Study on the Mechanism of Jiedu Sanjie Formula in the Treatment of Gastric Cancer Based on Network Pharmacology and Molecular Docking

Abstract

Objective: This study aimed to investigate the potential active ingredients, core targets and molecular mechanisms of Jiedu Sanjie Formula in the treatment of gastric cancer, thereby providing a theoretical basis for its clinical application and experimental research. Methods: The effective ingredients and corresponding targets of Jiedu Sanjie Formula were screened using TCMSP, TCMID and HERB databases, as well as network resources, including GeenMedical and Chinese literature. Gastric cancer-related targets were retrieved from DrugBank, OMIM, TTD and GeneCards databases. With STRING platform, the protein-protein interaction network was established, from which core targets were identified. GO functional enrichment and KEGG pathway enrichment analyses were performed using the DAVID database, and the pathway-target network diagram was visualized with Gephi 0.9.2. Finally, molecular docking was conducted with AutoDock Tool-1.5.7, and the results were visualized by PyMOL software. Results: A total of 38 active ingredients were identified in Jiedu Sanjie Formula, corresponding to 859 drug-related targets, among which 497 overlapped with gastric cancer targets. The main active ingredients included quercetin, stigmasterol, cinobufagin, and cinobufotalin. Mechanistically, the formula exerted anti-gastric cancer effects by acting on core targets such as AKT1, AKT3, MAP2K1, PIK3R1 and PIK3CD, thereby regulating tumor-related signaling pathways including the PI3K-Akt pathway, HIF-1 pathway and cancer-related pathways. Molecular docking results confirmed good binding affinity between core active ingredients and key targets. Conclusion: Based on network pharmacology prediction, Jiedu Sanjie Formula can synergistically mediate the pathological processes such as proliferation and apoptosis of gastric cancer cells through multi-component, multi-target and multi-pathway modes. Its anti-gastric cancer mechanism is closely related to the regulation of classical tumor signaling pathways, providing theoretical support for subsequent basic experimental validation and clinical translation.