基于网络药理学和分子对接方法研究在治疗氧化应激相关疾病中的作用机制。
Network Pharmacology and Molecular Docking Approaches to Investigating the Mechanism of Action of in the Treatment of Oxidative Stress-induced Diseases.
机构信息
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China.
College of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China.
出版信息
Comb Chem High Throughput Screen. 2021;24(10):1754-1768. doi: 10.2174/1386207323999201117112316.
BACKGROUND
Zanthoxylum bungeanum Maxim., a traditional Chinese herbal medicine, has been reported to possess therapeutic effects on diseases induced by oxidative stress (DOS), such as atherosclerosis and diabetes complication. However, the active components and their related mechanisms are still not systematically reported.
OBJECTIVE
The current study was aimed to explore the main active ingredients and their molecular mechanisms of Z. bungeanum for treating DOS using network pharmacology combined with molecular docking simulation.
METHODS
The active components of Z. bungeanum pericarps, in addition to the interacting targets, were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. These components were filtered using the parameters of oral bioavailability and drug-likeness, and the targets related to DOS were obtained from the Genecards and OMIM database. Furthermore, the overlapping genes were obtained, and a protein-protein interaction was visualized using the STRING database. Next, the Cytoscape software was employed to build a disease/drug/component/target network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R software. Finally, the potential active compounds and their related targets were validated using molecular docking technology.
RESULTS
A total of 61 active compounds, 280 intersection genes, and 105 signaling pathways were obtained. Functional enrichment analysis suggested that DOS occurs possibly through the regulation of many biological pathways, such as AGE-RAGE and HIF-1 signaling pathways. Thirty of the identical target genes showed obvious compact relationships with others in the STRING analysis. Three active compounds, quercetin, diosmetin, and beta-sitosterol, interacting with the four key targets, exhibited strong affinities.
CONCLUSION
The findings of this study not only indicate the main mechanisms involving in oxidative stress-induced diseases but also provide the basis for further research on the active components of Z. bungeanum for treating DOS.
背景
花椒，一种传统的中草药，据报道具有治疗氧化应激（DOS）相关疾病的疗效，如动脉粥样硬化和糖尿病并发症。然而，其活性成分及其相关机制仍未得到系统报道。
目的
本研究旨在采用网络药理学结合分子对接模拟方法，探讨花椒治疗 DOS 的主要活性成分及其分子机制。
方法
从中药系统药理学（TCMSP）数据库中鉴定花椒果皮的活性成分及相互作用靶点，采用口服生物利用度和类药性参数进行筛选，从 Genecards 和 OMIM 数据库中获得与 DOS 相关的靶点。然后，获得重叠基因，并使用 STRING 数据库可视化蛋白质-蛋白质相互作用。接下来，使用 Cytoscape 软件构建疾病/药物/成分/靶点网络，使用 R 软件进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。最后，采用分子对接技术验证潜在的活性化合物及其相关靶点。
结果
共获得 61 种活性化合物、280 个交集基因和 105 条信号通路。功能富集分析表明，DOS 可能通过调节 AGE-RAGE 和 HIF-1 信号通路等多种生物学途径发生。STRING 分析中 30 个相同的靶基因与其他基因之间存在明显的紧密关系。三种活性化合物槲皮素、橙皮苷和β-谷甾醇与四个关键靶点相互作用，表现出较强的亲和力。
结论
本研究不仅表明了花椒治疗氧化应激相关疾病的主要作用机制，也为进一步研究花椒治疗 DOS 的活性成分提供了依据。
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