Document Detail


A bitter melon extract inhibits the P-glycoprotein activity in intestinal Caco-2 cells: monoglyceride as an active compound.
MedLine Citation:
PMID:  15630255     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Tomoko Konishi; Hideo Satsu; Yasuo Hatsugai; Koichi Aizawa; Takahiro Inakuma; Shinji Nagata; Sho-hei Sakuda; Hiromichi Nagasawa; Makoto Shimizu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  BioFactors (Oxford, England)     Volume:  22     ISSN:  0951-6433     ISO Abbreviation:  Biofactors     Publication Date:  2004  
Date Detail:
Created Date:  2005-01-04     Completed Date:  2005-04-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8807441     Medline TA:  Biofactors     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  71-4     Citation Subset:  IM    
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.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Chromatography, High Pressure Liquid
Colonic Neoplasms
Cucurbitaceae*
Daunorubicin / pharmacokinetics
Glycerides / pharmacology*
Humans
P-Glycoprotein / antagonists & inhibitors*,  drug effects
Palmitic Acid / pharmacology
Phytotherapy
Plant Extracts / isolation & purification,  pharmacology*
Chemical
Reg. No./Substance:
0/Glycerides; 0/P-Glycoprotein; 0/Plant Extracts; 20830-81-3/Daunorubicin; 57-10-3/Palmitic Acid

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