OBJECTIVE  To explore the mechanism of action of Shidan Granules in the treatment of chronic atrophic gastritis by combining network pharmacology and experimental validation.

  METHODS  The active ingredients of Shidan Granules were screened through the TCMSP database and their target sites were predicted. Screening and integrating targets related to chronic atrophic gastritis through GeneCards and OMIM databases. Screening and integrating related targets of chronic atrophic gastritis through GeneCards and OMIM databases. After the intersection of active ingredient targets and chronic atrophic gastritis targets, PPI network was constructed through String 11. 0 database and the core targets were screened by Cytoscape 3. 9. 0 software. GO and KEGG enrichment analysis of core targets were carried out through DAVID database to predict the mechanism. Molecular docking verification was carried out through the AutoDock platform. The cell model of chronic atrophic gastritis was established and the results of network pharmacological analysis were verified by ELISA qPCR and Western blot.

  RESULTS  A total of 268 active ingredient targets and 484 CAG-related targets were screened and 82 targets were obtained after intersection among which IL-6 Akt1 and TNF were the core targets. The enrichment analysis of GO and KEGG suggested that Shidan Granules mainly acted through IL-17 signal pathway TNF signal pathway and PI3K-Akt signal pathway. Molecular docking results show that most core targets have high binding activity with active components. The results of cell experiments show that Shidan Granules can improve chronic atrophic gastritis by regulating IL-6 Akt1 and TNF-α.

  CONCLUSION  The various effective components in Shidan Granules can inhibit the progression of chronic atrophic gastritis to gastric cancer through multiple targets and signaling pathways, thereby reversing gastric atrophy, which provides a reference basis for subsequent research.