基于网络药理学和分子对接探究白芍七物汤治疗结直肠癌的作用机制

doi:10.5246/jcps.2023.01.002

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (1): 17-31.DOI: 10.5246/jcps.2023.01.002

基于网络药理学和分子对接探究白芍七物汤治疗结直肠癌的作用机制

丁宁¹, 张涛¹, 罗吉², 刘皓辰¹, 邓宇¹, 何永恒²^,^*()

1. 湖南中医药大学研究生院, 湖南长沙 410208
2. 湖南省中医药研究院附属医院肛肠科, 湖南长沙 410006

收稿日期:2022-09-02 修回日期:2022-11-12 接受日期:2022-11-17 出版日期:2023-01-31 发布日期:2023-01-31
通讯作者: 何永恒
作者简介:
+ Tel.: +86-13517401858, E-mail: 2320990685@qq.com
基金资助:
The Hunan Administration of Traditional Chinese Medicine (Grant No. 2021017), the Natural Science Foundation of Hunan Province (Grant No. 2021JJ30419), the Education Department of Hunan Province (Grant No. 20B443), the Changsha Science and Technology Plan other Science and Technology Innovation Platform Project (Grant No. kh2201062), and the Hunan Graduate Scientific Research Innovation Project (Grant No. 2021CX29).

Study on the mechanism of Baishao Qiwu Decoction in the treatment of colorectal cancer based on network pharmacology and molecular docking

Ning Ding¹, Tao Zhang¹, Ji Luo², Haochen Liu¹, Yu Deng¹, Yongheng He²^,^*()

1 Graduate School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
2 Department of Anorectal Surgery, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha 410006, Hunan, China

Received:2022-09-02 Revised:2022-11-12 Accepted:2022-11-17 Online:2023-01-31 Published:2023-01-31
Contact: Yongheng He

摘要/Abstract

摘要：

基于网络药理学和分子对接技术, 探讨白芍七物汤(BSQWD)治疗结直肠癌(CRC)的作用机制。利用中药系统药理学数据库及分析平台(TCMSP)筛选中药的有效成分和靶标, 利用Cytoscape软件绘制综合靶标网络图。通过GeneCards、OMIM、PharmGKB、TTD和DrugBank数据库确定了潜在的CRC靶标。利用Cytoscape整合BSQWD的化学成分、靶标和疾病。通过STRING平台行蛋白-蛋白相互作用(PPI)分析。利用R行京都基因与基因组百科全书(KEGG)通路和基因本体(GO)分析, 最后利用AutoDock和SYBYL-X 2.0进行分子对接。结果表明, 7种药材中含有110种化学成分。CRC相关基因共9048个。BSQWD与184个靶基因相关。鉴定到Hub基因, 分别为JUN、HSP90AA1、TP53、AKT1、TNF等。富集了2589个GO项目, 包括2324个生物学过程、67个细胞组分、198个分子功能。KEGG分析得到179条通路。分子对接结果表明, 潜在有效成分cynaropicrin和rivularin与中心基因HSP90AA1和TP53具有良好的结合。本研究表明, BSQWD通过多成分、多靶点、多途径的协同调控实现了抗CRC的机制, 为BSQWD的应用提供了理论和科学依据。

关键词: 白芍七物汤, 结直肠癌, 网络药理学, 分子对接

Abstract:

In the present study, we investigated the mechanism of Baishao Qiwu Decotion (BSQWD) in the treatment of colorectal cancer (CRC) based on network pharmacology and molecular docking technology. The active components and all targets of traditional Chinese medicine (TCM) were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the compositive target network diagram was drawn by Cytoscape software. Potential CRC targets were identified by GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases. Cytoscape was used to integrate chemical components, targets, and diseases in BSQWD. The STRING platform line protein-protein interaction (PPI) analysis was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were performed using R language. Finally, AutoDock and SYBYL-X 2.0 were used to perform molecular docking. The results showed that seven kinds of medicinal materials in BSQWD contained 110 chemical components. There were 9048 CRC-related genes. BSQWD was associated with 184 target genes. Hub genes were identified, which were JUN, HSP90AA1, TP53, AKT1, and TNF. Moreover, 2589 GO items were enriched, including 2324 biological processes, 67 cell components, and 198 molecular functions. KEGG analysis obtained 179 pathways. The molecular docking results showed that the potentially active ingredients, cynaropicrin and rivularin, had good binding with the hub genes HSP90AA1 and TP53. Collectively, the reaseach showed that BSQWD achieved the anti-CRC mechanism through the synergistic regulation of multiple components, multiple targets, and multiple pathways, providing a theoretical basis and scientific basis for the application of BSQWD.

Key words: Baishao Qiwu Decoction, Colorectal cancer, Network pharmacology, Molecular docking

Supporting:

丁宁, 张涛, 罗吉, 刘皓辰, 邓宇, 何永恒. 基于网络药理学和分子对接探究白芍七物汤治疗结直肠癌的作用机制[J]. 中国药学(英文版), 2023, 32(1): 17-31.

Ning Ding, Tao Zhang, Ji Luo, Haochen Liu, Yu Deng, Yongheng He. Study on the mechanism of Baishao Qiwu Decoction in the treatment of colorectal cancer based on network pharmacology and molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(1): 17-31.

图/表 11

Table 1. Active compounds in BSQWD.

Figure 1. Venn diagram of CRC gene target database intersection.

Figure 2. Venn diagram of co-expression targets of BSQWD and CRC.

Figure 3. Drug-component-target network diagram.

Table 2. Information of key components in the top 10 of the Degree.

Figure 4. PPI network diagram of key targets.

Figure 5. The rank of hub genes.

Figure 6. GO enrichment analysis bubble of CRC treated by BSQWD.

Figure 7. KEGG pathway enrichment analysis of CRC treated by BSQWD.

Figure 8. Total score heatmap of main compounds docking with a core target.

Figure 9. Molecular docking diagram of main compounds with the target protein.

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基于网络药理学和分子对接探究白芍七物汤治疗结直肠癌的作用机制

Study on the mechanism of Baishao Qiwu Decoction in the treatment of colorectal cancer based on network pharmacology and molecular docking

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