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Exploring the potential pharmacodynamic material basis and pharmacologic mechanism of the Fufang-Xialian-Capsule in chronic atrophic gastritis by network pharmacology approach based on the components absorbed into the blood.

ABSTRACT: In this study, a new network pharmacology approach based on the components absorbed into the blood was used to investigate the pharmacodynamic material basis and the pharmacologic mechanism of the Fufang-Xialian-Capsule (FXL) in treating chronic atrophic gastritis (CAG). Initially, we confirmed the components absorbed into the blood by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the network approach, which was based on the results of components absorbed into the blood, was used to analyse the pharmacodynamic material basis and the pharmacologic mechanism of FXL on treating CAG. As a result, 22 absorbed components were found in rat plasma. Given the results of the absorption analysis of the components, eight pathways associated with CAG development were found. The targets linked to these pathways are the drug targets of FXL in CAG treatment. The components associated with these targets are the potential pharmacodynamic material basis and exert synergy in regulating pathways during CAG treatment.

SUBMITTER: Li S

PROVIDER: S-EPMC6030346 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Exploring the potential pharmacodynamic material basis and pharmacologic mechanism of the Fufang-Xialian-Capsule in chronic atrophic gastritis by network pharmacology approach based on the components absorbed into the blood.

Li Shizhe S Xu Tengfei T Liu Shu S Liu Zhiqiang Z Pi Zifeng Z Song Fenrui F Jin Yongri Y

Royal Society open science 20180613 6

In this study, a new network pharmacology approach based on the components absorbed into the blood was used to investigate the pharmacodynamic material basis and the pharmacologic mechanism of the Fufang-Xialian-Capsule (FXL) in treating chronic atrophic gastritis (CAG). Initially, we confirmed the components absorbed into the blood by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the network approach, which was based o ...[more]

PMID: 30110485

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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: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.

Dataset Information

Exploring the potential pharmacodynamic material basis and pharmacologic mechanism of the Fufang-Xialian-Capsule in chronic atrophic gastritis by network pharmacology approach based on the components absorbed into the blood.

Publications

Exploring the potential pharmacodynamic material basis and pharmacologic mechanism of the <i>Fufang-Xialian-Capsule</i> in chronic atrophic gastritis by network pharmacology approach based on the components absorbed into the blood.

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