scholarly journals Exploration in the Mechanism of Kaempferol for the Treatment of Gastric Cancer Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Liangjun Yang ◽  
Haiwen Li ◽  
Maoyi Yang ◽  
Weijian Zhang ◽  
Mianli Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Mendelian Inheritance ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Novel Approach ◽  
Disease Associated Genes

Background. Kaempferol is a natural polyphenol in lots of Chinese herbs, which has shown promising treatment for gastric cancer (GC). However, the molecular mechanisms of its action have not been systematically revealed yet. In this work, a network pharmacology approach was used to elucidate the potential mechanisms of kaempferol in the treatment of GC. Methods. The kaempferol was input into the PharmMapper and SwissTargetPrediction database to get its targets, and the targets of GC were obtained by retrieving the Online Mendelian Inheritance in Man (OMIM) database, MalaCards database, Therapeutic Target Database (TTD), and Coolgen database. The molecular docking was performed to assess the interactions between kaempferol and these targets. Next, the overlap targets of kaempferol and GC were identified for GO and KEGG enrichment analyses. Afterward, a protein-protein interaction (PPI) network was constructed to get the hub targets, and the expression and overall survival analysis of the hub target were investigated. Finally, the overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool. Results. A total of 990 genes related to GC and 10 overlapping genes were determined through matching the 24 potential targets of kaempferol with disease-associated genes. The result of molecular docking indicated that kaempferol can bind with these hub targets with good binding scores. These targets were further mapped to 140 GO biological process terms and 11 remarkable pathways. In the PPI network analysis, 3 key targets were identified, including ESR1, EGFR, and SRC. The mRNA and protein expression levels of EGFR and SRC were obviously higher in GC tissues. High expression of these targets was related to poor OS in GC patients. Conclusions. This study provided a novel approach to reveal the therapeutic mechanisms of kaempferol on GC, which will ease the future clinical application of kaempferol in the treatment of GC.

scholarly journals Network Pharmacology-Based Systematic Analysis of Molecular Mechanisms of Dingji Fumai Decoction for Ventricular Arrhythmia

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yi Liang ◽  
Bo Liang ◽  
Xin-Rui Wu ◽  
Wen Chen ◽  
Li-Zhi Zhao
Keyword(s):  
Molecular Docking ◽  
Ventricular Arrhythmia ◽  
Molecular Mechanisms ◽  
Mendelian Inheritance ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Systematic Analysis ◽  
Chemical Structures ◽  
Function Modules ◽  
Underlying Mechanisms

Background. Dingji Fumai Decoction (DFD), a traditional herbal mixture, has been widely used to ventricular arrhythmia (VA) in clinical practice in China. However, research on the bioactive components and underlying mechanisms of DFD in VA is still scarce. Methods. Components of DFD were collected from TCMSP, ETCM, and literature. The chemical structures of each component were obtained from PubChem. Next, SwissADME and SwissTargetPrediction were applied for compounds screening and targets prediction of DFD; meanwhile, targets of VA were collected from DrugBank and Online Mendelian Inheritance in Man (OMIM). Then, the H-C-T-D network and the protein-protein interaction (PPI) network were constructed based on the data obtained above. CytoNCA was utilized to filter hub genes and VarElect was used to analyze the relationship between genes and diseases. At last, Metascape was employed for systematic analysis on the potential targets of herbals against VA, and AutoDock was applied for molecular docking to verify the results. Results. A total of 434 components were collected, 168 of which were qualified, and there were 28 shared targets between DFD and VA. Three function modules of DFD were found from the PPI network. Further systematic analysis of shared genes and function modules explained the potential mechanism of DFD in the treatment of VA; molecular docking has verified the interactions. Conclusions. DFD could be employed for VA through mechanisms, including complex interactions between related components and targets, as predicted by network pharmacology and molecular docking. This work confirmed that DFD could apply to the treatment of VA and promoted the explanation of DFD for VA in the molecular mechanisms.

scholarly journals Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Liangjun Yang ◽  
Zhipeng Hu ◽  
Jiajie Zhu ◽  
Qiting Liang ◽  
Hengli Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Docking ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Online Tool ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Novel Approach ◽  
Therapeutic Mechanisms ◽  
Kaplan Meier Plotter

This study was aimed at elucidating the potential mechanisms of quercetin in the treatment of gastric cancer (GC). A network pharmacology approach was used to analyze the targets and pathways of quercetin in treating GC. The predicted targets of quercetin against GC were obtained through database mining, and the correlation of these targets with GC was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, the protein-protein interaction (PPI) network was constructed, and overall survival (OS) analysis of hub targets was performed using the Kaplan–Meier Plotter online tool. Finally, the mechanism was further analyzed via molecular docking of quercetin with the hub targets. Thirty-six quercetin-related genes were identified, 15 of which overlapped with GC-related targets. These targets were further mapped to 319 GO biological process terms and 10 remarkable pathways. In the PPI network analysis, six hub targets were identified, including AKT1, EGFR, SRC, IGF1R, PTK2, and KDR. The high expression of these targets was related to poor OS in GC patients. Molecular docking analysis confirmed that quercetin can bind to these hub targets. In conclusion, this study provided a novel approach to reveal the therapeutic mechanisms of quercetin on GC, which will ease the future clinical application of quercetin in the treatment of GC.

scholarly journals Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Biting Wang ◽  
Zengrui Wu ◽  
Weihua Li ◽  
Guixia Liu ◽  
Yun Tang
Keyword(s):  
Molecular Docking ◽  
Liver Fibrosis ◽  
Molecular Mechanisms ◽  
Docking Simulation ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Bipartite Network ◽  
Metabolomics Data ◽  
Metabolic Products ◽  
Compound Target

Abstract Background The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods. Methods Firstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein–protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed. Results 68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway. Conclusions This study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.

scholarly journals Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza Against Diabetic Nephropathy Using Network Pharmacology and Molecular Docking

2020 ◽  
Author(s):  
Li-Li Zhang ◽  
Lin Han ◽  
Xin-Miao Wang ◽  
Yu Wei ◽  
Jing-Hui Zheng ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Docking ◽  
Therapeutic Effect ◽  
Molecular Mechanisms ◽  
Function Analysis ◽  
Salvia Miltiorrhiza ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Active Ingredients

Abstract BackgroundThe mechanisms underlying the therapeutic effect of Salvia Miltiorrhiza (SM) against diabetic nephropathy (DN) using systematic network pharmacology and molecular docking methods were examined.MethodsTCMSP database was used to screen the active ingredients of SM. Gene targets were obtained using Swiss Target Prediction and TCMSP databases. Related targets of DN were retrieved from the Genecards and DisGeNET databases. Next, a PPI network was constructed using the common targets of SM-DN in the STRING database. The Metascape platform was used for GO function analysis and Cytoscape plug-in ClueGO was used for KEGG pathway enrichment analysis. Molecular docking was performed using iGEMDOCK and AutoDock Vina software. Pymol and LigPlos were used for mapping the network. ResultsSixty-six active ingredients and 189 targets were screened from SM. Among them, 64 targets overlapped with DN targets. The PPI network diagram revealed that AKT1, VEGFA, IL6, TNF, MAPK1, TP53, EGFR, STAT3, MAPK14, and JUN were the top 10 relevant targets. GO and KEGG analyses mainly focused on advanced glycation end products, oxidative stress, inflammatory response, and immune regulation. Molecular docking revealed that the potential target genes closely related to DN, including TNF, NOS2, and AKT1, were more stable in combination with salvianolic acid B, and their stability was better than that of tanshinone IIA.ConclusionThis study reveals the active components and potential molecular mechanisms involved in the therapeutic effect of SM against DN and provides a reference for the wide application of SM in clinically managing DN.

scholarly journals Prediction of Rhizoma Drynariae Targets in the Treatment of Osteoarthritis Based on Network Pharmacology and Experimental Verification

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Guang-yao Chen ◽  
Xiao-yu Liu ◽  
Jia-qi Chen ◽  
Xin-bo Yu ◽  
Jing Luo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Network Pharmacology ◽  
Inflammatory Factor ◽  
In Vitro Experiments ◽  
Ppi Network ◽  
Rhizoma Drynariae

Rhizoma Drynariae has been widely used for the treatment of osteoarthritis (OA), but its potential targets and molecular mechanisms remain to be further explored. Targets of Rhizoma Drynariae and OA were predicted by relevant databases, and a protein-protein interaction (PPI) network was constructed to identify key targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to obtain related pathways and then select significant pathways associated with OA. The OA chondrocyte model was established by inflammatory factor-induced SW1353 chondrocytes, and molecular docking was conducted to verify the above theoretical prediction. The results showed that a total of 86 Rhizoma Drynariae-OA interaction targets were identified, among which IL-6 and AKT1 were the key targets in the PPI network. Luteolin was the most critical component of Rhizoma Drynariae. KEGG results indicated that the effects of Rhizoma Drynariae on OA are associated with the PI3K/AKT, TNF, IL-17, apoptosis, and HIF-1 signaling pathway. The PI3K/AKT pathway can activate the downstream NF-κB pathway and further regulate the transcription and expression of downstream IL-6, IL-17, HIF-1α, Bax, and TNF, suggesting that the PI3K/AKT/NF-κB pathway is the critical pathway in the treatment of OA with Rhizoma Drynariae. Active components of Rhizoma Drynariae and key proteins of the PI3K/AKT/NF-κB signaling pathway were subjected to molecular docking, whose results showed that luteolin and IKK-α played a critical role. In vitro experiments indicated that both aqueous extracts of Rhizoma Drynariae (AERD) and luteolin inhibited the expression of IL-6 and HIF-1α and suppressed the activation of PI3K/AKT/NF-κB, IL-17, and TNF pathways. The measurement of mitochondrial membrane potential (Δψm) indicated that AERD and luteolin can decrease the LPS-induced early apoptotic cells. Luteolin had a more prominent inhibitory effect than AERD in the abovementioned in vitro experiments. In conclusion, the therapeutic mechanism of Rhizoma Drynariae against OA may be closely related to the inhibition of the PI3K/AKT/NF-κB pathway and downstream pathways, and luteolin plays a vital role in the treatment.

scholarly journals Network Pharmacology-based Systematic Analysis of Molecular Mechanisms of Dingji Fumai Decoction for Ventricular Arrhythmia

2020 ◽  
Author(s):  
Yi Liang ◽  
Bo Liang ◽  
Rui Xin Wu ◽  
Wen Chen ◽  
Li-zhi ZHAO
Keyword(s):  
Molecular Docking ◽  
Ventricular Arrhythmia ◽  
Molecular Mechanisms ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Systematic Analysis ◽  
Chemical Structures ◽  
Function Modules ◽  
Underlying Mechanisms ◽  
And Function

Abstract Background: Dingji Fumai decoction (DFD), a traditional herbal mixture, has been widely used to ventricular arrhythmia (VA) in clinical practice in China. However, research on the bioactive components and underlying mechanisms of DFD in VA is still scarce. Methods: Components of DFD were collected from TCMSP, ETCM, and literature. Then, the chemical structures of each component were obtained from PubChem. Next, SwissADME and SwissTargetPrediction were applied for compounds screening and targets prediction of DFD, meanwhile, targets of VA were collected from DrugBank and OMIM. Then, the H-C-T-D network as well as the PPI network were constructed based on the data obtained above. CytoNCA was utilized to filter hub genes and VarElect was used to analyze the relationship between genes and diseases. At last, Metascape was employed for systematic analysis on the potential targets of herbals against VA, and AutoDock was applied for molecular docking to verify the results.Results: A total of 434 components were collected, 168 of which were qualified, and there were 28 shared targets between DFD and VA. Three function modules of DFD were found from the PPI network. Further systematic analysis of shared genes and function modules explained the potential mechanism of DFD in the treatment of VA, molecular docking has verified the interactions. Conclusions: DFD could be employed for VA through mechanisms, including complex interactions between related components and targets, as predicted by network pharmacology and molecular docking. This work confirmed DFD could apply for the treatment of VA and promoted the explaining of DFD for VA in the molecular mechanisms.

scholarly journals Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mingxu Zhang ◽  
Jiawei Yang ◽  
Xiulan Zhao ◽  
Ying Zhao ◽  
Siquan Zhu
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Enrichment Analysis ◽  
Docking Study ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Ingredients ◽  
Molecular Docking Study

AbstractDiabetic retinopathy (DR) is a leading cause of irreversible blindness globally. Qidengmingmu Capsule (QC) is a Chinese patent medicine used to treat DR, but the molecular mechanism of the treatment remains unknown. In this study, we identified and validated potential molecular mechanisms involved in the treatment of DR with QC via network pharmacology and molecular docking methods. The results of Ingredient-DR Target Network showed that 134 common targets and 20 active ingredients of QC were involved. According to the results of enrichment analysis, 2307 biological processes and 40 pathways were related to the treatment effects. Most of these processes and pathways were important for cell survival and were associated with many key factors in DR, such as vascular endothelial growth factor-A (VEGFA), hypoxia-inducible factor-1A (HIF-1Α), and tumor necrosis factor-α (TNFα). Based on the results of the PPI network and KEGG enrichment analyses, we selected AKT1, HIF-1α, VEGFA, TNFα and their corresponding active ingredients for molecular docking. According to the molecular docking results, several key targets of DR (including AKT1, HIF-1α, VEGFA, and TNFα) can form stable bonds with the corresponding active ingredients of QC. In conclusion, through network pharmacology methods, we found that potential biological mechanisms involved in the alleviation of DR by QC are related to multiple biological processes and signaling pathways. The molecular docking results also provide us with sound directions for further experiments.

Molecular Mechanism of The Effect of Huanglian Jiedu Decoction On Ulcerative Colitis Based On Network Pharmacology And Molecular Docking

2021 ◽  
Author(s):  
Jing Yang ◽  
Chao-Tao Tang ◽  
Ruiri Jin ◽  
Bixia Liu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Signal Pathway ◽  
Intestinal Barrier Function ◽  
Network Pharmacology ◽  
Bioactive Components ◽  
Ppi Network ◽  
Active Components

Abstract Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC by means of network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are considered to be very important to PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had good affinity with Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.

scholarly journals NMPA-approved traditional Chinese medicine-Pingwei Pill: new indication for colistin recovery against MCR-positive bacteria infection

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qiushuang Sheng ◽  
Runbao Du ◽  
Cunhui Ma ◽  
Yonglin Zhou ◽  
Xue Shen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Bacterial Infection ◽  
Molecular Mechanisms ◽  
Topological Analysis ◽  
Network Pharmacology ◽  
Synergistic Activity ◽  
Colistin Resistance ◽  
Western Blot Assay ◽  
Gram Negative

Abstract Background The wide spread of plasmid-mediated colistin resistance by mobile colistin resistance (MCR) in Enterobacteriaceae severely limits the clinical application of colistin as a last-line drug against bacterial infection. The identification of colistin potentiator from natural plants or their compound preparation as antibiotic adjuncts is a new promising strategy to meet this challenge. Methods Herein, the synergistic activity, as well as the potential mechanism, of Pingwei pill plus antibiotics against MCR-positive Gram-negative pathogens was examined using checkerboard assay, time-killing curves, combined disk test, western blot assay, and microscope analysis. Additionally, the Salmonella sp. HYM2 infection models of mouse and chick were employed to examine the in vivo efficacy of Pingwei pill in combination with colistin against bacteria infection. Finally, network pharmacology and molecular docking assay were used to predicate other actions of Pingwei pill for Salmonella infection. Results Our results revealed that Pingwei Pill synergistically potentiated the antibacterial activity of colistin against MCR-1-positive bacteria by accelerating the damage and permeability of the bacterial outer membrane with an FIC (Fractional Inhibitory Concentration) index less than 0.5. The treatment of Pingwei Pill neither inhibited bacterial growth nor affected MCR production. Notably, Pingwei Pill in combination with colistin significantly prolonged the median survival in mouse and chick models of infection using the Salmonella sp. strain HYM2, decreased bacteria burden and organ index of infected animal, alleviated pathological damage of cecum, which suggest that Pingwei Pill recovered the therapeutic performance of colistin for MCR-1- positive Salmonella infection in mice and the naturally infected host chick. Pharmacological network topological analysis, molecular docking, bacterial adhesion, and invasion pathway verification assays were performed to identify the other molecular mechanisms of Pingwei Pill as a colistin potentiator against Gram-negative bacteria infection. Conclusion Taken together, NMPA (National Medical Products Administration)-approved Pingwei Pill is a promising adjuvant with colistin for MCR-positive bacterial infection with a shortened R&D (research and development) cycle and affordable R&D cost and risk.

scholarly journals The Underlying Mechanism of Chinese Herb of Regulating Marrow in the Treatment of  Osteonecrosis of the Femoral Head Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Xiaojian Wang ◽  
Rui Wang ◽  
Ting Xu ◽  
Hongting Jin ◽  
Peijian Tong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Active Components ◽  
Pathway Enrichment

Abstract Background The lesion of marrow is a crucial factor in orthopedic diseases, which is recognized by orthopedics-traumatology expert from "Zhe-School of Chinese Medicine". The Chinese herbs of regulating marrow has been widely used to treat osteonecrosis of the femoral head (ONFH) in China, while the interaction mechanisms were still elucidated. Thus, we conducted this study to explore the underlying mechanism of the five highest-frequency Chinese herbs of regulating marrow(HF-CHRM) in the treatment of ONFH with the aid of network pharmacology(NP) and molecular docking(MD). Methods The active components and potential targets of HF-CHRM were obtained through several online databases, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), UniProt database. The gene targets related to ONFH were collected with the help of the OMIM and GeneCards disease-related databases. The "drug- component-target-disease" network and protein-protein interaction(PPI) network of the drug and disease intersecting targets were constructed by using Cytoscape software and the STRING database. R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The MD of critical components and targets was carried out using Autodock Vina and Pymol to validate the binding affinity. Results A total of 54 active components, 1074 drug targets and 195 gene targets were obtained. There were 1219 ONFH related targets. 39 drug and disease intersection targets(representative genes: IL6, TP53, VEGFA, ESR1, IL1B) were obtained and considered potential therapeutic targets. 1619 items were obtained by the GO enrichment analysis, including 1517 biological processes, 10 cellular components and 92 molecular functions, which is mainly related to angiogenesis, bone and lipid metabolism and inflammatory reaction. The KEGG pathway enrichment analysis revealed 119 pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway. MD results showed that quercetin, wogonin, and kaempferol active components had good affinity with IL6, TP53, and VEGFA core proteins. Conclusion The HF-CHRM can treat ONFH by multi-component, multi-target, and multi-pathway comprehensive action.

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