摘要
目的:研究延胡索甲素(d-corydaline,CDL)和延胡索乙素(tetrahydropalmatine,THP)的人源肠内菌丛生物转化,在人源结肠腺癌细胞系Caco-2细胞单层模型的吸收转运。方法:应用人源肠内菌丛在厌氧、37℃条件下分别与CDL和THP共温孵培养;利用人源结肠腺癌细胞系Caco-2细胞单层模型测试CDL和THP从绒毛面(AP端)到基底面(BL端)、BL端到AP端双向的转运过程。计算转运参数和表观渗透系数(Papp),并与吸收良好的阳性对照药普萘洛尔和吸收不良的阿替洛尔进行比较。应用高效液相色谱法对CDL和THP进行分析。结果:CDL和THP在人源肠内菌丛温孵体系没有发生生物转化。它们与普萘洛尔在Caco-2细胞单层模型双向转运的Papp皆在1×10-5cm.s-1数量级;在0～180 min,转运效率与转运时间呈正相关。结论:CDL和THP在人源肠内菌丛温孵体系中稳定;在Caco-2细胞单层模型的转运机制可能为被动扩散。
Objective： To study the biotransformation by human intestinal flora, and the absorption and transportation charac- teristic in a model of human colon adenocarcinoma cell lines （ Caco-2 cell） monolayer of d-corydaline （CDL） and tetrahydropalmatine （THP）. Method： CDL or THP was incubated with crude enzymes of human intestinal flora under the anaerobic environment and 37 ℃ conditions to transform CDL or THP. Caco-2 eel1 monolayer was used as an intestinal epithelial cell model for determination of the per- meability of CDL or THP from apical side （ AP side） to basolateral side （ BL side） or from BL side to AP side. Transportation parame- ters and permeability coefficients （Papp） were then calculated, and Papp values were compared with the reported values for model com- pounds, propranolol as a well absorbed drug and atenolol as a poor absorbed drug. The concentration of CDL or THP was measured by HPLC coupled with photodiode array detector. Result： CDL or THP in the human intestinal flora incubation system did not happen bio- transformation. In the Caco-2 cell monolayer model, the Papp, magnitudes of both CDL and THP were 1 ×10^-5cm·s^-1 in the bi-di- reetional transport, which were identical with propranolol. And their transports were concentration dependent between 0-180 min. Con- clusion： Both CDL and THP may be stable in the human intestinal flora incubation system, and their absorption and transportation in the human Caco-2 cell monolayer model are mainly via passive diffusion mechanism.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2013年第1期112-118,共7页
China Journal of Chinese Materia Medica
基金
国家科技支撑计划项目(2012BAI29B02,2011BAI07B00)
国家“重大新药创制”科技重大专项(2009ZX09301-005-028)
国家自然科学基金重点项目(30830118)
