Dataset Information

Network Pharmacology-Based Investigation of Protective Mechanism of Aster tataricus on Lipopolysaccharide-Induced Acute Lung Injury.

ABSTRACT: Acute lung injury (ALI) is a common clinical condition that badly influences people's health. Recent studies indicated that Aster tataricus (RA) had potential effects on ALI, but the effective components and their mechanism is not clear. In this study, we found that the Fraction-75 eluted from RA extract could significantly protect the lipopolysaccharide (LPS)-induced ALI in mice, including alleviating the severity of lung pathology, attenuating the pulmonary edema, and reducing the release of inflammatory cells. Further ingredient analyses demonstrated that there were mainly 16 components in it, among which 10 components were collected according to their relative peak area and oral bioavailability. Next, the components-disease targets network suggested that the candidate components had extensive associations with 49 known therapeutic targets of ALI, among which 31 targets could be regulated by more than one component. Herein, GO functional and pathway analysis revealed that the common targets were associated with four biological processes, including the inflammatory response to stimulus, cellular process, chemokine biosynthetic process and immune system process. Furthermore, the ELISA validation indicated that the candidate components in RA extract may protect the LPS-induced ALI mainly through inhibiting the release of inflammatory cytokines and promoting the repair of vascular endothelial.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6387216 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Network Pharmacology-Based Investigation of Protective Mechanism of <i>Aster tataricus</i> on Lipopolysaccharide-Induced Acute Lung Injury.

Chen Yijun Y Dong Jiaojiao J Liu Jie J Xu Wenjuan W Wei Ziyi Z Li Yueting Y Wu Hao H Xiao Hongbin H

International journal of molecular sciences 20190128 3

Acute lung injury (ALI) is a common clinical condition that badly influences people's health. Recent studies indicated that <i>Aster tataricus</i> (RA) had potential effects on ALI, but the effective components and their mechanism is not clear. In this study, we found that the Fraction-75 eluted from RA extract could significantly protect the lipopolysaccharide (LPS)-induced ALI in mice, including alleviating the severity of lung pathology, attenuating the pulmonary edema, and reducing the relea ...[more]

PMID: 30696024

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Project description:BackgroundLeonurus japonicus Houtt has an obvious efficacy on cardiovascular diseases. As the most representative component in the herb, leonurine has attracted increasing attention for its potential in myocardial ischemia. However, its protective mechanism against myocardial ischemia remains incompletely elucidated.ObjectivesThe present study aimed to reveal the potential mechanism of leonurine in acute myocardial ischemia using a strategy combining metabolomics and network pharmacology.MethodsFirst, a metabolomics method was proposed to identify the differential metabolites of plasma in rats. Then, network pharmacology was performed to screen candidate targets of leonurine against acute myocardial ischemia. A compound-reaction-enzyme-gene network was thus constructed with the differential metabolites and targets. Finally, molecular docking was carried out to predict the binding capability of leonurine with key targets.ResultsA total of 32 differential metabolites were identified in rat plasma, and 16 hub genes were detected through network pharmacology. According to the results of compound-reaction-enzyme-gene network and molecular docking, what was screened included six key targets (GSR, CYP2C9, BCHE, GSTP1, TGM2, and PLA2G2A) and seven differential metabolites (glycerylphosphorylcholine, lysophosphatidylcholine, choline phosphate, linoleic acid, 13-HpODE, tryptophan and glutamate) with four important metabolic pathways involved: glycerophospholopid metabolism, linoleic acid metabolism, tryptophan metabolism and glutamate metabolism. Among them, glycerophospholipid and tryptophan metabolism were shown to be important, since the regulation of leonurine on these two pathways was also observed in our previous metabolomics study conducted on clinical hyperlipidemia patients.ConclusionThis is the first study of its kind to reveal the underlying mechanism of leonurine against acute myocardial ischemia through a strategy combining metabolomics and network pharmacology, which provides a valuable reference for the research on its future application.

Project description:Background: The beneficial effects of colchicine on cardiovascular disease have been widely reported in recent studies. Previous research demonstrated that colchicine has a certain protective effect on ischemic myocardium and has the potential to treat myocardial ischemia reperfusion injury (MIRI). However, the potential targets and pharmacological mechanism of colchicine to treat MIRI has not been reported. Methods: In this study, we used network pharmacology and experimental verification to investigate the pharmacological mechanisms of colchicine for the treatment of MIRI. Potential targets of colchicine and MIRI related genes were screened from public databases. The mechanism of colchicine in the treatment of MIRI was determined by protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Additionally, we evaluated the effect of colchicine on H9C2 cell activity using CCK-8 assays, observed the effect of colchicine on H9C2 cell apoptosis via flow cytometry, and further verified the expression of key targets after colchicine treated by Western blot. Results: A total of 626 target genes for colchicine and 1549 MIRI disease targets were obtained. 138 overlapping genes were determined as potential targets of colchicine in treating MIRI. the PPI network analysis demonstrated that the targets linked to MIRI were ALB, TNF, ACTB, AKT1, IL6, TP53, IL1B, CASP3 and these targets showed nice affinity with colchicine in molecular docking experiments. The results of GO analysis and KEGG pathway enrichment demonstrated that the anti-MIRI effect of colchicine involves in apoptotic signaling pathway. Further tests suggested that colchicine can protect H9C2 cell from Hypoxia/Reoxygenation (H/R) injury through anti-apoptotic effects. Western blot results demonstrated that colchicine can inhibited MIRI induced apoptosis of H9C2 cell by enhancing the decreased levels of Caspase-3 in myocardial injure model induced by H/R and activating the PI3K/AKT/eNOS pathway. Conclusions: we performed network pharmacology and experimental evaluation to reveal the pharmacological mechanism of colchicine against MIRI. The results from this study could provide a theoretical basis for the development and clinical application of colchicine.

Dataset Information

Network Pharmacology-Based Investigation of Protective Mechanism of Aster tataricus on Lipopolysaccharide-Induced Acute Lung Injury.

Publications

Network Pharmacology-Based Investigation of Protective Mechanism of <i>Aster tataricus</i> on Lipopolysaccharide-Induced Acute Lung Injury.

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