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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00029

The ethanolic extract of Caesalpinia sappan heartwood inhibits cerebral ischemia/reperfusion injury in a rat model through a multi-targeted pharmacological mechanism

 Wan Y. Jun1, Xu Li2, Song W. Ting2, Liu Y. Qi3, Wang L. Chao1, Zhao M. Bo1,  Yong Jiang1, Liu L. Ying3, Zeng K. Wu1* and Tu P. Fei1
  • 1Peking University, China
  • 2China Academy of Chinese Medical Sciences, China
  • 3Beijing University of Chemical Technology, China

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.

Keywords: Caesalpinia sappan L., middle cerebral artery occlusion, Oxygen-glucose deprivation/reperfusion, Neuroprotection, Multi-target mechanism

Received: 09 Sep 2018; Accepted: 11 Jan 2019.

Edited by:

Hector J Caruncho, University of Victoria, Canada

Reviewed by:

Shuai Ji, Xuzhou Medical University, China
Dong Liang, Guangxi Normal University, China  

Copyright: © 2019 Jun, Li, Ting, Qi, Chao, Bo, Jiang, Ying, Wu and Fei. 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.

* Correspondence: Prof. Zeng K. Wu, Peking University, Beijing, China, ZKW@bjmu.edu.cn