Open AccessCompound MQA , a Caffeoylquinic Acid Derivative, Protects Against NMDA ‐Induced Neurotoxicity and Potential Mechanisms In Vitro
Author(s) -
Tian Xing,
An Li,
Gao LingYue,
Bai JunPeng,
Wang Jian,
Meng WeiHong,
Ren TianShu,
Zhao QingChun
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12408
Subject(s) - nmda receptor , neuroprotection , chemistry , creb , pharmacology , apoptosis , medicine , receptor , biochemistry , transcription factor , gene
Summary Aims Compound MQA (1,5‐ O ‐dicaffeoyl‐3‐ O ‐[4‐malic acid methyl ester]‐quinic acid) is a natural derivative of caffeoylquinic acid isolated from A rctium lappa L. roots. However, we know little about the effects of MQA on the central nervous system. This study aims to investigate the neuroprotective effects and underlying mechanisms of MQA against the neurotoxicity of N ‐methyl‐ d ‐aspartate ( NMDA ). Methods and Results Pretreatment with MQA attenuated the loss of cell viability after SH ‐ SY 5Y cells treated with 1 mM NMDA for 30 min by MTT assay. Hoechst 33342 and Annexin V‐ PI double staining showed that MQA inhibited NMDA ‐induced apoptosis. In addition to preventing Ca 2+ influx, the potential mechanisms are associated with increases in the Bcl‐2/Bax ratio, attenuation of cytochrome c release, caspase‐3, caspase‐9 activities, and expressions. Also, MQA inhibited NMDA ‐induced phosphorylation of ERK 1/2, p38, and JNK 1/2. Furthermore, deactivation of CREB , AKT , and GSK ‐3 β , upregulation of GluN2B‐containing NMDA receptors ( NMDAR s), and downregulation of GluN2A‐containing NMDAR s were significantly reversed by MQA treatment. Computational docking simulation indicates that MQA possesses a well affinity for NMDAR s. Conclusion The protective effects of MQA against NMDA ‐induced cell injury may be mediated by blocking NMDAR s. The potential mechanisms are related with mitochondrial apoptosis, ERK ‐ CREB , AKT / GSK ‐3 β , p38, and JNK 1/2 pathway.