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《Chinese Journal of Natural Medicines》 2008-02
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Intestinal Transport of Free Anthraquinones in Caco-2 Cell Model

WANG Ying,YANG Xiu-WeiThe State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines,School of Pharmaceutical Sciences,Peking University,Beijing 100083,P.R.China  
AIM: To investigate the transepithelial transport of the six free anthraquinones 1,8-dihydroxyanthraquinone (DQ),chrysophanol (CP),emodin (EN),rhein (RN),aloe-emodin (AE) and citreorosein (CN) in the human intestinal Caco-2 cell monolayer model. METHODS: The monolayers of the human intestinal epithelial cancer cell line Caco-2 were incubated with DQ,CP,EN,RN,AE and CN to model its intestinal absorption and transport,respectively. The determination of the compounds was performed by high-performance liquid chromatography. RESULTS: The apparent permeability coefficients (Papp) in the Caco-2 cell monolayers for DQ,CP,EN,RN,AE and CN were (2.16±0.38)×10-6,(3.00±0.09)×10-7,(1.99±0.94)×10-6,(4.58±0.20)×10-6,(6.24±0.19)×10-6 and (7.34±0.61)×10-6 cm ·s-1 from the apical-to-basolateral direction,respectively,and (3.20±0.10)×10-6,(4.50 ± 0.02)×10-7,(2.22 ± 0.62)×10-6,(4.94 ± 0.39)×10-6,(2.87 ± 0.18)×10-6 and (6.80 ± 0.37)×10-6 cm ·s-1 from the basolateral-to-apical direction,respectively. The Papp values of DQ,EN,RN,AE and CN were about 10 times less than those (6.30 ± 0.26)×10-5 cm ·s-1 of propranolol as a reference standard compound of high permeability and the main mechanism of intestinal absorption by passive diffusion,and about 10 times higher than those ( 1×10-7 cm ·s-1) of atenolol as a reference standard compound of poor permeability and the main mechanism of intestinal absorption by passive diffusion. Whereas,the Papp value of CP was at nearly the same magnitude with those of atenolol. In the presence of iodoacetamide,the Papp of AE were not affected in both apical-to-basolateral and basolateral-to-apical directions. CONCLUSION: The intestinal absorption of all test compounds was passive diffusion as the dominating process in Caco-2 cell monolayer model. DQ,EN,RN,AE and CN will be moderately absorbed compounds and CP was estimated to be a poorly absorbed compound.
【Key Words】： 1 8-dihydroxyanthraquinone Chrysophanol Emodin Rhein Aloe-emodin Citreorosein Intestinal permeability Caco-2 cell monolayers
【Fund】： 国家高新技术发展计划(No.2002AA2Z343C;2004AA2Z3783);; 国家科技项目(No.2006BAI06A01-02);; 北京科学基金(No.Z0004105040311)~~
【CateGory Index】： R285
【DOI】： CNKI:SUN:ZGTR.0.2008-02-023
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