Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques

Qi-mei YANG; Ming-hao ZHOU; Peng-jiao WANG; Si-yuan CAO; Shuo ZHANG; Sheng-gang YANG; Min ZHANG; Xiu-li GAO

doi:10.13422/j.cnki.syfjx.20211447

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Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques

更新时间：2021-10-21

- Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 22, Pages: 131-138(2021)
- 作者机构：
  
  贵州医科大学药用植物功效与利用国家重点实验室，药学院，微生物与生化药学工程中心，实验动物中心，贵阳 550025
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211447
  CLC： R857.3;R969.1;R28;O657
- Received：23 February 2021，
  
  Published Online：08 April 2021，
  
  Published：20 November 2021
- 稿件说明：
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杨七妹,周明皓,王鹏娇等.基于UPLC-MS/MS和分子对接技术考察聚乙二醇400对黄芩苷药代动力学、抗炎作用的影响[J].中国实验方剂学杂志,2021,27(22):131-138.

YANG Qi-mei,ZHOU Ming-hao,WANG Peng-jiao,et al.Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(22):131-138.
杨七妹,周明皓,王鹏娇等.基于UPLC-MS/MS和分子对接技术考察聚乙二醇400对黄芩苷药代动力学、抗炎作用的影响[J].中国实验方剂学杂志,2021,27(22):131-138. DOI： 10.13422/j.cnki.syfjx.20211447.

YANG Qi-mei,ZHOU Ming-hao,WANG Peng-jiao,et al.Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(22):131-138. DOI： 10.13422/j.cnki.syfjx.20211447.

摘要

目的

考察药用辅料聚乙二醇400（PEG400）对黄芩苷药代动力学及抗炎作用的影响，利用分子对接技术初步探讨黄芩苷及其主要代谢物黄芩素6-

-葡萄糖醛酸苷（B6G）的抗炎作用。

方法

大鼠随机分为2组，分别以水和PEG400为溶解基质，给大鼠灌胃相等剂量的黄芩苷水溶液（黄芩苷+水组）与黄芩苷PEG400溶液（黄芩苷+PEG400组），不同时间段血浆样品经处理后，利用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定大鼠血浆中黄芩苷及其主要代谢物B6G的浓度，运用DAS 3.2.2软件处理药代动力学参数；将小鼠随机分为空白组（生理盐水，20 mL·kg

-1

），阿司匹林组（0.2 g·kg

-1

），黄芩苷/黄芩苷+PEG400高、低剂量（3.0，1.5 g·kg

-1

）组，连续给药7 d，建立小鼠耳肿胀及足肿胀模型，计算肿胀度及肿胀抑制率。

结果

药代动力学研究结果显示，与黄芩苷+水组相比，大鼠灌胃黄芩苷PEG400溶液后黄芩苷及B6G的血药浓度增加，药时曲线下面积（AUC

）分别提高了2.36，1.97倍，药峰浓度（

max

）分别提高了2.12，1.65倍；小鼠耳肿胀和足肿胀炎症模型结果表明，小鼠灌胃黄芩苷PEG400溶液后抗炎效果增强。此外，分子对接结果表明黄芩苷与B6G可以与多靶点蛋白［肿瘤坏死因子（TNF）-

，白细胞介素（IL）-6，IL-1

，前列腺素E

（PGE

），核转录因子-

B（NF-

B）］位点结合，具有较高亲和力，且优于阳性药阿司匹林。

结论

PEG400可提高黄芩苷及其主要代谢物B6G的血药浓度，且抗炎效果增强，黄芩苷与B6G可以与多种炎症因子及核转录因子靶点蛋白形成较强的氢键，推测黄芩苷及B6G共同发挥了抗炎作用。

Abstract

Objective

To investigate the effects of polyethylene glycol 400 （PEG400） on the pharmacokinetics and anti-inflammatory effect of baicalin， and to preliminarily explore the anti-inflammatory effects of baicalin and its main metabolite baicalein 6-

-glucuronide （B6G） by molecular docking.

Method

Rats were randomly divided into two groups with water and PEG400 as the dissolving matrix， and rats were administrated the equal dose of baicalin aqueous solution （baicalin+water group） and baicalin PEG400 solution （baicalin+PEG400 group）. After the plasma samples were processed at different time periods， the concentrations of baicalin and B6G in rat plasma were determined by ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and pharmacokinetic parameters were processed by DAS 3.2.2 software. Mice were randomly divided into a blank group （normal saline， 20 mL·kg

-1

）， aspirin group （dose of 0.2 g·kg

-1

）， baicalin/baicalin+PEG400 high and low dose （3.0， 1.5 g·kg

-1

） groups， after continuous administration for 7 days， the mouse ear swelling and foot swelling models were established， and the swelling degree and swelling inhibition rate were calculated.

Result

The pharmacokinetic study showed that compared with baicalin+water group， the plasma concentrations of baicalin and B6G increased after administration of baicalin PEG400 solution， and the area under the curve （AUC

） increased by 2.36， 1.97 times， and the peak concentration （

max

） increased by 2.12， 1.65 times， respectively. The results of mouse ear and foot swelling inflammation models showed that the anti-inflammatory effect was enhanced after intragastric administration of baicalin PEG400 solution. In addition， molecular docking results showed that baicalin and B6G could site bind to multiple target proteins ［tumor necrosis factor （TNF）-

， interleukin （IL）-6， IL-1

， prostaglandin E

（PGE

） and nuclear transcription factor-

B （NF-

B）］ with higher affinity， which was superior to the positive drug aspirin.

Conclusion

PEG400 can increase the plasma concentration of baicalin and its main metabolite B6G， and enhance the anti-inflammatory effect. Baicalin and B6G can form strong hydrogen bonds with various inflammatory factors and of nuclear transcription factors， it is speculated that baicalin and B6G jointly play an anti-inflammatory role.

关键词

Keywords

references

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