Intestinal absorption mechanism of saikosaponin d <i>in vitro </i>and<i> in vivo</i>

XING Yuanyue; REN Siqi; LIU Qiwei; YANG Jinni; DONG Haijuan; SONG Rui; ZHANG Zunjian

doi:10.11665/j.issn.1000-5048.20220410

Journal of China Pharmaceutical University > 2022 > 53(4): 473-480. > DOI: 10.11665/j.issn.1000-5048.20220410

XING Yuanyue, REN Siqi, LIU Qiwei, YANG Jinni, DONG Haijuan, SONG Rui, ZHANG Zunjian. Intestinal absorption mechanism of saikosaponin d in vitro and in vivo[J]. Journal of China Pharmaceutical University, 2022, 53(4): 473-480. DOI: 10.11665/j.issn.1000-5048.20220410

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Intestinal absorption mechanism of saikosaponin d in vitro and in vivo

1.
Key Laboratory of Drug Quality Control & Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009
2.
The Public Laboratory Platform of China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the Natural Science Foundation of Jiangsu Province (No. BK20161456), Jiangsu Provincial Drug Administration Scientific Research Program (No.202016) and the Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance (No.DQCP20/21PQ06)

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Received Date: April 10, 2022
Revised Date: June 07, 2022

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Abstract

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 (P_app) and effective permeability coefficient (P_eff) 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.
- saikosaponin d,
- absorption,
- Caco-2 monolayers,
- single pass perfusion model,
- UPLC-MS/MS

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References

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