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异黄酮对大鼠中主要环烯醚萜类药物代谢动力学特征的影响。

Isoflavones' effects on pharmacokinetic profiles of main iridoids from in rats.

作者信息

Chang Ruirui, Liu Jialin, Luo Yusha, Huang Taohong, Li Qiang, Wen Jun, Chen Weidong, Zhou Tingting

机构信息

School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.

School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230031, China.

出版信息

J Pharm Anal. 2020 Dec;10(6):571-580. doi: 10.1016/j.jpha.2019.11.004. Epub 2019 Nov 14.

Abstract

(GF) and Praeparatum (SSP) are both medicine food homologies and widely used in Chinese clinical prescriptions together. The research investigated the pharmacokinetics of four iridoids in normal rats and isolfavones-fed rats, which were administered with isolfavones from SSP for 7, 14, 21 and 28 consecutive days. A validated LC-MS/MS method was developed for determining shanzhiside, genipin-1-gentiobioside, geniposide and their metabolite genipin in rat plasma. Plasma samples were pretreated by solid-phase extraction using paeoniflorin as the internal standard. The chromatographic separation was performed on a Waters Atlantis T3 (4.6 mm × 150 mm, 3 μm) column using a gradient mobile phase consisting of acetonitril and water (containing 0.06% acetic acid). The mass detection was under the multiple reaction monitoring (MRM) mode via polarity switching between negative and positive ionization modes. The calibration curves exhibited good linearity ( > 0.997) for all components. The lower limit of quantitation was in the range of 1-10 ng/mL. The intra-day and inter-day precisions (RSD) at three different levels were both less than 12.2% and the accuracies (RE) ranged from -10.1% to 16.4%. The extraction recovery of them ranged from 53.8% to 99.7%. Pharmacokinetic results indicated the bioavailability of three iridoid glycosides and the metabolite, genipin in normal rats was higher than that in rats exposed to isoflavones. With the longer time of administration of isoflavones, plasma concentrations of iridoids decreased, while genipin sulfate, the phase Ⅱ metabolite of genposide and genipin-1-gentiobioside, appeared the rising exposure. The pharmacokinetic profiles of main iridoids from GF were altered by isoflavones.

摘要

(GF)和制备物(SSP)均为药食同源物质,在中国临床处方中共同广泛使用。该研究调查了正常大鼠和食用异黄酮大鼠中四种环烯醚萜苷的药代动力学,这些大鼠连续7、14、21和28天给予来自SSP的异黄酮。建立了一种经过验证的液相色谱-串联质谱(LC-MS/MS)方法,用于测定大鼠血浆中山栀苷、京尼平-1-龙胆双糖苷、栀子苷及其代谢产物京尼平。血浆样品以芍药苷为内标通过固相萃取进行预处理。色谱分离在Waters Atlantis T3(4.6 mm × 150 mm,3μm)柱上进行,使用由乙腈和水(含0.06%乙酸)组成的梯度流动相。质量检测在多反应监测(MRM)模式下通过正负离子模式之间的极性切换进行。所有成分的校准曲线均显示出良好的线性( > 0.997)。定量下限在1-10 ng/mL范围内。三个不同水平的日内和日间精密度(RSD)均小于12.2%,准确度(RE)范围为-10.1%至16.4%。它们的提取回收率在53.8%至99.7%之间。药代动力学结果表明,三种环烯醚萜苷及其代谢产物京尼平在正常大鼠中的生物利用度高于暴露于异黄酮的大鼠。随着异黄酮给药时间的延长,环烯醚萜苷的血浆浓度降低,而栀子苷和京尼平-1-龙胆双糖苷的Ⅱ相代谢产物硫酸京尼平的暴露量出现上升。来自GF的主要环烯醚萜苷的药代动力学特征被异黄酮改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84f9/7775847/34d3f059a058/fx1.jpg

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