摘要
目的:运用网络药理学、分子对接、实验验证等手段探讨补骨脂抗肺腺癌的作用和机制。方法:在症状映射数据库(SymMap)、中药系统药理学数据库与分析平台(TCMSP)、中药分子机制的生物信息学分析工具(BATMANTCM)、中草药数据库(TCMID)和基因表达谱互动分析平台(GEPIA)中检索补骨脂活性成分、对应靶点及肺腺癌有关的潜在靶点;利用韦恩图获取补骨脂活性成分作用于肺腺癌的靶点,Cystoscape 3.7.2软件构建补骨脂活性成分作用于肺腺癌靶点网络图。采用STRING数据库进行蛋白质-蛋白质相互作用分析;采用注释、可视化和综合发现数据库(DAVID)进行富集分析,Origin 2021软件构建补骨脂“活性成分-靶点-通路”网络关系图。采用AutoDockTools 1.5.6和PyMOL进行分子对接。结果:①筛选获得补骨脂治疗肺腺癌的交集靶点55个,涉及β1-肾上腺素能受体(ADRB1)、β2-肾上腺素能受体(ADRB2)等核心靶点,以及环磷酸鸟苷酸(cGMP)-蛋白激酶G(PKG)和细胞缺氧诱导因子-1(HIF-1)等信号通路。②分子对接结果提示,补骨脂酚与肺腺癌核心治疗靶点ADRB1、ADRB2均有较低的结合能。③实验验证结果证实,补骨脂酚能够抑制肿瘤细胞增殖及肾上腺素能受体亚型ADRB1、ADRB2、α1A-肾上腺素受体(ADRA1A)等基因的表达水平,与网络药理学分析结果相符。结论:补骨脂及其活性成分补骨脂酚可通过干预β-肾上腺素能受体及其信号通路,从而发挥抗肺腺癌的作用。
Objective:To investigate effect and mechanism of Fructus Psoraleae on lung adenocarcinoma using network pharmacology,molecular docking and experimental validation.Methods:Active ingredients of Fructus Psoraleae and the potential targets related to lung adenocarcinoma(LUAD)were searched in Symptom Mapping(SymMap),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM),Traditional Chinese Medicine Integrated Database(TCMID)and Gene Expression Profiling Interactive Analysis(GEPIA);Venn diagram was used to obtain the targets of the active ingredient of Fructus Psoraleae acting on LUAD,Cystoscape 3.7.2 software was used to construct the network diagram of active ingredient from Fructus Psoraleae on LUAD targots.STRING database was used for protein-protein interaction analysis;Database for Annotation,Visualization and Integrated Discovery(DAVID)was used for enrichment analysis,and Origin 2021 software was used for constructing“active ingredient-target-pathway”network diagram.AutoDockTools 1.5.6 and PyMOL was used for molecular Docking.Results:①Fifty-five intersection targets of Fructus Psoraleae for lung adenocarcinoma treatment were obtained,involving core targets such asβ1-adrenoceptor(ADRB1)andβ2-adrenoceptor(ADRB2),as well as signaling pathways such as cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)and hypoxia inducible factor-1(HIF-1).②The molecular docking results suggested that bakuchiol had low binding energy with ADRB1 and ADRB2,which were core therapeutic targets of lung adenocarcinoma.③The experimental validation results confirmed that bakuchiol could inhibit tumor cell proliferation and expression levels of genes such as adrenergic receptor subtypes ADRB1,ADRB2 andα1A-adrenoreceptor(ADRA1A),which were consistent with results of the network pharmacology analysis.Conclusion:Fructus Psoraleae and its active ingredient bakuchiol may exert anti-lung adenocarcinoma effects by intervening withβ-adrenergic receptors and their signaling pathways.
作者
叶桐
张璐
葛广波
赵咏芳
刘俊
YE Tong;ZHANG Lu;GE Guangbo;ZHAO Yongfang;LIU Jun(Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai201203,China;Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《上海中医药大学学报》
CAS
2023年第4期36-46,共11页
Academic Journal of Shanghai University of Traditional Chinese Medicine
基金
上海市卫健委中医药科研项目(2022CX005)
上海中医药大学产业发展中心医养结合科创项目(YYKC-2021-01-116)
上海中医药大学大学生创新项目(202110268219)。
关键词
补骨脂
肺腺癌
网络药理学
分子对接
Β-肾上腺素能受体
Fructus Psoraleae
lung adenocarcinoma
network pharmacology
molecular docking
β-adrenergic receptors
