Liu Zelin, Dai Lihua, Jiang Qian, Zhong Simei, Xiong Jiale, Yang Zhe, Jing Ning, Zhang Yu-Hui, Ma Yan
MOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.
Wuhan Blood Center, Wuhan, 430030, China.
Exp Cell Res. 2025 Jul 15;450(2):114671. doi: 10.1016/j.yexcr.2025.114671. Epub 2025 Jul 10.
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.
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.
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.
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.
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.
胶质瘤因其侵袭性和对传统疗法的耐药性而难以治疗。最近的研究表明，淡竹叶提取物对纤维肉瘤细胞具有抗癌特性。然而，其对胶质瘤的药用效果和作用机制尚未得到探索。
研究淡竹叶提取物在体外和体内的详细抗胶质瘤作用及其具体的药理作用途径，重点关注自噬、凋亡、增殖和迁移。
制备淡竹叶乙醇提取物，并用高效液相色谱法对活性成分进行鉴定。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子显微镜观察自噬体。使用各种检测方法评估细胞活力、增殖、迁移和死亡情况。在动物模型中进一步测试其抗肿瘤作用。采用网络药理学研究作用于胶质瘤的主要化合物的潜在靶点。此外，进行RNA测序以进行转录组分析，并使用分子对接进行鉴定。
该提取物在体外和体内均显著降低了胶质瘤细胞的活力、增殖和迁移能力，同时促进了自噬、凋亡和细胞死亡。鉴定出五种活性成分：绿原酸、异荭草素、荭草素、牡荆素和异牡荆素。共鉴定出1472个胶质瘤靶点以及这五种化合物的219个药物靶点。差异表达基因的综合分析表明，二氢叶酸还原酶可能是这些化合物的关键靶点，分子对接分析确定了这一点。
淡竹叶提取物通过靶向二氢叶酸还原酶在细胞和动物模型中均表现出显著的抗胶质瘤作用，为其在胶质瘤治疗中的潜在应用提供了新的见解。
