摘要
目的:研究槟榔(areca catechu L,AC)降血糖、兴奋中枢神经等作用,运用网络药理学等方法探究其治疗糖尿病(diabetes mellitus,DM)和神经退行性疾病(neurodegenerative diseases,NDs)的潜在作用。方法:本研究通过筛选数据库及文献得出AC的主要活性成分和靶点基因;利用GeneCards等数据库获取与DM和NDs相关的疾病靶点基因。运用Rstudio对共有靶点进行基因本体(GO)和信号通路(KEGG)富集分析,应用STRING11.5在线数据库构建共有靶点蛋白互作网络(PPI)。运用分子对接观察AC主要活性成分(配体)与核心靶点(受体)的结合能力。利用CCK8检测不同浓度槟榔碱对细胞活力的影响,以确定给药浓度。利用葡萄糖检测试剂盒检测槟榔碱对细胞外葡萄糖含量的影响,评价槟榔碱调节葡萄糖代谢改善DM的功效。结果:网络药理学分析结果显示,AKT1、TP53、PPARG等因子和PI3K-Akt信号通路作为AC改善DM和NDs的核心靶点和通路。分子对接结果也显示AC的有效成分与DM和NDs的核心靶点有较高的结合能力。CCK8实验结果显示在给予槟榔碱0.5 mg/mL的浓度及刺激24 h后,细胞增殖能力最强(P<0.01)。0.5 mg/mL、1 mg/mL的槟榔碱浓度均增加了细胞的葡萄糖摄取量(P<0.01),且以0.5 mg/mL槟榔碱剂量的药效最好。结论:AC可能通过调节AKT1、TP53、PPARG等因子和PI3K-Akt信号通路来改善DM和NDs。且槟榔碱对细胞的增殖和葡萄糖代谢具有明显效果。
Objective:To study the effects of Areca catechu L(AC)on lowering blood glucose and stimulating central ner⁃vous system.The potential effects on the treatment of diabetes mellitus(DM)and neurodegenerative diseases(NDs)were investi⁃gated by means of network pharmacology.Methods:In this study,the main active components and target genes of AC were ob⁃tained by screening databases and literature.Disease target genes related to DM and NDs were obtained using GeneCards and oth⁃er databases.Common target gene ontology(GO)and signaling pathway(KEGG)were enriched with Rstudio,and common tar⁃get protein interaction network(PPI)was constructed with STRING11.5 online database.Molecular docking was used to observe the binding ability of the main active component(ligand)of AC to the core target(receptor).CCK8 was used to detect the effects of different concentrations of arecoline on cell viability to determine the dose concentration.The effect of arecoline on extracellular glucose content was detected with glucose detection kit,and the efficacy of arecoline in improving DM by regulating glucose me⁃tabolism was evaluated.Results:Network pharmacological analysis showed that AKT1,TP53,PPARG and PI3K⁃Akt signaling pathway were the core targets and pathways for AC to improve DM and NDs.Molecular docking results also showed that the ac⁃tive components of AC had high binding ability with the core targets of DM and NDs.The results of CCK8 experiment showed that the cell proliferation ability was the highest when arecoline was given 0.5 mg/mL and stimulated for 24 h(P<0.01).0.5 mg/mL,1 mg/mL arecoline concentration increased the glucose uptake of cells(P<0.01),and 0.5 mg/mL arecoline dose has the best efficacy.Conclusion:Areca nut may improve DM and NDs by regulating AKT1,TP53,PPARG and PI3K⁃Akt signaling pathway.Arecoline has obvious effect on cell proliferation and glucose metabolism.
作者
张晶
张佐妹
于书仪
刘俊言
尹德辉
林昱欣
刘颖
ZHANG Jing;ZHANG Zuomei;YU Shuyi;LIU Junyan;YIN Dehui;LIN Yuxin;LIU Ying(Hainan Medical University,Haikou 571199,China;The First Affiliated Hospital of Jiamusi University,Jiamusi 154002,China)
出处
《海南医学院学报》
CAS
北大核心
2024年第17期1290-1303,共14页
Journal of Hainan Medical University
基金
海南省自然科学基金高层次人才项目(822RC705)。
关键词
槟榔
神经退行性疾病
糖尿病
网络药理学
Areca catechu L
Neurodegenerative diseases
Diabetes mellitus
Network pharmacology
