title: In vitro characterization of ABC transporters involved in the absorption and distribution of liensinine and its analogs.
abstract: BACKGROUND
  Lotus plumule, the dried young cotyledon and radicle of the Nelumbo nucifera Gaertn. (Fam. Nymphaeaceae) ripe seed, is a famous Traditional Chinese Medicine to remove heat from the heart, anchor the mind, improve seminal emission, and arrest bleeding for centuries in China. Liensinine and its analogs neferine and isoliensinine are the major active components in lotus plumule. Aim of the study is to investigate the association of liensinine, neferine, and isoliensinine with efflux transporters.
  
  
  METHODS
  Caco-2, MDCK, MDCK-MDR1, and MDCK-MRP2 were used as cell models for the transcellular transport and accumulation studies.
  
  
  RESULTS
  The results obtained in Caco-2 cells suggested that P-glycoprotein (P-gp) might be involved in transcellular transport. Cellular accumulation and transport experiments were further performed in MDCK-MDR1 cells. GF120918 and cyclosporine A were found to completely inhibit the efflux, and the net efflux ratios of these alkaloids exhibited saturation over the concentration range. No significant differences in liensinine accumulation and transport were observed between MDCK and MDCK-MRP2 cells.
  
  
  CONCLUSIONS
  These results demonstrated that liensinine, neferine, and isoliensinine are substrates of P-gp, whereas MRP2 is not involved in the transport process, suggesting that P-gp might be responsible for the absorption and distribution of the 3 alkaloids.
authors.affiliation: Laboratory of Pharmaceutical of Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Lushan
authors.initials: L
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Huidi
authors.initials: H
authors.lastname: Jiang
authors.forename: Huichang
authors.initials: H
authors.lastname: Bi
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000042:Absorption; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001692:Biological Transport; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D061985:Madin Darby Canine Kidney Cells; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044182:Benzylisoquinolines; D007546:Isoquinolines; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010636:Phenols; C000715087:ABCC2 protein, human; C499779:isoliensinine; C057222:neferine; C080095:liensinine
keywords: AP; BL; Calcein AM; Calcein acetoxymethyl ester; Cellular accumulation; CsA; ER; GF120918; Liensinine; MDCK; MDR-associated protein 2; MDR1; MRP2; Madin-Darby canine kidney cell line; N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide; NER; P(app); P-glycoprotein; P-gp; Rho-123; TEER; Transcellular transport; apical side; apparent permeability coefficient; basolateral side; cyclosporin A; efflux ratio; net efflux ratio; reverse multidrug resistance 1; rhodamine 123; transepithelial electrical resistance