Exploring the neuroprotective effects of ginkgolides injection in a rodent model of cerebral ischemia-reperfusion injury by GC-MS based metabolomic profiling
Autor: | Wei Xiao, Jianliang Geng, Siqi Feng, Jiankun Wang, Zhen-Zhong Wang, Bingchen Ouyang, Yue Zhang, Pei Wang, Wen-Zhe Huang, Jiye Aa, Yejin Zhu, Shu-Yao Wang, Guangji Wang |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Clinical Biochemistry Ischemia Pharmaceutical Science Pharmacology Neuroprotection Gas Chromatography-Mass Spectrometry Analytical Chemistry Brain Ischemia Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Metabolomics parasitic diseases Drug Discovery medicine Animals Glycolysis Ginkgolides Spectroscopy Cerebral infarction Chemistry Lipid metabolism Infarction Middle Cerebral Artery medicine.disease Rats 030104 developmental biology Neuroprotective Agents Reperfusion Injury Reperfusion injury 030217 neurology & neurosurgery |
Zdroj: | Journal of pharmaceutical and biomedical analysis. 142 |
ISSN: | 1873-264X |
Popis: | Cerebral ischemia-reperfusion (I/R) injury usually contributes to mortality and disability after ischemic stroke. Ginkgolides injection (GIn), a standard preparation composed of ginkgo diterpene lactones extract, is clinically used for neuroprotective treatment on reconvalescents of cerebral infarction. However, the understanding about its therapeutic mechanism is still lacking. In this study, a gas chromatography-mass spectrometry (GC-MS) based metabolomic approach coupled with multivariate data analysis (MVDA) was applied to explore the neuroprotective effects of GIn in a rodent model of focal ischemic stroke induced by transient middle cerebral artery occlusion (tMCAO). Metabolomic profiling revealed a series of metabolic perturbations that underlie the cerebral I/R pathological events. GIn can reverse the I/R induced brain metabolic deviations by modulating multiple metabolic pathways, such as glycolysis, Krebs cycle, pentose phosphate pathway (PPP), γ-aminobutyrate (GABA) shunt and lipid metabolism. Moreover, the main bioactive components of GIn were distributed to brain tissue much more easily in tMCAO rats than in normal rats after an intravenous administration, suggesting that the increased cerebral exposure to ginkgolides in I/R pathological condition potentially facilitated the neuroprotective effects of GIn by directly targeting at brain. The present study provided valuable information for our understanding about metabolic changes of cerebral I/R injury and clinical application of GIn. |
Databáze: | OpenAIRE |
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