目的 探索苁蓉益肾颗粒治疗糖尿病肾病(diabetic nephropathy,DN)的多成分、多靶点、多通路间的复杂网状关系,预测其潜在作用机制。方法 通过TCMSP等多个数据库在线检索并筛选苁蓉益肾颗粒活性成分及其作用于DN的相关靶点。利用STRING和Cytoscape分析软件对所得靶点进行网络可视化处理,筛选关键成分和核心靶点。借助ClueGO插件对核心靶点KEGG富集分析,预测苁蓉益肾颗粒治疗DN的潜在作用机制。结果 从苁蓉益肾颗粒中筛选出69个活性成分及37个作用于DN的核心靶标。通路富集分析显示,中药复方可能作用于糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路、流体剪切应力和动脉粥样硬化等94条显著相关信号通路,涉及炎性反应、对活性氧的反应、细胞增殖等352个显著相关生物过程。结论 苁蓉益肾颗粒可能是通过AKT1、IL-6、TNF、VEGFA等关键靶点,干预人体AGE-RAGE信号通路、TNF信号通路,进而参与到炎性反应、对活性氧的反应、氧化应激等生物过程来发挥治疗DN的作用。
Abstract
Objective To explore the non-single network correlations between multiple components,targets, and pathways of Congrong Yishen granules(CYGs) in the treatment of diabetic nephropathy (DN) via network pharmacology in order to predict the potential mechanism of action.Methods TCMSP and other online databases were searched for the active components of CYGs and the relevant targets on DN before they were screened. The screened targets were submitted to STRING and Cytoscape tools for network visualization. KEGG enrichment analysis of the core targets was performed with ClueGO plugin to predict the potential mechanism of CYGs against DN.Results A total of 69 active components and 37 core targets against DN were screened from CYGs. After enrichment analysis, 94 significantly related signaling pathways were identified, including the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, fluid shear stress and atherosclerosis, involving 352 significantly related biological processes including response to lipopolysaccharide, response to reactive oxygen species, and cell proliferation.Conclusions CongRong YiShen granules may contribute to the treatment of DN by intervening in the AGE-RAGE signaling pathway and TNF signaling pathway in the human body through AKT1, IL-6, TNF, VEGFA and other key targets before participating in such biological processes as inflammatory response, response to reactive oxygen species and oxidative stress.
关键词
网络药理学 /
苁蓉益肾颗粒 /
糖尿病肾病 /
作用机制
Key words
network pharmacology /
Congrong Yishen granules /
diabetic nephropathy /
mechanism of action
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基金
天津市自然科学基金资助项目(17JCYBJC26700)
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