基于网络药理学探讨大复方祛邪胶囊治疗结直肠癌的作用机制

Exploring the Mechanism of a Great Prescription(Quxie Capsule)in Treatment of Colorectal Cancer Based on Network Pharmacology

目的:大复方祛邪胶囊是基于明代医家李中梓治疗积聚的名方——阴阳攻积丸研制而成,文章通过网络药理学方法挖掘其对结直肠癌的作用机制,为揭示经典名方阴阳攻积丸的临床价值和现代机制提供借鉴。方法:通过中药系统药理学数据库与分析平台(TCMSP)、中医药百科全书(ETCM)等数据库筛选祛邪胶囊的活性成分及靶点,通过Swiss Target Prediction靶标垂钓,取药物靶点的并集。通过TTD、OMIM、Drugbank和GeneCards数据库筛选结直肠癌的靶点,取并集。取药物靶点与疾病靶点的交集,并依据化合物的Degree值筛选,建立"中药-成分-靶点"数据库,依据核心靶点构建蛋白质-蛋白质相互作用(PPI)网络,进行基因本体(GO)功能和京都基因和基因组百科全书(KEGG)富集分析,与前期研究结果进行对比。结果:构建祛邪胶囊治疗结直肠癌的活性成分127个,靶向254个核心基因,核心基因的PPI网络包含248个节点,共有5个核心网络。富集分析显示祛邪胶囊可能主要通过调控RNA聚合酶的启动、DNA转录、翻译、蛋白的激活和增殖、凋亡、耐药、炎症反应等过程介导HIF-1α、PI3K/Akt、TNF、FoxO、Toll样受体等多个信号通路,其中凋亡、免疫方面的调节及FoxO信号通路得到本团队前期研究的验证。结论:祛邪胶囊治疗结直肠癌的作用机制与介导凋亡、免疫及FoxO信号通路方面有关,此外还可能调控HIF-1α、PI3K/Akt、TNF、Toll样受体等多个信号通路,体现了祛邪胶囊治疗结直肠癌成分多、调控通路和靶点复杂的特点,同时展现了古人"反激逆从"和"温阳通下"论治肿瘤的理论魅力和临床价值,为后续的深入研究提供指导。

Objective:Dafufang Quxie Capsules are developed based on the famous prescription Yinyang Gongji Pills used by the physician LI Zhongzi in the Ming Dynasty to treat accumulation.The uses network pharmacology to explore its mechanism of action on colorectal cancer,in order to reveal the classic prescription Yin Yang Gongji Pills Provide reference for clinical value and modern mechanism.Methods:TCMSP,ETCM and other databases were searched to establish the database of active ingredients and targets of Quxie Capsules.Fishing through the Swiss Target Prediction target,we took the union of the drug targets.Through TTD,OMIM,Drugbank and GeneCards databases,we screened the targets of colorectal cancer and took the union.We took the intersection of drug target and disease target,and screened according to the degree value of the compound,established a"Chinese medicine-component-target"database,constructed a PPI network based on the core target,performed GO function and KEGG enrichment analysis,and compared the results with preliminary research.Results:The final data about Quxie Capsule for the treatment of colorectal cancer had 127 active ingredients targeting 254 core genes.The PPI network contains 248 core genes,and there were 5 subnet networks in total.Enrichment analysis results showed that Quxie Capsules may mediate HIF1α,PI3 K/AKT,TNF,FoxO,Toll-like receptors through processes such as the initiation of RNA polymerase,DNA transcription,translation,protein activation and proliferation,apoptosis,drug resistance,and inflammation.And many other signaling pathways,among which the regulation of apoptosis,immunity and FoxO signaling pathway have been verified by our team′s previous research.Conclusion:Mechanism of Quxie Capsules on the treatment of colorectal cancer is related to mediating apoptosis,immunity and FoxO signaling pathway.In addition,it may also regulate multiple signaling pathways such as HIF1α,PI3 K/AKT,TNF,and Toll-like receptors.This revealed that Quxie Capsules have many components in the treatment of colorectal cancer,and its regulatory pathways and targets are complex.At the same time,it demonstrates the theoretical charm and clinical value of the ancients′"anti-excitement and rebellion"and"warming yang and ventilating the lower part"theory of treating tumors,providing guidance for follow-up in-depth research.