Systems pharmacology dissection of the anti-stroke mechanism for the Chinese traditional medicine Xing-Nao-Jing

Xing-Nao-Jing ( XNJ) is a well-known injection that has been extensively applied in clinical treatment of stroke in China. However, the underlying mechanism of clinical administration of XNJ in stroke remains unclear. In this study, a systems pharmacology strategy based on pharmacokinetic and pharmacodynamics data was applied to analyze the pharmacological effect of XNJ on stroke. Sixteen active compounds were filtered from XNJ through Drug-likeness ( DL) and Brain-blood-barrier ( BBB) evaluations. Ninety-four potential targets of these active components were identified by SysDT and SEA. Biological process and pathway enrichment analyses of these targets demonstrated that XNJ exerted anti-stroke effects by biological processes and pathways, such as the response to oxidative stress, regulation of blood pressure, calcium signaling pathway, and apoptosis. Integrating the compound-target network and stroke-related PPI network, we found that Akt1, HIF-1 alpha and ITGB2 may play key roles in the treatment of stroke. The experiments demonstrated that oxycurcumenol may prevent PC12 cells from oxidative stress-induced cell damage. Our study indicates that XNJ has an effect on stroke by protecting neuro cells from oxidative stress-induced cell damage via HIF1 alpha, and the research strategy at the systems pharmacology level is feasible to reveal the mechanisms of novel lead compounds from natural products. (C) 2018 The Authors. Production and hosting by Elsevier B. V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license.