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Abstract：
The objective of this study was to investigate the potential targets and mechanism of Rheum palmatum L in the treatment of colorectal cancer based on the network pharmacology and molecular docking, which could provide the theoretical basis for clinical applications. The potential components were screened using TCMSP database and articles. The gene targets of colorectal cancer were screened through the Genecards database and Online Mendelian Inheritance in Man database. Then, the common targets of components and colorectal cancer were used to construct the network diagram of active components and targets in Cytoscape 3.7.0. The protein-protein interaction (PPI) diagram was generated using String database, and the targets were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular docking between gene targets and active components was analyzed via AutoDock, and visualized through PyMol. Among this study, main targets might be TP53, EGF, MYC, CASP3, JUN, PTGS2, HSP90AA1, MMP9, ESR1, PPARG. And 10 key elements might associate with them, such as aloe-emodin, beta-sitosterol, gallic acid, eupatin, emodin, physcion, cis-resveratrol, rhein, crysophanol, catechin. The treatment process was found to involve nitrogen metabolism, p53 signaling pathway, and various cancer related pathway, as well as the AGE-RAGE signaling pathway, estrogen signaling pathway, interleukin-17 signaling pathway and thyroid hormone signaling pathway. The molecular docking was verified the combination between key components and their respective target proteins. Network pharmacological analysis demonstrated that R palmatum was could regulated p53, AGE-RAGE, interleukin-17 and related signaling pathway in colorectal cancer, which might provide a scientific basis of mechanism.
摘要：
本研究以网络药理学和分子对接为基础,探讨掌叶大黄治疗结直肠癌的潜在靶点和作用机制。为临床应用提供理论依据。使用TCMSP数据库和文章筛选潜在成分。通过Genecards数据库和Man中的在线孟德尔遗传数据库筛选结直肠癌的基因靶标。然后，用组分和结直肠癌的共同靶点构建Cytoscape3.7.0中活性组分和靶点的网络图。使用String数据库生成蛋白质-蛋白质相互作用(PPI)图，并通过基因本体论和京都基因和基因组百科全书对靶标进行了进一步分析。通过AutoDock分析基因靶标和活性成分之间的分子对接，并通过PyMol可视化。在这项研究中,主要目标可能是TP53，EGF，MYC,CASS3,JUN,PTGS2、HSP90AA1、MMP9、ESR1、PPARG。10个关键要素可能与它们相关，如芦荟大黄素,β-谷甾醇,没食子酸,eupatin,大黄素,physcion,顺式白藜芦醇,rhein,冰黄酚,儿茶素.发现处理过程涉及氮代谢，p53信号通路,和各种癌症相关途径，以及AGE-RAGE信号通路，雌激素信号通路，白细胞介素-17信号通路和甲状腺激素信号通路。分子对接验证了关键组分与其各自靶蛋白之间的结合。网络药理分析表明，掌叶可以调节p53，AGE-RAGE，白细胞介素-17和相关信号通路在结直肠癌中的作用,这可能为机制提供科学依据。
