大鼠小肠原位灌流与Caco-2细胞法研究柠檬苦素吸收机制

柠檬苦素广泛存在于柑橘类水果中, 具有抗菌、抗病毒、镇痛、抗炎和抗癌等活性, 但其口服生物利用度较低。本文意在研究柠檬苦素在肠道内的吸收机制, 为其今后的研究奠定基础。实验通过大鼠原位肠灌流和体外Caco-2细胞法进行。大鼠原位肠灌流结果显示, 柠檬苦素可能通过肠道促进扩散机制吸收, 吸收差且在全肠段都有吸收, 没有部位选择性。Caco-2细胞实验结果显示, 维拉帕米和酮康唑能显著提高柠檬苦素的吸收, 而丙磺舒的影响不明显。柠檬苦素吸收较低和生物利用度较差, 可能是P-gp外排以及CYP3A4代谢共同参与的结果。柠檬苦素的肠吸收机制研究将为其剂型设计和临床应用提供重要的参考。

Transport of limonin in rat intestine in situ and Caco-2 cells in vitro

Limonin existed in citrus fruits has been shown to have anti-bacterial, anti-viral, anti-feedant, anti-nociceptive, anti-inflammatory activities and anti-carcinogenic activities.  But the clinical use is limited by its low bioavailability.  The aim of this study is to observe the absorption and secretion transport mechanisms of limonin in intestine which can pave the way for the further study and clinical use.  The transport characteristics and mechanisms of limonin in rat were studied by in situ intestine perfusion and in vitro Caco-2 cells method.  The intestinal absorption of limonin was probably via a facilitated diffusion pathway which was poor and without segment-selection.  Verapamil and ketoconazole improved the absorption remarkably according to the result of in vitro Caco-2 cells study; however, probenecid had no significant effect on the absorption.  The P-gp efflux and CYP3A4 metabolism were involved in the poor intestinal absorption and low bioavailability of limonin.  The exploration of the intestinal absorption mechanism is crucial to the design of dosage form and clinical use of limonin.