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盐制方法对口服厚朴提取物药代动力学及组织分布的影响

Effects of the Salt-Processing Method on the Pharmacokinetics and Tissue Distribution of Orally Administered How. Extract.

作者信息

Shi Ji, Ren Xiaohang, Wang Jia, Wei Xiaofeng, Liu Bonan, Jia Tianzhu

机构信息

School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.

出版信息

J Anal Methods Chem. 2020 Feb 11;2020:5754183. doi: 10.1155/2020/5754183. eCollection 2020.

Abstract

Salt processing, which involves steaming with salt water, directs herbs into the kidney channel. After being salt processed, kidney invigorating effects occur. However, the underlying mechanism of this method remains elusive. The compounds monotropein, rubiadin, and rubiadin 1-methyl ether are the major effective components of How. To clarify the pharmacokinetics and tissue distribution of these three compounds, we employed liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine the contents of the three components in rat plasma and tissues. Separation was achieved on an Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 m, Waters). Formic acid aqueous solution (0.1%; A) and acetonitrile (containing 0.1% formic acid; B) were used as the mobile phase system with a programmed elution of 0∼5 min with 70% A and then 5∼7 min with 60% A. All analytes were measured with optimized multiple reaction monitoring (MRM) in negative ion mode. Geniposide and 1,8-dihydroxyanthraquinone were used as the internal standards (IS). The linear ranges were 1.2∼190, 1.3∼510, and 0.047∼37.5 g/mL, respectively. Compared with the without wood (MO) group, the Cx and AUC parameters of rubiadin and rubiadin 1-methyl ether elevated remarkably for the salt-processed (SMO) groups, which indicates that steaming by salt could increase the bioavailability of rubiadin and rubiadin 1-methyl ether. The for monotropein is shorter (0.5 h) in SMO groups than that in MO group, which means that monotropein was quickly absorbed in the SMO extract. Moreover, the contents of three compounds in the small intestine were the highest.

摘要

盐制,即将药物与盐水共蒸,可引导药物入肾经。盐制后,药物产生补肾作用。然而,这种方法的潜在机制仍不清楚。山栀苷甲酯、茜草素和茜草素1 - 甲醚是山栀的主要有效成分。为阐明这三种化合物的药代动力学和组织分布,我们采用超高效液相色谱 - 串联质谱法(UPLC - MS/MS)测定大鼠血浆和组织中这三种成分的含量。采用Acquity UPLC HSS T3柱(100 mm × 2.1 mm,1.8 μm,Waters公司)进行分离。以0.1%甲酸水溶液(A)和含0.1%甲酸的乙腈(B)作为流动相系统,采用梯度洗脱,0~5分钟内A相为70%,然后5~7分钟内A相为60%。所有分析物均在负离子模式下采用优化的多反应监测(MRM)进行测定。栀子苷和1,8 - 二羟基蒽醌用作内标(IS)。线性范围分别为1.2~190、1.3~510和0.047~37.5 μg/mL。与无木山栀(MO)组相比,盐制山栀(SMO)组中茜草素和茜草素1 - 甲醚的Cmax和AUC参数显著升高,这表明盐蒸可提高茜草素和茜草素1 - 甲醚的生物利用度。SMO组中山栀苷甲酯的t1/2(0.5小时)比MO组短,这意味着山栀苷甲酯在SMO提取物中吸收较快。此外,三种化合物在小肠中的含量最高。

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