芍药苷类化合物在人源肠Caco-2细胞单层模型中的吸收转运研究  

Absorption and transport characteristic of paeoniflorin and its derivatives in model of Caco-2 cell monolayers

作　　者：杨秀伟[1] 郭洁[1] 徐嵬[1] 

机构地区：[1]北京大学天然药物及仿生药物国家重点实验室北京大学药学院天然药物学系,北京100191

出　　处：《中草药》2013年第15期2097-2104,共8页Chinese Traditional and Herbal Drugs

基　　金："十二五"国家科技支撑计划资助项目(2011BAI07B08)

摘　　要：目的研究芍药苷、羟基芍药苷、苯甲酰芍药苷、四乙酰芍药苷、五乙酰芍药苷和五乙酰芍药内酯苷在人源结肠腺癌细胞系Caco-2细胞单层模型中的吸收特性。方法利用Caco-2细胞单层模型检测上述6个化合物从孔板顶端(AP)→底端(BL)、BL→AP的双向转运过程。应用偶联紫外检测器的HPLC法测定上述6个化合物,计算转运参数和表观渗透系数(Papp),并与阳性对照药普萘洛尔和阿替洛尔进行比较。结果芍药苷双向转运的Papp值与阿替洛尔的Papp值皆在10 7cm/s数量级;其他5个化合物的Papp值介于在Caco-2细胞单层模型中吸收良好的普萘洛尔与难以吸收的阿替洛尔的Papp值之间。芍药苷、羟基芍药苷、苯甲酰芍药苷浓度为10～200μmol/L,四乙酰芍药苷和五乙酰芍药内酯苷浓度为10～150μmol/L,五乙酰芍药苷浓度为10～100μmol/L时,其转运效率与浓度呈正相关。结论 6个受试化合物可以通过小肠上皮细胞被动吸收进入体内,芍药苷属于难吸收的化合物,羟基芍药苷、苯甲酰芍药苷、四乙酰芍药苷、五乙酰芍药苷和五乙酰芍药内酯苷属于中等吸收的化合物;苯甲酰芍药苷具有促进阿替洛尔在Caco-2细胞单层模型吸收转运的作用。Objective To study the absorption and transport characteristic of paeoniflorin （PF）, oxypaeoniflorin （OP）, benzoylpaeoniflorin （BP）, tetraacetylpaeoniflorin （TP）, pentaacetylpaeoniflorin （PP）, and pentacacetylalbiflorin （PA） in human colon adenocarcinoma cell line Caco-2 cell monolayer model. Methods The Caco-2 cell monolayers were used as an intestinal epithelial cell model. The permeability of the tested compounds from apical （AP） side to basolateral （BL） side or from BL side to AP side was evaluated. The concentration of the tested compounds was measured by HPLC coupled with UV detector. The transport parameters and apparent permeability coefficients （Papp） were calculated, and the Papp values were compared with the reported values for model compounds, Propranolol and AtenoloL Results The Papp values of PF in the bi-directional transport and atenolol were at the quantitative degree of 10-7 cm/s. Whereas those of OP, BP, TP, PP, and PA were between atenolol and propranolol used as a controt substance for low and high permeability, respectively. The absorption and transport of the tested compounds were concentration-dependent at the concentration range of 10--200 μmol/L for PF, OP, and BP, 10-- 150 I.tmol/L for TP and PA, and 10-- 100 μmol/L for PP. Conclusion The six tested compounds could be absorbed across the intestinal epithelial cells by passive diffusion mechanism. PF is poorly absorbed compound and OP, BP, TP, PP, and PA are moderately absorbed compounds. BP has a role to promote atenolol uptake transporters in Caco-2 cell monolayer model.

关 键 词：芍药苷 羟基芍药苷 苯甲酰芍药苷 四乙酰基芍药苷 五乙酰基芍药苷 五乙酰基芍药内酯苷 CACO-2细胞单层 表观渗透系数 

分 类 号：R282.710.5[医药卫生—中药学]