Abstract

Many plant-derived compounds, including polyphenols, are able to affect the function of MDR-1/P-glycoprotein (P-gp ABCB1) multidrug transporter, leading to potential herb-drug interactions. This study evaluated the effects of mango (Mangifera indica L.) stem bark extract, MSBE, and related phenols on P-gp activity in both the HK-2 proximal tubule cell line, constitutively expressing P-gp, and in a Caco-2 cell sub-line selected by resistance to vincristine (Caco-2/VCR) and overexpressing P-gp. The effects of MSBE, mangiferin, norathyriol, catechin, quercetin and gallic acid on P-gp activity were tested by the rhodamine-123 accumulation as well as by the Calcein-AM assays. Effects on esterase activity, which could influence the results of Calcein-AM test, were also assessed. All investigated compounds except for catechin and gallic acid inhibited P-gp activity in HK-2 cells, in the order of mangiferin < norathyriol < quercetin < MSBE. MSBE, quercetin and norathyriol also inhibited significantly esterase activity. Similar effects were obtained in resistant Caco-2/VCR cells, but were negligible in the wild-type ones, expressing low amounts of P-gp. Our results demonstrate, for the first time, that M. indica and polyphenols derived may affect the activity of the multidrug transporter P-gp ABCB1, suggesting the possibility of herb-drug interactions to be explored in depth. © 2009 Elsevier Ltd. All rights reserved.