关键词: 结直肠癌, 白芍, 半边莲, 信号通路

Abstract: Objective　To explore the active ingredients and molecular mechanism of Paeonia-Lobelia against colorectal cancer based on network pharmacological analysis. Methods　The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search the active ingredients and targets of Paeonia and Lobelia until December 2024. The GeneCards, Therapeutic Target Database (TTD), and other databases were used to screen colorectal cancer related targets. The Cytoscape (Version 3.9.1) software was used to build a drug component potential target network diagram. A protein-protein interaction (PPI) network diagram was constructed using the STRING database platform to screen out the core genes. The expression and survival analysis of the core targets were validated using the GEPIA and HPA databases. Finally, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analyses on the potential targets were performed using the WebGestalt and Metascape databases. Results　Fifteen active ingredients of Paeonia and 17 active ingredients of Lobelia were screened through the TCMSP. The intersection of Paeonia and Lobelia with colorectal cancer targets was obtained using the Venn diagram, with a total of 19 potential targets. Further calculation and analysis of the drug target network relationship diagram resulted in the identification of five key components in the anti-colorectal cancer properties of Paeonia and Lobelia, including quercetin, luteolin, kaempferol, acacetin, and catechin. Through PPI network analysis, 10 core targets that may be drug-acting diseases were identified, including tumor protein P53 (TP53), MYC gene, AKT serine/threonine kinase 1 (AKT1), caspase 3 (CASP3), cyclin D1 (CCND1), NF-kappa-B inhibitor alpha (NFKBIA), matrix metallopeptidase 9 (MMP9), inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)), prostaglandin-endoperoxide synthase 2 (PTGS2), and heat shock protein family A (Hsp70) member 5 (HSPA5). The GO enrichment analysis showed that Paeonia and Lobelia were mainly related to biological functions such as enzyme regulatory activity, antioxidant activity, and cell proliferation; the KEGG enrichment analysis showed that the main signaling pathways involved in the anti-colorectal cancer effect of Paeonia and Lobelia were the TNF signaling pathway, PI3K/AKT signaling pathway, FoxO signaling pathway, etc. Conclusion　Paeonia and Lobelia may exert their anti-colorectal cancer effects through multiple ingredients, targets, and pathways.

Key words: Colorectal cancer, Paeonia, Lobelia, Signal pathways