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论著.生物信息技术 | 更新时间:2023-12-05
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基于网络药理学探讨复方丹参滴丸治疗糖尿病周围神经病变的作用机制
Mechanism of Compound Danshen Dripping Pills for the treatment of diabetic peripheral neuropathy: an exploration based on network pharmacology

广西医学 2023第45卷18期 页码:2237-2243

作者机构:杨锐锋,在读硕士研究生,研究方向:中医康复学。

基金信息:科技部中医药防治糖尿病国际联合研究中心(2015B01022);兵团财政科技计划项目(2020AA005)

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目的 基于网络药理学探讨复方丹参滴丸治疗糖尿病周围神经病变(DPN)的作用机制。方法 (1)在中药系统药理学数据库和分析平台中检索复方丹参滴丸3种药物(丹参、三七和冰片)的活性成分,在SwissTargetPrediction平台对活性成分进行反向靶点预测。利用GeneCards数据库和OMIM数据库预测DPN相关靶点。对上述两类靶点取交集后获得药物-疾病共同靶点。(2)针对药物-疾病共同靶点及其对应的活性成分、药物,采用Cytoscape软件构建药物-活性成分-靶点网络后筛选关键活性成分。针对药物-疾病共同靶点,利用STRING数据库构建蛋白-蛋白互相作用网络,再利用Cytoscape软件进行拓扑分析以获得关键靶点。(3)针对药物-疾病共同靶点,在微生信平台进行功能富集分析和通路富集分析。(4)利用AutoDock Vina软件,将关键活性成分和关键靶点进行分子对接。结果 (1)最终获得99个药物-疾病共同靶点。(2)关键活性成分包括甘草素、积雪草酸、木犀草素和丹参醇B; 关键靶点包括热休克蛋白90α家族A类成员1(HSP90AA1)、信号转导和转录激活因子3(STAT3)和白细胞介素6(IL-6)。(3)功能富集分析结果显示,药物-疾病共同靶点涉及类固醇代谢过程等生物过程,膜筏等细胞组分,核受体活性、配体激活的转录因子活性等分子功能;通路富集分析结果显示,药物-疾病共同靶点富集的信号通路包含糖尿病并发症中的晚期糖基化终末化产物-晚期糖基化终末化产物受体信号通路。(4)分子对接结果显示,4个关键活性成分与3个关键靶点的结合能均≤-5.0 kcal/mol,结合活性良好。结论 复方丹参滴丸可通过甘草素、积雪草酸、木犀草素和丹参醇B等多种活性成分,作用于HSP90AA1、STAT3、IL-6等关键靶点,发挥抗氧化应激、抗炎、调控机体代谢等作用,从而治疗DPN。
ObjectiveTo explore the mechanism of Compound Danshen Dripping Pills for the treatment of diabetic peripheral neuropathy (DPN) based on network pharmacology. Methods(1) The active components of 3 categories of drugs (Salvia miltiorrhiza, Panax notoginseng, and Dryobalanops aromatica) from Compound Danshen Dripping Pills were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and then reverse target prediction was performed on active components by the SwissTargetPrediction platform. The GeneCards database and OMIM database were used to predict targets related to DPN. After the intersection of the two targets as above was obtained, the drug-disease common targets were acquired. (2) For the drug-disease common targets and their corresponding active components and drugs, the Cytoscape software was used to establish the drugs-active components-targets network for screening the key active components. For the drug-disease common targets, the protein-protein interaction network was established by using the STRING database, and then the topology analysis was performed for obtaining the key targets by using Cytoscape again. (3) For the drug-disease common targets, the functional enrichment analysis and pathway enrichment analysis were performed in the microbial informatics platform. (4) The AutoDock Vina software was used to perform molecular docking on the key active components and key targets. Results(1) A total of 99 drug-disease common targets were eventually obtained. (2) The key active components contained liquiritigenin, asiatic acid, luteolin, and danshenol B, and the key targets included heat shock protein 90 alpha family class A member 1 (HSP90AA1), signal transducer and activator of transcription 3 (STAT3), and interleukin 6 (IL-6). (3) The results of functional enrichment analysis revealed that the biological processes involved in the drug-disease common targets were steroid metabolic process, etc., cellular compositions in the drug-disease common targets were membrane raft, etc., and molecular functions in the drug-disease common targets were nuclear receptor activity and ligand-activated transcription factor activity, etc. The results of pathway enrichment analysis indicated that signaling pathways enriched in the drug-disease common targets included the advanced glycation end-products-receptor for advanced glycation end-products signaling pathway in diabetic complications. (4) The molecular docking results depicted that binding energy of the four key active components with three core targets were all≤-5.0 kcal/mol, indicating a favorable binding activity. ConclusionCompound Danshen Dripping Pills may act on HSP90AA1, STAT3, IL-6, and other key targets, so as to exert effects concerning anti-oxidative stress, anti-inflammation, and metabolic regulation of the body, and further to treat DPN through multiple active components including liquiritigenin, asiatic acid, luteolin, and danshenol B, etc.

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