Protective effect of Hydroxysafflor Yellow A on cerebral ischemia reperfusion-injury by regulating GSK3β-mediated pathways.

Abstract

Ischemia-reperfusion (I/R) injury is accompanied by high mortality and morbidity. Unfortunately, there are few effective therapeutic medicines and strategies to enhance its outcome. Hydroxysafflor Yellow A (HSYA) exerts multiple biological activities and has potential protective effects against I/R injury in the brain, liver and heart. However, its underlying mechanism is still unclear. Here, we investigated whether HSYA modulates apoptosis and neuro-inflammation through the Glycogen synthase kinase-3β(GSK3β)-mediated pathway in a transient middle cerebral artery occlusion (MCAO) rat model and oxygen/glucose deprivation (OGD)-challenged primary neuronal cultures both in vivo and in vitro. Male Wistar rats were subjected to MCAO for 2 h, followed by 24 h of reperfusion. HSYA was administered 15 min after occlusion, SB216763 (GSK3β inhibitor) was injected to the left ventricle of the rat 6 h prior to MCAO. After 24 h of perfusion, apoptosis-associated protein and inflammatory markers were detected by western blotting. Meanwhile, terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay was used to evaluate the number of apoptotic cells in OGD-challenged neurons, cleaved caspase-3 were evaluated by Immunofluorescence (IF). Our data indicated that HSYA administration reduced infarct volume, decreased neurological deficit scores, elevated GSK3β phosphorylation and inhibited the activation of iNOS, NF-κB, and capase-3 in the penumbra of I/R rats. Moreover, blockade of GSK3β partly reversed the protective effect of HSYA on I/R by regulating NF-κB and caspase-3 both in vivo and in vitro. Collectively, we found that HSYA ameliorates I/R injury through its anti-inflammatory and anti-apoptotic effects via modulation of GSK-3β phosphorylation.

• Authors: Xiaomei Yang, Lin Chen, Yun Li, Feng Gao, Zhibo Yan, Peng Zhang, Jianbo Wu, Huanliang Wang, Baozhu Sun
• Journal: Neuroscience letters (Neurosci Lett) Vol. 736 Pg. 135258 (09 25 2020) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 32693014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Neuroprotective Agents
• Quinones
• hydroxysafflor yellow A
• Chalcone
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat

Topics

• Animals
• Apoptosis (drug effects)
• Brain (drug effects, metabolism, pathology)
• Brain Ischemia (metabolism, pathology)
• Chalcone (analogs & derivatives, pharmacology)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Infarction, Middle Cerebral Artery (metabolism, pathology)
• Male
• Neuroprotective Agents (pharmacology)
• Quinones (pharmacology)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, pathology)
• Signal Transduction (physiology)