An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardiocerebral ischemic diseases  

作　　者：Fang LI Yan-ni LV Yi-sha TAN Kai SHEN Ke-feng ZHAI Hong-lin CHEN Jun-ping KOU Bo-yang YU 

机构地区：[1]Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, ChinaPharmaceutical University, Nanjing 211198, China

出　　处：《Acta Pharmacologica Sinica》2015年第11期1337-1348,共12页中国药理学报（英文版）

基　　金：Acknowledgements This research work was supported by the National Natural Science Foundation of China （No 81274004）, 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）, and the Graduate Student Scientific Research Innovation Plan of Jiangsu Higher Education Institutions （CXLX13_30）.

摘　　要：Aim： SMXZF （a combination of ginsenoside Rbl, ginsenoside Rgl, schizandrin and DT-13） derived from Chinese traditional medicine formula ShengMai preparations） is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases. Methods： Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H202-treated rat PC12 cells. Results： Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKαβ in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2- treated PC12 cells. Conclusion： NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.Aim： SMXZF （a combination of ginsenoside Rbl, ginsenoside Rgl, schizandrin and DT-13） derived from Chinese traditional medicine formula ShengMai preparations） is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases. Methods： Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H202-treated rat PC12 cells. Results： Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKαβ in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2- treated PC12 cells. Conclusion： NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.

关 键 词：ShengMai San cardio-cerebral ischemic diseases network pharmacology traditional Chinese medicines target-pathwayinteraction network gene ontology NF-κB oxidative stress EA.hy926 cells PC12 cells 

分 类 号：TQ461[化学工程—制药化工] Q784[生物学—分子生物学]