Tian Xiao-Juan, Yang Xiu-Wei, Yang Xiaoda, Wang Kui
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
Int J Pharm. 2009 Feb 9;367(1-2):58-64. doi: 10.1016/j.ijpharm.2008.09.023. Epub 2008 Sep 21.
To investigate the structure-permeability relationship of dietary/nutriceutic flavonoids, the transepithelial transport and cellular uptake of 36 flavonoids (including flavones, flavonols, dihydroflavones, dihydroflavonols, isoflavones, chalcones, flavanes, flavanols, methylated and glycosidic derivatives) were investigated using the Caco-2 cell monolayer. The apparent permeability coefficients (P(app)) of the flavonoids were calculated from bilateral transport assays in the Transwell system with flavonoid determination using a high performance liquid chromatography (HPLC) coupled with a UV detector. The most flavonoids exhibited concentration-independent P(app) values and a ratio of 0.5-1.8 for P(app AB to BL)/P(app BL to AB), suggesting passive diffusion pathways. However, certain flavonoids e.g. morin and some flavonoid glycosides may involve the efflux mechanisms. For isoflavones, flavones, and dihydroflavones, the oil/water partition coefficients (additionally modified by the number and position of the three hydroxyl groups) was the key determinant for Caco-2 cell permeation. However, the permeability of flavonols is more complex with their structure possibly related to their high rate of cell accumulation. Overall, the parental skeleton structure, the number and position of free hydroxyl groups, accumulation and efflux in Caco-2 cell play the key roles in the transport of flavonoids across Caco-2 cell monolayer.
为研究膳食/营养类黄酮的结构-渗透性之间的关系，利用Caco-2细胞单层模型研究了36种黄酮类化合物（包括黄酮、黄酮醇、二氢黄酮、二氢黄酮醇、异黄酮、查耳酮、黄烷、黄烷醇、甲基化和糖苷衍生物）的跨上皮转运和细胞摄取情况。黄酮类化合物的表观渗透系数（P(app)）通过Transwell系统中的双向转运实验计算得出，采用高效液相色谱（HPLC）结合紫外检测器测定黄酮类化合物。大多数黄酮类化合物表现出与浓度无关的P(app)值，且P(app AB至BL)/P(app BL至AB)的比值为0.5 - 1.8，表明其通过被动扩散途径。然而，某些黄酮类化合物，如桑色素和一些黄酮糖苷可能涉及外排机制。对于异黄酮、黄酮和二氢黄酮，油/水分配系数（另外由三个羟基的数量和位置进行修正）是决定其在Caco-2细胞中渗透的关键因素。然而，黄酮醇的渗透性更为复杂，其结构可能与其在细胞中的高积累率有关。总体而言，母体骨架结构、游离羟基的数量和位置、在Caco-2细胞中的积累和外排在黄酮类化合物跨Caco-2细胞单层转运中起关键作用。
