Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of Deng-Zhan-Xi-Xin injection in the treatment of ischemic stroke

Zhao, Jing; Lv, Chao; Wu, Qirui; Zeng, Hua‐Wu; Guo, Xin; Yang, Jian; Tian, Sai; Zhang, Weidong

doi:10.1016/j.phrs.2019.104365

Cited by 71 publications

(46 citation statements)

References 49 publications

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“…e topological analysis was further carried out on the nodes in the C-T network of CSCC using the calculations of Cytoscape's NetworkAnalyzer tool on the main topological features (degree, betweenness centrality, average shortest-path length, and closeness centrality) [27,28]. A major C-T network of CSCC was established with node degrees higher than an average node degree value of 5.022; the detailed information is shown in Figure 3(b).…”

Section: Network Topological Analysismentioning

confidence: 99%

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

Ding

Chen

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Ulcerative colitis (UC) has multifactorial pathogenesis that acts synergistically, such as immune system dysregulation and expansion of infectious gut microbiota. Therefore, a multicomponent treatment derived from Chinese herbal medicine that interacts with multiple targets synergistically is needed. Composite sophora colon-soluble capsule (CSCC) is a Chinese herbal formula that has shown therapeutic efficacy against UC in randomized clinical trials. However, its bioactive components and potential target genes against UC remain unclear. Here, we used a network pharmacology approach to detect component-target-pathway interactions of CSCC against UC. A total of 29 gene targets, 91 bioactive components, and 20 enriched pathways of CSCC were identified. The IL-17 signaling pathway activated by infectious gastrointestinal microbes and predicted by the network analysis to be a major pathway modulated by CSCC against UC was studied in a dextran sulfate sodium-induced colitis model. CSCC showed remarkable efficacy against UC with respect to the attenuation of colon length, body weight loss, and disease activity index through gut microbiota recovery and intestinal immune homeostasis. The rectal administration of CSCC reduced the numbers of Th17 cells isolated from both mesenteric lymph nodes and lamina propria mononuclear cells and the levels of IL-17A, IL-6, IL-1β, and TNF-α. Additionally, the percentage of Treg cells and the levels of their hallmark cytokines were upregulated. Rectal administration of CSCC led to microbiota regulation with a significant correlation between suppression of Verrucomicrobiaceae and Ruminococcaceae, as well as the elevation of Lactobacillaceae, and CSCC administration via microbiome correlation heatmaps and cooccurrence network analysis at multiple time points. Thus, our study presents an effective herbal formula, CSCC, for UC treatment and explores its components and mechanisms of efficacy through the examination of gut microbiota and hallmark cytokines in the IL-17 pathway.

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Section: Network Topological Analysismentioning

confidence: 99%

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

Ding

Chen

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…The mean plasma concentration-time profiles of the ten analytes after intravenous administration of DZXXI: chlorogenic acid (1); neochlorogenic acid (2); cryptochlorogenic acid (3); 1,3-O-dicaffeoylquinic acid (4); erigeside I (5); scutellarin (6); isochlorogenic acid B (7); isochlorogenic acid A (8); apigenin-7-O-glucuronide (9); isochlorogenic acid C (10) F I G U R E 5 Pharmacokinetic parameters of chlorogenic acid (3-CQA), neochlorogenic acid (5-CQA), cryptochlorogenic acid (4-CQA), 1,3-O-dicaffeoylquinic acid (1,3-diCQA), erigeside I, scutellarin, isochlorogenic acid B (3,4-diCQA), isochlorogenic acid A (3,5-diCQA), apigenin-7-O-glucuronide (apigenin-7-O-gluA), and isochlorogenic acid C (4,5-diCQA) in sham and MCAO rats after intravenous administration of DZXXI (mean ± SD, n = 6). *P < 0.05 compared with the sham group; **P < 0.01 compared with the sham group…”

Section: F I G U R Ementioning

confidence: 99%

A sensitive ultra‐fast liquid chromatography with tandem mass spectrometry method for simultaneous determination of ten constituents of Deng‐Zhan‐Xi‐Xin injection in rat plasma and its application to a comparative pharmacokinetic study in sham and middle cerebral artery occlusion rats

Guo

Lin

Liang

et al. 2020

J of Separation Science

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Deng-Zhan-Xi-Xin injection is widely used to treat cerebrovascular and cardiovascular diseases in clinical practice. A rapid and selective method based on ultra-fast liquid chromatography with tandem mass spectrometry was established and validated to simultaneously quantify chlorogenic acid, 1,3-Odicaffeoylquinic acid, isochlorogenic acid A, neochlorogenic acid, erigeside I, cryptochlorogenic acid, apigenin-7-O-glucuronide, scutellarin, isochlorogenic acid B, and isochlorogenic acid C of Deng-Zhan-Xi-Xin injection in both sham and middle cerebral artery occlusion rats. This was the first quantitative analysis of these ten constituents in both sham and middle cerebral artery occlusion rats. Chromatographic separation of these ten constituents was accomplished on an Acquity HSS T3 column with the mobile phase consisting of acetonitrile and 0.1% formic acid in water. Mass analysis was performed in negative ion mode with an electrospray ionization source using multiple reaction monitoring technology. The pharmacokinetic study of the ten constituents in sham and middle cerebral artery occlusion rats after intravenous administration of Deng-Zhan-Xi-Xin injection was successfully accomplished by using this validated method. Based on the results of pharmacokinetic parameters, significant differences were observed between the two groups, which might be due to the pathological factors of middle cerebral artery occlusion and pharmacological effects of Deng-Zhan-Xi-Xin injection.

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“…The application of systematic biological methods to determine the pharmacological action, mechanism, and safety of TCM are of great value to the research and development of modern TCM. It has been widely applied in the research on the mechanism of TCM treatment of complex diseases, such as ischemic stroke, cancer, chronic atrophic gastritis, type 2 diabetes, and cardiovascular disease [6,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Quan¹,

Miao²

2020

Preprint

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Background: Dilated cardiomyopathy (DCM) is a non-ischaemic cardiac muscle disease with structural and functional myocardial aberration can lead to extensive morbidity and mortality due to complications in particular heart failure and arrhythmia. Two classic Chinese medicine formulas, Shenfu decoction and Linguizhugan decoction, were both shown to exert therapeutic effects on heart disease. Thus, modified Shenfu and Linguizhugan decoction (SFLGZGD) is recommended for treatment DCM. However, its chemical and pharmacological characteristics remain to be elucidated. In the current study, a network pharmacology approach was applied to characterize the action mechanism and target genes of SFLGZGD on DCM.Methods: The gene expression of DCM was obtained from the Gene Expression Omnibus (GEO). All compounds were obtained from the correlative databases, and active mixture were selected according to their oral bioavailability (OB) and drug-likeness (DL) index. The potential targets of SFLGZGD were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database. The compound-target and target-pathway networks were constructed. The protein-protein interactive (PPI) network generated by R software was visualized by Cytoscape, and the topology scores, functional regions, and gene annotations were analyzed using plugins of Bisogenet and CytoNCA. The potential pathways related to target genes were determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.Results: A total of 963 differentially expressed genes (DEGs), including 538 upregulated genes and 425 downregulated, were obtained from GSE19303. A total of 636 ingredients in SFLGZGD were obtained, among which, 93 were chosen as bioactive components. The compound-target network included 10 bioactive components and 18 potential targets and a total of 1939 genes obtained in the PPI network, among them, a total of 16 genes were screened out. Moreover,129 terms on the GO analysis and six pathways obtained. Among these potential targets, EGFR, CDKN1A, MMP1, COL1A1, COL3A1, MMP3, ICAM1, and HSPB1 were identified as relatively high-degree targets.Conclusions: The network pharmacology-based approach in the current study has shown promising potential in identifying major therapeutic targets from TCM formulations. Besides, our study suggested that network pharmacology prediction may provide a useful tool for describing the molecular mechanism of SFLGZGD on DCM.

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Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of Deng-Zhan-Xi-Xin injection in the treatment of ischemic stroke

Cited by 71 publications

References 49 publications

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

A sensitive ultra‐fast liquid chromatography with tandem mass spectrometry method for simultaneous determination of ten constituents of Deng‐Zhan‐Xi‐Xin injection in rat plasma and its application to a comparative pharmacokinetic study in sham and middle cerebral artery occlusion rats

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

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