scholarly journals Network pharmacology integrated with experimental validation revealed the anti-inflammatory effects of Andrographis paniculata

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naiqiang Zhu ◽  
Jingyi Hou ◽  
Ning Yang
Keyword(s):  
Molecular Docking ◽  
Western Blot ◽  
Cancer Immunology ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Rt Pcr ◽  
Hub Genes ◽  
Bioactive Ingredients ◽  
Anti Inflammatory ◽  
Key Pathways

AbstractInflammation is a key factor in the development and complications of various diseases because it has a complex pathogenesis. Andrographis paniculate (Burm. f.) Nees (Chuan Xinlian) is a well-known form of Traditional Chinese Medicine (TCM) applied in clearing heat and detoxification. Also, it is rich in bioactive lactones, with various anti-inflammatory activities. Here, network pharmacology combined with molecular biology experimental approach was used to predict and verify the potential molecular mechanism of Chuan Xinlian in treating inflammation. The bioactive ingredients of Chuan Xinlian were obtained from the TCMSP database and literature. Besides, the targets of Chuan Xinlian and inflammation were collected based on the multi-source databases and used to generate the PPI network. Network topology analysis and functional enrichment analysis were used to screen hub genes and their mechanisms. Molecular docking simulation was performed to evaluate the binding activity between the predicted hub genes and the bioactive ingredients. Additionally, LPS-induced NO production in RAW264.7 cell inflammatory response, RT-PCR and Western blot were used to validate the efficacy of the Chuan Xinlian in the treatment of inflammation. Network analysis outcomes indicated that five targets (IL-6, VEGFA, PTGST2, TNF-α, and MMP-9) were identified as the key targets of Chuan Xinlian in the treatment of inflammation. Further, molecular docking findings revealed that the majority of the bioactive ingredients exhibited a strong binding efficacy towards the predicted hub genes. Functional analysis results showed that the potential mechanisms were primarily concentrated in key pathways including cancer, immunology, and inflammation process. Moreover, RT-PCR and Western blot analysis indicated that Chuan Xinlian extract suppressed the production of inflammatory mediators with anti-inflammatory effects. Our study shows that Chuan Xinlian potentially exerts an anti-inflammatory effect via key pathways including cancer, immunology, and inflammation process. This suggests that Chuan Xinlian has a potential anti-inflammatory action, thereby providing a scientific reference for clinical studies.

scholarly journals To Predict Anti-Inflammatory and Immunomodulatory Targets of Guizhi Decoction in Treating Asthma Based on Network Pharmacology, Molecular Docking, and Experimental Validation

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Rui Sun ◽  
Gonghao Xu ◽  
Dongyang Gao ◽  
Qi Ding ◽  
Yuanyuan Shi
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Network Pharmacology ◽  
Chronic Respiratory Diseases ◽  
Guizhi Decoction ◽  
Anti Inflammatory ◽  
Key Pathways ◽  
Core Genes ◽  
Inflammatory Effect

Asthma, characterized by the continuous inflammatory response caused by a variety of immune cells, is one of the most common chronic respiratory diseases worldwide. Relevant clinical trials proved that the traditional Chinese medicine formula Guizhi Decoction (GZD) had multitarget and multichannel functions, which might be an effective drug for asthma. However, the effective ingredients and mechanisms of GZD against asthma are still unclear. Therefore, network pharmacology, molecular docking, and cell experiments were performed to explore the antiasthma effects and potential mechanisms of GZD. First, we applied the TCMSP database and literature to obtain the bioactivated ingredients in GZD. SwissTargetPrediction, TCMSP, GeneCards, OMIM, PharmGkb, TTD, DrugBank, and STRING database were used to get core genes. In addition, the key pathways were analyzed by the DAVID database. Molecular docking was used to predict whether the important components could act on the core target proteins directly. Finally, qPCR was carried out to verify the network pharmacology results and the possible mechanisms of GZD in the treatment of asthma. We collected 134 active ingredients in GZD, 959 drug targets, and 3223 disease targets. 431 intersection genes were screened for subsequent analysis. Through GO and KEGG analyses, enriched pathways related to inflammation and immune regulation were presented. Through the qPCR method to verify the role of essential genes, we found that GZD had an excellent anti-inflammatory effect. Direct or indirect inhibition of MAPK and NF-κB pathways might be one of the crucial mechanisms of GZD against asthma. GZD might be a promising potential drug for the treatment of asthma. This article provided a reference for the clinical application of GZD.

scholarly journals Studies on the Mechanism of Gegen Qinlian Decoction in Treating Diabetes Mellitus Based on Network Pharmacology

2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098213
Author(s):  
Xiaodong Deng ◽  
Yuhua Liang ◽  
Jianmei Hu ◽  
Yuhui Yang
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Network Pharmacology ◽  
Hub Genes ◽  
Topological Parameters

Diabetes mellitus (DM) is a chronic disease that is very common and seriously threatens patient health. Gegen Qinlian decoction (GQD) has long been applied clinically, but its mechanism in pharmacology has not been extensively and systematically studied. A GQD protein interaction network and diabetes protein interaction network were constructed based on the methods of system biology. Functional module analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Gene Ontology (GO) enrichment analysis were carried out on the 2 networks. The hub nodes were filtered by comparative analysis. The topological parameters, interactions, and biological functions of the 2 networks were analyzed in multiple ways. By applying GEO-based external datasets to verify the results of our analysis that the Gene Set Enrichment Analysis (GSEA) displayed metabolic pathways in which hub genes played roles in regulating different expression states. Molecular docking is used to verify the effective components that can be combined with hub nodes. By comparing the 2 networks, 24 hub targets were filtered. There were 7 complex relationships between the networks. The results showed 4 topological parameters of the 24 selected hub targets that were much higher than the median values, suggesting that these hub targets show specific involvement in the network. The hub genes were verified in the GEO database, and these genes were closely related to the biological processes involved in glucose metabolism. Molecular docking results showed that 5,7,2', 6'-tetrahydroxyflavone, magnograndiolide, gancaonin I, isoglycyrol, gancaonin A, worenine, and glyzaglabrin produced the strongest binding effect with 10 hub nodes. This compound–target mode of interaction may be the main mechanism of action of GQD. This study reflected the synergistic characteristics of multiple targets and multiple pathways of traditional Chinese medicine and discussed the mechanism of GQD in the treatment of DM at the molecular pharmacological level.

scholarly journals Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

2021 ◽  
Author(s):  
Dianna Liu ◽  
Shicheng Lin ◽  
Yuan Li ◽  
Tian Zhou ◽  
Kaiwen Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Network Pharmacology ◽  
Phytochemical Analysis ◽  
Sequencing Analysis ◽  
Lewis Lung ◽  
Hub Genes

Abstract BackgroundLung adenocarcinoma (LUAD) is one of the most common malignancies with a rise in new cases worldwide each year. Recurrence significantly influences the survival in patients with LUAD. Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung cancer relapse by “nourishing yin and clearing heat”. MethodsIn this study, the mechanism of YHT in LUAD recurrence was investigated. Firstly, the bioactive compounds-targets network and the protein–protein interaction network were constructed, and functional annotation and pathway enrichment analyses were performed. Pivotal compounds and hub genes were selected from the networks. Subsequently, the effectiveness of YHT was confirmed in lewis lung carcinoma mice. RNA sequencing was used to explore the mRNA expression differences between tumor tissues in the model mouses and YHT-treated mouses. The pathways screened by network pharmacology and RNA sequencing analysis at the same time were considered the most important pathways. At last, qualitative phytochemical analysis, molecular docking technology, PCR and WB analysis were used to validate the pivotal active ingredients, hub genes and main pathways.ResultsThere were 128 active compounds, 419 targets interacting with LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Target genes mainly focused on inflammation, metabolism, immune responses and apoptosis. We confirmed that YHT could inhibit the recurrence of lung adenocarcinoma through animal experimental study. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub genes related with the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis of the water extract of YHT confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The results of molecular docking verified the pivotal compounds of YHT could good affinity with the S1PR5. The PCR and WB analysis verified YHT suppressed lewis lung cancer cells proliferation by inhibiting S1P/S1PR5/Gi/Ras/Raf/MEK/ERK pathway, and inhibited migration through S1P/S1PR5/Gi/PI3K/RAC pathway.ConclusionThe results confirmed the therapeutic effect of YHT on the recurrence of LUAD by multi-component-multi-target mode, the sphingolipid signaling pathway was one of the most relevant potential signaling pathways.

scholarly journals Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

2021 ◽  
Author(s):  
Varun Alur ◽  
Varshita Raju ◽  
Basavaraj Mallikarjunayya Vastrad ◽  
Anandkumar Revanasiddappa Tengli ◽  
Chanabasayya Vastrad ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Small Molecules ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Therapeutic Agents ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Transcription Profiling ◽  
Hub Gene

Gestational diabetes mellitus (GDM) is the metabolic disorder appears during pregnancy. The current investigation aimed to identify central differentially expressed genes (DEGs) in GDM. The transcription profiling by array data (E-MTAB-6418) was obtained from the ArrayExpress database. The DEGs between GDM samples and non GDM samples were analyzed. Functional enrichment analysis were performed using ToppGene. Then we constructed the protein-protein interaction (PPI) network of DEGs by the Search Tool for the Retrieval of Interacting Genes database (STRING) and module analysis was performed. Subsequently, we constructed the miRNA-hub gene network and TF-hub gene regulatory network. The validation of hub genes was performed through receiver operating characteristic curve (ROC). Finally, the candidate small molecules as potential drugs to treat GDM were predicted by using molecular docking. Through transcription profiling by array data, a total of 869 DEGs were detected including 439 up regulated and 430 down regulated genes. Functional enrichment analysis showed these DEGs were mainly enriched in reproduction, cell adhesion, cell surface interactions at the vascular wall and extracellular matrix organization. Ten genes, HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3, and PRKCA were associated with GDM, according to ROC analysis. Finally, the most significant small molecules were predicted based on molecular docking. This investigation identified hub genes, signal pathways and therapeutic agents, which might help us, enhance our understanding of the mechanisms of GDM and find some novel therapeutic agents for GDM.

scholarly journals Network pharmacology, molecular docking, and experimental study for the mechanisms of Qishen Yiqi Pills against Cardiovascular Diseases

2021 ◽  
Author(s):  
Jie-wen Zhao ◽  
Hai-dong Liu ◽  
Ming-yin Man ◽  
Lv-ya Wang ◽  
Ning Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cardiovascular Diseases ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Literature Mining ◽  
Therapeutic Effects ◽  
Active Components

Abstract Background Qishen Yiqi Pills (QSYQP) is a traditional Chinese compound recipe. However, our understanding of its mechanism has been hindered due to the complexity of its components and targets. In this work, the network pharmacology-based approaches were used to explore QSYQP’s pharmacological mechanism on treating cardiovascular diseases (CVD). Results From ETCM and TCM MESH databases we collected QSYQP’s 333 active components and their 674 putative targets. We constructed the sub-network influence by CVD genes and found that 40% QSYQP targets appeared in 20 modules, in which QSYQP’s targets and CVD genes co-existed as hub nodes in the sub-network. Functional enrichment analysis suggested that the 42 key targets were mainly expressed in platelets, blood vessels, cardiomyocytes, and other tissues. The main signaling pathways regulated and controlled by the key targets were inflammation, immunity, blood coagulation and energy metabolism. Network and pathway analysis identified 7 key targets, which were regulated by 7 compounds of QSYQP. 26 of the 42 important targets, including the 7 key targets were verified by literature mining. Twelve pairs of interactions between key targets and QSYQP’s compounds were validated by molecular docking. Further validation experiments suggested that QSYQP suppressed H/R induced apoptosis and cytoskeleton disruption of cardiomyocytes. Western blotting showed that the expression of cardiovascular diseases-related genes including ACTC1, FoxO1 and DIAPH1 was significantly decreased by establishing the hypoxia-reoxygenation model in vitro, while the protein expression of experimental group was significantly increased by adding QSYQP or its ingredients. Conclusion These results indicated the correlation of QSYQP treatment to the therapeutic effects of CVD. At the molecular level, this study revealed the multicomponent and multitargeting mechanisms of QSYQP in the regulation and treatment of cardiovascular diseases, potentially providing a reference for the further utilization of QSYQP.

scholarly journals Dissecting the Mechanism of Yuzhi Zhixue Granule on Ovulatory Dysfunctional Uterine Bleeding by Network Pharmacology and Molecular Docking

2020 ◽  
Author(s):  
Jialin Li ◽  
Hua Luo ◽  
Xinkui Liu ◽  
Jingyuan Zhang ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Uterine Bleeding ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Dysfunctional Uterine Bleeding

Abstract Background: Yuzhi Zhixue Granule (YZG)is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.Methods: The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein-protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.Results: The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds.Conclusion: This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Luo ◽  
Xuan Shi ◽  
Jiarong Ding ◽  
Zhenzhen Ma ◽  
Xumei Chen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Western Blot ◽  
Therapeutic Targets ◽  
Target Prediction ◽  
Mg63 Cell ◽  
Integrated Approach ◽  
Biochanin A ◽  
Network Pharmacology ◽  
Oncology Research ◽  
Mg63 Cells

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.

scholarly journals Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jialin Li ◽  
Hua Luo ◽  
Xinkui Liu ◽  
Jingyuan Zhang ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Uterine Bleeding ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Dysfunctional Uterine Bleeding

Abstract Background Yuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG. Methods The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein–protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules. Results The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds. Conclusion This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

scholarly journals Network Pharmacology Prediction: The Possible Mechanisms of Cinobufotalin against Osteosarcoma

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Riyu Chen ◽  
Zeyi Guan ◽  
Xianxing Zhong ◽  
Wenzheng Zhang ◽  
Ya Zhang
Keyword(s):  
Survival Curve ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Hub Genes ◽  
Survival Prognosis ◽  
Active Compounds ◽  
Protein Protein Interaction

Objective. To explore the active compounds and targets of cinobufotalin (huachansu) compared with the osteosarcoma genes to obtain the potential therapeutic targets and pharmacological mechanisms of action of cinobufotalin on osteosarcoma through network pharmacology. Methods. The composition of cinobufotalin was searched by literature retrieval, and the target was selected from the CTD and TCMSP databases. The osteosarcoma genes, found from the GeneCards, OMIM, and other databases, were compared with the cinobufotalin targets to obtain potential therapeutic targets. The protein-protein interaction (PPI) network of potential therapeutic targets, constructed through the STRING database, was inputted into Cytoscape software to calculate the hub genes, using the NetworkAnalyzer. The hub genes were inputted into the Kaplan-Meier Plotter online database for exploring the survival curve. Functional enrichment analysis was identified using the DAVID database. Results. 28 main active compounds of cinobufotalin were explored, including bufalin, adenosine, oleic acid, and cinobufagin. 128 potential therapeutic targets on osteosarcoma are confirmed among 184 therapeutic targets form cinobufotalin. The hub genes included TP53, ACTB, AKT1, MYC, CASP3, JUN, TNF, VEGFA, HSP90AA1, and STAT3. Among the hub genes, TP53, ACTB, MYC, TNF, VEGFA, and STAT3 affect the patient survival prognosis of sarcoma. Through function enrichment analysis, it is found that the main mechanisms of cinobufotalin on osteosarcoma include promoting sarcoma apoptosis, regulating the cell cycle, and inhibiting proliferation and differentiation. Conclusion. The possible mechanisms of cinobufotalin against osteosarcoma are preliminarily predicted through network pharmacology, and further experiments are needed to prove these predictions.

Sign in / Sign up

Export Citation Format

Share Document