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柴胡皂苷d的体内外肠道吸收机制研究

邢媛月, 任偲琪, 刘奇玮, 杨晋妮, 董海娟, 宋瑞, 张尊建

邢媛月, 任偲琪, 刘奇玮, 杨晋妮, 董海娟, 宋瑞, 张尊建. 柴胡皂苷d的体内外肠道吸收机制研究[J]. 中国药科大学学报, 2022, 53(4): 473-480. DOI: 10.11665/j.issn.1000-5048.20220410
引用本文: 邢媛月, 任偲琪, 刘奇玮, 杨晋妮, 董海娟, 宋瑞, 张尊建. 柴胡皂苷d的体内外肠道吸收机制研究[J]. 中国药科大学学报, 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
Citation: 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

柴胡皂苷d的体内外肠道吸收机制研究

基金项目: 江苏省自然科学基金资助项目(No.BK20161456);江苏省药品监督管理局科研计划课题资助项目(No.202016);药物质量与安全预警教育部重点实验室开放课题资助项目(No.DQCP20/21PQ06)

Intestinal absorption mechanism of saikosaponin d in vitro and in vivo

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)
  • 摘要: 为揭示柴胡皂苷d(SSd)的体内外肠道吸收机制,采用Caco-2单层和大鼠在体单向肠灌流模型,研究了不同实验条件(时间、浓度、温度、pH、肠段)、转运蛋白抑制剂、细胞旁途径增强剂、代谢酶抑制剂等因素对SSd体内外肠道吸收的影响。研究结果表明,SSd的表观渗透系数(Papp)和有效渗透系数(Peff)分别为4.75 × 10-7 ~ 6.38 × 10-7 cm/s和0.19 × 10-4 ~ 0.27 × 10-4 cm/s,提示其属于低渗透性化合物,SSd的跨膜转运具有浓度(0.5 ~ 5 μmol/L)和时间(0 ~ 180 min)依赖性,回肠是其主要吸收部位;P-糖蛋白抑制剂和细胞旁途径增强剂均显著增强SSd的体内外吸收(P < 0.05);有机阴离子转运多肽(OATPs)抑制剂和有机阳离子转运蛋白(OCTs)抑制剂对SSd肠道吸收影响的体内外相关性较差,这可能与上述转运蛋白在空肠中表达量较低有关。本研究结果表明,SSd的肠道吸收涉及被动扩散、主动转运以及细胞旁通路途径等方式,P-糖蛋白在SSd的主动转运中发挥重要作用。
    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.
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出版历程
  • 收稿日期:  2022-04-10
  • 修回日期:  2022-06-07
  • 刊出日期:  2022-08-24

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