基于网络药理学探讨黄芪-丹参药对治疗慢性肾小球肾炎的作用机制

doi:10.5246/jcps.2024.07.046

摘要/Abstract

摘要：

本研究基于网络药理学方法探讨黄芪-丹参药对治疗慢性肾小球肾炎(CGN)的作用机制。通过TCMSP数据库搜集黄芪、丹参的化学成分、靶点, 在Genecards数据库搜集CGN的疾病靶点, 将两者进行交集取交集基因即为黄芪-丹参药对治疗CGN的潜在靶点。构建蛋白互作网络及"化学成分-靶点"网络, 对核心靶点进行GO及KEGG 信号通路富集分析。结果发现, 黄芪、丹参化学成分分别为20、65个, 两者对应靶点共240个, 筛选出治疗CGN的潜在靶点86个, 其核心靶点29个, 包括TNF、JUN、TP53、IL1B、RELA、MMP9、CASP3、IL10、MAPK14、MYC、TGFB1等。KEGG富集分析得到与CGN相关的信号通路包括IL-17 信号通路、TNF信号通路、糖尿病并发症中的AGE-RAGE信号通路等。结果可得, 黄芪-丹参药对可能通过TNF、JUN、TP53、IL1B、MAPK14等对IL-17 信号通路、TNF信号通路、糖尿病并发症中的AGE-RAGE信号通路等来改善炎症反应及血管钙化发挥抗炎、改善肾损伤的作用。

关键词: 黄芪, 丹参, 慢性肾炎, 药对, 信号通路

Abstract:

To elucidate the mechanism underlying the therapeutic impact of Astragalus-Danshen in chronic glomerulonephritis (CGN), a comprehensive exploration was conducted utilizing network pharmacology. The TCMSP database was employed to aggregate the chemical constituents and targets associated with Astragalus and Danshen. Simultaneously, disease targets specific to CGN were sourced from the Genecards database. The convergence of these datasets yielded a set of intersection genes, representing potential targets for CGN treatment through Astragalus-Danshen formulations. Subsequently, protein interaction networks and "chemical composition-target" networks were meticulously constructed. Core targets were subjected to GO and KEGG enrichment analyses. The investigation revealed a total of 240 targets corresponding to 20 and 65 chemical components of Astragalus and Danshen, respectively. From this pool, 86 potential targets associated with CGN treatment were discerned, ultimately identifying 29 core targets. Noteworthy among these were TNF, JUN, TP53, IL1B, RELA, MMP9, CASP3, IL10, MAPK14, MYC, and TGFB1. KEGG enrichment analysis illuminated pathways pertinent to CGN, encompassing the IL-17 signaling pathway, TNF signaling pathway, and the AGE-RAGE signaling pathway in diabetic complications. In summary, Astragalus-Danshen exhibited a potential anti-inflammatory and renoprotective effect on CGN, particularly through modulating the IL-17 signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway in diabetic complications, involving key regulators such as TNF, JUN, TP53, IL1B, MAPK14, and others.

Key words: Astragalus, Salvia, Chronic nephritis, Drug pairs, Signaling pathway

Supporting:

齐年景, 杨明勋, 毛姗. 基于网络药理学探讨黄芪-丹参药对治疗慢性肾小球肾炎的作用机制[J]. 中国药学(英文版), 2024, 33(7): 620-630.

Nianjing Qi, Mingxun Yang, Shan Mao. Exploring the mechanism of Astragalus and Salvia miltiorrhiza in the treatment of chronic glomerulonephritis: A network pharmacology approach[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(7): 620-630.

图/表 8

Table 1. Relevant information on active components of Astragalus membranaceus.

Table 2. Relevant information on active components of Salvia miltiorrhiza.

Figure 1. Network diagram of active components and targets in Huangqi-Danshen.

Figure 2. Venn diagram of intersecting genes for Huangqi-Danshen therapy in treating CGN.

Figure 3. Network diagram for the identification of core target genes in the treatment of CGN by Huangqi-Danshen herbal pair.

Table 3. Core target genes for the treatment of CGN by Huangqi-Danshen herbal pair.

Figure 4. GO enrichment analysis of target genes for the therapeutic effects of Huangqi-Danshen formula on CGN.

Figure 5. KEGG pathway enrichment analysis of target genes involved in the therapeutic effects of Huangqi-Danshen formula on CGN.

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