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

摘要：

目的　基于网络药理学分析方法探讨防己-红参抗结直肠癌的有效成分和潜在分子机制。方法　通过中药系统药理学数据库和分析平台（Chinese Medicine System Pharmacology Database，TCMSP）筛选防己和红参的有效活性成分及对应靶点，与结直肠癌相关靶点进行交集，获得药物抗结直肠癌的潜在靶点，构建药物-靶点网络关系图，筛选关键成分。通过String数据库构建蛋白质-蛋白质相互作用（PPI）网络图筛选核心靶点，其次在GEPIA和HPA数据库验证核心靶点表达情况。利用WebGestalt和Metascape数据库对潜在靶点进行基因本体论（GO）和京都基因与基因组大百科全书数据库（KEGG）富集分析。以P0.05为差异有统计学意义。结果　通过TCMSP平台筛选获得防己有效成分10种，红参有效成分19种，利用维恩图交集获得药物抗结直肠癌潜在靶点71个，对药物-靶点网络关系图进一步计算分析获得防己-红参抗结直肠癌5种关键成分，包括β-谷甾醇（beta-Sitosterol）、千金藤碱［（+）-Stepharine］、蝙蝠葛林碱（Menisperine）、木兰花碱（Magnoflorine）、人参皂苷Rh2（ginsenoside Rh2），通过PPI网络图筛选获得6个核心靶点，分别是肿瘤坏死因子（TNF）、热休克蛋白90ɑB1（HSP90AB1）、前列腺素内过氧化物合酶（PTGS2）、蛋白激酶A催化亚基（PRKACA）、多巴胺受体D2（DRD2）和5-羟色胺转运蛋白（SLC6A4）。GO富集分析显示，防己-红参抗结直肠癌主要参与细胞增殖、代谢进展、抗氧化活性等生物功能过程（均P0.01）；根据KEGG信号通路富集分析，防己-红参涉及结直肠癌、非小细胞肺癌、前列腺癌、动脉粥样硬化等疾病通路（均P0.01），信号通路主要富集于cAMP、cGMP-PKG、PI3K/AKT（均P0.01）。结论　通过网络药理学分析方法从分子水平阐明防己-红参抗结直肠癌的有效成分和潜在作用机制，防己-红参可能通过多种成分、多个靶点、多条途径协同发挥抗癌效果。

关键词:

防己, 红参, 结直肠癌, 网络药理学, 作用机制