Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease  

作　　者：LV Yan-Ni LI Shao-Xia ZHAI Ke-Feng KOU Jun-Ping YU Bo-Yang 

机构地区：[1]State Key Laboratory of Natural Medicines, China Pharmaceutical University [2]Department of Complex Prescription of TCM, China Pharmaceutical University

出　　处：《Chinese Journal of Natural Medicines》2014年第4期251-258,共8页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81274004);National Key Technologies R&D Program of China(No.2008BAI51B03);2011’Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education,a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,the Project Program of the State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.JKGZ201107);the Graduate Student Scientific Research Innovation Plan of Jiangsu Higher Education Institutions(No.CXZZ11_0795)

摘　　要：AIM： To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD： A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide （H202）-induced PC 12 cells by Western blotting. RESULTS： Twelve differentially expressed proteins （gene names： NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK 14, CREBI, IFNG, APR and BCL2） were confirmed as the central nodes of the interaction network （45 nodes, 93 edges）. The NF-KB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of 1KKct, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting. CONCLUSION： The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-arB signaling pathway as the key targets and pathways for schisandrin.AIM: To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD: A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide(H2O2)-induced PC12 cells by Western blotting. RESULTS: Twelve differentially expressed proteins(gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network(45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting. CONCLUSION: The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.

关 键 词：SCHISANDRIN Network pharmacology Cerebrovascular disease Molecular target NF-xB signaling pathway 

分 类 号：R96[医药卫生—药理学]