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        Glyceollin Transport, Metabolism, and Effects on P-Glycoprotein Function in Caco-2 Cells

        Chukwuemezie Chimezie,Adina C. Ewing,Syeda S. Quadri,Richard B. Cole,Stephen M. Boue,Christopher F. Omari,Melyssa Bratton,Elena Glotser,Elena Skripnikova,Ian Townley,Robert E. Stratford 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.4

        Glyceollins are phytoalexins produced in soybeans from their isoflavone precursor daidzein. Their impressive anticancer and glucose normalization effects in rodents have generated interest in their therapeutic potential. The aim of the present studies was to begin to understand glyceollin intestinal transport and metabolism, and their potential effects on P-glycoprotein (Pgp) in Caco-2 cells. At 10 and 25 lM, glyceollin permeability was 2.4 – 0.16 · 10- 4 cm/sec and 2.1 – 0.15 · 10- 4 cm/sec, respectively, in the absorptive direction. Basolateral to apical permeability at 25 lM was 1.6 – 0.10 · 10- 4 cm/sec. Results suggest high absorption potential of glyceollin by a passive-diffusion-dominated mechanism. A sulfate conjugate at the phenolic hydroxyl position was observed following exposure to Caco-2 cells. In contrast to verapamil inhibition of the net secretory permeability of rhodamine 123 (R123) and its enhancement of calcein AM uptake into Caco-2 cells, neither glyceollin nor genistein inhibited Pgp (MDR1; ABCB1) up to 300 lM. There was no significant change in MDR1 mRNA expression, Pgp protein expression, or R123 transport in cells exposed to glyceollin or genistein for 24 h up to 100 lM. Collectively, these results suggest that glyceollin has the potential to be well absorbed, but that, similar to the isoflavone genistein, its absorption may be reduced substantially by intestinal metabolism; further, they indicate that glyceollin does not appear to alter Pgp function in Caco-2 cells.

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