基于网络药理学的策略研究溪黄草治疗炎症疾病的药理机制

doi:10.5246/jcps.2022.04.022

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (4): 250-263.DOI: 10.5246/jcps.2022.04.022

基于网络药理学的策略研究溪黄草治疗炎症疾病的药理机制

解伟伟¹, 文旭清¹, 张德栋¹, 张玉倩¹, 张志清¹, 靳怡然¹^,^*(), 杜英峰²^,^*()

1. 河北医科大学第二医院, 河北石家庄 050000
2. 河北医科大学药学院药物分析教研室, 河北石家庄 050000

收稿日期:2021-12-04 修回日期:2021-12-31 接受日期:2022-01-12 出版日期:2022-04-30 发布日期:2022-04-30
通讯作者: 靳怡然, 杜英峰
作者简介:
+ Tel.: +86-311-86265625; Fax: +86-311-86266419; E-mail: jinyiran@sohu.com
+ E-mail: yingfengdu@hotmail.com
基金资助:
Hebei Administration of Traditional Chinese Medicine (Grant No. 2021133), the Natural Science Foundation of Hebei Province of China (Grant No. H2019206562) and the Key Projects of Hebei Education Department (Grant No. ZD2017244).

Network pharmacology-based strategy to investigate harmacological mechanisms of Isodon serra (Maxim.) Hara for treatment of inflammatory

Weiwei Xie¹, Xuqing Wen¹, Dedong Zhang¹, Yuqian Zhang¹, Zhiqing Zhang¹, Yiran Jin¹^,^*(), Yingfeng Du²^,^*()

1 The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
2 Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050000, Hebei, China

Received:2021-12-04 Revised:2021-12-31 Accepted:2022-01-12 Online:2022-04-30 Published:2022-04-30
Contact: Yiran Jin, Yingfeng Du

摘要/Abstract

摘要：

溪黄草最重要的活性成分是对映贝壳杉烷二萜类化合物, 此类化合物的主要作用是降低炎症的发生率, 有助于发挥溪黄草的抗炎药理作用。本研究的目的是利用网络药理学分析的方法寻找溪黄草中的活性成分, 将这些活性化合物与我们建立的二萜化合物库相匹配, 找到并确定所有符合条件的对映贝壳杉烷二萜化合物。其次, 在数据库中找到溪黄草的活性化合物的作用靶点以及人体内抗炎靶点, 结合得到交集, 这代表了溪黄草中活性化合物的潜在抗炎靶点。然后, 将抗炎靶点和活性化合物靶点进行蛋白质-蛋白质相互作用网络合并, 得到蛋白质相互作用网络交叉点和抗炎靶蛋白-相互作用网络中的核心基因。最后对溪黄草的抗炎靶点, 进行了基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析, 以确认溪黄草对抗炎症的基因功能。最终, TCMSP分析从48种对映贝壳杉烷中鉴定出10种活性化合物。通路分析显示糖尿病并发症、小细胞肺癌和人巨细胞病毒感染中AGE-RAGE信号通路等不同通路富集, 均与炎症有关。该方法清晰地鉴定了溪黄草中的对映-贝壳杉二萜类化合物, 首次得到了溪黄草的活性化合物。中药定性分析与网络药理学相结合的方法可以发现潜在的中药材作用靶点, 揭示中药材的生物学过程, 并为今后的中医药研究开辟一种新方法。

关键词: 溪黄草, 网络药理学, 活性化合物, 对映-贝壳杉二萜, 抗炎靶点

Abstract:

Widely distributed in plants, ent-kaurane diterpenoids could reduce the incidence of inflammatory. The most important active ingredient of Isodon serra (Maxim.) Hara is ent-kaurane diterpenoids, which contribute to the anti-inflammatory pharmacological effects of Isodon serra. However, the ingredients, the active compounds, drug targets, inflammatory targets and exact molecular mechanism of Isodon serra in treating inflammatory are still unclear. The purpose of this study was to use the method of network pharmacological analysis to find the active compounds in Isodon serra. These active compounds match the library of ent-kaurane diterpenoids compounds we established, and we find all the eligible ent-kaurane diterpenoids compounds. Isodon serra related and anti-inflammatory targets were found and then combined to get intersection, which represented potential anti-inflammatory targets of active compounds in Isodon serra. Moreover, anti-inflammatory targets and active compounds targets protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in anti-inflammatory target protein-protein interaction network. For the anti-inflammatory targets of Isodon serra, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were executed to confirm gene functions of Isodon serra in antagonizing inflammation. Finally, TCMSP analysis identified 10 active compounds out of 48 ent-kaurane. The pathway analysis showed enrichment for different pathways like AGE-RAGE signaling pathway in diabetic complications, small cell lung cancer and human cytomegalovirus infection, which were all connected to inflammatory. On the whole, the proposed method clearly identified the ent-kaurane diterpenoids of Isodon serra and the results gave the active compounds of Isodon serra for the first time. The combining use of the qualitative analysis of traditional Chinese medicine (TCM) and network pharmacological methods could discover potential drug targets and reveal the biological process of TCM, which would open up a new approach in the study of TCM in future.

Key words: Isodon serra (Maxim.) Hara, Network pharmacology, Active compounds, ent-Kaurane diterpenoids, Inflammatory targets

Supporting:

解伟伟, 文旭清, 张德栋, 张玉倩, 张志清, 靳怡然, 杜英峰. 基于网络药理学的策略研究溪黄草治疗炎症疾病的药理机制[J]. 中国药学(英文版), 2022, 31(4): 250-263.

Weiwei Xie, Xuqing Wen, Dedong Zhang, Yuqian Zhang, Zhiqing Zhang, Yiran Jin, Yingfeng Du. Network pharmacology-based strategy to investigate harmacological mechanisms of Isodon serra (Maxim.) Hara for treatment of inflammatory[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(4): 250-263.

图/表 7

Table 1. Detailed information about 12 active compounds in Isodon serra.

Figure 1. Venn diagram of disease and drug targets.

Figure 2. Isodon serra (Xihuangcao)-compound-targets-inflammatory network map.

Figure 3. PPI network of Isodon serra.

Figure 4. GO enrichment analysis of anti-inflammatory targets. (Figure 4A and 4B are the barplot and dotplot, respectively.)

Figure 5. KEGG enrichment analysis of anti-inflammatory targets. (Figure 5A and 5B are the barplot and dotplot, respectively.)

Figure 6. Isodon serra pathway and therapeutic modules. Three pathways constitute the compressed Isodon serra pathway.

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基于网络药理学的策略研究溪黄草治疗炎症疾病的药理机制

Network pharmacology-based strategy to investigate harmacological mechanisms of Isodon serra (Maxim.) Hara for treatment of inflammatory

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