N-Butylphthalide (NBP) ameliorated cerebral ischemia reperfusion-induced brain injury via HGF-regulated TLR4/NF-κB signaling pathway
| Autor: | Yu-sheng Li, Zhen-fang Guo, Ping Zhang, Yu-ming Xu, Jing-gui Song |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Cell Survival Brain damage Pharmacology Neuroprotection Brain Ischemia Rats Sprague-Dawley Brain ischemia 03 medical and health sciences 0302 clinical medicine medicine Animals Humans PI3K/AKT/mTOR pathway Benzofurans Inflammation Hepatocyte Growth Factor Akt/PKB signaling pathway Chemistry NF-kappa B General Medicine medicine.disease Up-Regulation Toll-Like Receptor 4 030104 developmental biology Astrocytes Reperfusion Injury Immunology TLR4 Hepatocyte growth factor medicine.symptom Reperfusion injury 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 83:658-666 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2016.07.040 |
| Popis: | N-Butylphthalide (NBP) has been known to have potential neuroprotective effects in Alzheimer's disease and stroke animal models. Hepatocyte-growth factor (HGF), with strong angiogenic properties, exerted protective role in brain injury. The present study was aimed to investigate the possible anti-inflammatory effects of NBP on the brain injury of rats with cerebral ischemia reperfusion (IR) and astrocytes activation induced by lipopolysaccharide (LPS) treatment. Our results showed that cerebral IR induced brain damage with down-regulation of HGF and astrocytes activation. NBP treatment significantly increased HGF expression and activated cMet/PI3K/AKT signaling pathway, stimulating mTOR activity and suppressing apoptosis in brain tissues. Also NBP inhibited pro-inflammatory cytokines expression, including IL-6, IL-1β, and TNFα, via TLR4/NF-κB suppression. Anti-HGF treatment enhanced TLR4 expression while HGF could suppress TLR4 activation and its down-streaming signals, attenuating inflammation finally. Notably, NBP up-regulated HGF and down-regulated TLR4 expression significantly in the astrocytes combined with the treatment of TLR4 inhibitor than the cells only treated with TLR4 inhibitor, suggesting that NBP could further suppress TLR4 activation, suggesting that NBP might impede TLR4 through up-regulating HGF expression. These results suggested that NBP treatment significantly ameliorated cerebral IR-induced brain injury by inhibiting TLR4/NF-κB-associated inflammation regulated by HGF. |
| Databáze: | OpenAIRE |
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