Explore and verify the mechanism of action of Lizhong Wan in treatment of chronic atrophic gastritis based on network pharmacology and in vitro experimental method
Objective To investigate the molecular mechanism of Lizhong Wan in treatment of chronic atrophic gastritis (CAG) using network pharmacology and in vitro experimental method. Methods The active ingredients of Lizhong Wan were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the related targets were obtained from PubChem and Swiss Target Prediction databases. The CAG-related targets were obtained from GeneCards,OMIM and DisGeNET databases. The drug-disease common targets of Lizhong Wan and CAG were obtained by Venn tool. The interaction network of common targets of Lizhong Wan and CAG was constructed with the help of STRING database,and the drug-disease-target-pathway network was constructed with the help of Cytoscape software. Gene function and pathway enrichment analyses were performed on the common targets. The molecular docking and binding ability of the active ingredients of the drug and the key targets were predicted by using Moe software. The mice of spleen and stomach deficiency cold syndrome CAG was established. The effects of Lizhong Wan on the morphological changes of gastric tissue,apoptosis of gastric mucosa cells and the expression of messenger RNA (mRNA) and protein of the key target of CAG were observed. Results A total of 57 active ingredients of Lizhong Wan were screened,including arachidonic acid,ginsenoside Rg5,gomisin B,aposiopolamine and ginsenoside Rh2. 869 active targets of Lizhong Wan were obtained. CAG and Lizhong Wan had 47 common targets,the key common targets including tumor protein P53 (TP53),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),epidermal growth factor receptor (EGFR),B-cell lymphoma 2 (Bcl-2),etc.. A total of 135 pathways were obtained by enrichment analysis,mainly including tumor pathogenesis,proteoglycan in tumor,cholinergic synapse,phosphoinositide 3-kinase/protein kinase B signaling pathway,etc.. Molecular docking results showed that TP53,IL-6,TNF-α,EGFR,Bcl-2 had good binding activity with gomisin B and ginsenoside Rh2. Meanwhile,in vitro experimental found that the scores of spleen and stomach deficiency cold syndrome in model group were significantly higher than those in blank group. Lizhong Wan could improve the pathological changes of CAG mice,could significantly reduce the apoptosis of gastric mucosa cells,could significantly reduce the expression of mRNA and protein of TP53,IL-6,TNF-α,EGFR,Bcl-2. Conclusion The effect of Lizhong Wan in treating CAG with spleen and stomach deficiency cold syndrome may be related to regulating the expression of TP53,IL-6,TNF-α,EGFR and Bcl-2,alleviating inflammation and reducing apoptosis of gastric mucosa cells.
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