title: A bitter melon extract inhibits the P-glycoprotein activity in intestinal Caco-2 cells: monoglyceride as an active compound.
abstract: P-glycoprotein (P-gp) is a 170 kDa membrane protein that belongs to the ATP-binding cassette (ABC) transporter superfamily. In normal tissues, P-gp functions as an ATP-dependent efflux pump that excretes highly hydrophobic xenobiotic compounds, playing an important role in protecting the cells/tissues from xenobiotics. In the present study, chemical substances that could directly modulate the intestinal P-gp activity were searched in vegetables and fruits. By using human intestinal epithelial Caco-2 cells as a model of the small intestinal cells, we observed that a bitter melon fraction extracted from 40% methanol showed the greatest increase of the rhodamine-123 accumulation by Caco-2 cells. Inhibitory compounds in the bitter melon fraction were then isolated by HPLC using Pegasil C4 and Pegasil ODS columns. The HPLC fraction having the highest activity was analyzed by (1)H-NMR and FAB-MS, and the active compound was identified as 1-monopalmitin. It is interesting that certain types of monoglyceride might be involved in the drug bioavailability by specifically inhibiting the efflux mediated by P-gp.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Konishi
authors.forename: Hideo
authors.initials: H
authors.lastname: Satsu
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hatsugai
authors.forename: Koichi
authors.initials: K
authors.lastname: Aizawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inakuma
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagata
authors.forename: Sho-hei
authors.initials: SH
authors.lastname: Sakuda
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000187:drug effects; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms; D019662:Cucurbitaceae; D003630:Daunorubicin / Q000493:pharmacokinetics; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D019308:Palmitic Acid / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005989:Glycerides; D010936:Plant Extracts; D019308:Palmitic Acid; D003630:Daunorubicin