title: Neuroprotective effect of schizandrin A on oxygen and glucose deprivation/reperfusion-induced cell injury in primary culture of rat cortical neurons.
abstract: 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 ([Ca(2+)]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.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, 226001, People's Republic of China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Gui-Cai
authors.initials: GC
authors.lastname: Li
authors.forename: Yun-Wei
authors.initials: YW
authors.lastname: Shi
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Zhang
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Li
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.forename: Xin-Miao
authors.initials: XM
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D034242:Cyclooctanes / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008516:Medicine, Chinese Traditional; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D008517:Phytotherapy; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032141:Schisandra; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D018696:Neuroprotective Agents; D011083:Polycyclic Compounds; D044087:Receptor, Anaphylatoxin C5a; D043562:Receptors, G-Protein-Coupled; C532341:anaphylatoxin receptor C3a, rat; C034734:schizandrin A; D007770:L-Lactate Dehydrogenase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005947:Glucose; D002118:Calcium