Exploring the anti-gastric cancer mechanism of action of Bidentis Bipinnatae Herba based on network pharmacology, molecular docking, and cellular experimental validation.

The purpose of this study is to explore the potential molecular mechanism of Bidentis Bipinnatae Herba against gastric cancer by using network pharmacology methods, molecular docking, and cellular experimental validation. Medicinal plants related to gastric cancer were queried through TCMSP, SymMap, and Herb databases. The TCSMP database (drug-likeness ≥ 0.18) was used to retrieve the bioactive constituents. TCSMP, SwissTargetPrediction, and Herb databases were used to retrieve the target genes, and Cytoscape software was used to construct the "active ingredient-target" network. After protein interaction analysis using String 11.0 platform, the hub genes were screened using CytoHubba. The obtained hub genes were uploaded to the cBioPortal for pathway enrichment. The genes involved in gastric cancer-related RTK-RAS pathway were molecularly docked and experimentally validated. Bidentis Bipinnatae Herba was common to TCMSP, SymMap, and Herb databases. A total of nine active ingredients were obtained in Bidentis Bipinnatae Herba, acting on 192 targets. Seven hub genes were obtained from these target genes and enriched in the RTK-RAS pathway in gastric cancer. MAPK1 and EGFR had good molecular docking results with their corresponding chemicals. Cellular experiments showed that the treatment of luteolin, quercetin, and Okanin reduced the expression of EGFR in AGS cells; the treatment of luteolin and quercetin could reduce the expression of MAPK1. Bidentis Bipinnatae Herba contained active components, which may be anti-gastric cancer in a multi-target (MAPK1 and EGFR) manner.