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Renal vectorial transport of berberine mediated by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 (MATE1) in rats.
Shi, Rong; Yang, Yuanyuan; Xu, Zhangyao; Dai, Yan; Zheng, Min; Wang, Tianming; Li, Yuanyuan; Ma, Yueming.
Afiliación
  • Shi R; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Yang Y; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Xu Z; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Dai Y; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Zheng M; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Wang T; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Li Y; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Ma Y; Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Biopharm Drug Dispos ; 39(1): 47-58, 2018 Jan.
Article en En | MEDLINE | ID: mdl-29065218
Berberine, a well-known plant alkaloid derived from Rhizoma coptidis, has potential applications as a therapeutic drug for diabetic nephropathy. However, the transporter-mediated renal transport of berberine remains largely unclear. This study aimed to investigate the renal transport mechanism of berberine using transfected cells, kidney slices and animal experiments. In Madin-Darby canine kidney (MDCK) cells stably expressing rat OCT2 (MDCK-rOCT2) and kidney slices, saturable and non-saturable uptake of berberine was observed, and corticosterone could inhibit the uptake of berberine, with IC50 values of 0.1 µm and 147.9 µm, respectively. In double-transfected cells, the cellular accumulation of berberine into MDCK-rOCT2 and MDCK-rOCT2-rMATE1 (MDCK cells stably expressing rOCT2 and rMATE1) cells was significantly higher than the uptake into MDCK cells. Meanwhile, berberine transcellular transport was considerably higher in double-transfected MDCK-rOCT2-rMATE1 cells than in MDCK and MDCK-rOCT2 cells. Corticosterone for MDCK-rMATE1 and MDCK-MDR1 and pyrimethamine for MDCK-rMATE1 at high concentrations could inhibit the efflux of berberine. In animal experiments, compared with the berberine alone group, the cumulative urinary excretion of berberine significantly decreased in the corticosterone or pyrimethamine pretreatment groups. In the rat kidney, pyrimethamine increased, and a low dose of corticosterone (5 mg/kg) decreased, the berberine concentration. However, there was no apparent change in the renal concentration of berberine in rats pretreated with corticosterone (10 or 20 mg/kg). Thus, berberine is not only a substrate of OCT2 and P-glycoprotein, but is also a substrate of MATE1. Both OCT2 and MATE1 mediate the renal vectorial transport of berberine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Berberina / Antiportadores / Proteínas de Transporte de Catión Orgánico / Transportador 2 de Cátion Orgánico / Riñón Límite: Animals Idioma: En Revista: Biopharm Drug Dispos Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Berberina / Antiportadores / Proteínas de Transporte de Catión Orgánico / Transportador 2 de Cátion Orgánico / Riñón Límite: Animals Idioma: En Revista: Biopharm Drug Dispos Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido