a11anoveldiarylacylhydrazonederivativeexertsneuroprotectionagainstischemicinjuryinvitroandinvivo | |
Feng Hongxuan1; Li Chunpu1; Shu Shuangjie2; Liu Hong1; Zhang Haiyan1 | |
刊名 | actapharmacologicasinica |
2019 | |
卷号 | 40期号:2页码:160 |
关键词 | FOCAL CEREBRAL-ISCHEMIA OXIDATIVE STRESS DRUG DISCOVERY COLORIMETRIC ASSAY TREAT STROKE MECHANISMS DISEASE OXYGEN PROTECTS MODELS ischemic stroke neuroprotection diaryl acylhydrazone oxygen glucose deprivation middle cerebral artery occlusion protein kinase B extracellular signal-regulated kinase |
ISSN号 | 1671-4083 |
DOI | 10.1038/s41401-018-0028-4 |
英文摘要 | There is an urgent need to develop effective therapies for ischemic stroke, but the complicated pathological processes after ischemia make doing so difficult. In the current study, we identified a novel diaryl acylhydrazone derivative, A11, which has multiple neuroprotective properties in ischemic stroke models. First, A11 was demonstrated to induce neuroprotection against ischemic injury in a dose-dependent manner (from 0.3 to 3 mu M) in three in vitro experimental ischemic stroke models: oxygen glucose deprivation (OGD), hydrogen peroxide, and glutamate-stimulated neuronal cell injury models. Moreover, A11 was able to potently alleviate three critical pathological changes, apoptosis, oxidative stress, and mitochondrial dysfunction, following ischemic insult in neuronal cells. Further analysis revealed that A11 upregulated the phosphorylation levels of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in OGD-exposed neuronal cells, suggesting joint activation of the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MEK)/ERK pathways. In rats with middle cerebral artery occlusion, single-dose administration of A11 (3 mg/kg per day, i.v.) at the onset of reperfusion significantly reduced the infarct volumes and ameliorated neurological deficits. Our study, for the first time, reports the anti-ischemic effect of diaryl acylhydrazone chemical entities, especially A11, which acts on multiple ischemia-associated pathological processes. Our results may provide new clues for the development of an effective therapeutic agent for ischemic stroke. |
资助项目 | [National Natural Science Foundation of China] |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/284174] |
专题 | 中国科学院上海药物研究所 |
作者单位 | 1.中国科学院上海药物研究所 2.中国科学院大学 |
推荐引用方式 GB/T 7714 | Feng Hongxuan,Li Chunpu,Shu Shuangjie,et al. a11anoveldiarylacylhydrazonederivativeexertsneuroprotectionagainstischemicinjuryinvitroandinvivo[J]. actapharmacologicasinica,2019,40(2):160. |
APA | Feng Hongxuan,Li Chunpu,Shu Shuangjie,Liu Hong,&Zhang Haiyan.(2019).a11anoveldiarylacylhydrazonederivativeexertsneuroprotectionagainstischemicinjuryinvitroandinvivo.actapharmacologicasinica,40(2),160. |
MLA | Feng Hongxuan,et al."a11anoveldiarylacylhydrazonederivativeexertsneuroprotectionagainstischemicinjuryinvitroandinvivo".actapharmacologicasinica 40.2(2019):160. |
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