摘要
目的:通过网络药理学思路,预测骨碎补活性成分的作用靶点,结合骨质疏松(OP)相关靶点进行映射,拓扑出相互作用的关键节点进行富集分析,全方位探讨骨碎补抗OP的药理作用机制。方法:首先,在中药系统药理学数据库和分析平台(TCMSP)中基于药代动力学特征筛选出骨碎补的主要活性成分,并使用有机小分子生物活性数据库(Pub Chem)和Swiss Target Prediction数据库根据二维或三维结构相似性预测出相关作用靶点,然后通过人类孟德尔遗传数据库(OMIM)和Pubmed文本挖掘已知的OP治疗靶点,结合预测靶点导入String数据库构建骨碎补治疗OP靶点相互作用网络图,借助Cyto NCA软件根据相关节点参数拓扑出相互作用的关键节点,再次导入String构建蛋白质相互作用网络图,最后通过DAVID数据库对关键节点进行生物功能及代谢通路分析。结果:筛选出16个骨碎补活性成分,根据靶点预测技术预测出相关靶点118个;经过文本挖掘检索出OP相关靶点316个,根据String网络数据库构建蛋白相互作用网络,经Cyto NCA拓扑后,筛选出关键节点97个,富集分析显示骨碎补可能通过多条通路,从增殖、分化、免疫、氧化应激等多个方面,对干细胞、成骨细胞、破骨细胞、免疫细胞等产生调控作用。结论:基于网络药理学研究表明,骨碎补可能通过直接或间接作用靶点,参与调控多条主要信号通路,影响多类细胞的增殖、分化,从而起到抗OP的作用,为阐释其抗骨质疏松的物质基础与作用机制提供了科学依据。
Objective: To predict the target of active components of Drynariae Rhizoma by the network pharmacology,map related targets of osteoporosis( OP),and analyze key nodes of interaction topologically,so as to comprehensively explore the pharmacological mechanism of anti-op of osteoclasts. Method: Firstly,the main active components of Drynariae Rhizoma were screened out from TCMSP based on the pharmacokinetic characteristics,and the related targets were predicted by Pubchem and Swiss Target Prediction database according to the Two-dimensional/Three-dimensional( 2 D/3 D) structural similarity. Then, through Online Mendelian Inheritance in Man( OMIM) and Pubmed text,known OP therapeutic targets were mined,based on putative targets,String database was imported to build Drynariae Rhizoma treatment target OP interaction network diagram.With the help of CytoNCA software,the interaction key nodes were topologically identified according to relevant node parameters,and then imported into String database to build the protein interaction network graph. Finally,biological functions and metabolic pathways of key nodes were analyzed through DAVID database. Result: Sixteen active components of Drynariae Rhizoma were screened out,and 118 related targets were predicted according to the target prediction technique. Totally 316 known therapeutic targets for OP were retrieved. The protein interaction network was constructed according to the String network database. A total of 97 key nodes were screened via CytoNCA topology. The enrichment analysis showed that Drynariae Rhizoma may play an anti-osteoporosis role by regulating stem cells,osteoblasts,osteoclasts and immune cells through multiple signaling pathways in aspects of proliferation,differentiation,immunity and oxidative stress. Conclusion: Studies based on network pharmacology have shown that Drynariae Rhizoma may play an anti-op role through direct or indirect targets and multiple major signaling pathways and affect the proliferation and differentiation of multiple types of cells,in order to provid a scientific basis for explaining the material basis and mechanism of Drynariae Rhizoma's anti-osteoporosis effect.
作者
甘东浩
陈德强
冯蓬
徐展望
GAN Dong-hao;CHEN De-qiang;FENG Peng;XU Zhan-wang(Shandong University of Traditional Chinese Medicine ( TCM) , Jihan 250355 , China;Affiliated Hospital of Shandong University of TCM, Jihan 250014 , China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第13期186-191,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金面上项目(81473709)
