Intestinal absorption mechanisms of MTBH, a novel hesperetin derivative, in Caco-2 cells, and potential involvement of monocarboxylate transporter 1 and multidrug resistance protein 2.

Intestinal absorption mechanisms of MTBH, a novel hesperetin derivative, in Caco-2 cells, and potential involvement of monocarboxylate transporter 1 and multidrug resistance protein 2. Eur J Pharm Sci. 2015 Jul 28; Authors: Shen C, Chen R, Qian Z, Meng X, Hu T, Li Y, Chen Z, Huang C, Hu C, Li J Abstract Hesperetin, the aglycone of hesperidin, occurs naturally in citrus fruits. It exerts extensive pharmacological activities. However, hesperetin's poor solubility and low bioavailability limits its wide application. In order to overcome these limitations, recently a series of novel hesperitin derivatives containing Mannich base moieties were synthesized and the anti-inflammatory activity was evaluated, among which MTBH (8-methylene-tert-butylamine-3',5,7-trihydroxy-4'-methoxyflavanone) showed a significantly improved water solubility, and promising anti-inflammatory activity in vitro and in vivo compared with hesperitin. Thus, the aim of this study was to investigate the permeability and transport mechanisms of MTBH, using Caco-2 cell monolayer. MTBH was effectively absorbed by Caco-2 cells in a concentration-dependent manner in both directions at 7.5-480μM. Moreover, MTBH showed pH dependent and TER values independent transport in both directions. Transport of MTBH was obviously decreased in the presence of sodium azide (an ATP inhibitor) or CCCP (a proton-ionophore). MTBH transport was markedly reduced by MCT inhibitors quercetin or ...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research