基于网络药理学及分子对接探讨当归补血汤治疗动脉粥样硬化的机制
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(1.辽宁中医药大学,辽宁省沈阳市 110847;2.浙江中医药大学,浙江省杭州市 310053)

作者简介:

王晨,博士研究生,研究方向为中医基础理论,E-mail:wangchen315318@163.com。通信作者朱爱松,博士,教授,博士研究生导师,研究方向为中医基础理论,E-mail:liaoningzhongyi@hotmail.com。

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国家自然科学基金面上项目(81874417)


Mechanism of Danggui Buxuetang in treating atherosclerosis based on network pharmacology and molecular docking
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1.Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, China;2.Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China)

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    摘要:

    目的]利用网络药理学及分子对接技术探讨当归补血汤治疗动脉粥样硬化(As)的作用机制。 [方法]借助TCMSP数据库获得当归补血汤的活性成分,使用Swiss Target Prediction平台预测其潜在作用靶点。应用GeneCards及DisGeNET数据库筛选As靶点,并将活性成分预测靶点与疾病靶点取交集获得关键交集靶点。采用STRING平台构建交集靶点PPI互作网络,Cytoscape软件网络拓扑分析筛选潜在关键靶点。再次使用Cytoscape软件构建药物-成分-靶点,并找到核心活性成分。通过Metascape数据库进行GO功能富集分析和KEGG通路富集分析,最后通过分子对接,进一步明确其发挥治疗效用的成分与靶点作用机制。 [结果]筛选当归补血汤活性成分共19个,预测靶点204个,疾病靶点5 213个,筛选得到治疗As的交集靶点176个,排名前5位的核心靶点为Akt1、JUN、TP53、TNF、IL-6。GO和KEGG富集分析主要指向氧化应激反应、转录调节复合物等功能,参与的信号转导主要包括FoxO信号通路、JAK-STAT信号通路、IL-17信号通路等。分子对接结果显示5个活性成分及5个重要核心靶点对接结合能均小于-5 kJ/mol,提示其受体蛋白与配体小分子之间结合稳定,数值越低,结合稳定性越高,且结合能排名前5位的包含β谷固醇与槲皮素两种活性成分,其中活性成分β谷固醇与TNF结合能最低,为-10.52 kJ/mol,说明β谷固醇与槲皮素两种中药有效成分可能在治疗动脉粥样硬化性疾病中起重要作用。 [结论]当归补血汤中槲皮素、β谷固醇等核心活性成分可能通过作用于Akt1、JUN、TP53、TNF、IL-6等核心靶点,调节炎症反应、脂质代谢和其他相关通路,从而发挥治疗As的作用。

    Abstract:

    Aim To investigate the mechanism of Danggui Buxuetang in treating atherosclerosis (As) by using network pharmacology and molecular docking technology. Methods The active ingredients of Danggui Buxuetang were obtained with the help of TCMSP database, and their potential targets were predicted using the Swiss Target Prediction platform. GeneCards and DisGeNET databases were used to screen As targets, and the intersection of active ingredient prediction targets and disease targets was used to obtain key intersection targets. The STRING platform was used to construct the intersection target PPI interaction network, and the Cytoscape software network topology analysis screened potential key targets. Cytoscape software was used to construct drug-ingredient-target and find the core active ingredient. GO function enrichment analysis and KEGG pathway enrichment analysis were carried out through the Metascape database, and finally, through molecular docking, the components and target mechanism of its therapeutic effect were further clarified. Results A total of 19 active ingredients of Danggui Buxue tang were screened, 204 predicted targets, 5 213 disease targets, and 176 intersection targets for the treatment of As were screened. The top five core targets were Akt1, JUN, TP53, TNF, IL-6. GO and KEGG enrichment analysis mainly pointed to functions such as oxidative stress response and transcriptional regulatory complex, and the signal transduction involved mainly included FoxO signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway, etc. Molecular docking results showed that the docking binding energies of the five active ingredients and five important core targets were all less than -5 kJ/mol, suggesting that the binding between the receptor protein and the ligand small molecule was stable, and the lower the value, the higher the binding stability, and the top five active ingredients in terms of binding energy included β-sitosterol and quercetin, among which the active ingredient β-sitosterol had the lowest binding energy to TNF, which was -10.52 kJ/mol, indicating that β-sitosterol alcohol and quercetin, two active ingredients of traditional Chinese medicine, may play an important role in the treatment of atherosclerotic diseases. Conclusion The core active ingredients such as quercetin and β-sitosterol in Danggui Buxuetang may regulate inflammatory response, lipid metabolism and other related pathways by acting on core targets such as Akt1, JUN, TP53, TNF and IL-6, thereby exerting role in the treatment of atherosclerosis.

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王晨,朱爱松.基于网络药理学及分子对接探讨当归补血汤治疗动脉粥样硬化的机制[J].中国动脉硬化杂志,2023,31(9):754~761, 778.

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  • 收稿日期:2023-05-13
  • 最后修改日期:2023-08-09
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  • 在线发布日期: 2023-10-19