Inhibitory effect of a bitter melon extract on the P‐glycoprotein activity in intestinal Caco‐2 cells

Abstract

1 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 Pglycoprotein (P-gp). 2 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. 3 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. 4 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. 5 Monoglycerides could therefore alter the pharmacokinetics of drugs by inhibiting the P-gpmediated efflux.

Pharmacokinetics of Mirabegron, a β3-Adrenoceptor Agonist for Treatment of Overactive Bladder, in Healthy East Asian Subjects

“…Lipids, in particular monoglycerides, contained in a high-fat meal or its digests have been reported to inhibit P-glycoprotein transport. 14,15 Mirabegron has also previously been reported to have been adsorbed to food components, especially by components of low-fat meals. 8 In studies in healthy Chinese subjects, mirabegron C max was reached approximately 4 hours after oral administration of a single dose and approximately 5 hours after multiple-dose administration.…”

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

“…Nanopore induction or the membrane perturbation (Anderson, 2005), and the intermediate phases formed in the intestine (Kossena et al, 2005) were considered important. In vitro study showed that monoglycerides can enhance the cellular absorption of drugs by inhibition of Pglycoproteins (Konishi et al, 2004). Further studies are required to explain the absorption enhancing mechanism of monoolein unequivocally.…”

Interaction between Food Substances and the Intestinal Epithelium

“…48) Monopalmitate was observed to inhibit multi-drug resistance protein1 (MDR1 or P-glycoprotein), an efflux transporter for hydrophobic xenobiotics. 49) Although these lipid compounds are surface active, their surface activity did not correlate with the transport-inhibitory activity. Specific structures or characteristics of these compounds affect cell membrane structure or transporter structure itself, thereby regulating the activity of these membrane transporters.…”