title: Permeability of rhynchophylline across human intestinal cell in vitro.
abstract: Rhynchophylline (Rhy) is the major component of Uncaria species, which is used in Chinese traditional medicine for the treatment of central nervous system disorders. However, its oral bioavailability has not been known. This study aims to investigate the intestinal permeability and related mechanisms of Rhy using cultured human epithelial Caco-2 cells. The cytotoxicity of Rhy on Caco-2 cells was evaluated with MTT assay. The effect of Rhy on the integrity of Caco-2 cell monolayer was assayed with transepithelial electrical resistance. The permeability of Rhy across cell monolayer was assayed by measuring Rhy quantity in received side with HPLC. The effect of Rhy on the expression of P-glycoprotein and MDR1 was detected with Western blot and flow cytometry, respectively. In the concentration of Rhy, which did not produce toxicity on cell viability and integrity of Caco-2 cell monolayer, Rhy crossed the monolayer with velocity 2.76~5.57×10^-6 cm/sec and 10.68~15.66×10^-6 cm/sec from apical to basolateral side and from basolateral to apical side, respectively. The permeability of Rhy was increased by verapamil, a P-glycoprotein inhibitor, or rhodamine123, a P-glycoprotein substrate. Rhy revealed an induction effect on P-glycoprotein expression in Caco-2 cells. These results demonstrate the low permeability of Rhy in intro, and suggest that P-glycoprotein may underlie the mechanism.
authors: Institute of Medicinal Plant Development, Chinese Academy Medical Sciences and Peking Union Medical College 151, Malianwa North Road, Haidian District, Beijing, 100193, PR China.
authors: Bo
authors: B
authors: Ma
authors: Institute of Medicinal Plant Development, Chinese Academy Medical Sciences and Peking Union Medical College 151, Malianwa North Road, Haidian District, Beijing, 100193, PR China.
authors: Jing
authors: J
authors: Wang
authors: Institute of Medicinal Plant Development, Chinese Academy Medical Sciences and Peking Union Medical College 151, Malianwa North Road, Haidian District, Beijing, 100193, PR China.
authors: Jing
authors: J
authors: Sun
authors: Institute of Medicinal Plant Development, Chinese Academy Medical Sciences and Peking Union Medical College 151, Malianwa North Road, Haidian District, Beijing, 100193, PR China.
authors: Ming
authors: M
authors: Li
authors: Jilin Academy of Traditional Chinese Medicine 1745, Works and Peasants Road, Chaoyang District, Changchun City, 130021, PR China.
authors: Huibo
authors: H
authors: Xu
authors: Institute of Medicinal Plant Development, Chinese Academy Medical Sciences and Peking Union Medical College 151, Malianwa North Road, Haidian District, Beijing, 100193, PR China.
authors: Guibo
authors: G
authors: Sun
authors: Institute of Medicinal Plant Development, Chinese Academy Medical Sciences and Peking Union Medical College 151, Malianwa North Road, Haidian District, Beijing, 100193, PR China.
authors: Xiaobo
authors: X
authors: Sun
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000378:metabolism; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000378:metabolism* / Q000633:toxicity; D017097:Electric Impedance; D006801:Humans; D026121:Indole Alkaloids / Q000378:metabolism* / Q000633:toxicity; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007700:Kinetics; D000078183:Oxindoles; D010539:Permeability; D020112:Rhodamine 123 / Q000494:pharmacology; D015854:Up-Regulation; D014700:Verapamil / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D000078183:Oxindoles; D020112:Rhodamine 123; C052714:rhyncophylline; D014700:Verapamil
keywords: Caco-2 cells; P-glycoprotein; Rhynchophylline; permeability