[Studies on predict of absorption of corynanthine, yohimbine, ajmalicine and ajmaline across human intestinal epithelial by using human Caco-2 cells monolayers].
OBJECTIVE
To predict the absorption of corynanthine (COR), yohimbine (YOH), ajmalicine (AMC) and ajmaline (AML) as chemical constituents of some traditional Chinese medicines in human intestinal epithelial.


METHODS
By using Caco-2 (the human colonic adenocarcinoma cell lines) cell monolayers as a human intestinal epithelial cell model, the permeability of COR, YOH, AMC and AML were studied from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. The four alkaloids were measured by high performance liquid chromatography (HPLC) coupled with UV detector. Transport parameters and apty) and atenolol (a control substance of poor permeability). The relationship between P(app) and log D values of four alkaloids was investigated by using drugs ADMET predict software.


RESULTS
The P(app) values of COR, YOH, AMC and AML were (1.863 +/- 0.055) x 10(-5), (1.540 +/- 0.082) x 10(-5), (2.522 +/- 0.246) x 10(-5) and (1.155 +/- 0.099) x 10(-5) cm x s(-1) from AP side to BL side, and (2.390 +/- 0.017) x 10(-5), (1.987 +/- 0.154) x 10(-5), (1.374 +/- 0.260) x 10(-5) and (2.418 +/- 0.124) x 10(-5) cm x s(-1) from BL side to AP side, respectively, which P(app) values were identical with that of propranolol [(2.23 +/- 0.10) x 10(-5) cm x s(-1) from AP to BL side]. The ratio of P(app B --> A)/P(app A -->B) of COR, YOH, AMC and AML were 1.28, 1.29, 0.54 and 2.09, respectively, which suggested that the efflux transport of AML was 2.09 times higher more than its influx transport.


CONCLUSIONS
COR, YOH, AMC and AML can be transported and absorbed across the human Caco-2 cells monolayers, and they belong to completely absorbed compounds. AML may have been involved in efflux mechanism in Caco-2 cells monolayers model from the BL to AP side direction. The oil-water partition coefficient play key roles in the transport and absorption of the four alkaloids.
Ma
Lian
L
State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Yang
Xiu-Wei
XW
D000404:Ajmaline / Q000378:metabolism*; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D015394:Molecular Structure; D046948:Secologanin Tryptamine Alkaloids / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism*
D046948:Secologanin Tryptamine Alkaloids; D000404:Ajmaline; D015016:Yohimbine; C005709:raubasine