Network Pharmacology and Molecular Docking-Based Prediction of the Mechanism of Qianghuo Shengshi Decoction against Rheumatoid Arthritis.
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ABSTRACT:
SUBMITTER: Zeng Z
PROVIDER: S-EPMC8437630 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Eucommia ulmoides (EU) is a kidney-tonifying Chinese medicine that has been applied to treat RA for decides. The present study aims to explore pharmacological mechanisms of EU against RA using network pharmacology approach. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of EU, and their relative targets were fished from UniProt database. RA-related targets were screened from GeneCards database and DisGeNET database. The overlapping genes between EU and RA were identified by Venn diagram, and further analyzed for protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). Fifty active ingredients were identified in EU, and corresponded to 207 targets. Meanwhile, 499 targets were closely associated with RA development. A total of 50 overlapping genes between EU and RA were identified, which were regarded as therapeutically relevant. GO enrichment analysis indicated that EU exerted antiRA effects depending on regulating multiple biological processes including inflammatory response, oxidative stress, cell apoptosis and matrix catabolism. Several key pathways such as TNF pathway, IL-17 pathway, T cell receptor pathway, NOD-like receptor pathway and Toll-like receptor pathway, were involved in the above biological processes. Network pharmacology revealed that EU exerts therapeutic effects on RA through multi-ingredients, multi-targets and multi-pathways, which provides basis for its clinical application and promising directions for subsequent research.
| S-EPMC9302290 | biostudies-literature
Project description:BackgroundRheumatoid arthritis (RA) is a type of difficult-to-cure arthralgia with a worldwide prevalence. It severely affects people's living standards. For a long time, bee venom has been used to treat RA and has shown good results. Melittin is the main active component of bee venom used for RA treatment, but the molecular mechanism of melittin in RA treatments remains unclear.MethodsPotential melittin and RA targets were obtained from relevant databases, and common targets of melittin and RA were screened. The STRING database was used to build the PPI network and screen the core targets after visualization. The core targets were enriched by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway. Finally, the binding of melittin to target proteins was evaluated through simulated molecular docking, which verified the reliability of the prediction results of network pharmacology.ResultsIn total, 138 melittin targets and 5795 RA targets were obtained from relevant databases, and 90 common targets were obtained through intersection. Eighteen core targets, such as STAT3, AKT1, tumor necrosis factor, and JUN, were screened out. Enrichment analysis results suggested that melittin plays an anti-RA role mainly through tumor necrosis factor, interleukin-17, toll-like receptors, and advanced glycation end products-RAGE signaling pathways, and pathogenic bacterial infection. Molecular docking results suggested that melittin has good docking activity with core target proteins.ConclusionRA treatment with melittin is the result of a multi-target and multi-pathway interaction. This study offers a theoretical basis and scientific evidence for further exploring melittin in RA therapy.
| S-EPMC10419517 | biostudies-literature
Project description:ObjectiveThe aim of this study was to identify the active components of Shengxian Decoction (SXT) and to elucidate the multi-component, multi-target, and multi-pathway regulatory mechanisms underlying the efficacy of SXT in treating lung adenocarcinoma (LUAD).MethodsThe effects of SXT extract on proliferation, migration, and invasion capabilities of human LUAD cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, and Transwell assays. High-Performance Liquid Chromatography (HPLC) was employed to pinpoint the primary active constituents of SXT. The SXT-active component-target-pathway network and protein-protein interaction (PPI) network were constructed based on network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID. The clinical significance of key targets was assessed using several external databases, and molecular docking confirmed the binding affinities between key targets and SXT active components.ResultsSXT significantly inhibited the proliferation, migration and invasion of human LUAD cells. HPLC identified and quantified seven active SXT components. Network pharmacology yielded 197 targets, 128 signaling pathways, and 448 GO terms. The PPI network and external validation underscored 13 key targets significantly associated with the influence of SXT on LUAD progression. Molecular docking demonstrated strong interactions between SXT active components and key targets.ConclusionSXT treats LUAD through a multifaceted approach involving various components, targets, and pathways. This research offers novel insights into the constituents and molecular mechanisms of SXT in LUAD therapy.
| S-EPMC10767532 | biostudies-literature
Project description:Aim: Vitamin D plays a vital role in Rheumatoid arthritis (RA). However, the mechanism of vitamin D and rheumatism is still unclear. Therefore, a strategy based on network pharmacology and molecular docking was used to explore the mechanism of vitamin D and RA. Methods: The targets of RA were obtained from the GeneCards database and Therapeutic Targets Database, and the targets of vitamin D were obtained from the Drugbank database and STITCH database. Next, overlapping genes were identified by Venny, and further Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking analyses were performed. Results: A total of 1,139 targets of RA and 201 targets of vitamin D were obtained. A total of 76 overlapping genes were identified by Venny. The enrichment analysis showed that cell proliferation, immune response, and apoptotic process were the critical biological processes of vitamin D in treating RA. Antifolate resistance, osteoclast differentiation, and the nuclear factor-kappa B (NF-κB) signalling pathway are fundamental mechanisms of vitamin D in treating RA. According to further molecular docking, ALB, TNF, CASP3, and TP53 may be important punctuation points or diagnostic markers for future RA treatment. Conclusion: By analysing overlapping genes of diseases and drugs, this study confirmed that ALB, TNF, CASP3, and TP53 may be essential markers or diagnostic markers for future RA treatment.
| S-EPMC9749856 | biostudies-literature
Project description:Silicosis is an incurable chronic disease characterized by lung fibrosis and inflammation. The combination of tetrandrine and Buyang Huanwu Decoction (BYHWD) has a curative effect on silicosis. However, the mechanism of action and the key active constituent in BYHWD are still unclear. The present study employed network pharmacology and molecular docking to determine the mechanism of action and the key active components of BYHWD of Tetrandrine in combination with BYHWD for silicosis. The primary elements and targets of BYHWD were obtained from the Traditional Chinese Medicine Systems Pharmacology and analysis platform. The targets associated with tetrandrine and silicosis were identified and extracted from the Comparative Toxicogenomics Database and GeneCards database. The potential targets for the treatment of silicosis using a combination of Tetrandrine and BYHWD were identified by considering the overlapping targets between compound drugs and silicosis. These targets were then utilized to construct protein-protein interaction networks, compound drug-ingredient-target networks, and perform enrichment analyses. The top 5 active ingredients present in the compound drug-ingredient-target network are tetrandrine, quercetin, luteolin, kaempferol, and beta-carotene. Similarly, the top 6 hub genes in the protein-protein interaction network are FGF2, MMP-9, MMP-1, IL-10, IL-17A, and IL-6. The molecular docking suggested that the active components may easily access the active pocket of the hub gene. The in-silico investigation suggested that quercetin might be the active component in BYHWD responsible for therapeutic effectiveness against silicosis. This study identified the active compound and potential molecular mechanism underlying the therapeutic effects of BYHWD in combination with tetrandrine for treating silicosis. Notably, we found that quercetin may serve as the key compound in BYHWD for the treatment of silicosis.
| S-EPMC10419795 | biostudies-literature
Project description:Background: Dingji Fumai Decoction (DFD), a traditional herbal mixture, has been widely used to treat arrhythmia in clinical practice in China. However, the exploration of the active components and underlying mechanism of DFD in treating atrial fibrillation (AF) is still scarce. Methods: Compounds of DFD were collected from TCMSP, ETCM, and literature. The targets of active compounds were explored using SwissTargetPrediction. Meanwhile, targets of AF were collected from DrugBank, TTD, MalaCards, TCMSP, DisGeNET, and OMIM. Then, the H-C-T-D and PPI networks were constructed using STRING and analyzed using CytoNCA. Meanwhile, VarElect was utilized to detect the correlation between targets and diseases. Next, Metascape was employed for systematic analysis of the mechanism of potential targets and protein complexes in treating AF. AutoDock Vina, Pymol, and Discovery Studio were applied for molecular docking. Finally, the main findings were validated through molecular biology experiments. Results: A total of 168 active compounds and 1,093 targets of DFD were collected, and there were 89 shared targets between DFD and AF. H-C-T-D network showed the relationships among DFD, active compounds, targets, and AF. Three functional protein complexes of DFD were extracted from the PPI network. Further systematic analysis revealed that the regulation of cardiac oxidative stress, cardiac inflammation, and cardiac ion channels were the potential mechanism of DFD in treating AF. Addtionally, molecular docking verified the interactions between active compounds and targets. Finally, we found that DFD significantly increased the level of SIRT1 and reduced the levels of ACE, VCAM-1, and IL-6. Conclusions: DFD could be utilized in treating AF through a complicated mechanism, including interactions between related active compounds and targets, promoting the explanation and understanding of the molecular biological mechanism of DFD in the treatment of AF.
| S-EPMC8631917 | biostudies-literature
Project description:BackgroundHuangqi Guizhi Wuwu decoction (HQGZWWD) has been used to treat and prevent deep vein thrombosis (DVT) in China. However, its potential mechanisms of action remain unclear. This study aimed to utilize network pharmacology and molecular docking technology to elucidate the molecular mechanisms of action of HQGZWWD in DVT.MethodsWe identified the main chemical components of HQGZWWD by reviewing the literature and using a Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. We used GeneCards and Online Mendelian Inheritance in Man databases to identify the targets of DVT. Herb-disease-gene-target networks using Cytascape 3.8.2 software; a protein-protein interaction (PPI) network was constructed by combining drug and disease targets on the STRING platform. Additionally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking verification of active components and core protein targets was conducted.ResultsA total of 64 potential targets related to DVT were identified in HQGZWWD, with 41 active components; quercetin, kaempferol, and beta-sitosterol were the most effective compounds. The PPI network analysis revealed that AKT1, IL1B, and IL6 were the most abundant proteins with the highest degree. GO analysis indicated that DVT treatment with HQGZWWD could involve the response to inorganic substances, positive regulation of phosphorylation, plasma membrane protein complexes, and signaling receptor regulator activity. KEGG analysis revealed that the signaling pathways included pathways in cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. The molecular docking results indicated that quercetin, kaempferol, and beta-sitosterol exhibited strong binding affinities for AKT1, IL1B, and IL6.ConclusionOur study suggests that AKT1, IL1B, and IL6 are promising targets for treating DVT with HQGZWWD. The active components of HQGZWWD likely responsible for its effectiveness against DVT are quercetin, kaempferol, and beta-sitosterol, they may inhibit platelet activation and endothelial cell apoptosis by regulating the PI3K/Akt and MAPK signaling pathways, slowing the progression of DVT.
| S-EPMC10314554 | biostudies-literature
Project description:ObjectiveThis study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking.MethodsThe main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of "drugs-active components-disease targets" was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software.ResultsSeventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities.ConclusionModified Danggui Sini Decoction has the hierarchical network characteristics of "multicomponent, multitarget, multifunction, and multipathway" in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.
| S-EPMC7895562 | biostudies-literature
Project description:Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.
| S-EPMC9423997 | biostudies-literature
Project description:BackgroundA new viral outbreak caused by monkeypox has appeared after COVID-19. As of yet, no specific drug has been found for its treatment. Shengma-Gegen decoction (SMGGD), a pathogen-eliminating and detoxifying agent composed of four kinds of Chinese herbs, has been demonstrated to be effective against several viruses in China, suggesting that it may be effective in treating monkeypox, however, the precise role and mechanisms are still unknown.MethodsNetwork pharmacology was used to investigate the monkeypox-specific SMGGD targets. These targets were analyzed via String for protein-to-protein interaction (PPI), followed by identification of hub genes with Cytoscape software. Function enrichment analysis of the hub targets was performed. The interactions between hub targets and corresponding ligands were validated via molecular docking.ResultsThrough screening and analysis, a total of 94 active components and 8 hub targets were identified in the TCM-bioactive compound-hub gene network. Molecular docking results showed that the active components of SMGGD have strong binding affinity for their corresponding targets. According to functional analysis, these hub genes are mainly involved in the TNF, AGE-RAGE, IL-17, and MAPK pathways, which are linked to the host inflammatory response to infection and viral replication. Therefore, SMGGD might suppress the replication of monkeypox virus through the MAPK signaling pathway while also reducing inflammatory damage caused by viral infection.ConclusionSMGGD may have positive therapeutic effects on monkeypox by reducing inflammatory damage and limiting virus replication.
| S-EPMC9692928 | biostudies-literature