Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Division of Medical Physics, Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79108, Freiburg, Germany.
BMC Complement Med Ther. 2023 Sep 27;23(1):342. doi: 10.1186/s12906-023-04174-7.
Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors. Yi Qi Qu Yu Jie Du Fang (YYQQJDF) is a traditional Chinese medicine (TCM) prescription for GBM. The present study aimed to use a network pharmacology method to analyze the underlying mechanism of YQQYJDF in treating GBM.
GBM sample data, active ingredients and potential targets of YQQYJDF were obtained from databases. R language was used to screen differentially expressed genes (DEGs) between GBM tissues and normal tissues, and to perform enrichment analysis and weighted gene coexpression network analysis (WGCNA). The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to perform a protein‒protein interaction (PPI) analysis. A Venn diagram was used to obtain the core target genes of YQQYJDF for GBM treatment. Molecular docking was used to verify the binding between the active ingredient molecules and the proteins corresponding to the core target genes. Cell proliferation assays and invasion assays were used to verify the effect of active ingredients on the proliferation and invasion of glioma cells.
A total of 73 potential targets of YQQYJDF in the treatment of GBM were obtained. Enrichment analyses showed that the biological processes and molecular functions involved in these target genes were related to the activation of the G protein-coupled receptor (GPCR) signaling pathway and the regulation of hypoxia. The neuroactive ligand‒receptor pathway, the cellular senescence pathway, the calcium signaling pathway, the cell cycle pathway and the p53 signaling pathway might play important roles. Combining the results of WGCNA and PPI analysis, five core target genes and their corresponding four core active ingredients were screened. Molecular docking indicated that the core active ingredient molecules and the proteins corresponding to the core target genes had strong binding affinities. Cell proliferation and invasion assays showed that the core active ingredients of YQQYJDF significantly inhibited the proliferation and invasion of glioma cells (P < 0.01).
The present study predicted the possible active ingredients and targets of YQQYJDF in treating GBM, and analyzed its possible mechanism. These results may provide a basis and ideas for further research.
胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤之一。益气祛瘀解毒方（YYQQJDF）是一种治疗 GBM 的中药方剂。本研究旨在采用网络药理学方法分析 YYQQJDF 治疗 GBM 的潜在机制。
从数据库中获取 GBM 样本数据、YYQQJDF 的活性成分和潜在靶点。使用 R 语言筛选 GBM 组织与正常组织之间的差异表达基因（DEGs），并进行富集分析和加权基因共表达网络分析（WGCNA）。使用 Search Tool for the Retrieval of Interacting Genes/Proteins（STRING）数据库进行蛋白质-蛋白质相互作用（PPI）分析。使用 Venn 图获取 YYQQJDF 治疗 GBM 的核心靶点基因。分子对接验证活性成分分子与核心靶点基因相应蛋白的结合。细胞增殖实验和侵袭实验验证活性成分对神经胶质瘤细胞增殖和侵袭的影响。
共获得 73 个 YYQQJDF 治疗 GBM 的潜在靶点。富集分析表明，这些靶基因涉及的生物学过程和分子功能与 G 蛋白偶联受体（GPCR）信号通路的激活和缺氧调节有关。神经活性配体-受体通路、细胞衰老通路、钙信号通路、细胞周期通路和 p53 信号通路可能发挥重要作用。结合 WGCNA 和 PPI 分析结果，筛选出 5 个核心靶点基因及其对应的 4 个核心活性成分。分子对接表明，核心活性成分分子与核心靶点基因相应蛋白具有较强的结合亲和力。细胞增殖和侵袭实验表明，YYQQJDF 的核心活性成分显著抑制神经胶质瘤细胞的增殖和侵袭（P<0.01）。
本研究预测了 YYQQJDF 治疗 GBM 的可能活性成分和靶点，并分析了其可能的作用机制。这些结果可能为进一步研究提供依据和思路。
