基于网络药理学和分子对接的天麻钩藤汤治疗胶质母细胞瘤的机制分析

Mechanistic Analysis of the Treatment of Glioblastoma with Tianma Gouteng Decoction Based on Network Pharmacology and Molecular Docking

摘要: 目的：胶质母细胞瘤(GBM)是一种侵袭性高、病死率高的原发脑肿瘤。天麻钩藤汤(TMGTD)是一种具有降压、神经保护和潜在抗肿瘤作用的中药制剂，但对其抗肿瘤作用机制的研究较少。因此，我们对TMGTD和GBM之间的相互作用进行了检验和测试。方法：TMGTD的有效成分和靶点是从TCMSP和HERB数据库下载的，GBM靶点由来自GEO数据库的差异表达基因和来自DisGeNET和GeneCards数据库的靶点组成。在此基础上，构建了成分–目标网络和PPI网络，找出了GBM TMGTD的核心网络。最后，通过分子对接验证了成分与疾病靶点之间的关系。结果：我们从中草药数据库中获得了937个成分指标，438个疾病指标和115个交叉指标。生物信息学分析结果表明，这些交叉基因与细胞的存活、增殖和凋亡相关。拓扑分析确定了在核心网络中重要的12个核心基因(TP53, STAT3, CDK1, HDAC1, CCNB1, CCND1, ESR1, BIRC5, ABL1, AURK1, CDK2, PLK1)，尤其是CDK1。单细胞测序分析发现，与其他核心PPI基因相比，STAT3在GBM组织中高表达，而TP53则具有最高的平均表达水平。在分子对接结果中，CDK1与Corynoxeine的结合能最低。结论：本研究揭示了天麻钩藤汤抗胶质母细胞瘤的有效成分及其多靶点和信号通路，为天麻钩藤汤治疗胶质母细胞瘤提供了理论支持。

Abstract: Objective: Glioblastoma (GBM), an aggressive primary brain tumor with a high fatality rate. Tianma Gouteng Decoction (TMGTD), a traditional Chinese medicine formulation, which has antihypertensive, neuroprotective and potentially antitumor effects, but research on the mechanism of antitumor is lacking. Therefore, we have examined and tested the interaction between the TMGTD and GBM. Methods: Active ingredients and targets of TMGTD were downloaded from the TCMSP and HERB databases, and GBM targets consist of the intersection of differentially expressed genes from the GEO database and targets from the DisGeNET and GeneCards databases. Next, the ingredient-target network and PPI network were constructed to find the core network of TMGTD for GBM. Finally, Molecular docking was used to verify the relationship between the ingredients and disease targets. Results: We got 937 ingredient targets from TCMSP and the HERB database, 438 disease targets and 115 intersecting targets. The results of bioinformatics analysis show that these intersecting genes were associated with cellular survival, proliferation, and apoptosis. The topological analysis identified 12 core genes (TP53, STAT3, CDK1, HDAC1, CCNB1, CCND1, ESR1, BIRC5, ABL1, AURK1, CDK2, PLK1) that are important in the core network, especially CDK1. Single-cell sequencing analysis identified STAT3, which was highly expressed in GBM tissues compared to other core PPI genes, and TP53, which had the highest average expression level. In the results of molecular docking, CDK1 exhibited the lowest binding energy with Corynoxeine. Conclusion: This study showed the effective ingredients of TMGTD against GBM, as well as multiple targets and signaling pathways, providing theoretical support for the treatment of TMGTD with GBM.