Cargando…

The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism

Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechani...

Descripción completa

Detalles Bibliográficos
Autores principales: Wan, Yan-Jun, Xu, Li, Song, Wen-Ting, Liu, Yu-Qi, Wang, Li-Chao, Zhao, Ming-Bo, Jiang, Yong, Liu, Lian-Ying, Zeng, Ke-Wu, Tu, Peng-Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370896/
https://www.ncbi.nlm.nih.gov/pubmed/30804781
http://dx.doi.org/10.3389/fphar.2019.00029
_version_ 1783394453006843904
author Wan, Yan-Jun
Xu, Li
Song, Wen-Ting
Liu, Yu-Qi
Wang, Li-Chao
Zhao, Ming-Bo
Jiang, Yong
Liu, Lian-Ying
Zeng, Ke-Wu
Tu, Peng-Fei
author_facet Wan, Yan-Jun
Xu, Li
Song, Wen-Ting
Liu, Yu-Qi
Wang, Li-Chao
Zhao, Ming-Bo
Jiang, Yong
Liu, Lian-Ying
Zeng, Ke-Wu
Tu, Peng-Fei
author_sort Wan, Yan-Jun
collection PubMed
description Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 μg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.
format Online
Article
Text
id pubmed-6370896
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-63708962019-02-25 The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism Wan, Yan-Jun Xu, Li Song, Wen-Ting Liu, Yu-Qi Wang, Li-Chao Zhao, Ming-Bo Jiang, Yong Liu, Lian-Ying Zeng, Ke-Wu Tu, Peng-Fei Front Pharmacol Pharmacology Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 μg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury. Frontiers Media S.A. 2019-02-05 /pmc/articles/PMC6370896/ /pubmed/30804781 http://dx.doi.org/10.3389/fphar.2019.00029 Text en Copyright © 2019 Wan, Xu, Song, Liu, Wang, Zhao, Jiang, Liu, Zeng and Tu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wan, Yan-Jun
Xu, Li
Song, Wen-Ting
Liu, Yu-Qi
Wang, Li-Chao
Zhao, Ming-Bo
Jiang, Yong
Liu, Lian-Ying
Zeng, Ke-Wu
Tu, Peng-Fei
The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism
title The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism
title_full The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism
title_fullStr The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism
title_full_unstemmed The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism
title_short The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism
title_sort ethanolic extract of caesalpinia sappan heartwood inhibits cerebral ischemia/reperfusion injury in a rat model through a multi-targeted pharmacological mechanism
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370896/
https://www.ncbi.nlm.nih.gov/pubmed/30804781
http://dx.doi.org/10.3389/fphar.2019.00029
work_keys_str_mv AT wanyanjun theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT xuli theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT songwenting theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT liuyuqi theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT wanglichao theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT zhaomingbo theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT jiangyong theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT liulianying theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT zengkewu theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT tupengfei theethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT wanyanjun ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT xuli ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT songwenting ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT liuyuqi ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT wanglichao ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT zhaomingbo ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT jiangyong ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT liulianying ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT zengkewu ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism
AT tupengfei ethanolicextractofcaesalpiniasappanheartwoodinhibitscerebralischemiareperfusioninjuryinaratmodelthroughamultitargetedpharmacologicalmechanism