Inhibitory Effect of Flavonoids on the Efflux of N-Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells
Joint Authors
Kentaro, Kawano
Narumi, Sugihara
Koji, Furuno
Shin, Yoshimura
Ryusuke, Matsumura
Source
Journal of Biomedicine and Biotechnology
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-08-13
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
N-acetyl 5-aminosalicylic acid (5-AcASA) that was intracellularly formed from 5-aminosalicylic acid (5-ASA) at 200 μM was discharged 5.3, 7.1, and 8.1-fold higher into the apical site than into the basolateral site during 1, 2, and 4-hour incubations, respectively, in Caco-2 cells grown in Transwells.
The addition of flavonols (100 μM) such as fisetin and quercetin with 5-ASA remarkably decreased the apically directed efflux of 5-AcASA.
When 5-ASA (200 μM) was added to Caco-2 cells grown in tissue culture dishes, the formation of 5-AcASA decreased, and, in addition, the formed 5-AcASA was found to be accumulated within the cells in the presence of such flavonols.
Thus, the decrease in 5-AcASA efflux by such flavonols was attributed not only to the inhibition of N-acetyl-conjugation of 5-ASA but to the predominant cellular accumulation of 5-AcASA.
Various flavonoids also had both of the effects with potencies that depend on their specific structures.
The essential structure of flavonoids was an absence of a hydroxyl substitution at the C5 position on the A-ring of flavone structure for the inhibitory effect on the N-acetyl-conjugation of 5-ASA, and a presence of hydroxyl substitutions at the C3′ or C4′ position on the B-ring of flavone structure for the promoting effect on the cellular accumulation of 5-AcASA.
Both the decrease in 5-AcASA apical efflux and the increase in 5-AcASA cellular accumulation were also caused by MK571 and indomethacin, inhibitors of MRPs, but not by quinidine, cyclosporin A, P-glycoprotein inhibitors, and mitoxantrone, a BCRP substrate.
These results suggest that certain flavonoids suppress the apical efflux of 5-AcASA possibly by inhibiting MRPs pumps located on apical membranes in Caco-2 cells.
American Psychological Association (APA)
Shin, Yoshimura& Kentaro, Kawano& Ryusuke, Matsumura& Narumi, Sugihara& Koji, Furuno. 2009. Inhibitory Effect of Flavonoids on the Efflux of N-Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells. Journal of Biomedicine and Biotechnology،Vol. 2009, no. 2009, pp.1-8.
https://search.emarefa.net/detail/BIM-473822
Modern Language Association (MLA)
Shin, Yoshimura…[et al.]. Inhibitory Effect of Flavonoids on the Efflux of N-Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells. Journal of Biomedicine and Biotechnology No. 2009 (2009), pp.1-8.
https://search.emarefa.net/detail/BIM-473822
American Medical Association (AMA)
Shin, Yoshimura& Kentaro, Kawano& Ryusuke, Matsumura& Narumi, Sugihara& Koji, Furuno. Inhibitory Effect of Flavonoids on the Efflux of N-Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells. Journal of Biomedicine and Biotechnology. 2009. Vol. 2009, no. 2009, pp.1-8.
https://search.emarefa.net/detail/BIM-473822
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-473822