黄连-甘草药对的药代动力学不相容性。
Pharmacokinetic incompatibility of the Huanglian-Gancao herb pair.
机构信息
Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Road 1200, Shanghai, 201203, China.
出版信息
BMC Complement Med Ther. 2020 Feb 22;20(1):61. doi: 10.1186/s12906-020-2845-5.
BACKGROUND
Pharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao (Glycyrrhizae Radix et Rhizoma) and Huanglian (Coptidis Rhizoma) are commonly used traditional Chinese medicines (TCMs). In this study, the influence of Gancao on the pharmacokinetics of Huanglian was systematically studied by using berberine as a pharmacokinetic marker.
METHODS
Extracts of the herbal pieces of Huanglian and the herb pair (Huanglian plus Gancao) were prepared with boiling water. The concentration of berberine in the samples was analyzed using liquid chromatography-mass spectrometry. The total amounts of berberine in all extract samples were compared. Comparative pharmacokinetic studies of Huanglian and the herb pair were conducted in ICR mice. In vitro berberine absorption and efflux were studied using mice gut sacs. The equilibrium solubility of berberine in the extracts was determined. The in vitro dissolution of berberine was comparatively studied using a rotating basket method.
RESULTS
Gancao significantly reduced berberine exposure in the portal circulation (425.8 ng·h/mL vs. 270.4 ng·h/mL) and the liver (29,500.8 ng·h/mL vs. 15,422.4 ng·h/mL) of the mice. In addition, Gancao decreased the peak concentration (C) of berberine in the portal circulation (104.3 ng·h/mL vs. 76.5 ng·h/mL) and liver (4926.1 ng·h/mL vs. 2642.8 ng·h/mL) of mice. Significant influences of Gancao on the amount of berberine extracted (32% reduction), the solubility of berberine (34.7% compared with the control group), and dissolution (88.7% vs. 66.1% at 15 min in acid buffer and 68% vs. 51.8% at 15 min in phosphate buffer) were also revealed. Comparative pharmacokinetic studies in ICR mice indicated that the formation of sediment was unfavorable in terms of berberine absorption (345.3 ng·h/mL vs. 119.8 ng·h/mL).
CONCLUSIONS
Gancao was able to reduce intestinal absorption and in vivo exposure of berberine in Huanglian via the formation of sediment, which caused reductions in the extracted amount, solubility, and dissolution of berberine.
背景
药代动力学相互作用是评估草药相容性的最重要指标之一。甘草（Glycyrrhizae Radix et Rhizoma）和黄连（Coptidis Rhizoma）都是常用的中药。本研究采用黄连素作为药代动力学标志物，系统研究了甘草对黄连药代动力学的影响。
方法
用沸水制备黄连和药对（黄连加甘草）的草药片提取物。使用液相色谱-质谱法分析样品中黄连素的浓度。比较所有提取物样品中黄连素的总量。在 ICR 小鼠中进行黄连和药对的比较药代动力学研究。采用小鼠肠囊研究黄连素的体外吸收和外排。测定黄连素在提取物中的平衡溶解度。采用旋转篮法比较研究黄连素的体外溶解。
结果
甘草显著降低了门静脉循环（425.8ng·h/mL 比 270.4ng·h/mL）和肝脏（29500.8ng·h/mL 比 15422.4ng·h/mL）中黄连素的暴露量。此外，甘草降低了门静脉循环（104.3ng·h/mL 比 76.5ng·h/mL）和肝脏（4926.1ng·h/mL 比 2642.8ng·h/mL）中黄连素的峰浓度。甘草对黄连素提取量（减少 32%）、黄连素溶解度（与对照组相比减少 34.7%）和溶解（在酸性缓冲液中 15 分钟时为 88.7%，而在磷酸盐缓冲液中为 68%，在酸性缓冲液中 15 分钟时为 51.8%）也有显著影响。在 ICR 小鼠中的比较药代动力学研究表明，形成沉淀物不利于黄连素的吸收（345.3ng·h/mL 比 119.8ng·h/mL）。
结论
甘草通过形成沉淀物降低了黄连中黄连素的肠吸收和体内暴露，从而减少了黄连素的提取量、溶解度和溶解。
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