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Adaptation in Caco-2 Human Intestinal Cell Differentiation and Phenolic Transport with Chronic Exposure to Blackberry (Rubus sp.) Extract

Redan, Benjamin W., Albaugh, George P., Charron, Craig S., Novotny, Janet A., Ferruzzi, Mario G.
Journal of agricultural and food chemistry 2017 v.65 no.13 pp. 2694-2701
ABC transporters, Rubus, absorption, anthocyanins, bioavailability, blackberries, cell differentiation, chronic exposure, dietary exposure, enzymes, epicatechin, gene expression, glucosides, human cell lines, humans, intestines, kaempferol, messenger RNA, metabolism, phenolic acids, uridine diphosphate
As evidence mounts for a health-protective role of dietary phenolics, the importance of understanding factors influencing bioavailability increases. Recent evidence has suggested chronic exposure to phenolics may impact their absorption and metabolism. To explore alterations occurring from chronic dietary exposure to phenolics, Caco-2 cell monolayers were differentiated on Transwell inserts with 0–10 μM blackberry (Rubus sp.) total phenolics extracts rich in anthocyanins, flavonols, and phenolic acids. Following differentiation, apical to basolateral transport of phenolics was assessed from an acute treatment of 100 μM blackberry phenolics from 0 to 4 h. Additionally, differences in gene expression of transport and phase II metabolizing systems including ABC transporters, organic anion transporters (OATs), and uridine 5'-diphospho (UDP) glucuronosyltransferases (UGTs) were probed. After 4 h, 1 μM pretreated monolayers showed a significant (P < 0.05) decrease in the percentage of cumulative transport including less epicatechin (42.1 ± 0.53), kaempferol glucoside (23.5 ± 0.29), and dicaffeoylquinic acid (31.9 ± 0.20) compared to control. Finally, significant (P < 0.05) alterations in mRNA expression of key phase II metabolizing enzymes and transport proteins were observed with treatment. Therefore, adaptation to blackberry extract exposure may impact intestinal transport and metabolism of phenolics.