苦参4种生物碱类有效成分生物药剂学分类及转运机制研究

Biopharmaceutical classification and transport mechanism of 4 alkaloids in Mongolian herbal medicine Sophorae Flavescentis Radix

该研究选择蒙药苦参的4种生物碱类有效成分(苦参碱、氧化苦参碱、槐定碱、氧化槐果碱)作为模型物质,研究其溶解性和渗透性,进一步采用Caco-2细胞模型评价其吸收和转运机制。结果发现苦参碱、氧化苦参碱、槐定碱和氧化槐果碱均属于高溶解性和高渗透性药物,吸收效果好,属于生物药剂学分类系统(biopharmaceutical classification system,BCS)之Ⅰ类药物;苦参碱和氧化苦参碱的细胞吸收(AP→BL侧)和细胞排泄(BL→AP侧)不受浓度影响,其吸收过程受P-gp蛋白介导;氧化槐果碱和槐定碱的单位时间转运量在AP→BL侧和BL→AP侧均与浓度和时间呈正相关,但其吸收过程不受P-gp蛋白介导,上述研究结果可进一步为中药(民族药)的传统方剂开发以及成药性评价提供科学依据。

In this study,we studied the solubility and permeability of matrine,oxymatrine,sophoridine,and oxysophocarpine,four alkaloids in the Mongolian herbal medicine Sophorae Flavescentis Radix,and evaluated the absorption mechanism with the Caco-2 cell model,so as to provide a basis for the new drug development and efficacy evaluation of Sophorae Flavescentis Radix.The results showed that all the four alkaloids had high solubility and high permeability and can be well absorbed,belonging to the class-I drugs of Biopharmaceutical Classification System(BCS).The absorption(AP→BL)and excretion(BL→AP)of matrine and oxymatrine were not affected by the concentration while the absorption depended on P-gp protein.The absorption(AP→BL)and excretion(BL→AP)of sophoridine and oxysophocarpine were positively related to the concentration and time,and the absorption process was independent from P-gp protein.The results provide scientific reference and an experimental basis for the development of Mongolian medical prescriptions containing Sophorae Flavescentis Radix.