Fond farewell to clinical utility gene cards

McNeill, Alisdair

doi:10.1038/s41431-021-00957-z

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…Inflammation-related targets were clarified by combining data from the following databases: Human genetic database (GeneCards) [ 21 ], DrugBank [ 22 ], Therapeutic Target Database (TTD) [ 23 ], and Mendelian Genetic Database (OMIM) [ 24 ]. The key word was “inflammation or bacteria”, and the results were restricted to “human”.…”

Section: Methodsmentioning

confidence: 99%

Exploring the Molecular Mechanism of HongTeng Decoction against Inflammation based on Network Analysis and Experiments Validation

Yang

et al. 2024

CAD

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Background: HongTeng Decoction (HTD) is a traditional Chinese medicine that is widely used to treat bacterial infections and chronic inflammation. However, its pharmacological mechanism is not clear. Here, network pharmacology and experimental verification were applied to investigate the drug targets and potential mechanisms of HTD in inflammation treatment. Materials and methods: The active ingredients of HTD were collected from the multi-source databases and clarified by Q Exactive Orbitrap analysis in the treatment of inflammation. Then, molecular docking technology was used to explore the binding ability of key active ingredients and targets in HTD. In vitro experiments, the inflammatory factors and MAPK signaling pathways are detected to verify the anti-inflammatory effect of HTD on the RAW264.7 cells. Finally, the anti-inflammatory effect of HTD was evaluated in LPS induced mice model. Result: A total of 236 active compounds and 492 targets of HTD were obtained through database screening, and 954 potential targets of inflammation were identified. Finally, 164 possible targets of HTD acting on inflammation were obtained. The PPI analysis and KEGG enrichment analyses showed that the targets of HTD in inflammation were mostly related to the MAPK signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. By integrating the results of the network analysis, the core targets of HTD in inflammation mainly include MAPK3, TNF, MMP9, IL6, EGFR, and NFKBIA. The molecular docking results indicated solid binding activity between MAPK3-naringenin and MAPK3-paeonol. It has been shown that HTD could inhibit the levels of inflammatory factors, IL6 and TNF-α, as well as the splenic index in the LPS-stimulated mice. Moreover, HTD could regulate protein expression levels of p-JNK1/2, and p-ERK1/2, which reflects the inhibitory effect of HTD on the MAPKS signaling pathway. Conclusion: Our study is expected to provide the pharmacological mechanisms by which HTD may be a promising anti-inflammatory drug for future clinical trials.

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Section: Methodsmentioning

confidence: 99%

Exploring the Molecular Mechanism of HongTeng Decoction against Inflammation based on Network Analysis and Experiments Validation

Yang

et al. 2024

CAD

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“…The NAFLD-related human gene targets were mainly retrieved from three databases: Human genetic database (GeneCards) ( He et al, 2020 ; McNeill, 2021 ), Human Online Mendelian Genetic Database (OMIM) ( Amberger et al, 2015 ), and Genetic Pharmacology and Pharmacogenomics Database (PharmGKB) ( Barbarino et al, 2018 ; Mitra-Ghosh et al, 2020 ). The gene names were calibrated using the UniProt database ( UniProt, 2019 ; UniProt, 2021 ).…”

Section: Methodsmentioning

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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Fond farewell to clinical utility gene cards

Cited by 2 publications

References 10 publications

Exploring the Molecular Mechanism of HongTeng Decoction against Inflammation based on Network Analysis and Experiments Validation

Exploring the Molecular Mechanism of HongTeng Decoction against Inflammation based on Network Analysis and Experiments Validation

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

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