Key Laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi University of TCM, Nanchang 330004, China.
J Ethnopharmacol. 2013 Nov 25;150(2):553-9. doi: 10.1016/j.jep.2013.09.011. Epub 2013 Sep 25.
Angelicae Dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav combined with Radix Scutellariae baicalensis Georgi has been widely used in traditional Chinese medicine (TCM) as an antipyretic analgesic and anti-inflammatory drug. Modern pharmacological studies have demonstrated that the compatible application of these two drugs is an effective treatment for hepatitis. A previous study indicated that a Radix Angelicae Dahuricae extract enhanced the intestinal absorption of the baicalin found in Radix Scutellariae; however, the underlying compatibility mechanism of these two herbs remains unknown. In this study, we further examined the effect of a Radix Angelicae Dahuricae extract on the absorption and transport properties of baicalin in a Caco-2 cell model to determine the compatibility mechanism of these two herbs.
The aim of this work was to study the transport properties of baicalin in Radix Scutellariae across cell membranes and the effects of a Radix Angelicae Dahuricae extract on baicalin absorption using the well-characterized, human-based intestinal Caco-2 cell model.
We assessed the absorption, bidirectional transport and toxicity of baicalin using a range of parameters, including drug concentration, pH, a P-glycoprotein (P-gp) inhibitor (Verapamil), an MRP inhibitor (MK-571) and EDTA-Na2 (tight junction modulator). Next, we studied the influence of a Radix Angelicae Dahuricae extract on the transport of baicalin under the same conditions. Drug concentration was measured by HPLC, and the apparent permeability coefficient (Papp) and apparent permeability ratio (PDR) were subsequently calculated.
The results showed that baicalin is non-toxic within a concentration range of 800 µg/mL to 4800 µg/mL. The transport of baicalin showed time and concentration dependence. The absorption of baicalin was optimal at pH 7.4 in 37 °C; however, the absorption decreased at 4 °C. The Papp of baicalin transport through the Caco-2 cell monolayer model was altered when specific inhibitors of P-gp or MRP were added to the cells. However, there was no significant difference in the PDR value. The Papp of baicalin improved when it was combined with the Radix Angelicae Dahuricae extract. The influence of EDTA-Na2 on the transport of baicalin showed that the permeability of baicalin significantly increased. The result further indicated that the mechanism of baicalin intestinal absorption in the Caco-2 cell monolayer involves passive transcellular diffusion.
Passive diffusion is the main mode of intestinal absorption of bacalin and it involved in the efflux of proteins. The enhanced intestinal absorption of baicalin by Radix Angelicae Dahuricae can be due to opening of the tight junctions between cells and inhibition of MRP efflux protein expression or function.
白芷（Hoffm.）Benth. 和 Hook. f. ex Franch. 和 Sav 与黄芩根的组合在中药（TCM）中被广泛用作解热镇痛药和抗炎药。现代药理学研究表明，这两种药物的联合应用是治疗肝炎的有效方法。先前的研究表明，白芷提取物增强了黄芩中的黄芩苷在肠道中的吸收；然而，这两种草药的潜在配伍机制尚不清楚。在这项研究中，我们进一步研究了白芷提取物对 Caco-2 细胞模型中黄芩苷吸收和转运特性的影响，以确定这两种草药的配伍机制。
本工作旨在使用经过充分表征的人源肠 Caco-2 细胞模型，研究黄芩苷穿过细胞膜的转运特性以及白芷提取物对黄芩苷吸收的影响。
我们使用一系列参数评估黄芩苷的吸收、双向转运和毒性，包括药物浓度、pH 值、P-糖蛋白（P-gp）抑制剂（维拉帕米）、多药耐药相关蛋白（MRP）抑制剂（MK-571）和 EDTA-Na2（紧密连接调节剂）。接下来，我们在相同条件下研究了白芷提取物对黄芩苷转运的影响。通过 HPLC 测量药物浓度，随后计算表观渗透系数（Papp）和表观渗透比（PDR）。
结果表明，黄芩苷在 800μg/mL 至 4800μg/mL 的浓度范围内是无毒的。黄芩苷的转运呈现时间和浓度依赖性。在 37°C 时，黄芩苷的吸收在 pH7.4 时最佳，但在 4°C 时吸收减少。当向细胞中加入 P-gp 或 MRP 的特定抑制剂时，黄芩苷通过 Caco-2 细胞单层模型的转运 Papp 发生改变。然而，PDR 值没有显著差异。当与白芷提取物结合时，黄芩苷的 Papp 得到改善。EDTA-Na2 对黄芩苷转运的影响表明，黄芩苷的通透性显著增加。结果进一步表明，黄芩苷在 Caco-2 细胞单层中的肠吸收机制涉及被动跨细胞扩散。
黄芩苷的肠吸收主要是通过被动扩散，涉及到蛋白质的外排。白芷能增强黄芩苷的肠道吸收，这可能是由于细胞间紧密连接的开放以及抑制 MRP 外排蛋白的表达或功能。
