关键词:

防己, 红参, 结直肠癌, 网络药理学, 作用机制

Abstract:

Objective　To explore the effective ingredients and potential molecular mechanism of stephania tetrandra (ST)-red ginseng (RG) in the treatment of patients with colorectal cancer based on network pharmacology analysis methods. Methods　The effective active ingredients and corresponding targets of ST and RG were screened by the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and were intersected with colorectal cancer related targets to obtain potential targets for drug resistance to colorectal cancer. A drug-target network relationship diagram was constructed to screen the key components. The core targets were screened through the protein-protein interaction (PPI) network diagram in the String database, and the expression of core targets in the GEPIA and HPA databases were verified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the potential targets using the WebGestalt and Metascape databases. When P0.05, there is a statistical difference. Results　Ten effective ingredients of ST and 19 effective ingredients of RG were screened from the TCMSP. Seventy-one potential targets for drugs against colorectal cancer were obtained by the Wayne diagram. Further calculation and analysis of the drug target network relationship diagram obtained 5 key components of ST-RG against colorectal cancer, including beta-Sitosterol, (+)-Stepharine, Menisperine, Magnoflorine, and Ginsenoside Rh2; 6 core targets were obtained through PPI network screening, including tumor necrosis factor (TNF), heat shock protein 90ɑB1 (HSP90AB1), prostaglandin-endoperoxide synthase (PTGS2), protein kinase A catalytic subunit (PRKACA), dopamine receptor D2 (DRD2), and serotonin transporter (SLC6A4). The GO enrichment analysis showed that ST-RG was mainly involved in biological function processes, such as cell proliferation, metabolic progress, antioxidant activity, etc. (all P0.01). According to the enrichment analysis of KEGG signal pathway, ST-RG involved in colorectal cancer, non-small cell lung cancer, prostate cancer, arterial atherosclerosis, and other disease pathways (all P0.01); the signal pathways were mainly enriched in cAMP, cGMP-PKG, PI3K/AKT (all P0.01), etc. Conclusion　Through network pharmacology analysis, the effective ingredients and potential mechanisms of ST-RG in the treatment of patients with colorectal cancer are elucidated at the molecular level, indicating that ST-RG may synergistically exert anti-cancer effects through multiple components, targets, and pathways.

Key words:

Stephania tetrandra, Red ginseng, Colorectal cancer, Network pharmacology, Mechanism