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Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice
- Source :
- Free radical biologymedicine. 99
- Publication Year :
- 2016
-
Abstract
- Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SalA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA (50 and 100μg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-κB) and a pro-apoptotic kinase p25/Cdk5. SalA also intensively limited cortical infarction and promoted the expression of neurogenesis protein near the peri-infarct cortex and subgranular zone of the hippocampal dentate gyrus by compromising the activation of GSK3β and p25/Cdk5, which in turn upregulated β-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor. We conclude that SalA blocks inflammatory responses by impairing NF-κB signaling, thereby limiting inflammation/nitrosative stress and preserving the integrity of the BBB; SalA also concomitantly promotes neurogenesis-related protein expression by compromising GSK3β/Cdk5 activity to enhance the expression levels of β-catenin/DCX and Bcl-2 for neuroprotection.
- Subjects :
- 0301 basic medicine
Doublecortin Domain Proteins
Male
Apoptosis
Pharmacology
Biochemistry
Antioxidants
Subgranular zone
Brain Ischemia
Mice
0302 clinical medicine
Neurotrophic factors
Medicine
beta Catenin
Mice, Inbred ICR
biology
Neurogenesis
Anti-Inflammatory Agents, Non-Steroidal
Stroke
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Blood-Brain Barrier
Reperfusion Injury
Injections, Intravenous
Lactates
Microtubule-Associated Proteins
Signal Transduction
Doublecortin Protein
Neuroprotection
Drug Administration Schedule
03 medical and health sciences
Caffeic Acids
Physiology (medical)
Animals
Protein kinase B
PI3K/AKT/mTOR pathway
Glycogen Synthase Kinase 3 beta
business.industry
Dentate gyrus
Brain-Derived Neurotrophic Factor
Neuropeptides
Transcription Factor RelA
Cyclin-Dependent Kinase 5
Survival Analysis
Doublecortin
Disease Models, Animal
030104 developmental biology
nervous system
Gene Expression Regulation
biology.protein
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18734596
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Free radical biologymedicine
- Accession number :
- edsair.doi.dedup.....559083f43b0f946889849bb45bb74387