BACKGROUND

Gastric cancer (GC) is a common fatal malignancy. The aim of this study was to explore and validate the tumor-suppressive role and mechanism of in GC.

METHODS

The active constituents of were screened using TCMSP database. SwissTargetPrediction database was used to predict potential target genes of the compounds. GeneCards, TTD, DisGeNET, OMIM, and PharmGKB databases were used to search for GC-related targets. STRING database and Cytoscape 3.10 software were used for protein-protein interaction network construction and screening of core targets. DAVID database was used for GO and KEGG analyses. Core targets were validated using molecular docking. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry after GC cells were treated with isorhamnetin. The mRNA and protein expression levels of genes were detected using qRT PCR and Western blot. The metastasis potential of GC cells was evaluated in a nude mouse model.

RESULTS

A total of 371 potential targets were retrieved by searching the intersection of and GC targets. Petunidin, 3',4',5',3,5,6,7-Heptamethoxyflavone, quercetin, kaempferol, and isorhamnetin were identified as the main bioactive compounds in . SRC, HSP90AA1, AKT1, and EGFR, were core targets through which suppressed GC. The tumor-suppressive effect of on GC was mediated by multiple pathways, including PI3K-AKT, cAMP, and TNF signaling. The key compounds of had good binding affinity with the core target. Isorhamnetin, a key component of , could inhibit proliferation and metastasis, and induces apoptosis of GC cells. In addition, isorhamnetin could also reduce the mRNA expression of core targets, and the activation of PI3K/AKT pathway.

CONCLUSION

This study identified potential targets and pathways of against GC through network pharmacology and molecular docking, providing new insights into the pharmacological mechanisms of in GC treatment.