Journal
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
Volume 70, Issue 3, Pages 735-747Publisher
SPRINGER
DOI: 10.1007/s13105-014-0342-3
Keywords
Schizandrin A; Apoptosis; Ischemia; Mitogen-activated protein kinase (MAPK); C5aR
Categories
Funding
- Provincial Key Lab of Jiangsu Province of China [05012066]
- Natural Science Research Program of Jiangsu Education Department [13KJB310014]
- [03080374]
- [03080364]
- [03041236]
- [03080471]
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Brain ischemia appears to be associated with innate immunity. Recent reports showed that C3a and C5a, as potent targets, might protect against ischemia induced cell death. In traditional Chinese medicine, the fruit of Schizandra chinesis Baill (Fructus schizandrae) has been widely used as a tonic. In the present study, we sought to evaluate the neuroprotective effects of schizandrin A, a composition of S. chinesis Baill, against oxygen and glucose deprivation followed by reperfusion (OGD/R)-induced cell death in primary culture of rat cortical neurons, and to test whether C3a and C5a affected cortical neuron recovery from ischemic injury after schizandrin A treatment. The results showed that schizandrin A significantly reduced cell apoptosis and necrosis, increased cell survival, and decreased intracellular calcium concentration ([Ca2+](i)) and lactate dehydrogenase (LDH) release in primary culture of rat cortical neurons after OGD/R. Mechanism studies suggested that the modulation of extracellular-regulated kinase (ERK), c-Jun NH2-terminal kinases (JNK), and p38, as well as caspase-3 activity played an important role on the progress of neuronal apoptosis. C5aR participated in the neuroprotective effect of schizandrin A in primary culture of rat cortical neurons after OGD/R. Our findings suggested that schizandrin A might act as a candidate therapeutic target drug used for brain ischemia and related diseases.
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