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Published on: January 30, 2018
Inhibitory effect of a bitter melon extract on the P-glycoprotein activity in intestinal Caco-2 cells
Tomoko Konishi1, Hideo Satsu, Yasuo Hatsugai
1Department 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.
Abstract:
Extracts of bitter melon, soybean, dokudami and welsh onion by 40% methanol increased the accumulation of rhodamine-123 by Caco-2 cells, suggesting that these extracts inhibited P-glycoprotein (P-gp). The extract of bitter melon was separated in a tC18 cartridge column and the eluate from 80% acetonitrile most markedly increased the [(3)H]-daunomycin accumulation by Caco-2 cells. The inhibitory compounds in the bitter melon fraction were isolated by HPLC with 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. The inhibitory activities of 1-monopalmitin and its related compounds suggested that the inhibition of P-gp activity was not dependent on the degree of unsaturation of fatty acid in the monoglyceride, but on the chain length. It was also suggested that the monoglyceride structure played an important role in the inhibition of P-gp activity. Monoglycerides could therefore alter the pharmacokinetics of drugs by inhibiting the P-gp-mediated efflux.
Insights
Certain plant extracts, including bitter melon, inhibit P-glycoprotein (P-gp), a transporter affecting drug absorption. Researchers identified 1-monopalmitin as a key compound that alters drug pharmacokinetics by blocking P-gp.
Area of Science:
- Pharmacology
- Biochemistry
- Natural Products Chemistry
Background:
- P-glycoprotein (P-gp) is a key efflux transporter in drug pharmacokinetics.
- Inhibiting P-gp can enhance drug absorption and efficacy.
- Natural compounds are explored for their potential to modulate P-gp activity.
Purpose of the Study:
- To investigate the P-gp inhibitory effects of various plant extracts.
- To identify the specific compound responsible for P-gp inhibition in bitter melon.
- To elucidate the structural features of monoglycerides responsible for P-gp inhibition.
Main Methods:
- Caco-2 cell assays using rhodamine-123 and [(3)H]-daunomycin accumulation.
- Chromatographic separation of bitter melon extract (tC18, HPLC with Pegasil C4 and ODS columns).
- Structural elucidation using Nuclear Magnetic Resonance ((1)H-NMR) and Fast Atom Bombardment Mass Spectrometry (FAB-MS).
Main Results:
- Bitter melon, soybean, dokudami, and welsh onion extracts inhibited P-gp.
- 1-monopalmitin was identified as the active P-gp inhibitory compound from bitter melon.
- Inhibitory activity correlated with monoglyceride chain length, not fatty acid unsaturation.
Conclusions:
- 1-monopalmitin is a potent inhibitor of P-gp.
- Monoglycerides can alter drug pharmacokinetics by inhibiting P-gp-mediated efflux.
- The chain length of monoglycerides is crucial for P-gp inhibitory activity.
