1. Intestinal absorption of pallidifloside D are limited by P-glycoprotein in mice
- Author
-
Jiu-Xing Yan, Jun Zhang, Pi-Yong Hou, Ming-Yu Wang, Xiu-Bo Chen, Xiao-Hui Wu, Hong-Gang Li, Ming Yang, and Yan-Wen Zhang
- Subjects
Male ,medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,ATPase ,Administration, Oral ,Biological Availability ,Ileum ,Pharmacology ,Toxicology ,Models, Biological ,030226 pharmacology & pharmacy ,Biochemistry ,Intestinal absorption ,Substrate Specificity ,Jejunum ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Oral administration ,Internal medicine ,medicine ,Animals ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Intestinal Mucosa ,P-glycoprotein ,biology ,digestive, oral, and skin physiology ,General Medicine ,Saponins ,Small intestine ,Perfusion ,medicine.anatomical_structure ,Endocrinology ,Intestinal Absorption ,030220 oncology & carcinogenesis ,Cyclosporine ,biology.protein ,Duodenum - Abstract
1. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be very effective in hyperuricemic control. But it is poorly bioavailable after oral administration. Here, we determined the role of P-glycoprotein (P-gp) in the intestinal absorption of Pallidifloside D.2. We found that Pallidifloside D significantly stimulated P-gp ATPase activity in vitro ATPase assay with a small EC50 value of 0.46 µM.3. In the single-pass perfused mouse intestine model, the absorption of Pallidifloside D was not favored in the small intestine (duodenum, jejunum and ileum) with a P*w value of 0.35–0.78. By contrast, this compound was well absorbed in the colon with a P*w value of 1.23. The P-gp inhibitors cyclosporine significantly enhanced Pallidifloside D absorption in all four intestinal segments (duodenum, jejunum, ileum and colon) and the fold change ranged from 5.5 to 15.3. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of P...
- Published
- 2017