Post-injury administration of allicin attenuates ischemic brain injury through sphingosine kinase 2: In vivo and in vitro studies
| Autor: | Zhuyi Li, Wen-Ke Cai, Yong-Xiang Yang, Wei-Xin Li, Zhuo Zhang, Chao Sun, Jia-Ji Lin, Ting Chang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cell Survival Sphingosine kinase Pharmacology Neuroprotection Drug Administration Schedule Brain Ischemia Cerebral edema Rats Sprague-Dawley Brain ischemia Cellular and Molecular Neuroscience chemistry.chemical_compound medicine Animals Disulfides Cells Cultured Cerebral Cortex TUNEL assay Allicin Sphingosine business.industry Cell Biology Sulfinic Acids medicine.disease Rats Enzyme Activation Phosphotransferases (Alcohol Group Acceptor) SPHK2 nervous system chemistry Biochemistry Brain Injuries business |
| Zdroj: | Neurochemistry International. 89:92-100 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2015.07.022 |
| Popis: | Allicin, one of the main biologically active compounds derived from garlic, has been shown to exert various pharmacological activities and is considered to have therapeutic potential for many pathologic conditions. In the present study, we investigated the potential post-ischemic neuroprotective effects of allicin and its underlying mechanisms. Using a rat middle cerebral artery occlusion (MCAO) model, we found that intraperitoneal treatment with 50 mg/kg allicin significantly reduced brain infarct volume, attenuated cerebral edema and decreased the neurological deficit score. Allicin treatment also diminished TUNEL positive cells and inhibited the activation of caspase-3 after MCAO. These protective effects could be observed even if the administration was delayed to 6 h after injury. In addition, we evaluated the in vitro protective effects of allicin against oxygen glucose deprivation (OGD) induced neuronal injury in primary cultured cortical neurons. Allicin (50 μM) increased neuronal viability, decreased lactate dehydrogenase (LDH) release and inhibited apoptotic neuronal death after OGD. These protective effects could be observed even if the administration was delayed to 4 h after injury. Furthermore, allicin significantly increased the expression of sphingosine kinases 2 (Sphk2) both in vivo and in vitro. Pretreatment with the Sphk2 inhibitor ABC294640 partially reversed the protective effects of allicin against MCAO and OGD injury, indicating that an Sphk2-mediated mechanism was involved in allicin-induced protection in our models. The combination of findings suggests that post-injury administration of allicin has potential as a neuroprotective strategy for ischemic stroke. |
| Databáze: | OpenAIRE |
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