基于网络药理学的黄柏治疗痔疮有效成分及其作用机制探讨

Xianchang Yu, Xiongdong Zhong
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摘要

背景:黄柏,拉丁文又称黄柏,是一种具有清热、燥湿、泻火、解毒等药理作用的重要药物。近年来,有报道称黄柏还具有治疗痔疮的活性。目的:探讨黄柏治疗痔疮的有效成分及其作用机制。研究设计:对中药系统药理学(TCMSP)数据库和分析平台中黄柏的有效成分和靶基因进行分析。然后,我们在GeneCards数据库中搜索与痔疮相关的靶基因,以及这些基因与黄柏皮层活性成分的交集。与痔疮相关的靶基因被认为是黄柏常见的潜在靶基因,可以对痔疮起作用。使用R编程语言,我们绘制了这些常见的潜在目标基因的维恩图。利用Cytoscape 3.7.1版软件建立黄柏治疗痔疮的“组分-靶基因-疾病”网络;在相互作用基因/蛋白质检索工具(STRING)数据库中构建蛋白质-蛋白质相互作用网络。借助R和Perl语言,对黄柏治疗痔疮的潜在靶基因进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)途径富集分析。结果:从黄柏中共提取到槲皮素、芦果松果素等10种有效成分,以及29种可能的痔疮靶基因。根据Cytoscape3.7.1软件的Degree排序,前10位的潜在靶基因分别是白细胞介素-6 (IL-6)、CCL2、CXCL8、MMP9、血管内皮生长因子A (VEGFA)、Myc、IL-10、ICAM1、MMP2、MMP3。通路富集主要涉及糖尿病并发症的晚期糖基化终产物和晚期糖基化终产物受体(AGE-RAGE)信号通路、缺氧诱导因子1 (HIF-1)、IL-17、松弛素等信号通路。结论:基于网络药理学,黄柏有望成为治疗痔疮的候选中药。其治疗这种疾病的机制通过多种成分和途径运作。本研究为进一步的研究提供了基础理论和依据。
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An Exploration of the Active Ingredients of Cortex phellodendri in the Treatment of Hemorrhoids and Its Mechanism Based on Network Pharmacology
Background: Huangbo, also known as Cortex phellodendri in Latin, is an important drug which has the pharmacological action of clearing heat, drying dampness, purging fire and detoxifying. In recent years, it has been reported that Huangbo also has the activity of treating hemorrhoids. Objective: The aim of this study was to explore the Active Ingredients of Cortex phellodendri in the Treatment of hemorrhoids and Its Mechanism. Study Design: We analyzed Active components and target genes of Cortex phellodendri in the Traditional Chinese Medicine System Pharmacology (TCMSP) database and analysis platform. We then searched the GeneCards database for target genes related to hemorrhoids and the intersection of these genes with the active components of Cortex phellodendri. Target genes related to hemorrhoids were taken as common potential target genes of Cortex phellodendri, which could act on hemorrhoids. Using the R programming language, we drew a Venn map of these common potential target genes. The “component–target gene–disease” network of Cortex phellodendri in the treatment of hemorrhoids was established using Cytoscape software version 3.7.1; the protein–protein interaction (PPI) network was constructed in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. With the help of R and Perl languages, we performed gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of potential target genes of Cortex phellodendri in the treatment of hemorrhoids. Results: We extracted a total of 10 active components from Cortex phellodendri, including quercetin and rutaecarpine and so on, as well as 29 potential target genes for hemorrhoids. According to the Degree ranking in Cytoscape3.7.1 software, the top 10 potential target genes were interleukin-6 (IL-6), CCL2, CXCL8, MMP9, vascular endothelial growth factor A (VEGFA), Myc, IL-10, ICAM1, MMP2, and MMP3. Pathway enrichment mainly involved signaling pathways such as advanced glycation end products and receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, hypoxia-inducible factor 1 (HIF-1), IL-17, and Relaxin. Conclusion: Based on network pharmacology, Cortex phellodendri is expected to be mined as a candidate Traditional Chinese Medicine (TCM) for the treatment of hemorrhoids. Its mechanism for treating this disease operates via multiple components and pathways. This study provides the basic theory and the basis for further research.
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