Intestinal permeability of sesquiterpenes in the caco-2 cell monolayer model.
The intestinal permeability of eight sesquiterpenes which are active constituents of some traditional Chinese medicines, were studied by using the Caco-2 cell monolayer; they include tanacetin, artesin, magnolialide, crossostephin, atractylon, isocalamenediol (ICL), bisabolangelone (BSE) and (3 R)-des- O-methyllasiodiplodin (DML). The bidirectional permeability of the eight sesquiterpenes was studied from the apical (AP) side to the basolateral (BL) side or from the BL side to the AP side. The eight compounds were assayed by HPLC. Transport parameters and apparent permeability coefficients ( P(app)) were then calculated. The bidirectional P(app) values of the eight compounds were compared with those of propranolol, a marker of high permeability and transcellular transport. The transport of the eight sesquiterpenes was concentration-dependent in the range of 10-200 microM. Lower recoveries of ICL, BSE and DML than other sesquiterpenes were found during transport. The results indicated that all the sesquiterpenes are well absorbed mainly by the passive diffusion via the transcellular pathway and metabolism may be involved during the absorption of ICL, BSE and DML.
Wu
Qi
Q
State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, PR China.
Zhao
Bo
B
Yang
Xiu-Wei
XW
Xu
Wei
W
Zhang
Peng
P
Zou
Lei
L
Zhang
Lian-Xue
LX
D001692:Biological Transport; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D011433:Propranolol; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000493:pharmacokinetics*
D004365:Drugs, Chinese Herbal; D012717:Sesquiterpenes; D011433:Propranolol