Li Shuai, Wang Yuanhong, Jiang Tingfu, Wang Han, Yang Shuang, Lv Zhihua
Marine Drug and Food Institute, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Mar Drugs. 2016 Jun 17;14(6):114. doi: 10.3390/md14060114.
The present study is focused on the intestinal absorption of sea cucumber saponins. We determined the pharmacokinetic characteristics and bioavailability of Echinoside A and Holotoxin A₁; the findings indicated that the bioavailability of Holotoxin A₁ was lower than Echinoside A. We inferred that the differences in chemical structure between compounds was a factor that explained their different characteristics of transport across the intestine. In order to confirm the absorption characteristics of Echinoside A and Holotoxin A₁, we examined their transport across Caco-2 cell monolayer and effective permeability by single-pass intestinal perfusion. The results of Caco-2 cell model indicate that Echinoside A is transported by passive diffusion, and not influenced by the exocytosis of P-glycoprotein (P-gp, expressed in the apical side of Caco-2 monolayers as the classic inhibitor). The intestinal perfusion also demonstrated well the absorption of Echinoside A and poor absorption of Holotoxin A₁, which matched up with the result of the Caco-2 cell model. The results demonstrated our conjecture and provides fundamental information on the relationship between the chemical structure of these sea cucumber saponins and their absorption characteristics, and we believe that our findings build a foundation for the further metabolism study of sea cucumber saponins and contribute to the further clinical research of saponins.
本研究聚焦于海参皂苷的肠道吸收。我们测定了海参素A和海参毒素A₁的药代动力学特征及生物利用度;结果表明,海参毒素A₁的生物利用度低于海参素A。我们推断化合物之间化学结构的差异是解释它们在肠道转运特性不同的一个因素。为了确认海参素A和海参毒素A₁的吸收特征,我们通过Caco-2细胞单层转运实验和单通道肠道灌注实验检测了它们的有效渗透率。Caco-2细胞模型的结果表明,海参素A通过被动扩散转运,且不受P-糖蛋白(P-gp,作为经典抑制剂表达于Caco-2单层细胞的顶端侧)胞吐作用的影响。肠道灌注实验也很好地证明了海参素A的吸收以及海参毒素A₁的吸收较差,这与Caco-2细胞模型的结果相符。这些结果证实了我们的推测,并提供了关于这些海参皂苷化学结构与其吸收特征之间关系的基础信息,我们相信我们的发现为海参皂苷的进一步代谢研究奠定了基础,并有助于皂苷的进一步临床研究。