Intestinal absorption mechanism of saikosaponin d in vitro and in vivo
10.11665/j.issn.1000-5048.20220410
- VernacularTitle:柴胡皂苷d的体内外肠道吸收机制研究
- Author:
Yuanyue XING
1
;
Siqi REN
;
Qiwei LIU
;
Jinni YANG
;
Haijuan DONG
;
Rui SONG
;
Zunjian ZHANG
Author Information
1. 中国药科大学药物质量与安全预警教育部重点实验室
- Publication Type:Journal Article
- Keywords:
saikosaponin d;
absorption;
Caco-2 monolayers;
single pass perfusion model;
UPLC-MS/MS
- From:
Journal of China Pharmaceutical University
2022;53(4):473-480
- CountryChina
- Language:Chinese
-
Abstract:
In order to reveal the intestinal absorption mechanism of saikosaponin d (SSd) in vitro and in vivo, the current research investigated the effects of different experimental conditions (time, concentration, temperature, pH, intestinal segments), transporter inhibitors, paracellular pathway enhancer, metabolic enzyme inhibitors on the intestinal absorption of SSd, in Caco-2 monolayers and a single pass perfusion model in rats.The results showed that the apparent permeability coefficient (Papp) and effective permeability coefficient (Peff) of SSd were 4.75 × 10-7 - 6.38 × 10-7 cm/s and 0.19 × 10-4- 0.27 × 10-4 cm/s, respectively, indicating that it was a low permeability compound, and that the transmembrane transport of SSd was concentration-dependent (0.5-5 μmol/L) and time-dependent (0-180 min).Ileum was the main absorption site for SSd. Experimental results based on Caco-2 monolayers showed that the P-gp inhibitor and paracellular permeability enhancer significantly increased the absorption of SSd (P < 0.05), which was consistent with the results obtained in rats. Inhibitors of OATPs and OCTs showed different results in vitro and in vivo, which may be related to the lower expression of them in jejunum.In summary, the intestinal absorption of SSd occurs through a carrier-mediated and energy-dependent transport, as well as passive diffusion, and P-glycoprotein plays an important role in the active transport of SSd.
