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学科主题: 药学
题名:
The Membrane Transport of Flavonoids from Crossostephium chinense across the Caco-2 Monolayer
作者: Wang, Ying1; Wu, Qi1; Yang, Xiu-Wei1; Yang, Xiaoda2; Wang, Kui1,2
关键词: flavonoids ; selagin ; Caco-2 ; efflux ; MRP
刊名: BIOPHARMACEUTICS & DRUG DISPOSITION
发表日期: 2011
DOI: 10.1002/bdd.735
卷: 32, 期:1, 页:16-24
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: CELL LINE CACO-2 ; MULTIDRUG-RESISTANCE PROTEIN-1 ; IN-VITRO ; INTESTINAL-ABSORPTION ; DRUG-RESISTANCE ; METABOLISM ; EFFLUX ; SPECIFICITY ; QUERCETIN ; VIVO
英文摘要:

The permeation and efflux of six polysubstituted flavonoids isolated from Crossostephium chinense, a Chinese traditional and herbal drug for the treatment of diabetes, were investigated using the Caco-2 cell monolayer. The six flavonoids (selagin, apometzgerin, tricetin-3′,4′,5′- trimethylether, quercetagetin-3,6,7-trimethylether, hispidulin and quercetagetin) sharing a similar parent skeleton structure with varied substituents in the heterocyclic ring B were selected for the study. Quercetagetin exhibited a low bi-directional permeability comparable to that of atenolol, suggesting a paracellular diffusion mechanism. The remaining compounds exhibited time- and concentration-dependent permeation with apparent permeability coefficient (P(app)) values in the range 10(-6)-10(-5) cm/s, suggesting transcellular diffusion pathways. Selagin exhibited significantly larger basolateral to apical P(app) than that of the reverse direction, suggesting the existence of efflux mechanisms. ATP-depletion and probenecid pretreatment led to a significant inhibition of the efflux of selagin, whereas verapamil had no effect on the basolateral to apical transport of selagin, suggesting that multidrug resistance proteins (MRPs) and not P-glycoprotein play a role in the intestinal efflux of selagin. Based on present and previous results, the structure-permeation relationship and the role of MRPs in mediating the efflux of flavonoids are discussed. Experimental results in this study provide useful information for pharmacological applications of the flavonoids from C. chinense. Copyright (C) 2010 John Wiley & Sons, Ltd.

语种: 英语
所属项目编号: 2009ZX09502-006 ; Z0004105040311
项目资助者: Major New Medicine Project in Mega-projects of Science Research of China ; Beijing Municipal Special purpose Science Foundation of China
WOS记录号: WOS:000285392400002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56668
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Ying,Wu, Qi,Yang, Xiu-Wei,et al. The Membrane Transport of Flavonoids from Crossostephium chinense across the Caco-2 Monolayer[J]. BIOPHARMACEUTICS & DRUG DISPOSITION,2011,32(1):16-24.
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