Integrated Network Pharmacology Approach to Mongolian Medicine: Linking Bioactive Components to Anti-Gastric Cancer Pathways

This study applied a network pharmacology approach to elucidate the mechanisms underlying the therapeutic effects of Atragene sibirica L., Ranunculus repens L., and Pulsatilla bungeana C.A. Mey. in the treatment of gastric cancer (GC). In traditional Mongolian medical literature, these three Ranunculaceae species are collectively referred to as the “Hot-Natured Three Herbs” (HN3h-s). Active ingredients were screened using Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), followed by target retrieval from GeneCards, and DrugBank. “Protein–protein interaction” (PPI) networks were constructed with STRING, GO annotation and KEGG pathway enrichment analyses were performed using Metascape, and Cytoscape 3.8.0 was used to construct the compound–target–pathway network. Quantities of phenolics and flavonoids were determined spectrophotometrically. Phytochemical analysis indicated that the HN3h-s extract is rich in flavonoids (2.16±0.05%) and contains a medium level of total phenolics (2.98±0.04%). Ten key phytochemicals were identified, including kaempferol, quercetin, anemonin, isovitexin, magnoflorine, isorhamnetin, ferulic acid, mairin, aureusidin, and β-sitosterol. These compounds were linked to 382 gastric cancer-related targets, of which 36 overlapped. Core targets such as TLR4, MMP2, MMP9, PTGS2, PPARG, STAT3, MAPK8, PIK3CG, and NFE2L2 were highlighted in the PPI network. Functional enrichment revealed significant involvement of pathways related to tumorigenesis, including TNF, MAPK, NF-κB, IL-6, and prostaglandin signaling cascades. HN3h-s may exert therapeutic benefits against gastric cancer through a multi-component, multi-target, and multi-pathway approach, providing a modern pharmacological basis for their traditional use.