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Title: Modulation of drug transport pathways by spices
Authors: HAN YI
Keywords: Piperine, Capsaicin, P-glycoprotein, MDR1, Caco-2 cell monolayer
Issue Date: 7-Sep-2007
Citation: HAN YI (2007-09-07). Modulation of drug transport pathways by spices. ScholarBank@NUS Repository.
Abstract: The hypothesis for this project was that co-administered spices may affect oral drug bioavailability by interfering with intestinal drug transporter systems. The P-glycoprotein (P-gp) was chosen as the representative transporter for the project. Piperine and capsaicin, the main active components of black pepper and hot chilli, respectively, were selected for the study following a preliminary screening of spices which also included the aqueous extract of garlic, DAS (diallylsulfide), DADS (diallydisulfide), and the ethanol extract of ginger. Piperine and capsaicin, at concentrations from 10 to 100 A?M, inhibited the P-gp-mediated digoxin transport across Caco-2 and L-MDR1 cell monolayers in a concentration dependent manner. Prolonged exposure of the Caco-2 cell monolayers to either spice, on the other hand, raised the cellular P-gp and the MDR1 mRNA level. The up-regulated P-gp and mRNA levels were accompanied by enhanced P-gp-efflux of digoxin across the cell monolayers. Intragastric administration of either piperine or capsaicin for 14 consecutive days also altered the intestinal, hepatic and renal P-gp expression in rats. The modulations of in vivo P-gp level were influenced by the type of spice and rodent organ. In addition, exposure of Caco-2 cell monolayers to piperine or capsaicin at 100 A?M for 18days moderately increased the paracellular mannitol transport across these cell monolayers. In addition, a slower rate of cell proliferation with moderate delay in G1/G0 phase of the cell cycle were observed after the three cell monolayers were exposed to piperine or capsaicin for 48 and 72h.
Appears in Collections:Ph.D Theses (Open)

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