Active components and potential mechanism of Taohong Siwu Decoction in regulating ischemic stroke based on target cell trapping combined with network pharmacology, molecular docking, and experimental validation.
10.19540/j.cnki.cjcmm.20230423.403
- Author:
Lin-Feng TANG
1
;
Hao CHANG
1
;
Dan-Dan WANG
2
;
Zhu-Qing LIU
1
;
Lan HAN
1
;
Dai-Yin PENG
3
Author Information
1. Anhui Provincial Key Laboratory of Modern Traditional Chinese Medicine, School of Pharmacy, Anhui University of Chinese Medicine Hefei 230012, China Anhui Provincial Key Laboratory of Traditional Chinese Medicine Compounds Hefei 230012, China.
2. Anhui Provincial Key Laboratory of Modern Traditional Chinese Medicine, School of Pharmacy, Anhui University of Chinese Medicine Hefei 230012, China.
3. Anhui Provincial Key Laboratory of Modern Traditional Chinese Medicine, School of Pharmacy, Anhui University of Chinese Medicine Hefei 230012, China Anhui Provincial Key Laboratory of Traditional Chinese Medicine Compounds Hefei 230012, China Xin'an Key Laboratory of Medicine, Ministry of Education Hefei 230012, China.
- Publication Type:Journal Article
- Keywords:
Taohong Siwu Decoction;
UPLC-Q-TOF-MS;
ischemic stroke;
network pharmacology;
target cell trapping
- MeSH:
Animals;
Rats;
Ischemic Stroke/drug therapy*;
Molecular Docking Simulation;
Network Pharmacology;
Endothelial Cells;
Phosphatidylinositol 3-Kinases;
Drugs, Chinese Herbal/pharmacology*
- From:
China Journal of Chinese Materia Medica
2023;48(17):4761-4773
- CountryChina
- Language:Chinese
-
Abstract:
The potential anti-stroke active components in Taohong Siwu Decoction(THSWD) were identified by target cell trapping coupled with ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of active components in THSWD in the treatment of ischemic stroke(IS) was explored by network pharmacology, molecular docking, and experimental validation. The UPLC-Q-TOF-MS technology combined with the UNIFI data analysis platform was used to analyze the composition of the cellular fragmentation fluid after co-incubation of THSWD with target cells. The targets of potential active components and IS were collected by network pharmacology, and the common targets underwent protein-protein interaction(PPI), Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analyses. The target cell trapping component-core target-signaling pathway network was constructed, and the active components were molecularly docked to the top targets in the PPI network, followed by pharmacodynamic validation in vitro. Fifteen active components were identified in the target cellular fragmentation fluid, including bicyclic monoterpenes, cyanoglycosides, flavonols, quinoid chalcones, phenylpropanoids, and tannins. As revealed by the analysis of network pharmacology, THSWD presumably regulated PI3K-AKT, FoxO, MAPK, Jak-STAT, VEGF, HIF-1, and other signaling pathways to affect inflammatory cascade reaction, angiogenesis, oxidative stress, pyroptosis, apoptosis, and other pathological processes via paeoniflorin, butylphthalide, dehydrated safflower yellow B, 3,4-dicaffeoylquinic acid, amygdalin, paeoniflorin, and ligusticolactone. Molecular docking and in vitro pharmacodynamic validation revealed that the target cell trapping active components could promote neovascularization in rat brain microvascular endothelial cells(rBMECs) in the oxygen-glucose deprivation/reoxygenation(OGD/R) model. The application of target cell trapping coupled with UPLC-Q-TOF-MS technology can rapidly screen out the potential active components in THSWD. The active components of THSWD can be predicted to intervene in the pathogenesis of IS through network pharmacology, and molecular docking combined with experimental validation can further clarify the efficacy, thus providing a theoretical basis for research ideas on the pharmacodynamic substance basis of traditional Chinese medicine compounds.
