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• W2005804312 abstract "Many plant compounds are able to modulate the activity and/or the expression of the major multidrug transporter ABCB1/P-glycoprotein (P-gp). In this study, mango (Mangifera indica L.) stem bark extract (MSBE), its main polyphenol mangiferin and the mangiferin aglycone derivative norathyriol, as well as catechin, gallic acid and quercetin, were investigated for their potential ability to influence ABCB1 gene and P-gp expression in HK-2 cells, a proximal tubule line constitutively expressing this transporter. Western blot analysis demonstrated a concentration-dependent decrease in P-gp in cells cultured in the presence of MSBE for 72 h. Gallic acid and quercetin also decreased the levels of P-gp at all studied concentrations, whereas catechin was almost ineffective. However, in cells exposed to mangiferin (10-200 microM), the P-gp amount showed a concentration- and time-dependent increase, being 2-fold higher than the controls after 72 h. Norathyriol (5 microM) induced P-gp, but the effect decreased at higher concentrations. The changes in the P-gp protein amount were correlated with relative changes in the ABCB1 mRNA content and with the efflux activity of the transporter. The transcriptional inhibitor 1-d-ribofuranosylbenzimidazole (DRB) contrasted the increased expression of ABCB1 by mangiferin, suggesting that the increase could be due to transcriptional up-regulation of ABCB1 mRNA. Mangiferin-treated cells overexpressing the transporter were protected against the cytotoxicity of the known P-gp substrate cyclosporine A. However, the opposite effect was not observed in cells pretreated with MSBE. These results demonstrate that MSBE and mango polyphenols, already shown in our previous studies to influence P-gp activity, may also interact with ABCB1/P-gp at the expression level. In particular, we show for the first time that the main mango polyphenol mangiferin up-regulates this multidrug transporter. The molecular mechanisms and the consequences of these effects, including the possibility of interactions with conventional drugs or other herbal constituents, remain to be elucidated." @default.
• W2005804312 created "2016-06-24" @default.
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• W2005804312 date "2010-08-01" @default.
• W2005804312 modified "2023-10-16" @default.
• W2005804312 title "In vitro modulation of ABCB1/P-glycoprotein expression by polyphenols from Mangifera indica" @default.
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• W2005804312 doi "https://doi.org/10.1016/j.cbi.2010.05.012" @default.
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