Deng Gai-Gai, Xu Wei, Yang Xiu-Wei
State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Beijing 100191, China.
Zhongguo Zhong Yao Za Zhi. 2021 Apr;46(8):2094-2103. doi: 10.19540/j.cnki.cjcmm.20201228.301.
The absorption is the key to the resulted efficacy of orally administered drugs and the small intestine is the main site to absorb the orally administered drug. In this paper, internationally recognized human colon adenocarcinoma cell line(Caco-2) monola-yer model which can simulate small intestinal epithelial cell was used to comparatively study the absorption and transportation diffe-rences of total coumarins and main individual coumarin in Angelica dahurica 'Yubaizhi' by separately using 6-and 12-well plates. It was found that apparent permeability coefficient(P_(app)) values of oxypeucedanin hydrate, byakangelicin and phellopterin were at the quantitative degree of 1 × 10(-5) cm·s(-1) when the individual administration was conducted independently, indicating that they were well-absorbed compounds. P_(app) ratio of their bi-directional transportation was close to 1, indicating that they can be absorbed across Caco-2 monolayer by passive diffusion mechanism without carrier mediation during the transportation. The similar trend of transportation was also observed for imperatorin, isoimperatorin and bergapten. The P_(app) values of oxypeucedanin hydrate, byakangelicin and bergapten were at quantitative degree of 1 × 10(-5) cm·s(-1) when the administration of total coumarins in Angelica dahurica 'Yubaizhi' was conducted, indicating that they were well-absorbed compounds. The results were consistent with those of independent administration of individual coumarins. Whereas, the P_(app) values of imperatorin, phellopterin and isoimperatorin in the total coumarins decreased, indicating that the interaction between compounds may exist although the P_(app) value ratio of bi-directional transportation was between 0.5 and 1.5. The results laid the foundation for intestinal absorption study of Angelica dahurica 'Yubaizhi' coumarins in compound Chinese medicine.
吸收是口服给药药物产生疗效的关键,而小肠是口服药物吸收的主要部位。本文采用国际公认的可模拟小肠上皮细胞的人结肠腺癌细胞系(Caco-2)单层模型,分别使用6孔板和12孔板,比较研究了白芷“禹白芷”中总香豆素及主要单体香豆素的吸收和转运差异。结果发现,当单独给药时,水合氧化前胡素、白当归素和异补骨脂素的表观渗透系数(P_(app))值处于1×10(-5) cm·s(-1) 的数量级,表明它们是吸收良好的化合物。其双向转运的P_(app) 比值接近1,表明它们在转运过程中可通过被动扩散机制跨Caco-2单层吸收,无需载体介导。欧前胡素、异欧前胡素和补骨脂素也观察到类似的转运趋势。当给予白芷“禹白芷”总香豆素时,水合氧化前胡素、白当归素和补骨脂素的P_(app) 值处于1×10(-5) cm·s(-1) 的数量级,表明它们是吸收良好的化合物。结果与单独给予单体香豆素的结果一致。然而,总香豆素中欧前胡素、异补骨脂素和异欧前胡素的P_(app) 值降低,表明尽管双向转运的P_(app) 值比值在0.5至1.5之间,但化合物之间可能存在相互作用。该结果为复方中药中白芷“禹白芷”香豆素的肠道吸收研究奠定了基础。