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Network Pharmacology Approach to Investigate the Mechanism of Modified Liu Jun Zi Decoction in the Treatment of Chronic Atrophic Gastritis.

ABSTRACT: Although modified Liu Jun Zi decoction (MLD) has favorable outcomes for chronic atrophic gastritis (CAG) in clinics, the identification of its active ingredients and the molecular mechanism of pharmacology are still unknown and need to be solved urgently. In the study, we screened 170 active components of MLD based on oral bioavailability ≥30% and drug-likeness ≥0.18 via the TCMSP platform. We further establish a dataset containing 315 CAG targets from PharmGkb, GeneCard, OMIM, DrugBank database, and Therapeutic Target database. Network pharmacology found that there are 110 active components of MLD and 26 potential targets for CAG in the "ingredient-target" network. The results of gene ontology analysis show that these targets are involved mainly in reactive oxygen species metabolic process, regulation of vasculature development, and T cell activation. KEGG pathways analysis indicates that these signaling pathways in the treatment of CAG include HIF-1 signaling pathway, neurodegeneration-multiple diseases pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. Finally, docking of the active component quercetin and clinical medicine Omeprazole with the core targets was carried out. We found that quercetin, a crucial active ingredient in MLD, has good binding activity with potential targets of CAG, and its molecular conformation is stable, which is better than the binding energy of Omeprazole. So, the active ingredients of MLD exhibit good potential drugs for the treatment of CAG.

SUBMITTER: Zhou M

PROVIDER: S-EPMC9232340 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Network Pharmacology Approach to Investigate the Mechanism of Modified Liu Jun Zi Decoction in the Treatment of Chronic Atrophic Gastritis.

Zhou Ming M

Evidence-based complementary and alternative medicine : eCAM 20220617

Although modified Liu Jun Zi decoction (MLD) has favorable outcomes for chronic atrophic gastritis (CAG) in clinics, the identification of its active ingredients and the molecular mechanism of pharmacology are still unknown and need to be solved urgently. In the study, we screened 170 active components of MLD based on oral bioavailability ≥30% and drug-likeness ≥0.18 via the TCMSP platform. We further establish a dataset containing 315 CAG targets from PharmGkb, GeneCard, OMIM, DrugBank database ...[more]

PMID: 35754680

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Project description:BackgroundChronic atrophic gastritis (CAG) is an important stage in the normal gastric mucosa's transformation into gastric cancer. Huazhuojiedu decoction (HZJD), a Chinese herbal preparation, has proven clinically effective to treat CAG. However, few studies have explored the mechanism of HZJD in CAG treatment.PurposeThis study aimed to shed light on the mechanisms underlying HZJD decoction CAG treatment using a network pharmacology approach and experimental validation.MethodsThe active components of HZJD decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Their targets were predicted through the SwissTargetPrediction database. Disease targets were screened using the GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets, which then were input into the Search Tool for the Retrieval of Interacting Genes to build a protein-protein interaction network. The "herb-compound-target-disease" and the "herb-target-pathway" network diagrams were constructed in Cytoscape 3.3.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of effective targets were performed using the Database for Annotation, Visualization, and Integrated Discovery. Finally, the core targets were preliminarily verified by CAG rat model. The gastric mucosa's histopathological changes were observed via hematoxylin-eosin staining. The expressions of MAPK1, AKT1, TNF, VEGFA, and EGFR were detected by western blot and quantitative real-time reverse transcription-polymerase chain reaction.ResultsA total of 155 nodes, including 20 putative targets of HZJD decoction, were selected as core hubs based on topological importance and were closely associated with the regulation of cell proliferation, apoptotic process, and cancer-related pathways (AKT1, TNF, VEGFA, and EGFR) in CAG. Further animal experiments showed that the expression of AKT1 in CAG rats was significantly increased, which was suppressed by HZJD decoction. TNF and VEGFA expression increased in the model group, but did not change in the HZJD group. MAPK1 and EGFR expression showed no significant differences among control, model, and HZJD groups.ConclusionTaken together, the results suggest that the components of HZJD decoction can alleviate and prevent the severity of gastric precancerous lesions via AKT1 inhibition in CAG.

Project description:PurposeThe aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs).MethodsA predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials (RCTs) were included for meta-analysis to provide clinical evidence of the intervention effects. A network meta-analysis using Bayesian networks was conducted to observe the relative effects of different intervention measures and possible ranking of effects. The composition of the TCM formulation in the experimental group was analysed, and association rule mining was performed to identify hub herbal medicines. Target genes for CAG were searched in GeneCards, Online Mendelian Inheritance in Man, PharmGKB, Therapeutic Target Database and DrugBank. A regulatory network was constructed to connect the target genes with active ingredients of the hub herbal medicines. Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the central targets from a comprehensive viewpoint. Protein-protein interaction networks (PPINs) were constructed to identify hub genes and conduct molecular docking with differentially expressed genes (DEGs) and corresponding active molecules.ResultsA total of 1140 participants from 12 RCTs were included in the statistical analysis, confirming that the experimental group receiving the addition of TCM intervention had better clinical efficacy. Seven hub TCMs (Paeonia lactiflora, Atractylodes macrocephala, Pinellia ternata, Citrus reticulata, Codonopsis pilosula, Salvia miltiorrhiza and Coptis chinensis) were identified through association rule analysis of all included TCMs. Thirteen hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14 and AKT1) were obtained from 90 gene PPINs. Differential gene expression analysis between the disease and normal gastric tissue identified MAPK1 and MAPK3 as the significant genes. Molecular docking analysis revealed that naringenin, luteolin and quercetin were the main active compounds with good binding activities to the two hub targets. GO analysis demonstrated the function of the targets in protein binding, while KEGG analysis indicated their involvement in important pathways related to cancer.ConclusionsThe results of a meta-analysis of 12 RCTs indicate that TCM intervention can improve the clinical treatment efficacy of CAG. NPAs identified seven hub TCM and 13 target genes associated with their actions, while bioinformatics analysis identified two DEGs between normal and CAG gastric tissues. Finally, molecular docking was employed to reveal the mechanism of action of the active molecules in TCM on the DEGs. These findings not only reveal the mechanisms of action of the active components of the TCMs, but also provide support for the development of new drugs, ultimately blocking the progression from chronic gastritis to gastric cancer.

Project description:BackgroundCutaneous squamous cell carcinoma (cSCC), a kind of skin cancer with high rates of morbidity and mortality, occurs frequently in the clinic. Although early surgical treatment can achieve good results, there is no effective prevention and treatment for the recurrence and metastasis of cSCC. As a useful resource to protect humans from disease, traditional Chinese medicine (TCM) has been adopted by clinicians for thousands of years.MethodsIn this study, we collected a Chinese medicine formula and then employed a data mining method to analyze drug combinations of Si-Jun-Zi (SJZ) decoction. Multiple databases were used in this study to predict various ingredients, compounds, and their targets in the decoction. The potential targets of cSCC were also obtained from the database in the same way. In addition, as bioinformatics analysis methods, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used in our research as supplementary means to network pharmacology. Finally, we used ultra-performance liquid chromatography (UPLC) fingerprinting to analyze the effective components of the TCM decoction.ResultsWe detected 559 active compounds from Ginseng, Largehead Atractylodes, India Bread, and Glycyrrhiza Inflata, and selected 136 molecules under specific conditions. The mechanisms of the TCM formula were illustrated by the network pharmacology, such as compounds-herb network, compounds-target network, disease-target network, and target-target interaction network, as well as characteristics of the TCM. Then, GO analysis and KEGG analysis were performed on the compounds in the network using multiple methods of data mining and bioinformatics, and 10 candidate targets were identified. In addition, the UPLC fingerprinting method was used to analyze the components of SJZ decoction.ConclusionsNetwork pharmacology was performed to investigate the characteristics and mechanism of SJZ decoction, and a bioinformatics method was used to analyze the relationship between the effective compounds of the SJZ TCM decoction and cSCC-related specific targets and pathways, to find a variety of candidate compounds with multi-target activity.

Dataset Information

Network Pharmacology Approach to Investigate the Mechanism of Modified Liu Jun Zi Decoction in the Treatment of Chronic Atrophic Gastritis.

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Network Pharmacology Approach to Investigate the Mechanism of Modified Liu Jun Zi Decoction in the Treatment of Chronic Atrophic Gastritis.

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