Comprehensive network pharmacology and experimental study to investigate the effects and mechanisms of Lophatherum gracile Brongn. for glioma treatment

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-07-15 DOI:10.1016/j.yexcr.2025.114671

Zelin Liu , Lihua Dai , Qian Jiang , Simei Zhong , Jiale Xiong , Zhe Yang , Ning Jing , Yu-Hui Zhang , Yan Ma

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引用次数: 0

Abstract

Background

Gliomas are challenging to treat due to their invasive nature and resistance to conventional therapies. Recent study has revealed that Lophatherum gracile Brongn. extract has anti-cancer properties on fibrosarcoma cell. Nevertheless, its medicinal effects and mechanistic pathways on gliomas have not been explored.

Aim of the study

To investigate the detailed anti-glioma roles of Lophatherum gracile Brongn. extract and its specific pharmacological routes of action both in vitro and in vivo, focusing on autophagy, apoptosis, proliferation, and migration.

Methods

Ethanol extracts of Lophatherum gracile Brongn. were prepared, and the active compounds were appraised by high-performance liquid chromatography. Human glioma cells (A172, LN229, U-87 MG, and U251) were treated with various concentrations of the extract. Immunofluorescence and transmission electron microscopy were employed to investigate the autophagosomes. Cell viability, proliferation, migration, and death were assessed using various assays. The anti-tumor effects were further tested in animal models. Network pharmacology was employed to investigate the potential targets of the main compounds acting on glioma. Furthermore, RNA sequencing was conducted for transcriptome analysis and molecular docking was used for identification.

Results

The extract significantly attenuated glioma cell viability, proliferation, and migration, both in vitro and in vivo, while promoting autophagy, apoptosis, and cell death. Five active compounds were identified: chlorogenic acid, isoorientin, orientin, vitexin, and isovitexin. A total of 1472 glioma targets were identified, along with 219 drug targets for the five compounds. Combining analysis of differentially expressed genes revealed that dihydrofolate reductase may be a key target of these compounds, as determined by molecular docking analysis.

Conclusions

Lophatherum gracile Brongn. extract exhibits significant anti-glioma effects in both cellular and animal models by targeting dihydrofolate reductase, providing novel insights into its therapeutic potential for glioma.

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综合网络药理学和实验研究探讨了细叶莲的作用和机制。用于神经胶质瘤治疗。

背景：神经胶质瘤由于其侵袭性和对常规治疗的抗性而具有挑战性。最近的研究表明，长柄草。提取物对纤维肉瘤细胞具有抗癌作用。然而，其对胶质瘤的药物作用和机制途径尚未探讨。目的：探讨细叶草抗胶质瘤的详细作用。提取物及其在体外和体内作用的具体药理途径，重点是自噬、凋亡、增殖和迁移。方法：用乙醇提取物提取细草。并通过高效液相色谱法对其活性成分进行了鉴定。用不同浓度的提取物处理人胶质瘤细胞（A172、LN229、U-87 MG和U251）。采用免疫荧光和透射电镜对自噬体进行观察。采用各种方法评估细胞活力、增殖、迁移和死亡。在动物模型上进一步检测其抗肿瘤作用。网络药理学研究了主要作用于胶质瘤的化合物的潜在靶点。通过RNA测序进行转录组分析，分子对接进行鉴定。结果：该提取物在体外和体内均能显著降低胶质瘤细胞的活力、增殖和迁移，同时促进自噬、凋亡和细胞死亡。鉴定出5种活性成分：绿原酸、异荭草苷、异荭草苷、牡荆素和异牡荆素。总共确定了1472个胶质瘤靶点，以及这五种化合物的219个药物靶点。结合差异表达基因的分析表明，二氢叶酸还原酶可能是这些化合物的关键靶点，并通过分子对接分析确定。结论：细叶草。提取物通过靶向二氢叶酸还原酶在细胞和动物模型中显示出显著的抗胶质瘤作用，为其治疗胶质瘤的潜力提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.