SMND-309, a novel derivative of salvianolic acid B, protects rat brains ischemia and reperfusion injury by targeting the JAK2/STAT3 pathway

Autor: Jingwei Tian, Yubai Gao, Li-bo Zou, Haibo Zhu, Guangying Du
Rok vydání: 2013
Předmět:
Male
STAT3 Transcription Factor
Vascular Endothelial Growth Factor A
Ischemia
Neovascularization
Physiologic
Pharmacology
Neuroprotection
Brain Ischemia
Rats
Sprague-Dawley
Brain ischemia
chemistry.chemical_compound
Caffeic Acids
Receptors
Erythropoietin
medicine
Animals
Erythropoietin
Benzofurans
Janus kinase 2
biology
business.industry
Brain
Water
Infarction
Middle Cerebral Artery
Kinase insert domain receptor
Cerebral Infarction
Dendrites
Recovery of Function
Janus Kinase 2
Phosphoproteins
medicine.disease
Survival Analysis
Vascular Endothelial Growth Factor Receptor-2
Axons
Rats
Erythropoietin receptor
Platelet Endothelial Cell Adhesion Molecule-1
Vascular endothelial growth factor
Neuroprotective Agents
Gene Expression Regulation
chemistry
Biochemistry
Reperfusion Injury
biology.protein
business
Reperfusion injury
Signal Transduction
Zdroj: European Journal of Pharmacology. 714:23-31
ISSN: 0014-2999
DOI: 10.1016/j.ejphar.2013.05.043
Popis: SMND-309 is a novel derivative of salvianolic acid B, and has shown protective effects against rat cortical neuron damage in vitro and in vivo. However the molecular mechanisms through which SMND-309 affords this protection are unclear. The present study aimed to investigate the mechanisms associated with the protective activities of SMND-309 in a cerebral ischemia and reperfusion injury rat model. In this study, we used AG490, a specific inhibitor of the signaling pathway involving the Janus Kinase 2 (JAK2)/Signal Transducers and Activators of Transcription 3 (STAT3) signaling molecules and suramin, a potent inhibitor of vascular endothelial growth factor (VEGF), to investigate the mechanisms of SMND-309. The cerebral ischemia and reperfusion injury model was induced by performing middle cerebral artery occlusion (MCAO) in the rats. SMND-309 mitigated the effects of ischemia and reperfusion injury on brain by decreasing the infract volume, improving neurological function, increasing the survival of neurons and promoting angiogenesis by increasing the levels of erythropoietin (EPO), erythropoietin receptor (EPOR), phosphorylated JAK2 (P-JAK2), phosphorylated STAT3 (P-STAT3), VEGF and VEGF receptor 2 (Flk-1) in the brain. Our results suggest that SMND-309 provides significant neuroprotective effects against cerebral ischemia and reperfusion injury. The mechanisms of this protection may be attributed to the increased VEGF expression occurring from the JAK2/STAT3 pathway, activated by the increased EPO/EPOR expression in the brain.
Databáze: OpenAIRE
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