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Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.

ABSTRACT: Porcine reproductive and respiratory syndrome (PRRS) is an epidemic animal infectious disease worldwide. In our previous research it was suggested that matrine could inhibit PRRSV infection both in vitro and in vivo, but the antiviral mechanisms are still undecided. Network pharmacology can well solve the difficult problem of "multiple targets, multiple pathways" in the research of TCM action targets. The results of network pharmacology indicated that matrine exerts its anti-PRRSV effect by targeting HSPA8 and HSP90AB1. The results of real-time fluorescent quantitative PCR and western blot showed that infection with PRRSV induced a significant increase in the expression of HSPA8 and HSP90AB1 whereas matrine treatment could significantly reverse it, and the number of viruses of PRRSV also decreased. In this study, the method of network pharmacology was used to explore HSPA8 and HSP90AB1 which were the potential targets of matrine against PRRSV on Marc-145 cells.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC10064242 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.

Zhao Yaxiang Y Ling Xiaoya X Zhang Hua H Sun Panpan P Sun Yaogui Y Yin Wei W Fan Kuohai K Yang Huizhen H Zhong Jia J Zhang Zhenbiao Z Wang Jianzhong J Li Hongquan H Sun Na N

iScience 20230310 4

Porcine reproductive and respiratory syndrome (PRRS) is an epidemic animal infectious disease worldwide. In our previous research it was suggested that matrine could inhibit PRRSV infection both <i>in vitro</i> and <i>in vivo</i>, but the antiviral mechanisms are still undecided. Network pharmacology can well solve the difficult problem of "multiple targets, multiple pathways" in the research of TCM action targets. The results of network pharmacology indicated that matrine exerts its anti-PRRSV ...[more]

PMID: 37009229

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Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a long-term respiratory disorder marked by restricted airflow and persistent respiratory symptoms. According to previous studies, icariin combined with nobiletin (I&N) significantly ameliorates COPD, but the therapeutic mechanisms remain unclear.PurposeThe aim of the study is to investigate the therapeutic mechanisms of I&N against COPD using network pharmacology and experimental validation.MethodsThe targets of I&N and related genes of COPD were screened and their intersection was selected. Next, the protein-protein interaction (PPI) networks, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Further, a COPD rat model was established to validate the effect and mechanisms of I&N.Results445 potential targets I&N were obtained from SwissTargetPrediction, STITCH 5.0, and PharmMapper databases. 1831 related genes of COPD were obtained from GeneCards, DrugBank, and DisGeNet databases. 189 related genes were screened via matching COPD targets with I&N. 16 highest score targets among 189 targets were obtained according to PPI networks. GO and KEGG pathway enrichment analyses of 16 highest score targets suggested that these key genes of I&N were mostly enriched in the tumor necrosis factor (TNF) pathway, mitogen-activated protein kinase (MAPK) pathway, and phosphatidyl inositol 3-kinase (PI3K)-protein kinase B (AKT) pathway. Therefore, the treatments of I&N for COPD were connected with inflammation-related pathways. In in vivo experiments, the studies indicated that I&N improved the lung function and alleviated the damage of pulmonary histopathology. Moreover, I&N reduced levels of interleukin (IL)-6, IL-1β, and TNF-α in lung tissues of COPD rats and inhibited the activation of the MAPK pathway and PI3K-Akt pathway.ConclusionsIcariin combined with nobiletin has therapeutic effects on COPD by inhibiting inflammation. The potential mechanisms of I&N may relate to the MAPK pathway and PI3K-Akt pathway.

Project description: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.

Project description:BackgroundMatrine has been reported inhibitory effects on ovarian cancer (OC) cell progression, development, and apoptosis. However, the molecular targets of matrine against OC and the underlying mechanisms of action remain elusive.ObjectiveThis study endeavors to unveil the potential targets of matrine against OC and to explore the intricate relationships between these targets and the pathogenesis of OC.MethodsThe effects of matrine on the OC cells (A2780 and AKOV3) viability, apoptosis, migration, and invasion was investigated through CCK-8, flow cytometry, wound healing, and Transwell analyses, respectively. Next, Matrine-related targets, OC-related genes, and ribonucleic acid (RNA) sequence data were harnessed from publicly available databases. Differentially expressed analyses, protein-protein interaction (PPI) network, and Venn diagram were involved to unravel the core targets of matrine against OC. Leveraging the GEPIA database, we further validated the expression levels of these core targets between OC cases and controls. Mendelian randomization (MR) study was implemented to delve into potential causal associations between core targets and OC. The AutoDock software was used for molecular docking, and its results were further validated using RT-qPCR in OC cell lines.ResultsMatrine reduced the cell viability, migration, invasion and increased the cell apoptosis of A2780 and AKOV3 cells (P< 0.01). A PPI network with 578 interactions among 105 candidate targets was developed. Finally, six core targets (TP53, CCND1, STAT3, LI1B, VEGFA, and CCL2) were derived, among which five core targets (TP53, CCND1, LI1B, VEGFA, and CCL2) differential expressed in OC and control samples were further picked for MR analysis. The results revealed that CCND1 and TP53 were risk factors for OC. Molecular docking analysis demonstrated that matrine had good potential to bind to TP53, CCND1, and IL1B. Moreover, matrine reduced the expression of CCND1 and IL1B while elevating P53 expression in OC cell lines.ConclusionsWe identified six matrine-related targets against OC, offering novel insights into the molecular mechanisms underlying the therapeutic effects of matrine against OC. These findings provide valuable guidance for developing more efficient and targeted therapeutic approaches for treating OC.

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Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.

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Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.

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