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

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.

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

Scientific Reports ◽

10.1038/s41598-021-89257-6 ◽

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.

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Extraction of Oleic Acid from Animals Oil and Its Anti-inflammatory Effect on Network Pharmacology

Iranian Journal of Science and Technology Transactions A Science ◽

10.1007/s40995-021-01168-3 ◽

2021 ◽

Author(s):

Jiuwang Yu ◽

Lu Wang ◽

Jiang Ding ◽

Lan Wu

Keyword(s):

Molecular Docking ◽

Oleic Acid ◽

Drug Targets ◽

Network Pharmacology ◽

Literature Mining ◽

Go Annotation ◽

Anti Inflammatory ◽

Mongolian Horse ◽

Database Platform ◽

Endogenous Interactions

AbstractThe purpose of this paper is to explore the possible mechanisms of anti-inflammatory and scar repair by Mongolian horse oil. We used TCM database and literature mining to collect active compounds of horse oil and used Swiss TargetPrediction and SuperPred server to find targets of compounds. Anti-inflammatory drug targets were collected through the CTD database. Go annotation of targets and KEGG pathway were enriched and analyzed through Metascape database platform. Molecular docking between active ingredients and targets was verified by AutoDock software. Metascape analysis revealed that the key candidate targets were significantly enriched in a number of pathways associated with inflammatory pathology. The results of molecular docking showed that oleic acid, a major component of animals oil, could influence the regulatory functions of TNF, NGF, IL6, IL1B, Jun, and CDK1. This suggests that animals oil can regulate the development of inflammation through its active ingredient, oleic acid, and can influence the expression of multiple signaling pathways, with theoretical endogenous interactions with TNF, NGF, IL6, IL1B, JUN, and CDK1 proteins.

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Molecular mechanism of luteolin against inflammation based on integration of network pharmacology, transcriptomics and proteomics

10.21203/rs.3.rs-29569/v1 ◽

2020 ◽

Author(s):

XiuFang Huang ◽

Jia-Lin Zhang ◽

Ai-Si Huang ◽

Dan-Ping Huang ◽

Hui-Ting Huang ◽

...

Keyword(s):

Signaling Pathway ◽

Gene Function ◽

Venn Diagram ◽

Network Pharmacology ◽

Mrna Levels ◽

Pathway Enrichment ◽

Inflammatory Mechanism ◽

Anti Inflammatory ◽

Core Genes ◽

Inflammatory Effect

Abstract Background: Luteolin (3', 4', 5,7-tetrahydroxyflavone), a natural flavonoid exists in various medicinal plants, has strong anti-inflammatory effect. However, anti-inflammatory mechanism of luteolin has not been fully explored. Hence, we aimed to systematically investigate druggability and anti-inflammatory mechanism of luteolin based on network pharmacology. Methods: The absorption, distribution, metabolism, excretion, and toxicity of luteolin were evaluated by TCMSP server. Targets associated with luteolin and inflammation were collected from public databases, and the overlapping targets between luteolin and inflammation were analyzed by Draw Venn diagram. Then the protein-protein interaction network of luteolin against inflammation was constructed to get core genes. Further, gene function and pathway enrichment analysis were performed. Finally, in vitro experiment was carried out to estimate the accuracy of predicted target genes. Results: ADME results indicated that luteolin has great potential to be developed into a drug. 226 overlapping targets (targets of luteolin against inflammation) were screened by matching 280 targets of luteolin with 9015 targets of inflammation. 9 core targets of luteolin against inflammation were identified, including MMP9, MAPK1, HSP90AA1, CASP3, ALB, EGFR, SRC, HRAS and ESR1. Gene function were mainly involved in metabolism, energy pathways and signal transduction. Pathway enrichment results suggested that metabolic pathways, pathways in cancer, PI3K-AKT signaling pathway, Ras signaling pathway and so on might be the critical pathways of luteolin against inflammation. RT-qPCR and ELISA results indicated that luteolin decreased the expression of most of core genes at protein and mRNA levels (MMP9, MAPK1, HSP90AA1, EGFR, SRC and HRAS). Conclusions: The anti-inflammatory mechanism of luteolin were systematically investigated based on network pharmacology, RT-qPCR and ELISA. Luteolin is expounded to have great potential to be developed into a drug and target various genes and pathways to perform systematic anti-inflammatory effect.

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Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

10.21203/rs.3.rs-919289/v1 ◽

2021 ◽

Author(s):

jianjun wu ◽

Ping-an Zhang ◽

Ming-zhe Chen ◽

Yi-xuan Li ◽

Ying-xue Zhang ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Target Genes ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Active Ingredients ◽

Ppi Networks ◽

Core Proteins ◽

Anti Inflammatory ◽

Inflammatory Effect

Abstract PurposeJinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of HDAC2. But the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear. ObjectiveTo explore whether Jinwei decoction can enhance the anti-inflammatory effect of GC on COPD through microRNA21 (miR-21) by network pharmacology. MethodsThe TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-21. COPD-related genes were identified by searching GeneCards and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. ResultsTwo hundred ninety-two active ingredients, 316 Jinwei drug targets, 10170 miR-21 target genes, 6617 COPD target genes, and 184 intersection gene were identified. Eleven core proteins of PPI networks may be involved. GO enrichment analysis showed that oxidative stress, regulation of inflammatory response, hormone transport, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, neutrophil extracellular bactericidal network, and other signaling pathways. ConclusionJinwei decoction can regulate histone deacetylase-2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-21. Its mechanism of action may be related to its effect on the PI3K Akt, MAPK, and TNF signaling pathways and neutrophil extracellular trap formation through miR-21.

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Molecular docking of active compounds from Phoenix pusilla root extract against antidiabetic and anti-inflammatory drug targets

Journal of Applied Biology & Biotechnology ◽

10.7324/jabb.2021.95.1s5 ◽

2021 ◽

Vol 9 ◽

pp. 26-30

Keyword(s):

Molecular Docking ◽

Drug Targets ◽

Root Extract ◽

Active Compounds ◽

Inflammatory Drug ◽

Anti Inflammatory

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Discussing the Mechanism of Dahuang Huanglian Xiexin Decoction in the Treatment of Type 2 Diabetes Mellitus via Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-531851/v1 ◽

2021 ◽

Author(s):

Xi Cen ◽

Yan Wang ◽

LeiLei Zhang ◽

XiaoXiao Xue ◽

Yan Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Molecular Docking ◽

Target Genes ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Overlapping Genes ◽

Potential Mechanism ◽

Active Components ◽

The Core ◽

Core Genes

Abstract BackgroundType 2 diabetes mellitus (T2DM) is regarded as Pi Dan disease in traditional Chinese medicine (TCM). Dahuang Huanglian Xiexin Decoction (DHXD), a classical TCM formula, has been used for treating Pi Dan disease in clinic, its pharmacological mechanism has not been elucidated. MethodsThis study used network pharmacological analysis and molecular docking approach to explore the mechanism of DHXD on T2DM. Firstly, the compounds in DHXD were obtained from TCMSP and TCMID databases, the potential targets were determined based on TCMSP and UniProt databases. Next, Genecards, Digenet and UniProt databases were used to identify the targets of T2DM. Then, the protein-protein interaction (PPI) network was established with overlapping genes of T2DM and compounds, and the core targets in the network were identified and analyzed. Then, the David database was used for GO and KEGG enrichment analysis. Finally, the target genes were selected and the molecular docking was completed by Autodock software to observe the binding level of active components with target genes.ResultsA total of 397 related components and 128 overlapping genes were identified. After enrichment analysis, it was found that HIF-1, TNF, IL-17 and other signaling pathways, as well as DNA transcription, gene expression, apoptosis and other cellular biological processes had the strongest correlation with the treatment of T2DM by DHXD, and most of them occurred in the extracellular space, plasma membrane and other places, which were related to enzyme binding and protein binding. In addition, 42 core genes of DHXD, such as VEGFA, TP53 and MAPK1, were considered as potential therapeutic targets, indicating the potential mechanism of DHXD on T2DM. Finally, the results of molecular docking showed that HIF-1 pathway had strong correlation with the target genes INSR and GLUT4, quercetin and berberine had the strongest binding power with them respectively.ConclusionThis study summarized the main components of DHXD in the treatment of T2DM, identified the core genes and pathways, and systematically analyzed the interaction of related targets, trying to lay the foundation for clarifying the potential mechanism of DHXD on T2DM, so as to carry out further research in the future.

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The Role of Simvastatin in the Therapeutic Approach of Rheumatoid Arthritis

Autoimmune Diseases ◽

10.1155/2013/326258 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Lucia Cojocaru ◽

Andrei Constantin Rusali ◽

Cristina Şuţa ◽

Anca Mihaela Rădulescu ◽

Maria Şuţa ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cardiovascular Disease ◽

Active Rheumatoid Arthritis ◽

Therapeutic Potential ◽

Efficacy And Safety ◽

Good Safety Profile ◽

Study Support ◽

Anti Inflammatory ◽

Inflammatory Effect

The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.

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