Medicine for Chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis

Abstract

AbstractPurpose The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine in the clinical intervention for chronic atrophic gastritis through meta-analysis and network pharmacology verification. Methods A predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wang Fang Data, and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials 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 traditional Chinese medicine formulation in the experimental group was analyzed, and association rule mining was performed to identify hub herbal medicines. Target genes for chronic atrophic gastritis 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 (PPI) networks were constructed to identify hub genes and conduct molecular docking with differentially expressed genes and corresponding active molecules. Results A total of 1,140 participants from 12 randomized controlled trials were included in the statistical analysis, confirming that the experimental group receiving the addition of traditional Chinese medicine (TCM) intervention had better clinical efficacy. Seven hub TCMs (White Peony Root, Largehead Atractylodes Rhizome, Pinellia Tuber, Tangerine Peel, Root of Pilose Asiabell, Danshen Root, and Coptis Root) were identified through association rule analysis of all included TCMs. Thirteen core hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14, AKT1) were obtained from 90 gene PPI networks. Differential gene expression analysis between the disease and normal gastric tissue identified FOS and JUN as the significant genes. Molecular docking analysis revealed that Baicalein, Quercetin, Tanshinone iia, Kaempferol, Luteolin, Beta-sitosterol, and Nobiletin 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. Conclusion The study indicates that TCM intervention can improve the clinical treatment efficacy of chronic atrophic gastritis (CAG). The identified hub genes and hub TCM targets 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.