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

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.