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

• Published in: 中国药理学报：英文版 2015 (11), p.1337-1348
• Main Author: Fang LI Yan-ni LV Yi-sha TAN Kai SHEN Ke-feng ZHAI Hong-lin CHEN Jun-ping KOU Bo-yang YU
• Format: Article
• Language: English
• Subjects: 制剂; 心脑血管; 有效成分; 治疗; 生脉; 相互作用; 缺血性疾病; 网络
• ISSN: 1671-4083; 1745-7254

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.