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 mechanis...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00029/full |
| _version_ | 1818914694254034944 |
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| author | Yan-Jun Wan Li Xu Wen-Ting Song Yu-Qi Liu Li-Chao Wang Ming-Bo Zhao Yong Jiang Lian-Ying Liu Ke-Wu Zeng Peng-Fei Tu |
| author_facet | Yan-Jun Wan Li Xu Wen-Ting Song Yu-Qi Liu Li-Chao Wang Ming-Bo Zhao Yong Jiang Lian-Ying Liu Ke-Wu Zeng Peng-Fei Tu |
| author_sort | Yan-Jun Wan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T23:50:27Z |
| format | Article |
| id | doaj.art-bc1bb147ffd94c878525b63bcbe288b9 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T23:50:27Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bc1bb147ffd94c878525b63bcbe288b92022-12-21T20:01:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-02-011010.3389/fphar.2019.00029423949The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological MechanismYan-Jun Wan0Li Xu1Wen-Ting Song2Yu-Qi Liu3Li-Chao Wang4Ming-Bo Zhao5Yong Jiang6Lian-Ying Liu7Ke-Wu Zeng8Peng-Fei Tu9State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaCollege of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaCollege of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaBackground: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.https://www.frontiersin.org/article/10.3389/fphar.2019.00029/fullCaesalpinia sappan L.middle cerebral artery occlusionoxygen-glucose deprivation/reperfusionneuroprotectionmulti-target mechanism |
| spellingShingle | Yan-Jun Wan Li Xu Wen-Ting Song Yu-Qi Liu Li-Chao Wang Ming-Bo Zhao Yong Jiang Lian-Ying Liu Ke-Wu Zeng Peng-Fei Tu The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism Frontiers in Pharmacology Caesalpinia sappan L. middle cerebral artery occlusion oxygen-glucose deprivation/reperfusion neuroprotection multi-target 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 | Caesalpinia sappan L. middle cerebral artery occlusion oxygen-glucose deprivation/reperfusion neuroprotection multi-target mechanism |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00029/full |
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