title: In vitro effects of Mangifera indica and polyphenols derived on ABCB1/P-glycoprotein activity.
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.
authors.affiliation: Dipartimento di Patologia Sperimentale, Università degli Studi di Pisa, via Roma 55, 56126 Pisa, Italy. chieli@biomed.unipi.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Chieli
authors.forename: Nadia
authors.initials: N
authors.lastname: Romiti
authors.forename: Idania
authors.initials: I
authors.lastname: Rodeiro
authors.forename: Gabino
authors.initials: G
authors.lastname: Garrido
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D031022:Mangifera / Q000737:chemistry*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D059808:Polyphenols
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols