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Journal of Physiology and Biochemistry

, Volume 70, Issue 3, pp 735–747 | Cite as

Neuroprotective effect of schizandrin A on oxygen and glucose deprivation/reperfusion-induced cell injury in primary culture of rat cortical neurons

  • Cai-Ping Wang
  • Gui-Cai Li
  • Yun-Wei Shi
  • Xiao-Chuan Zhang
  • Jian-Long Li
  • Zhi-Wei WangEmail author
  • Fei DingEmail author
  • Xin-Miao LiangEmail author
Original Paper

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 ([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.

Keywords

Schizandrin A Apoptosis Ischemia Mitogen-activated protein kinase (MAPK) C5aR 

Abbreviations

JNK

c-Jun NH2-terminal kinases

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

DMEM

Dulbecco’s Modified Eagle’s Medium

ERK

Extracellular-regulated kinase

FBS

Fetal bovine serum

[Ca2+]i

Intracellular calcium concentrations

LDH

Lactate dehydrogenase

Luc2-3xCRE

Luciferase reporter construct has three copies of CRE in the 5′ region

MAPK

Mitogen-activated protein kinase

OGD/R

Oxygen and glucose deprivation followed by reperfusion

PI

Propidium iodide

PCR

Polymerase chain reaction

C3

The third complement component

C5

The fifth complement component

Notes

Acknowledgments

This study was supported by funding for scientific research of Nantong University (Program No. 03080374, 03080364, 03041236, and 03080471), research funding funded by Provincial Key Lab of Jiangsu Province of China (Program No. 05012066), and research funding funded by Natural Science Research Program of Jiangsu Education Department (Program No.13KJB310014).

Conflict of interests

The authors declare no competing interests.

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Copyright information

© University of Navarra 2014

Authors and Affiliations

  1. 1.Jiangsu Key Laboratory of NeuroregenerationNantong UniversityNantongPeople’s Republic of China
  2. 2.Department of PharmacologyUniversity of CaliforniaIrvineUSA
  3. 3.Dalian Institute of Chemical PhysicsThe Chinese Academy of SciencesDalianPeople’s Republic of China

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