM, and transport of flavonoid glycosides was obviously decreased when experiments performed in the presence of 1mM sodium azide (an ATP inhibitor). Uptake of quercetin-3-O-β-D-glucoside or kaempferol-3-O-β-D-glucoside was inhibited by 50 μM phloridzin, a specific and competitive inhibitor of SGLT. Moreover, the flavonoids exhibited significantly larger basolateral to apical Papp than that of the reverse direction, suggesting the existence of efflux mechanisms. The 50 μM verapamil, a chemical inhibitor of P-glycoprotein (P-gp), had no effect on the transport of four flavonoid glycosides. However, 50 μM MK-571 or 1 mM probenecid, MRP2 inhibitors, led to an apparently decrease in the efflux of flavonoid glycosides. Therefore, MRP2 but P-gp may be involved in the transport of the four flavonoid glycosides. Taken together, the experimental observations in our study provide useful information for pharmacological applications of flavonoids with different glycosidic units from flavonoids of L. coreana L.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004285:Dogs; D005419:Flavonoids / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D032862:Litsea; D061985:Madin Darby Canine Kidney Cells; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D013696:Temperature; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D006027:Glycosides; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011339:Probenecid; D011422:Propionates; D011804:Quinolines; D051269:Sodium-Glucose Transporter 1; D014700:Verapamil; C000715087:ABCC2 protein, human; C059141:verlukast
keywords: Efflux; Flavonoids; MDCK; MRPs; P-gp; SGLT