Exploring the neuroprotective effects of ginkgolides injection in a rodent model of cerebral ischemia-reperfusion injury by GC-MS based metabolomic profiling. 2017

Jian-Liang Geng, and Ji-Ye Aa, and Si-Qi Feng, and Shu-Yao Wang, and Pei Wang, and Yue Zhang, and Bing-Chen Ouyang, and Jian-Kun Wang, and Ye-Jin Zhu, and Wen-Zhe Huang, and Zhen-Zhong Wang, and Wei Xiao, and Guang-Ji Wang
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.

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.

UI MeSH Term Description Entries
D008401 Gas Chromatography-Mass Spectrometry A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds. Chromatography, Gas-Liquid-Mass Spectrometry,Chromatography, Gas-Mass Spectrometry,GCMS,Spectrometry, Mass-Gas Chromatography,Spectrum Analysis, Mass-Gas Chromatography,Gas-Liquid Chromatography-Mass Spectrometry,Mass Spectrometry-Gas Chromatography,Chromatography, Gas Liquid Mass Spectrometry,Chromatography, Gas Mass Spectrometry,Chromatography, Mass Spectrometry-Gas,Chromatography-Mass Spectrometry, Gas,Chromatography-Mass Spectrometry, Gas-Liquid,Gas Chromatography Mass Spectrometry,Gas Liquid Chromatography Mass Spectrometry,Mass Spectrometry Gas Chromatography,Spectrometries, Mass-Gas Chromatography,Spectrometry, Gas Chromatography-Mass,Spectrometry, Gas-Liquid Chromatography-Mass,Spectrometry, Mass Gas Chromatography,Spectrometry-Gas Chromatography, Mass,Spectrum Analysis, Mass Gas Chromatography
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D046934 Ginkgolides DITERPENES with three LACTONES and a unique tert-butyl group, which are found in GINKGO plants along with BILOBALIDES. Ginkgolide
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018696 Neuroprotective Agents Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. Neuroprotectant,Neuroprotective Agent,Neuroprotective Drug,Neuroprotectants,Neuroprotective Drugs,Neuroprotective Effect,Neuroprotective Effects,Agent, Neuroprotective,Agents, Neuroprotective,Drug, Neuroprotective,Drugs, Neuroprotective,Effect, Neuroprotective,Effects, Neuroprotective
D020244 Infarction, Middle Cerebral Artery NECROSIS occurring in the MIDDLE CEREBRAL ARTERY distribution system which brings blood to the entire lateral aspects of each CEREBRAL HEMISPHERE. Clinical signs include impaired cognition; APHASIA; AGRAPHIA; weak and numbness in the face and arms, contralaterally or bilaterally depending on the infarction. Cerebral Infarction, Middle Cerebral Artery,Embolic Infarction, Middle Cerebral Artery,MCA Infarct,Middle Cerebral Artery Embolus,Middle Cerebral Artery Infarction,Stroke, Middle Cerebral Artery,Thrombotic Infarction, Middle Cerebral Artery,Embolus, Middle Cerebral Artery,Left Middle Cerebral Artery Infarction,MCA Infarction,Middle Cerebral Artery Circulation Infarction,Middle Cerebral Artery Embolic Infarction,Middle Cerebral Artery Occlusion,Middle Cerebral Artery Stroke,Middle Cerebral Artery Syndrome,Middle Cerebral Artery Thrombosis,Middle Cerebral Artery Thrombotic Infarction,Occlusion, Middle Cerebral Artery,Right Middle Cerebral Artery Infarction,Thrombosis, Middle Cerebral Artery,Infarct, MCA,Infarcts, MCA,MCA Infarcts

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