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)

Huang-Lian-Jie-Du-Tang (HLJDT) is a classical recipe for relieving fever and toxicity for thousands of years in China. Geniposide is one of the main components in HLJDT. The present study was conducted in order to investigate the differences of absorption of geniposide after oral administration of geniposide alone and HLJDT in rats. Pharmacokinetic differences of geniposide following oral administrations of pure geniposide and HLJDT were investigated in vivo. The absorption of geniposide in pure compound and HLJDT was evaluated using intestinal perfusion and Caco-2 models. The in vivo and in vitro studies showed good relevance and consistent results. The co-occurring components in HLJDT were found to promote the absorption of geniposide from the pharmacokinetic study in vivo, intestinal perfusion, and Caco-2 model. Geniposide had better absorption in the duodenum and jejunum from the intestinal perfusion model, which was mainly absorbed by passive diffusion. Verapamil influenced the transportation of geniposide, while EDTA did not, demonstrating that geniposide might be the potential substance of P-glycoprotein in intestinal perfusion and Caco-2 models. The absorption of geniposide was studied systematically to guide the design of the oral dosage of geniposide and HLJDT in clinical therapy.
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PMID:Study on the Absorption Mechanism of Geniposide in the Chinese Formula Huang-Lian-Jie-Du-Tang in Rats. 2753 66

Geniposide is a water-soluble iridoid glucoside with anti-oxidant and anti-inflammatory biological functions. It has been indicated that geniposide may increase doxorubicin (DOX) accumulation in drug-resistant tumor cells. The present study aimed to investigate the resistance-reversing effect of geniposide in DOX-resistant cells and assess the underlying mechanisms of its action. The results revealed that geniposide itself weakly inhibited tumor cell growth. Furthermore, geniposide effectively reversed DOX resistance in a dose-dependent manner in human osteosarcoma DOX-resistant (MG63/DOX) cells. The action of geniposide was confirmed by increased accumulation of intracellular DOX detected in MG63/DOX cells. Notably, geniposide enhanced the efficacy of DOX against MG63/DOX cancer cell-derived xenografts in nude mice. To study the mechanism, intracellular accumulation of rhodamine 123 was measured using flow cytometry. At concentrations that reversed multidrug resistance (MDR), geniposide significantly downregulated P-glycoprotein (P-gp) expression. Therefore, geniposide reverses P-gp-mediated MDR by reducing the expression of P-gp and its transport function. The present study therefore indicated that geniposide may be administered in combination with conventional anti-neoplastic drugs to prevent MDR.
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PMID:Geniposide reverses multidrug resistance in vitro and in vivo by inhibiting the efflux function and expression of P-glycoprotein. 2835 12