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Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A.

ABSTRACT: Background:As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered. Objective:To identify the potential therapeutic targets of biochanin A in treating osteosarcoma. Methods:In present study, an integrated approach including network pharmacology and molecular docking technique was conducted, which mainly comprises target prediction, network construction, gene ontology, and pathway enrichment. CCK8 test was employed to evaluate the cell viability of MG63 cells. Western-blot was used to verify the target proteins of biochanin A. Results:Ninety-six and 114 proteins were obtained as the targets of biochanin A and osteosarcoma, respectively. TP53, IGF1, JUN, BGLAP, ATM, MAPK1, ATF3, H2AFX, BAX, CDKN2A, and EGF were identified as the potential targets of biochanin A against osteosarcoma. Based on the western-blot detection, the expression of BGLAP, BAX, and ATF3 in MG63 cell line changed under the treatment of biochanin A. Conclusion:Biochanin A can effectively suppress the proliferation of osteosarcoma and regulate the expression of BGLAP, BAX, and ATF3, which may act as the potential therapeutic targets of osteosarcoma.

SUBMITTER: Luo Q

PROVIDER: S-EPMC6339762 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A.

Luo Qing Q Shi Xuan X Ding Jiarong J Ma Zhenzhen Z Chen Xumei X Leng Yuanxiu Y Zhang Xuhui X Liu Yang Y

Evidence-based complementary and alternative medicine : eCAM 20190106

<h4>Background</h4>As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered.<h4>O ...[more]

PMID: 30723510

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Project description:BackgroundThe Coronavirus disease 2019 pneumonia broke out in 2019 (COVID-19) and spread rapidly, which causes serious harm to the health of people and a huge economic burden around the world.PurposeIn this study, the network pharmacology, molecular docking and surface plasmon resonance technology (SPR) were used to explore the potential compounds and interaction mechanism in the Toujie Quwen Granules (TQG) for the treatment of coronavirus pneumonia 2019.Study designThe chemical constituents and compound targets of Lonicerae Japonicae Flos, Pseudostellariae Radix, Artemisia Annua L, Peucedani Radix, Forsythiae Fructus, Scutellariae Radix, Hedysarum Multijugum Maxim, Isatidis Folium, Radix Bupleuri, Fritiliariae Irrhosae Bulbus, Cicadae Periostracum, Poria Cocos Wolf, Pseudobulbus Cremastrae Seu Pleiones, Mume Fructus, Figwort Root and Fritillariae Thunbrgii Bulbus in TQG were searched. The target name was translated to gene name using the UniProt database and then the Chinese medicine-compound-target network was constructed. Protein-protein interaction network (PPI), Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the core targets were performed in the Metascape to predict its mechanism. The top 34 compounds in the Chinese medicine-compound-target network were docked with SARS-CoV-2 3CL enzyme and SARS--CoV--2 RNA-dependent RNA polymerase (RdRp) and then the 13 compounds with lowest affinity score were docked with angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 Spike protein and interleukin 6 to explore its interaction mechanism. Lastly, SPR experiments were done using the quercetin, astragaloside IV, rutin and isoquercitrin, which were screened from the Chinese medicine-compound-target network and molecular docking.ResultsThe Chinese medicine-compound-target network includes 16 medicinal materials, 111 compounds and 298 targets, in which the degree of PTGS2, TNF and IL-6 is higher compared with other targets and which are the disease target exactly. The result of GO function enrichment analysis included the response to the molecule of bacterial origin, positive regulation of cell death, apoptotic signaling pathway, cytokine-mediated signaling pathway, cytokine receptor binding and so on. KEGG pathway analysis enrichment revealed two pathways: signaling pathway- IL-17 and signaling pathway- TNF. The result of molecular docking showed that the affinity score of compounds including quercetin, isoquercitrin, astragaloside IV and rutin is higher than other compounds. In addition, the SPR experiments revealed that the quercetin and isoquercitrin were combined with SARS-CoV-2 Spike protein rather than Angiotensin-converting enzyme 2, while astragaloside IV and rutin were combined with ACE2 rather than SARS-CoV-2 Spike protein.ConclusionTQG may have therapeutic effects on COVID-19 by regulating viral infection, immune and inflammation related targets and pathways, in the way of multi-component, multi-target and multi-pathway.

Project description:BackgroundLegg-Calvé-Perthes disease is a special self-limited disease in pediatric orthopedics with a high disability rate and a long-term course, and there is still no clear and effective therapeutic drug in clinic. This study aimed to investigate the potential efficacy of biochanin A, a kind of oxygen-methylated isoflavone compound, in treating Perthes disease based on network pharmacology, molecular docking and in vitro experiments.MethodsIL-6 was used to stimulate human umbilical vein endothelial cells to construct endothelial cell dysfunction model. We demonstrated whether biochanin A could alleviate endothelial dysfunction through CCK8 assay, immunofluorescence. Targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. Targets of endothelial dysfunction were obtained from Genecards and OMIM databases. Protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomics analyses were used to analyze the potential target and the key pathway of the anti-endothelial dysfunction activity of biochanin A. To validate the potential target-drug interactions, molecular docking and molecular dynamics simulations were performed and the result was proved by western blot.ResultsIt was found that biochanin A can promote the expression of ZO-1, reduce the expression of ICAM-1, which means improving endothelial dysfunction. A total of 585 targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. A total of 10,832 targets of endothelial dysfunction were obtained from Genecards and OMIM databases. A total of 527 overlapping targets of endothelial dysfunction and biochanin A were obtained. AKT1, TNF-α, VCAM1, ICAM1, and NOS3 might be the key targets of the anti-endothelial dysfunction activity of biochanin A, and the key pathways might be PI3K-Akt and TNF signaling pathways. Molecular docking results indicated that the AKT1 and TNF-α had the highest affinity binding with biochanin A.ConclusionThis study indicates that biochanin A can target AKT1 and TNF-α to alleviate endothelial dysfunction induced by IL-6 in Perthes disease, which provides a theoretical basis for the treatment of Perthes disease by using biochanin A.

Project description:BackgroundDue to unhealthy diet and living habits, the incidence of gout is on the rise and has become a common disease with a high incidence. Danggui Niantong decoction (DGNTD), as a classic formula composed of 15 common herbs, has been widely used in clinical practice since ancient times to prevent and treat gout. However, the pharmacological mechanism and target of DGNTD are not clear.MethodsThe potential active compounds and targets of DGNTD were obtained by traditional Chinese medicine systems pharmacology (TCMSP) database, and the differential genes of gout patients and controls were analyzed in gene expression omnibus (GEO) database. GSEA analysis of differential genes with GSEA 4.1.0 software and then the differential genes were intersected with the gout-related disease targets searched by GeneCard, CTD and OMIM disease database to obtain the final disease target. The "Traditional Chinese medicine-Active compounds-Targets" network was constructed by Cytoscape3.7.2 software. The R packet is used for enrichment analysis. The molecular docking between the active compound of DGNTD and the core target was verified by AutoDockTools software.ResultsTwo hundred eighty six and 244 targets of DGNTD-related active components and 652 targets of gout were obtained, of which 13 targets were potential targets of DGNTD in the treatment of gout. GSEA analysis showed that the differential genes were mainly involved in apoptosis, inflammatory reaction, and receptor metabolism and so on. Gene ontology (GO) functional enrichment analysis shows that DGNTD regulates many biological processes, such as the response to purine-containing compound and response to lipopolysaccharide, positive regulation of acute inflammatory response and other cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that DGNTD treatment of gout is mainly related to interleukin-17 (IL-17), Toll-like receptor, rheumatoid arthritis, tumor necrosis factor (TNF) and so on. The results of molecular docking showed that the five active compounds in DGNTD had strong binding activity to core protein receptors.ConclusionsThe active compounds of DGNTD may achieve the purpose of treating gout by acting on the core target (CASP8, CXCL8, FOS, IL1B, IL6, JUN, PTGS2, STAT1, MMP1, TNF) to regulate cell metabolism, proliferation and apoptosis, and improve inflammatory response, which is the result of multi-component, multi-target and multi-pathway interaction. It provides an idea for the development of new combined drugs for gout.

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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Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A.

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Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A.

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