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Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome

Ischemic stroke is the third leading cause of death in the world. Our previous study found that cynandione A (CYNA), the main component from the root of Cynanchum bungei, exhibits anti-ischemic stroke activity. In this work, we investigated the therapeutic mechanisms of CYNA to ischemic stroke at pr...

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Autores principales: Fang, Haiyang, Yue, Rongcai, Ga, Yang, Zhang, Yi, Shan, Lei, Zhao, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425521/
https://www.ncbi.nlm.nih.gov/pubmed/25955557
http://dx.doi.org/10.1371/journal.pone.0124632
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author Fang, Haiyang
Yue, Rongcai
Ga, Yang
Zhang, Yi
Shan, Lei
Zhao, Jing
author_facet Fang, Haiyang
Yue, Rongcai
Ga, Yang
Zhang, Yi
Shan, Lei
Zhao, Jing
author_sort Fang, Haiyang
collection PubMed
description Ischemic stroke is the third leading cause of death in the world. Our previous study found that cynandione A (CYNA), the main component from the root of Cynanchum bungei, exhibits anti-ischemic stroke activity. In this work, we investigated the therapeutic mechanisms of CYNA to ischemic stroke at protein network level. First, PC12 cells and cerebellar granule neurons were prepared to validate the effects of CYNA against glutamate injury. Our experiments suggested that CYNA could dose-dependently mitigate glutamate-induced neurons neurotoxicity and inhibit glutamate-induced upregulation of KHSRP and HMGB1, further confirming the neuroprotective effects of CYNA in vivo. Then, on the pathway sub-networks, which present biological processes that can be impacted directly or in periphery nodes by drugs via their targets, we found that CYNA regulates 11 pathways associated with the biological process of thrombotic or embolic occlusion of a cerebral artery. Meanwhile, by defining a network-based anti-ischemic stroke effect score, we showed that CYNA has a significantly higher effect score than random counterparts, which suggests a synergistic effect of CYNA to ischemic stroke. This study may shed new lights on the study of network based pharmacology.
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spelling pubmed-44255212015-05-21 Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome Fang, Haiyang Yue, Rongcai Ga, Yang Zhang, Yi Shan, Lei Zhao, Jing PLoS One Research Article Ischemic stroke is the third leading cause of death in the world. Our previous study found that cynandione A (CYNA), the main component from the root of Cynanchum bungei, exhibits anti-ischemic stroke activity. In this work, we investigated the therapeutic mechanisms of CYNA to ischemic stroke at protein network level. First, PC12 cells and cerebellar granule neurons were prepared to validate the effects of CYNA against glutamate injury. Our experiments suggested that CYNA could dose-dependently mitigate glutamate-induced neurons neurotoxicity and inhibit glutamate-induced upregulation of KHSRP and HMGB1, further confirming the neuroprotective effects of CYNA in vivo. Then, on the pathway sub-networks, which present biological processes that can be impacted directly or in periphery nodes by drugs via their targets, we found that CYNA regulates 11 pathways associated with the biological process of thrombotic or embolic occlusion of a cerebral artery. Meanwhile, by defining a network-based anti-ischemic stroke effect score, we showed that CYNA has a significantly higher effect score than random counterparts, which suggests a synergistic effect of CYNA to ischemic stroke. This study may shed new lights on the study of network based pharmacology. Public Library of Science 2015-05-08 /pmc/articles/PMC4425521/ /pubmed/25955557 http://dx.doi.org/10.1371/journal.pone.0124632 Text en © 2015 Fang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fang, Haiyang
Yue, Rongcai
Ga, Yang
Zhang, Yi
Shan, Lei
Zhao, Jing
Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome
title Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome
title_full Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome
title_fullStr Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome
title_full_unstemmed Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome
title_short Analysis of Cynandione A’s Anti-Ischemic Stroke Effects from Pathways and Protein-Protein Interactome
title_sort analysis of cynandione a’s anti-ischemic stroke effects from pathways and protein-protein interactome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425521/
https://www.ncbi.nlm.nih.gov/pubmed/25955557
http://dx.doi.org/10.1371/journal.pone.0124632
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