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基于网络药理学探讨消瘰丸治疗恶性淋巴瘤作用机制

Research on the mechanism of Xiaoluo Bolus in treating malignant lymphoma based on network pharmacology

摘要目的:基于网络药理学方法分析消瘰丸治疗恶性淋巴瘤的作用机制,为新药研发及经典方剂的临床运用提供参考。方法:通过TCMSP数据库获取玄参、浙贝母、牡蛎的主要化学成分及其靶点,根据ADME筛选中药活性成分;通过GeneCards、OMIN、TTD、DURGBANK数据库获取恶性淋巴瘤主要靶点,运用Cytoscape中BisoGenet功能筛选出消瘰丸治疗恶性淋巴瘤的主要靶点,并构建消瘰丸成分-恶性淋巴瘤靶点蛋白相互作用网络;应用Metascape数据平台对消瘰丸治疗恶性淋巴瘤的相关靶点进行生物信息学富集分析,应用Cytoscape软件构建消瘰丸成分-恶性淋巴瘤靶点-通路网络。结果:消瘰丸治疗恶性淋巴瘤的核心有效成分为玄参苷、浙贝素、花葵素、碳酸钙,作用靶点为PRS27A、TP53、PPP2CA,主要作用于NF-κB、HIF-1通路,其功能主要为通过rDNA染色体沉默、巨细胞分化程度的调控发挥作用,而2条通路共同作用的去泛素化功能可能是消瘰丸治疗恶性淋巴瘤的主要治疗靶点。结论:本研究揭示了消瘰丸治疗恶性淋巴瘤的多成分、多靶点、多通络的作用机制,为消瘰丸的临床开发利用提供基础。

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abstractsObjective:To analyze the pharmacological mechanism of Xiaoluo Bolus in treating Malignant Lymphoma based on network pharmacology so as to provide references for the R&D of new drugs and clinical use of classic formulation.Methods:This paper collected the main chemical components of Scrophulariaceae, Fritillaria, Oyster and their targets through TCMSP Database and selected active ingredients according to ADME. The main lymphoma target genes were acquired by GeneCards, OMIN, TTD, DURGBANK database. The main targets of Xiaoluo Bolus treating lymphoma were screened by using BisoGenet function in Cytoscape and PPI network of Xiaoluo Bolus compounds-Malignant Lymphoma target was constructed. Metascape data platform was used to analyze signal pathways of Xiaoluo Bolus and construct the network of Xiaoluo Bolus compounds-Malignant Lymphoma target-signal pathway.Results:The core effective ingredients of Xiaoluo Bolus which could treat Malignant Lymphoma were harpagoside, Zhebeiresinol, pelargonidin and the targets were PRS27A, TP53, PPP2CA, which mainly takes effect on NF-κB、HIF-1 pathways. The main function of them is to act on the rDNA chromatin silencing and megakaryocyte differentiation.The common deubiquitination function in these two pathways indicated the main therapeutic target of Xiaoluo Bolus treating malignant lymphoma.Conclusion:This study initially revealed the multi-component, multi-target, and multi-collateral mechanism of Xiaoluo Bolus, in the treatment of malignant lymphoma which provids the scientific base for the development and utilization of Xiaoluo Bolus in clinical use.

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