目的研究紫花前胡苷元(NANI)、紫花前胡苷(ND)、前胡苷V(DEV)和羌活苷(FDE)4个线型二氢呋喃香豆素类化合物在人源肠Caco-2细胞单层模型中的吸收特性.方法利用人源结肠腺癌细胞系Caco-2细胞单层模型测试4个香豆素类化合物从绒毛面(AP端)到基底面(BL端)、BL端到AP端2个方向的转运过程.应用偶联紫外检测器的高效液相色谱法对上述4个香豆素进行定量分析,计算转运参数和表观渗透系数(P_app),并与阳性对照药普萘洛尔和阿替洛尔进行比较.结果NANI双向转运的P_app值在1×10^-6cm/s数量级,介于在Caco-2细胞单层模型上呈良好吸收的普萘洛尔和难吸收的阿替洛尔的P_app值之间.ND、DEV和FDE的P_app值与阿替洛尔的P_app值皆在1×10^-7cm/s数量级.4个香豆素在25~400μmol/L的转运效率与浓度呈正相关.结论4个线型二氢呋喃类香豆素可以通过小肠上皮细胞被动吸收进入体内,NANI属于中等吸收的化合物;ND、DEV和FDE属于难吸收的化合物.

Objective To study the absorption and transportation characteristic of nodakenetin(NANI),nodakenin(ND),decuroside V(DEV),and forbeso-side[6'-O-(trans-feruloyl)-nodakenin,FDE] isolated from Rhizome et Radix Notopterygii,which were classified four linear dihydrofurocoumarins, in human intestinal epithelium.Methods Caco-2(the human colon adenocarcinoma cell lines)cell monolayers were used as an intestinal epith-elial cell model.The permeability of the four coumarins from apical side(AP side)to basolateral side(BL side)or from BL side to AP side was evaluated.The concentration of the four coumarins was measured by HPLC coupled with UV detector.Transportation parameters and permeabi-lity coefficients(P_app)were then calculated,and P_app values were compared with the reported values for model compounds, propranolol,and atenolol.Results The P_app values of NANI in the bi-directional transportation were quantitative degree of 1×10^-6cm/s,which laid between propranolol often used as a control substance for high permeability and Atenolol often used as a control substance for poor permeability.Whereas P_app values of ND,DEV,and FDE were quantitative degree of 1×10^-7cm/s, which was comparable with the P_appvalues of atenolol.The absorption and transportation of four coumarins were positive correlation to the concentration of 25-400 μmol/L.Conclusion Four linear dihydrofurocoumarins can be absorbed across intestinal epithelial cells by passive diffusion mechanism.The NANI is moderately,while ND,DEV,and FDE are poorly absorbed compounds

国家自然科学基金资助项目(30672609);“十一五”国家科技支撑计划项目(2006BAI06A01-02);天然药物及仿生药物国家重点实验室开放课题资助项目