基于网络药理学及实验验证探究当归补血汤治疗糖尿病性视网膜病变的作用机制

doi:10.5246/jcps.2023.07.044

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (7): 527-538.DOI: 10.5246/jcps.2023.07.044

基于网络药理学及实验验证探究当归补血汤治疗糖尿病性视网膜病变的作用机制

武东燕, 王小丹, 柴金苗^*(), 李钦青, 李悦, 毕梅, 桂婉威, 曹慧敏

山西中医药大学, 山西晋中 030600

收稿日期:2022-10-27 修回日期:2022-11-24 接受日期:2022-12-26 出版日期:2023-07-31 发布日期:2023-07-31
通讯作者: 柴金苗
作者简介:
+ Tel.: +86-351-3179748, E-mail: jinmiaoch@163.com
基金资助:
Scientific Research Project of Shanxi Provincial Health Commission (Grant No. 2021040); Postgraduate Education Innovation Plan of Shanxi Provincial Department of Education (Grant No. 2022Y710); Shanxi University of Traditional Chinese Medicine Postgraduate Innovation and Entrepreneurship Project (Grant No. 2022CX007).

Study on the mechanism of Danggui Buxue decoction in the treatment of diabetic retinopathy based on network pharmacology and experiment

Dongyan Wu, Xiaodan Wang, Jinmiao Chai^*(), Qinqing Li, Yue Li, Mei Bi, Wanwei Gui, Huimin Cao

Shanxi University of Chinese Medicine, Jinzhong 030600, Shanxi, China

Received:2022-10-27 Revised:2022-11-24 Accepted:2022-12-26 Online:2023-07-31 Published:2023-07-31
Contact: Jinmiao Chai

摘要/Abstract

摘要：

本研究使用网络药理学、分子对接结合实验验证探究当归补血汤在糖尿病视网膜病变(Diabetic retinopathy, DR)中的作用机制。从TCMSP、TCMID、Swiss Target Prediction数据库筛选当归补血汤活性成分及其靶点, 通过GeneCards、DisGeNET收集DR靶点, 利用Venny 2.1获得二者交集靶点。使用Cytoscape构建"疾病-药物-成分-靶点"、蛋白互作(PPI)网络; DAVID数据库对关键靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析; AutoDockVina对主要活性成分与关键靶点进行分子对接验证。最后, 通过动物实验验证网络药理学结果。收集到当归补血汤与DR共同靶点84个。GO分析显示220个条目; KEGG富集分析得到113条信号通路。分子对接结果显示关键靶点与槲皮素、豆甾醇等有效成分均具有较好的对接活性。动物实验表明当归补血汤可改善DR大鼠视网膜组织形态, 降低血糖, 增加胰岛素分泌, 降低DR大鼠视网膜组织VEGF、TNF-α蛋白表达水平、提高PI3K、Akt1表达水平(P < 0.05, P < 0.01)。当归补血汤治疗DR具有多活性成分、多靶点、多通路的特点, 可通过调节TNF-α、VEGFA、PI3K、AKT等核心靶点, 影响PI3K/AKT、TNF等信号通路发挥对DR的治疗作用。

关键词: 当归补血汤, 糖尿病性视网膜病变, 网络药理学, 分子对接

Abstract:

In the present study, we investigated the mechanism of action of Danggui Buxue decoction (DBD) in diabetic retinopathy (DR) using network pharmacology and molecular docking combined with experimental validation. GeneCards and DisGeNET were used to collect DR targets. The intersection of the two targets was obtained using Venny 2.1. Cytoscape was used to construct "disease-drug-component-target" and protein-protein interaction (PPI) networks. DAVID database was used to enrich key targets with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). AutoDockVina was used to perform molecular docking of primary active ingredients with key targets. Molecular docking validation was performed with key targets by AutoDockVina. Finally, the network pharmacological results were validated by animal experiments. A total of 84 common targets of DBD and DR were collected, 220 entries were revealed by GO analysis, and 113 signaling pathways were obtained by KEGG enrichment analysis. Molecular docking results showed that the key targets had suitable docking activities with quercetin, dousterol and other active ingredients. Animal experiments showed that DBD could improve retinal tissue morphology, lower blood glucose, increase insulin secretion, reduce VEGF and TNF-α protein expression levels and increase PI3K and Akt1 expression levels in the retinal tissues of DR rats (P < 0.05, P < 0.01). The treatment of DR by DBD had the characteristics of multiple active ingredients, multiple targets and multiple pathways, which could exert therapeutic effects on DR by regulating the core targets of TNF-α, VEGFA, PI3K, and AKT and affecting the signaling pathways of PI3K/AKT and TNF.

Key words: Danggui Buxue decoction, Diabetic retinopathy, Network pharmacology, Molecular docking

Supporting:

武东燕, 王小丹, 柴金苗, 李钦青, 李悦, 毕梅, 桂婉威, 曹慧敏. 基于网络药理学及实验验证探究当归补血汤治疗糖尿病性视网膜病变的作用机制[J]. 中国药学(英文版), 2023, 32(7): 527-538.

Dongyan Wu, Xiaodan Wang, Jinmiao Chai, Qinqing Li, Yue Li, Mei Bi, Wanwei Gui, Huimin Cao. Study on the mechanism of Danggui Buxue decoction in the treatment of diabetic retinopathy based on network pharmacology and experiment[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(7): 527-538.

图/表 11

Table 1. Active components of DBD.

Figure 1. Venn diagram of the interactive target of DBD in treating DR.

Figure 2. "Disease-drug-component-target" network for DR treatment with DBD.

Figure 3. DBD for DR target PPI network.

Figure 4. GO enrichment analysis of crucial targets of DBD for DR.

Figure 5. KEGG enrichment analysis of crucial targets of DBD in treating DR.

Table 2. The binding energy of the main chemical components in DBD to the core targets.

Figure 6. Effect of DBD on body weight, fasting blood glucose, and fasting insulin of DR rats (mean ± SD, n = 6). Note: Compared with the blank group, *P < 0.05, **P < 0.01; Compared with the model group, #P < 0.05; ##P < 0.01 (same below).

Figure 7. Effect of DBD on retinal morphology of DR rats (H&E, × 400). Note: The black arrow shows that the ganglion cells are in disorder, and the number of ganglion cells is reduced; the red arrow shows pathological angiogenesis.

Figure 8. Effect of DBD on the expressions of VEGF and TNF-α at the protein level in the retina of DR rats (mean ± SD, n = 6). Note: Compared with the blank group, *P < 0.05, **P < 0.01; Compared with the model group, #P < 0.05; ##P < 0.01.

Figure 9. Effect of DBD on PI3K and AKT1 protein expression in DR rat retina (mean ± SD, n = 6). Note: Compared with the blank group, *P < 0.05, **P < 0.01; Compared with the model group, #P < 0.05; ##P < 0.01.

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基于网络药理学及实验验证探究当归补血汤治疗糖尿病性视网膜病变的作用机制

Study on the mechanism of Danggui Buxue decoction in the treatment of diabetic retinopathy based on network pharmacology and experiment

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