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

Abstract

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-1α 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 HIF1α, and the research strategy at the systems pharmacology level is feasible to reveal the mechanisms of novel lead compounds from natural products.

• Authors: Yuhua Chen, Yue Sun, Wende Li, Hong Wei, Tianlin Long, Hua Li, Quanhua Xu, Wei Liu
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 136 Issue 1 Pg. 16-25 (Jan 2018) ISSN: 1347-8648 [Electronic] Japan
• PMID: 29336875 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Sesquiterpenes
• curcumenol
• oxycurcumenol

Topics

• Animals
• Drugs, Chinese Herbal (pharmacokinetics, pharmacology)
• Hypoxia-Inducible Factor 1, alpha Subunit (physiology)
• Oxidative Stress (drug effects)
• PC12 Cells
• Phytotherapy
• Rats
• Sesquiterpenes (pharmacology, therapeutic use)
• Stroke (drug therapy, genetics)
• Structure-Activity Relationship