Network Pharmacology-Based Approach to Investigate the Mechanisms of Hedyotis diffusa Willd. in the Treatment of Gastric Cancer

BACKGROUND: Hedyotis diffusa Willd. (HDW) is one of the renowned herbs often used in the treatment of gastric cancer (GC). However, its curative mechanism has not been fully elucidated. OBJECTIVE: To systematically investigate the mechanisms of HDW in GC. METHODS: A network pharmacology approach mainly comprising target prediction, network construction, and module analysis was adopted in this study. RESULTS: A total of 353 targets of the 32 bioactive compounds in HDW were obtained. The network analysis showed that CA isoenzymes, p53, PIK3CA, CDK2, P27(Kip1), cyclin D1, cyclin B1, cyclin A2, AKT1, BCL2, MAPK1, and VEGFA were identified as key targets of HDW in the treatment of GC. The functional enrichment analysis indicated that HDW probably produced the therapeutic effects against GC by synergistically regulating many biological pathways, such as nucleotide excision repair, apoptosis, cell cycle, PI3K/AKT/mTOR signaling pathway, VEGF signaling pathway, and Ras signaling pathway. CONCLUSIONS: This study holistically illuminates the fact that the pharmacological mechanisms of HDW in GC might be strongly associated with its synergic modulation of apoptosis, cell cycle, differentiation, proliferation, migration, invasion, and angiogenesis.