银杏叶治疗胶质母细胞瘤机制研究（英文）_杨甫.pdf

南 开 大 学 学 报（自然科学版）Acta Scientiarum Naturalium Universitatis NankaiensisVol.561Feb.2023第56卷第1期2023年2月Article ID:0465-7942(2023)01-0026-09Research on the Mechanism of Ginkgo Folium to Treat GlioblastomaYang Fu1,2,Wang Liuli3,Li Jinxing2,Sun Aigang2,Fu Yao4,Wang Zengyong4,Wang Mingguang2(1.Guangzhou University of Chinese Medicine,Guangzhou 510006,China;2.Department of Neurosurgery,Linyi Peoples Hospital,Linyin 371300,China;3.Lanshan Maternal and Child Health Hospital,Linyi 276003,China;4.Central Laboratory,Linyi People s Hospital,Linyin 371300,China)Abstract:Glioblastoma(GBM)is a malignant tumor with a high incidence rate and high invasion in hu-man central nervous system tumors.However,the causes of the occurrence and development of glioblasto-ma are not clear.Although Ginkgo Folium(GF)extract can reduce the growth of U-87 glioma cell linesin nude mice,the action mechanism remains unclear.In this study,network pharmacology,molecular dock-ing,and cell experiment were utilized to explore the underlying molecular mechanism of GF in treatingGBM.The effective ingredients and action targets of GF were obtained from the TCMSP database.STRING database was applied for protein interaction analysis and Cytoscape software was used to buildthe compound-target-disease network and PPI network.The R language was adopted as gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.AutoDock soft-ware was used for molecular docking verification.A cell experiment was employed to verify the inhibitionof GBM by the effective compounds in GF.The results showed that 27 potential effective components and112 potential targets of GF were selected.7 435 targets of GBM were screened from six databases,and98 overlapping targets were obtained.In active component-target network,quercetin,kaempferol,stigmas-terol,and luteolin were the important active components.In PPI network,ESR1,RELA,FOS,CCD1,EGFR,AR,HIF1A,MAPK8,NCOA1,and MDM2 were the core targets.GO and KEGG analysesshowed that the main pathways of GF in treating GBM involved PI3K-Akt,MAPK,and TNF signalingpathway.The results of molecular docking verified the good binding activity of the key pharmacodynamicmolecules with the core targets.Cell experiments showed that quercetin(QUE),luteolin(LUT),andkaempferol(KAE)can inhibit cell viability in GBM cell lines U251.It can be concluded GF is the resultof multi-component,multi-target,and multi-pathway interaction in the treatment of GBM,which provid-ed a theoretical basis for the clinical application of GF in the treatment of GBM.Keywords:glioblastoma;ginkgo folium;mechanism;network pharmacology;molecular docking technologyCLC number:O177Document code:A0IntroductionGlioma,originating from the neuroepithelium,is the most common central nervous system tumorin adults and accounts for 40%-50%of brain tumors.GBM(glioblastoma)is a highly malignant tumor,accounting for 70%of intracranial malignancies1.The median survival of GBM patients is only 12-15months,with the majority dying within 2 years and the 5-years survival rate less than 5%2-3.Untilnow surgical resection combined with postoperative chemoradiotherapy is the main treatment for glioma.Received date:2022-04-08Foundation item:Supported by the Doctoral Innovation Project of Linyi Peoples Hospital(2018LYBS12)Biography:Yang Fu(1986-),male,native place:Shandong Linyi,doctoral students,attending doctor.Corresponding author:Wang Mingguang(1975-),male,native place:Shandong Weihai,Deputy Chief Doctors,direction of research:brain tumor and verve spine.E-mail:杨 甫等：银杏叶治疗胶质母细胞瘤机制研究第1期杨 甫等：银杏叶治疗胶质母细胞瘤机制研究 27 Due to the characteristics of invasive growth and progressive malignancy of gliomas,radiation therapyand chemotherapy can only eliminate tumor cells or delay recurrence to a certain extent,residual tumorcells can cause a relapse in a short period4,and radiotherapy can also be damaging to patients to a certainextent5-6.Some patients develop drug resistance,which reduces the effectiveness of chemotherapy drugs,and the results achieved with individually targeted therapies are unsatisfactory7.Therefore,it is extremelyimportant to investigate new effective drugs for GBM treatment.Natural products have shown a wide range of pharmacological or biological activities,makingthem a treasure trove for research and the search for active drugs against GBM.Ginkgo Folium(GF)extract and its components have long been reported to be used for the treatment of cancerthousands of years ago in China.GF has achieved good effects in the treatment of hepatocellular car-cinoma8,lung cancer9,prostate cancer10,and other diseases.Studies have found that GF extractcan promote apoptosis of U87 glioma cells11,but there is no relevant study on the role of GF inGBM,and there is no in-depth study on the mechanism of GF inhibiting tumor cells.Network pharmacology can help explore the systemic effects of TCMs by combining the meth-ods of biology,pharmacology,and bioinformatics methods.These technologies