title: Effects of Kaempferia parviflora extracts and their flavone constituents on P-glycoprotein function.
abstract: The purpose of this study was to examine the effects of extracts and flavone derivatives from the rhizome of Kaempferia parviflora on P-glycoprotein (P-gp)-mediated transport in LLC-GA5-COL150, a transfectant cell line of a porcine kidney epithelial cell line LLC-PK1 with human MDR1 cDNA. Ethanol extract obtained from Kaempferia parviflora rhizome significantly increased the accumulation of rhodamine 123 and daunorubicin, P-gp substrates, in LLC-GA5-COL150 cells, but not in LLC-PK1 cells. The aqueous extract also increased the accumulation in LLC-GA5-COL150 cells with lower potency than the ethanol extract. The effects of flavone derivatives isolated from the rhizome of Kaempferia parviflora on P-gp function were examined. Among six flavones tested, 3,5,7,3',4'-pentamethoxyflavone most potently increased the accumulation of rhodamine 123 and daunorubicin in LLC-GA5-COL150 cells in a concentration-dependent manner. In addition, 5,7-dimethoxyflavone to lesser degree increased rhodamine 123 accumulation in LLC-GA5-COL150 cells. In contrast, the other four flavone derivatives had no significant effect on the accumulation of rhodamine 123 in LLC-GA5-COL150 cells in a concentration range tested. These results indicate that extracts and flavone derivatives from the rhizome of Kaempferia parviflora can inhibit P-gp function, which may be useful for overcoming P-gp-mediated multidrug resistance and improving the oral bioavailability of anticancer agents.
authors.affiliation: Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima 734-8553, Japan.
authors.forename: Denpong
authors.initials: D
authors.lastname: Patanasethanont
authors.forename: Junya
authors.initials: J
authors.lastname: Nagai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yumoto
authors.forename: Teruo
authors.initials: T
authors.lastname: Murakami
authors.forename: Khaetthareeya
authors.initials: K
authors.lastname: Sutthanut
authors.forename: Bung-Orn
authors.initials: BO
authors.lastname: Sripanidkulchai
authors.forename: Chavi
authors.initials: C
authors.lastname: Yenjai
authors.forename: Mikihisa
authors.initials: M
authors.lastname: Takano
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D000431:Ethanol / Q000737:chemistry; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D018374:LLC-PK1 Cells; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D027343:Rhizome; D020112:Rhodamine 123 / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013552:Swine; D013997:Time Factors; D014162:Transfection; D014867:Water / Q000737:chemistry; D030521:Zingiberaceae
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D047309:Flavones; D005419:Flavonoids; D005456:Fluorescent Dyes; D010936:Plant Extracts; D012997:Solvents; D014867:Water; D020112:Rhodamine 123; C060298:5,7-dimethoxyflavone; D000431:Ethanol; D003630:Daunorubicin