Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(-)-Epicatechin gallate (ECG) is one of the flavonoids in green tea, which has been demonstrated to have cancer-preventive properties in many model systems. However, the extent and mechanisms of accumulation of these flavonoids in cells is unknown. The objectives of this study were to determine the accumulation of ECG by the intestinal epithelial cell Caco-2 and to characterize the transport mechanism involved. The cells were exposed to ECG +/- various transport inhibitors and incubated at 37 degrees C. Absorbed flavonoids were extracted and quantified by high-performance liquid chromatography. The uptake of ECG included a nonsaturable initial rapid process as well as a much slower saturable process. The saturable ECG uptake by the Caco-2 cells was sodium-independent but clearly dependent on a pH gradient. Phloretin and benzoic acid, inhibitors of the monocarboxylate transporter (MCT), significantly reduced ECG uptake. The uptake of ECG in the Caco-2 cells increased 2-fold in the presence of 50 microM 3-[(3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl)-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK-571), suggesting the involvement of multidrug-associated protein (MRP)2 in efflux of ECG. This was confirmed using Madin-Darby canine kidney cells transfected with MRP2. Also P-glycoprotein was responsible for some ECG efflux. MK-571 also caused a dramatic increase in ECG accumulation in Chinese hamster ovary cells, suggesting that ECG was also a substrate for MRP1. Together, these observations demonstrate important roles of membrane transporters, i.e., MCT, MRP2, P-glycoprotein, and MRP1, in the cellular accumulation and potential effects of ECG.
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PMID:Cellular uptake and efflux of the tea flavonoid (-)epicatechin-3-gallate in the human intestinal cell line Caco-2. 1297 Mar 88

Phloretin is a natural dihydrochalcone flavonoid that is mainly distributed in apple, pear and other juicy fruit peels or root peels. Phloretin exhibits several pharmacological properties, such as antidiabetic, antioxidant, anti-inflammatory, and antitumor activities. However, the poor water solubility of phloretin limits its application in the treatment of numerous diseases. To date, the underlying mechanisms of phloretin absorption have not been investigated. In this study, the pharmacokinetics of phloretin orally administered to Sprague-Dawley (SD) rats were examined, and the absorption mechanisms of phloretin were investigated in a Caco-2 cell monolayer and single-pass intestinal perfusion in SD rat. The effects measured by basic parameters, such as compound concentration, time, temperature, paracellular pathway, in different intestinal segments were analyzed, and various inhibitors, such as the P-glycoprotein (P-gp) inhibitor verapamil, the multidrug resistance protein 2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, and the closely related regulator EDTA, were evaluated to determine their effects on the absorption of phloretin. The pharmacokinetics of phloretin was studied by oral and intravenous injection in rats. The bioavailability was 8.676 %.The SPIP experiments showed that P-gp, MRP2, BCRP protein inhibitor and closely related regulator, could significantly increase the apparent permeability coefficient (Papp) of phloretin. Monolayer transport experiments in Caco-2 cells showed that P-gp, MRP2 protein inhibitor and closely related regulator EDTA, significantly increased the Papp value of phloretin. In conclusion, phloretin is a substrate of P-gp and MRP2, and its modes of transport include active transport, efflux protein transport and cell bypass.
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PMID:Studies on pharmacokinetic properties and absorption mechanism of phloretin: In vivo and in vitro. 3304 84