A bitter melon extract inhibits the P-glycoprotein activity in intestinal Caco-2 cells: Monoglyceride as an active compound

Issue title: The Proceedings of the 3rd International Conference on Food Factors (ICoFF 03)

Article type: Research Article

Authors: Konishi, Tomoko | Satsu, Hideo | Hatsugai, Yasuo | Aizawa, Koichi | Inakuma, Takahiro | Nagata, Shinji | Sakuda, Sho-hei | Nagasawa, Hiromichi | Shimizu, Makoto

Affiliations: 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 | Research Institute, Kagome Co. Ltd., 17 Nishitomiyama, Nishinasuno-machi, Nasu-gun, Tochigi, 329-2762, Japan

Note: [] Corresponding author. Tel.: +81 3 5841 5127; Fax: +81 3 5841 8026; E-mail: [email protected]

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 ^1H-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.

Keywords: P-gp, bitter melon, Caco-2, 1-monopalmitin, daunomycin

Journal: BioFactors, vol. 22, no. 1-4, pp. 71-74, 2004