Comparison between Heat-Clearing Medicine and Antirheumatic Medicine in Treatment of Gastric Cancer Based on Network Pharmacology, Molecular Docking, and Tumor Immune Infiltration Analysis

Xu, Jiamin; Kang, Fuqin; Wang, Wei; Liu, Shujun; Xie, Jianhui; Yang, Xiaobo

doi:10.1155/2022/7490279

Cited by 4 publications

(3 citation statements)

References 80 publications

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“…The docking results showed that the two interacted by hydrogen bonding, and resveratrol and fisetin combined well with AKT1, CASP8, CASP3, and IL-1β, respectively. It was shown that a lower affinity represents a higher possibility of binding to both ( Liu et al, 2022 ; Xu et al, 2022 ). The core ingredients are related to resveratrol and fisetin.…”

Section: Resultsmentioning

confidence: 99%

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

et al. 2023

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Background: With the gradual increase in prevalence in recent years, non-alcoholic steatohepatitis (NASH) has become one of the significant health problems that urgently needs to be addressed worldwide. GanShuang Granules (GSG) is derived from the classical Chinese formula Xiaoyao San and mainly used in the clinical treatment of chronic liver diseases.Objective: In this study, we aim to gain a deeper insight into the inhibiting effects of GSG on non-alcoholic fatty liver disease (NAFLD) rats and preliminarily elucidate the underlying intervention mechanisms.Methods: First, High performance liquid chromatography (UHPLC-Q/Orbitrap-MS/MS) was used for the active compounds prediction in GSG. Then the data was mapped to mzCloud database. The targets corresponding to GSG compounds were collected from public databases, along with disease genes for NAFLD. The core targets and molecular mechanisms of GSG for NAFLD treatment were predicted by protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Molecular docking of the core target-component interactions was simulated using AutoDock Vina software. The effect of GSG on NASH rats was evaluated by pathological staining and analysis of various index results. Finally, the candidate targets were further validated by ELISA and western blot (WB) analyses.Results: Combining UHPLC-Q/Orbitrap-MS/MS data analysis and public database data, a total of 346 cross-targets were obtained, corresponding to 81 compounds. The subnetwork with an MCODE score of 53.623 is a potential core target group for this study. GO and KEGG enrichment analyses showed that the targets of GSG in NAFLD were mostly related to oxidative stress, the NF-κB signaling pathway, and the apoptosis signaling pathway. By integrating the results of network pharmacology analysis, the core objectives of this study mainly include AKT1, CASP9, TNF, and CASP8. The core ingredients are related to resveratrol and fisetin. The molecular docking results indicated key binding activity between AKT1-fisetin, AKT1-Resveratrol, and CASP8-fisetin. Moreover, GSG could improve the inflammatory status and restore the abnormal lipid accumulation of NAFLD/NASH liver, and these levels are further verified by pathological staining and detection of related indicators. Mechanistically, GSG could regulate protein expression levels in the liver for P65, p-P65, IKB, p-IKB, IKK, caspase-3, -8, -9, and cytochrome C, etc. It reflects the inhibitory effect of GSG on the NF-κB/IκB signaling pathway.Conclusion: Our results suggested that GSG demonstrated therapeutic effects on NAFLD/NASH rats, and these may be mainly reflected in the inhibitory effects on the NF-κB/IκB signaling pathway and its downstream inflammation and apoptosis signals.

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Section: Resultsmentioning

confidence: 99%

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

et al. 2023

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“…Studies suggest that having a low affinity indicates a higher probability of its binding [18]. Following blind docking of ligands and proteins, the free energy values were utilized to generate a heat map using the R studio (Figure 4(a)).…”

Section: E Results Of Molecular Dockingmentioning

confidence: 99%

Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer’s Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology

Liu

Wang

Hao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Yuanzhi powder (YZP) has been extensively investigated as a natural prescription with therapeutic benefits for Alzheimer’s disease (AD). However, its active compounds and underlying immune mechanism for treating AD are still unclear. This study aimed to investigate the immune mechanism of YZP against AD through high-performance liquid chromatography (HPLC)-based network pharmacology and gene chip technology. Methods. Active components of YZP were obtained from HPLC and public databases. Subsequently, GSE5281, GSE28146, GSE29378, and GSE97760 from the Gene Expression Omnibus (GEO) database were downloaded to extract AD difference genes (DEGs). The active components-targets network and protein interaction network were then constructed by Cytoscape. The biological processes and signaling pathways, which implicate the targets of YZP for AD, were analyzed using the ClueGo Cytoscape plug-in. Molecular docking experiments were performed to verify the affinity of targets and ligands. Ultimately, the link between the hub genes and immune cell infiltration was assessed via CIBERSORT. Results. 83 YZP active compounds and 641 DEGs associated with AD, including quercetin, berberine, 3,6′-disinapoylsucrose, coptisine, and palmatine, were evaluated. We showed that FOS, CCL2, and GJA1 were the core targets and that the gap junction is an essential signaling pathway in YZP for AD. Furthermore, the AD group had a higher infiltration level of naïve B cells and resting CD4 memory T cells, as determined by the CIBERSORT. Notably, the immune cells-targets network demonstrates that GJA1 and GRM1 are intimately related to naïve B cells and plasma cells. Conclusions. YZP may help treat AD by targeting proteins with key active compounds to regulate naïve B cells and plasma cells. Our results demonstrate a new immune mechanism for treating AD with YZP.

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“…Natural bioactive compounds are widely used to treat various diseases, especially cancers [23]. Natural products with potential for gastric cancer treatment have received much attention [24]. Te possible mechanisms responsible for the efect of the SLCs in the treatment of advanced gastric cancer were proposed in this study.…”

Section: Discussionmentioning

confidence: 99%

Natural Bioactive Compounds Promote Cell Apoptosis in Gastric Cancer Treatment: Evidence from Network Pharmacological Study and Experimental Analysis

Wang

2023

Journal of Chemistry

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Background. Gastric cancer (GC) is one of the most lethal cancers. Shenlian capsule (SLC) is a Chinese patent medicine made from 11 herbs containing numerous plant-derived compounds, and the clinical trials of SLCs confirmed that they had effective adjuvant therapy for a variety of cancer such as lung cancer and gastric cancer. Moreover, the HPLC fingerprint of SLCs was established from other research to find potential components. In this study, network pharmacology-based research was used to identify combinations with molecules, targets, and pathways to explore their interaction mechanisms. Methods. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and the Traditional Chinese Medicine Integrated Database (TCMID) were widely implemented in selecting the active chemical components of SLCs with an oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 18%. In addition, the TCMSP and TCMID databases obtained the targets of SLCs, and PharmMapper (PM) was used to predict targets of SLCs. Gastric cancer-related genes were provided by the GeneCards and TTD databases. Subsequently, the drug/target/pathway network was established and visualized using Cytoscape software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analyses were used to predict the potential genes and pathways of gastric cancer. Molecular docking was performed to study the interaction between ligands and targets; the interaction was visualized using Discovery Studio and PyMOL. Finally, the potential primary mechanism used by SLCs against gastric cancer was verified by cell experiments, including MTT cell apoptosis assay, flow cytometry cell cycle assay, and western blotting with HGC-27 cells (undifferentiated). Results. Of 213 active chemical components from SLCs, 35 primary active chemical components were identified, and 10 potential critical targets were selected from the 185 intersections of the targets of SLCs and GC, such as RAC-alpha serine/threonine kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin-6 (IL6), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), and epidermal growth factor receptor (EGFR). GO and KEGG enrichment analysis provided the PI3K/AKT, TNF, and p53 signaling pathways, which may be the primary signaling pathways modulating gastric cancer. Molecular docking verified targets such as AKT1, TP53, EGFR, and CASP3, which exhibited satisfactory binding capacity with active ingredients. Experiments with HCG-27 cells confirmed that SLCs may provide favorable treatment for GC by promoting CASP3 and TP53 expression to induce cell apoptosis and provided the predictions for network pharmacology and molecular docking. MTT and flow cytometry assays verified that SLCs promoted cell apoptosis and inhibited cell proliferation by triggering G0/G1 and S cell cycle arrest. In addition, western blot analysis confirmed that SLCs promoted TP53 and CASP3 overexpression, which led to HGC-27 gastric cell apoptosis. Conclusions. Our results confirmed that SLCs inhibit proliferation of HGC-27 gastric cell by promoting cell apoptosis and, therefore, have potential in the treatment of advanced gastric cancer. P53 signaling pathway was the key pathway. In addition, quercetin, matrine, and ursolic acid might be the main active ingredients.

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Comparison between Heat-Clearing Medicine and Antirheumatic Medicine in Treatment of Gastric Cancer Based on Network Pharmacology, Molecular Docking, and Tumor Immune Infiltration Analysis

Cited by 4 publications

References 80 publications

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer’s Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology

Natural Bioactive Compounds Promote Cell Apoptosis in Gastric Cancer Treatment: Evidence from Network Pharmacological Study and Experimental Analysis

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