羌活中二氢呋喃类香豆素在人源肠Caco-2细胞单层模型的吸收转运研究

Absorption and transportation characteristic of dihydrofurocoumarins from Rhizome et Radix Notopterygii in a model of Caco-2 cell monolayers

目的研究紫花前胡苷元（NAN1）、紫花前胡苷（ND）、前胡苷V（DEV）和羌活苷（FDE）4个线型二氢呋哺香豆素类化合物存人源肠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潜法对上述4个香豆素进行定量分析，计算转运参数和表观渗透系数（Papp），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Papp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荼洛尔和难吸收的阿替洛尔的Papp值之间。ND、DEV和FDE的Papp值与阿替洛尔的Papp值皆在1×10^7cm／s数量级。4个香豆素在25～100μmol／L的转运效率与浓度呈正相关。结论4个线型二氢呋哺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 forbesoside [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 epithelial cell model. The permeability of the four coumarins from apical side （AP side） to basolateralside （BL side） or from BL side to AP side was evaluated. Theconcen tration of the four eoumarins was measured by HPI.C coupled with UV detector. Transportation parameters and permeability coefficients （Papp） were then calculated, and Papp values were compared with the reported values for model compounds, propranolol, and atenolol. Results The P values of NANI in the bi-directional transportation were quantitative degree of 1×10^6 cm/s, which laid between propranololoften used as a control substance for high permeability and Atenolol often used as a control substance for poor permeability. Whereas Papp values of ND, DEV, and FDE were quantitative degree of 1 × 10^ 7 cm/s, which was comparable with the Papp values 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. TheNANI is moderately, while ND, I）EV, and FDE are poorly absorbed compounds.