摘要
目的:利用网络药理学和分子对接技术,研究程氏萆薢分清饮预防和治疗动脉粥样硬化(Atherosclerosis,AS)疾病的潜在作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)对该制剂的成分进行筛选,包括川萆薢、石菖蒲、车前子、黄柏、白术、茯苓、丹参和莲子心的有效成分和基因靶点,利用Cytoscape 3.9.1构建药物-成分-靶点网络图。利用GeneCards数据库进行目标筛选,并将其与局部目标进行交叉,将常用的基因目标引入STRING中,构建蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络,最终利用Cytoscape 3.9.1进行可视化,以筛选出核心基因靶点。在David平台上,进行了基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,并利用Cytoscape 3.9.1构建了成分-目标-路径网络图,最终通过Autodock软件进行了分子对接验证。结果:程氏萆薢分清饮中的有效成分可能为beta-谷甾醇、槲皮素、丹参酮IIA以及木犀草素等,这些成分可能对AS产生显著的影响。其潜在基因靶点为丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、Jun原癌基因(Jun Proto-Oncogee,JUN)、信号转导因子和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、一氧化氮合酶2(Nitric Oxide Synthase 2,NOS2)等。流体剪切应力与AS通路、晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Advanced Glycation End Product Receptor,RAGE)通路及白细胞介素(Interleukin,IL)-17通路等,为其影响AS的重要通路。分子对接显示薯蓣皂苷元和丹参酮IIA与β2肾上腺素受体(Adrenoceptor Beta 2,ADRB2)和前列腺素氧化环化酶2(Prostaglandin-Endoperoxide Synthase 2,PTGS2)等关键靶点之间存在氢键相互作用且结合构象较好,约89%低于–7.5 kcal/mol,且多数对接优于阿托伐他汀。结论:本项研究初步探讨程氏萆薢分清饮多靶点、多途径防治AS的潜�
Objective:To investigate the potential mechanism of CHENG’s Bixie Fenqing decoction(萆薢分清饮)in the prevention and treatment of atherosclerotic diseases by network pharmacology and molecular docking techniques.Methods:TCMSP was used to screen the active ingredients and gene targets of Bixie(Rhizoma Dioscoreae Hypoglaucae),Shichangpu(Rhizoma Acori Tatarinowii),Cheqian(Semen Plantaginis),Huangbai(Cortex Phellodendri Chinsis),Baizhu(Rhizoma Atractylodis Macrocephalae),Fuling(Poria),Danshen(Radix et Rhizoma Salviae Miltiorrhizae)and Lianzixin(Plumula Nelumbinis).The drug-ingredient-target network diagram was constructed by Cytoscape 3.9.1.Target screening was performed using Genecards database and intersected with local targets.Common gene targets were introduced into STRING to construct PPI network.Finally,Cytoscape 3.9.1 was used for visualization to screen out core gene targets.On the David platform,GO and KEGG enrichment analyses were performed,and the composition-target-path network diagram was constructed using Cytoscape 3.9.1.Finally,the molecular docking verification was performed using Autodock software.Results:The active ingredients in CHENG’s Bixie Fenqing decoction may be beta-Glutasterol,quercetin,Danshin IIA and luteolin,which may have significant effects on atherosclerosis.Potential genetic targets were AKT1,JUN,STAT3,NOS2,etc.Fluid shearing and atherosclerosis pathway,AGE-RAG pathway,and IL-17 pathway were important pathways affecting atherosclerosis.Molecular docking showed that there were hydrogen-bond interaction between diosgenin and tansherone IIA and key targets such as ADRB2 and PTGS2,and the binding conformation was good,with about 89%lower than–7.5 kcal/mol,and most docking was superior to atorvastatin.Conclusion:This study provides clinical and pharmacological insights into the potential mechanism of CHENG’s Bixie Fenging decoction in treating atherosclerosis by several targets and pathways.
作者
吴晓晗
刘光辉
王朕
王洋
WU Xiaohan;LIU Guanghui;WANG Zhen;WANG Yang
出处
《中医临床研究》
2023年第36期33-40,共8页
Clinical Journal Of Chinese Medicine
基金
国家自然科学基金青年基金项目(81904079)
辽宁省“兴辽英才计划”(XLYC2007012)
沈阳市科技计划(21-173-9-05)。
关键词
程氏萆薢分清饮
网络药理学
动脉粥样硬化
分子对接
作用机制
CHENG’s Bixie Fenqing decoction
Network pharmacology
Atherosclerosis
Molecular docking
Mechanism of action
