摘要
目的通过网络药理学和分子对接方法,探讨白及作用于糖尿病足的主要活性化合物、关键靶点及作用机制。方法使用中药系统药理学数据库分析平台(TCSMP),筛选白及药材的有效成分。将白及活性化合物的2D结构用Pubchem数据库导出,再通过Swiss Target Prediction数据库预测白及有效成分的作用靶点。使用CTD数据库及GeneCards数据库筛选并整合与糖尿病足相关的作用靶点,BioinfoGp网站绘制韦恩图,得到白及治疗糖尿病足的共同潜在靶点。通过STRING数据库得到初步PPI网络图后使用Cytoscape软件进一步进行网络拓扑参数分析后构建蛋白之间相互作用网络图(PPI)及“白及-活性化合物-作用靶点”图,筛选出白及的主要活性成分和治疗糖尿病足的关键作用靶点。再使用DAVID数据库对关键靶点进行GO功能富集分析及KEGG通路分析,并构建“白及-活性成分-作用靶点-疾病通路”网络图。最后利用AutoDockTools-1.5.6计算结合能,将结合能最低的靶点与活性成分在PyMOL中进行分子对接验证。结果研究发现白及活性成分主要通过表皮生长因子(EGFR)、苏氨酸激酶1(AKT1)、血管内皮生长因子(VEGFA)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶3(MAPK3)、胱天蛋白酶3(CASP3)、癌基因(HRAS)等关键作用靶点和KEGG信号通路中PI3K-AKT、MAPK及VEGF信号通路发挥治疗糖尿病足作用。分子对接发现白及活性成分中白及多糖、白及菲螺醇和白及二氢菲类与关键靶点结合活性较高,结合较稳定。结论该研究发现白及可能通过多成分多靶点多通路共同发挥抗细胞凋亡、促进细胞增殖、血管生成、抑制炎症等作用,从而达到治疗糖尿病足的目的。
Objective The aim of this paper was to explore the main active ingredients,key targets and the theraoeutic mechanism of Baiji(Bletillae Rhizoma)in diabetic foot based on network pharmacology and molecular docking.Methods The active ingredients of Baiji(Bletillae Rhizoma)was screened by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP).The 2D structures of the active ingredients of Baiji(Bletillae Rhizoma)were obtained by Pubchem database,and the potential targets of the active ingredients were screened by Swiss Target Prediction database.The potential targets of diabetic foot were predictd and screened through the GeneCards database and CTD database,BioinfoGp website mapped Venn diagram to get common potential targets of Baiji(Bletillae Rhizoma)treating diabetic foot.And then the“Baiji(Bletillae Rhizoma)-ingredie-target”network diagram was constructed by using Cytoscape software.The STRING database combined with Cytoscape software were used to draw the protein-protein interaction(PPI)network,and the topological parameters of PPI were analyzed to screen the key targets for Baiji(Bletillae Rhizoma)treating diabetic foot.The David database was used to perform GO function and KEGG pathway enrichment analysis on key targets,and a“Baiji(Bletillae Rhizoma)-ingredient-target-pathway”network was constructed.Finally,AutoDockTools-1.5.6 was used to calculate the binding energy,and the lowest binding energy of the targets and the active ingredients were used to docking in PyMOL.Results It was found that the Baiji(Bletillae Rhizoma)and its active ingredients play a role in the protection of diabetic foot through the key targets of EGFR,AKT1,VEGFA,TNF,MAPK3,CASP3,HRAS,etc.and the signaling pathway of PI3k-AKT,MAPK and VEGF,etc.It was found by molecular docking that bletillamannan,blespiroland bledihydrophenanthrene were highly active and stable in binding to key targets.Conclusion In this study,it was found that Baiji(Bletillae Rhizoma)may play a role in anti-apoptosis,promoting cell proliferation
作者
王安楠
范书源
侯铁军
李坤
刁云鹏
WANG Annan;FAN Shuyuan;HOU Tiejun;LI Kun;DIAO Yunpeng(Liaoning Normol University,Dalian 116029,Liaoning,China;Dalian Maiqike Biotechnology Limited Company,Dalian 116085,Liaoning,China;Dalian Medical University,Dalian 116044,Liaoning,China;Dalian Engineering Research Centre for Development of Anti-infective Chinese Medicine,Dalian 116044,Liaoning,China)
出处
《辽宁中医药大学学报》
CAS
2022年第5期161-169,共9页
Journal of Liaoning University of Traditional Chinese Medicine
基金
辽宁省自然基金(2020-MS-246)。
关键词
白及
糖尿病足
网络药理学
分子对接
活性成分
作用机制
Baiji(Bletillae Rhizoma)
diabetic foot
network pharmacology
molecular docking
active ingredients
mechanism of action
