Author:
Ye Qiuli,Zhang Ying,Yan Donghui,Sun Yue,Li Ming,Cao Hui,Wang Shumei,Meng Jiang
Abstract
Abstract
Background
Raw Moutan Cortex (RMC) has been used in China and other Asian countries for thousands of years. Its medical application is the treatment of cooling blood and promoting blood circulation. However, its therapeutic mechanism is still undefined.
Methods
In this study, the pharmacokinetics strategy that integrated network analysis was employed to explore the mechanism of RMC in blood-heat and blood stasis syndrome (BHS) model rats. Firstly, Ultra-High performance Liquid Chromatography coupled with Diode Array Detector (UHPLC-DAD) method was developed to determine nine absorbed compounds in rat serum in BHS and normal rats after oral administration of RMC extract respectively. Then the pharmacology network was established based on the relationship between nine compounds absorbed into the blood and BHS targets. Finally, the predicted hub targets were validated experimentally in human umbilical vein endothelial cells (HUVECs).
Results
Pharmacokinetic study showed that the pharmacokinetic parameters of nine absorbed compounds had significant differences between BHS and normal groups (p < 0.05). Network analysis showed that 8 target genes, namely, F2, F10, F7, PLAU, MAPK14, MAPK10, AKT1, and NOS3 may be the primary targets regulated by RMC for the treatment of BHS. Among them, targets (F2, F10, F7 and MAPK14, MAPK10, AKT) and 4 active ingredients (paeonol, paeoniflorin, quercetin and oxypaeoniflorin) were selected for evaluating the reliability in vitro experiments, which revealed that the mechanism of RMC against BHS syndrome may inhibit inflammatory pathways and regulate coagulation cascades pathway for cooling and promoting blood circulation.
Conclusion
The proposed pharmacokinetics study integrated network analysis strategy provides a combination method to explore the therapeutic mechanism of RMC on BHS.
Graphical Abstract
Funder
National Natural Science Foundation of China
the innovation project of Guangdong Province
Guangzhou science and technology planning project
Publisher
Springer Science and Business Media LLC
Subject
Complementary and alternative medicine,Pharmacology
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