The constituents of Cibotium barometz and their permeability in the human Caco-2 monolayer cell model.
BACKGROUND
Cibotium barometz (L.) J. Sm. (Dicksoniaceae) has been traditionally used as anti-inflammatory and anodyne.


OBJECTIVE
To investigate the constituents in the rhizomes of Cibotium barometz, and evaluate their permeability in the human Caco-2 model.


METHODS
The rhizomes extracts of Cibotium barometz were isolated by chromatographic techniques. Structures of isolated compounds were identified by spectroscopic methods. The permeability of the main constituents was evaluated using human Caco-2 cell monolayer as a model system.


RESULTS
Three unusual sesquiterpenes having 1-indanone nucleus (1, 3 and 4) and an unusual orthoester spiropyranosyl derivative of protocatechuic acid (2) were isolated from the rhizomes of Cibotium barometz. Among these, the bilateral permeation of 1, 3 and 4 in Caco-2 model was examined. The apparent permeability coefficients (P(app)) of 1 was identical with those of propranolol, which is often used as reference standard of high permeability. The P(app) values of 3 and 4 were in agreement with those of atenolol, which is often used as reference standard of poor permeability. The permeation rates of 1, 3 and 4 increased linearly as a function of time up to 180 min and with the concentration within the test range of 25-200 microM.


CONCLUSIONS
This is the first report on the presence of compounds 2 and 3 in this plant and 4 was a new compound. Compound 1 is assigned for a well-absorbed, and 2 and 3 are assigned for the poorly absorbed compounds in human intestine. A passive diffusion mechanism for transport of 1, 3 and 4 in Caco-2 model was proposed. The results provided some useful information for predicting the oral bioavailability of 1, 3 and 4.
Wu
Qi
Q
State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China.
Yang
Xiu-Wei
XW
D001692:Biological Transport; D018938:Caco-2 Cells; D002138:Calibration; D002463:Cell Membrane Permeability; D002681:China; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification; D018517:Plant Roots / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry; D012015:Reference Standards; D012717:Sesquiterpenes / Q000737:chemistry; D013997:Time Factors
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D012717:Sesquiterpenes