Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques
10.13422/j.cnki.syfjx.20211447
- VernacularTitle: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
- Author:
Qi-mei YANG
1
;
Ming-hao ZHOU
1
;
Peng-jiao WANG
1
;
Si-yuan CAO
1
;
Shuo ZHANG
1
;
Sheng-gang YANG
1
;
Min ZHANG
1
;
Xiu-li GAO
1
Author Information
1. State Key Laboratory of Functions and Applications of Medicinal Plants，School of Pharmaceutical Sciences，Engineering Center of Microbiology and Biochemical Pharmacy，Experimental Animal Center，Guizhou Medical University，Guiyang 550025，China
- Publication Type:Research Article
- Keywords:
baicalin;
baicalein 6-O-β-D-glucuronide （B6G）;
polyethylene glycol 400 （PEG400）;
bioavailability;
anti-inflammatory;
molecular docking;
liquid chromatography-mass spectrometry technology
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(22):131-138
- CountryChina
- Language:Chinese
-
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-O-β-D-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 （AUC0-t） increased by 2.36， 1.97 times， and the peak concentration （Cmax） 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）-α， interleukin （IL）-6， IL-1β， prostaglandin E2 （PGE2） and nuclear transcription factor-κB （NF-κB）］ 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.
