Based on studies suggesting that active transport mechanisms contribute to the absorption of flavonoids into human intestinal Caco-2 cells we here used the structurally similar fluorescent rhodamine 123 to test a possible influence of flavonoids on its uptake. Rhodamine absorption displayed saturation kinetics with a Km of 1.1 µM and a pH-optimum of 8.5 and was stimulated by flavone fourfold in its Vmax. Ring C of the other sixteen flavonoids tested turned out to be of special importance in order to act as potent competitive inhibitors for rhodamine transport, with a positive charge there, as present in the anthocyanidins, or a 2,3 double bond together with an aromatic ring fused to position 2, as present in flavones and flavonols, being essential structural requirements. Flavone-stimulated rhodamine uptake was unaffected by classical substrates of organic cation transporters or inhibitors of ATP-dependent efflux pumps. Also, inhibitors of MAP- or tyrosine-kinases did not influence the transport, whose stimulation, however, was essentially dependent on the simultaneous presence of flavone. The existence of a flavone-activated apical flavonoid transporter in Caco-2 cells was finally evidenced by the potently diminished transepithelial apical to basolateral fluxes of 14C-kaempferol in the presence of competing unlabeled flavonoid substrates.

Lies, B.; Martens, S.; Schmidt, S.; Boll, M.; Wenzel, U. (2012). Flavone potently stimulates transepithelial absorption of flavonoids by activating an apical transporter in human intestinal Caco-2 cells. MOLECULAR NUTRITION & FOOD RESEARCH, 56 (11): 1627-1635. doi: 10.1002/mnfr.201200370 handle: http://hdl.handle.net/10449/21486

Flavone potently stimulates transepithelial absorption of flavonoids by activating an apical transporter in human intestinal Caco-2 cells

Martens, Stefan;
2012-01-01

Abstract

Based on studies suggesting that active transport mechanisms contribute to the absorption of flavonoids into human intestinal Caco-2 cells we here used the structurally similar fluorescent rhodamine 123 to test a possible influence of flavonoids on its uptake. Rhodamine absorption displayed saturation kinetics with a Km of 1.1 µM and a pH-optimum of 8.5 and was stimulated by flavone fourfold in its Vmax. Ring C of the other sixteen flavonoids tested turned out to be of special importance in order to act as potent competitive inhibitors for rhodamine transport, with a positive charge there, as present in the anthocyanidins, or a 2,3 double bond together with an aromatic ring fused to position 2, as present in flavones and flavonols, being essential structural requirements. Flavone-stimulated rhodamine uptake was unaffected by classical substrates of organic cation transporters or inhibitors of ATP-dependent efflux pumps. Also, inhibitors of MAP- or tyrosine-kinases did not influence the transport, whose stimulation, however, was essentially dependent on the simultaneous presence of flavone. The existence of a flavone-activated apical flavonoid transporter in Caco-2 cells was finally evidenced by the potently diminished transepithelial apical to basolateral fluxes of 14C-kaempferol in the presence of competing unlabeled flavonoid substrates.
Intestinal absorption
Flavonoids
Caco-2 cells
ABC-transporter
Rhodamine 123
Lies, B.; Martens, S.; Schmidt, S.; Boll, M.; Wenzel, U. (2012). Flavone potently stimulates transepithelial absorption of flavonoids by activating an apical transporter in human intestinal Caco-2 cells. MOLECULAR NUTRITION & FOOD RESEARCH, 56 (11): 1627-1635. doi: 10.1002/mnfr.201200370 handle: http://hdl.handle.net/10449/21486
File in questo prodotto:
File Dimensione Formato  
2012 MNFR Lies et al.pdf

non disponibili

Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 831.49 kB
Formato Adobe PDF
831.49 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10449/21486
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact