Dataset Information

Systematic Elucidation of the Potential Mechanism of Erzhi Pill against Drug-Induced Liver Injury via Network Pharmacology Approach.

ABSTRACT: Objective:The purpose of this work was to investigate the bioactive compounds, core genes, and pharmacological mechanisms and to provide a further research orientation of Erzhi pill (EZP) on drug-induced liver injury (DILI). Methods:At first, we collected information of bioactive compounds of EZP from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and previous studies. And then, the targets related to bioactive compounds and DILI were obtained from 4 public databases. At last, Cytoscape was used to establish a visual network. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and network analysis were performed to investigate potential mechanism of EZP against DILI. Results:A total of 23 bioactive compounds and 89 major proteins of EZP were screened out as potential players against DILI. Association for bioactive compounds, core targets, and related pathways was analyzed, implying that core targets related to these pathways are ALB, AKT1, MAPK1, EGFR, SRC, MAPK8, IGF1, CASP3, HSP90AA1, and MMP9, and potential mechanisms of EZP acting on DILI are closely related to negative regulation of apoptosis process, improvement of lipid metabolism, and positive regulation of liver regeneration process. Conclusion:This study demonstrated the multicompound, multitarget, and multichannel characteristics of EZP, which provided a novel approach for further research the mechanism of EZP in the treatment of DILI.

SUBMITTER: Huang SJ

PROVIDER: S-EPMC6970004 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Systematic Elucidation of the Potential Mechanism of Erzhi Pill against Drug-Induced Liver Injury via Network Pharmacology Approach.

Huang Shao-Jie SJ Mu Fei F Li Fei F Wang Wen-Jun WJ Zhang Wei W Lei Lu L Ma Yang Y Wang Jing-Wen JW

Evidence-based complementary and alternative medicine : eCAM 20200107

<h4>Objective</h4>The purpose of this work was to investigate the bioactive compounds, core genes, and pharmacological mechanisms and to provide a further research orientation of Erzhi pill (EZP) on drug-induced liver injury (DILI).<h4>Methods</h4>At first, we collected information of bioactive compounds of EZP from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and previous studies. And then, the targets related to bioactive compounds and DILI were obta ...[more]

PMID: 31998398

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Project description:BackgroundKeyin pill (KP), a patented medicine in China, is used to treat psoriasis. However, KP has been reported to have liver toxicity, but its toxic substance basis and underlying mechanisms remain unclear. Therefore, this study aimed to explore the pharmacological mechanisms and components of KP-induced liver injury through animal experiments, UPLC-QTOF/MS combined with network pharmacology.MethodsFirstly, based on the immune stress mouse model, liver function parameters and hematoxylin-eosin (H&E) staining were detected to investigate KP-induced liver injury. The UPLC-QTOF/MS method was used to identify the components of KP. CTD database and literature mining were further applied to screen nonliver protective components. Subsequently, the nonliver protective components and their corresponding targets and targets of hepatotoxicity were analyzed by the method of network pharmacology. Finally, key targets from networked pharmacology were examined by the enzyme-linked immunosorbent assay (ELISA) and molecular docking.ResultsOur results indicated that KP had hepatotoxicity in male Kunming mice, which could favor hepatocyte necrosis and infiltration of inflammatory cells. A total of 70 nonliver protective compounds were identified and screened. The results of network pharmacology illustrated that methoxsalen, obacunone, limonin, and dictamnine might be the main compounds that caused liver damage. The potential hepatotoxicity mechanisms of KP might be through the IL17 and apoptosis pathways to regulate IL6, TNFα, CASP3, and CASP8 targets, thereby causing inflammation, excessive release of factors, and hepatocyte necrosis. The results of the ELISA experiments indicated that KP could increase the release of IL6 and TNFα inflammatory factors in liver tissues. Molecular docking suggested that methoxsalen, obacunone, limonin, and dictamnine had moderate binding ability with CASP3 and CASP8.ConclusionIn this study, the material basis and potential pharmacological mechanisms of KP-induced liver injury were preliminarily explored. Our research provides the initial theoretical basis for reducing the toxicity of KP.

Project description:This study aimed to investigate the active composition and mechanism of the Shuganfang (SGF) in treating drug-induced liver injury (DILI) using network pharmacology and molecular docking. The potential active ingredients and targets of SGF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. DILI-related targets were queried from various databases including GEO, GeneCards, OMIM, NCBI, and DisGeNET. The STRING database was used to establish a protein-protein interaction (PPI) network. DAVID was utilized for conducting gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The data visualization and analysis of herb-ingredient-target and disease-pathway-target-ingredient networks were conducted using Cytoscape software (version 3.7.2). PyMoL and AutoDock software was used to select the best binding target for molecular docking. A total of 177 active ingredients,126 targets and 10112 disease targets were obtained, including 122 intersection targets. The identified potential active ingredients consisted of quercetin, kaempferol, luteolin, tanshinone IIa, nobiletin, isorhamnetin, beta-sitosterol and naringenin. The core targets implicated in the study were IL6, estrogen receptor 1 (ESR1), hypoxia-inducible factor alpha subunit 1 (HIF1A), MYC and vascular endothelial growth factor A (VEGFA). KEGG analysis revealed that the treatment of DILI with SGF mainly acted through apoptosis, the PI3K-Akt signaling pathway, and the tumor necrosis factor (TNF) signaling pathway. Furthermore, the binding affinities between the potential ingredients and the core targets were subsequently confirmed through molecular docking experiments. The findings indicated that the docking outcomes remained consistent and demonstrated a favorable capacity for binding. SGF exerts a therapeutic effect on DILI through multiple active ingredients, multiple targets and multiple pathways. Our findings contribute to a positive investigation and establish a theoretical basis for further extensive exploration of SGF as a potential treatment for DILI in future research.

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Project description:Background: Paeoniflorin (PF), the major active compound isolated from the roots of Paeonia lactiflora Pall., has been used in the treatment of severe hepatic diseases for several decades and displays bright prospects in liver protective effect. However, its biological mechanism that regulates bile acid metabolism and cholestatic liver injury has not been fully elucidated. Our study aims to investigate the mechanism by which PF in the treatment of cholestatic liver injury using a comprehensive approach combining metabolomics and network pharmacological analysis. Methods: The hepatoprotective effect of PF against cholestasis liver injury, induced by α-naphthylisothiocyanate (ANIT), was evaluated in rats. The serum biochemical indices including ALT, AST, TBA, TBIL, ALP, ALB, and the pathological characteristics of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to explore the feces of rats with ANIT-induced cholestatic liver injury treated with PF and the potential biomarkers were screened by metabolomics. The targets for the regulation of potential biomarkers by PF were screened by network pharmacology, and then the relevant key targets were verified by immunohistochemical and western blotting methods. Results: PF significantly improved serum indexes and alleviated liver histological damage. Metabolomics analyses showed that the therapeutic effect of PF is mainly associated with the regulation of 13 metabolites involved in 16 metabolic pathways. The "PF-targets-metabolites" interaction network was constructed, and then five key targets including CDC25B, CYP2C9, MAOB, mTOR, and ABCB1 that regulated the potential biomarkers were obtained. The above five targets were further verified by immunohistochemistry and western blotting, and the results showed that PF significantly improved the expression of key proteins regulating these biomarkers. Conclusion: Our study provides direct evidence for the modulatory properties of PF treatment on ANIT-induced cholestatic liver injury using metabolomics and network pharmacology analyses. PF exhibits favorable pharmacological effect by regulating related signal pathways and key targets for biomarkers. Therefore, these findings may help better understand the complex mechanisms and provide a new and effective approach to the treatment of cholestatic liver injury.

Dataset Information

Systematic Elucidation of the Potential Mechanism of Erzhi Pill against Drug-Induced Liver Injury via Network Pharmacology Approach.

Publications

Systematic Elucidation of the Potential Mechanism of Erzhi Pill against Drug-Induced Liver Injury via Network Pharmacology Approach.

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