Study on the mechanism of Euscaphic acid in the treatment of non-Hodgkin lymphoma based on network pharmacology and molecular docking

Non-Hodgkin's lymphoma (NHL) is a highly heterogenous disease. 5-year survival duration after diagnosis is poor among patients with aggressive/relapsing form of NHL. Our previous research found for the first time that Euscaphic acid (EA) has anti-tumor effects in NHL. However, the underlying mechanism by which EA plays a role in NHL remains unclear. In this study, we used network pharmacology and molecular docking to investigate the target and mechanism of the pharmacological action of EA on NHL. The EA-related targets and NHL-related targets were collected from the public database and overlapped to obtain the potential targets of EA-related anti-NHL. Target interaction was analyzed using STRING database, and 10 core target genes (TNF, PPARG, MMP9, HSP90AA1, PTGS2, IGF1R, AR, ESR2, NR3C1, MMP2) was screened by Cytoscape software. In the GO enrichment analysis and KEGG pathway analysis, TNF, PTGS2, PPARG and MMP9 are mainly enriched in the IL-17 signaling pathway, PPAR signaling pathway. The molecular docking results show there was strong interaction between the top 10 core targets and the EA. In addition, we found that EA inhibited the proliferation of RAJI NHL cells and induced cell apoptosis. These results suggested that EA may act on TNF, PTGS2, PPARG, and MMP9 through the IL-17 and PPAR signaling pathways, thereby exerting anti-NHL effects.