[Absorption and transportation characteristics of scutellarin and scutellarein across Caco-2 monolayer model].
OBJECTIVE
To investigate the absorption and transepithelial transport characteristics of scutellarin and scutellarein in the human colonic adenocarcinoma cell (Caco-2) monolayer model. The influence factors on these two compounds' absorption were investigated, such as buffer solution, duration of culture, and inhibitors of multidrug resistance-associated protein 2 (MRP(2)), breast cancer drug resistance protein (BCRP) and P-glycoprotein (P-gp).


METHODS
By using Caco-2 monolayer as an intestinal epithelial cell model, the transport process was studied from apical (AP) side to basolateral (BL) side or from BL to AP. The two compounds were determined by high-performance liquid chromatography coupled with diode-array-detector detection. Transport parameters and apparent permeability coeffients (P(app)) were calculated.


RESULTS
The P(app) values of scutellarin and scutellarein were different in two buffer solutions, respectively. In phosphate buffered saline, scutellarin had no absorption from AP to BL, while its P(app) value was 0.74×10(-6) to 1.58×10(-6) cm/s from BL to AP. The P(app) values of scutellarein were 4.33×10(-6) to 6.79×10(-6) cm/s and 1.32×10(-6) to 2.56×10(-6) cm/s from AP to BL and from BL to AP, respectively. The P(app) value gradually decreased with time. The absorption of scutellarein was better than that of scutellarin. The scutellarin absorption was improved by verapamil, MK-571 and reserpine. The scutellarein absorption was improved by verapamil whereas its excretion was improved by MK-571.


CONCLUSIONS
Absorption of scutellarin is difficult in Caco-2 monolayer cells, which contributes to its low bioavailability. Scutellarein absorption is better than scutellarin absorption. Scutellarein transepithelial transport is passive diffusion. The inhibitor of P-gp can improve scutellarin and scutellarein transportation. The inhibitors of MRP(2) and BCRP can promote transportation of scutellarin. The inhibitor of MRP(2) can promote efflux of scutellarein. The multidrug resistance-associated protein may be the second reason for low bioavailability of scutellarin.
You
Hai-Sheng
HS
Department of Pharmacy, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Zhang
Hai-Feng
HF
Dong
Ya-Lin
YL
Chen
Si-Ying
SY
Wang
Mao-Yi
MY
Dong
Wei-Hua
WH
Xing
Jian-Feng
JF
D000230:Adenocarcinoma / Q000473:pathology*; D047310:Apigenin / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000473:pathology*; D005965:Glucuronates / Q000493:pharmacokinetics*; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2
C000715087:ABCC2 protein, human; D005965:Glucuronates; D000089762:Multidrug Resistance-Associated Protein 2; C484876:scutellarin; D047310:Apigenin; C458179:scutellarein