title: Compound MQA, a Caffeoylquinic Acid Derivative, Protects Against NMDA-Induced Neurotoxicity and Potential Mechanisms In Vitro.
abstract: OBJECTIVE
  Compound MQA (1,5-O-dicaffeoyl-3-O-[4-malic acid methyl ester]-quinic acid) is a natural derivative of caffeoylquinic acid isolated from Arctium 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).
  
  
  RESULTS
  Pretreatment with MQA attenuated the loss of cell viability after SH-SY5Y 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 ERK1/2, p38, and JNK1/2. Furthermore, deactivation of CREB, AKT, and GSK-3β, upregulation of GluN2B-containing NMDA receptors (NMDARs), and downregulation of GluN2A-containing NMDARs were significantly reversed by MQA treatment. Computational docking simulation indicates that MQA possesses a well affinity for NMDARs.
  
  
  CONCLUSIONS
  The protective effects of MQA against NMDA-induced cell injury may be mediated by blocking NMDARs. The potential mechanisms are related with mitochondrial apoptosis, ERK-CREB, AKT/GSK-3β, p38, and JNK1/2 pathway.
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, China.|Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Li
authors.initials: L
authors.lastname: An
authors.affiliation: Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Ling-Yue
authors.initials: LY
authors.lastname: Gao
authors.affiliation: Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Jun-Peng
authors.initials: JP
authors.lastname: Bai
authors.affiliation: Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Meng
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, China.
authors.forename: Tian-Shu
authors.initials: TS
authors.lastname: Ren
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, China.
authors.forename: Qing-Chun
authors.initials: QC
authors.lastname: Zhao
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000633:toxicity*; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000605855:1,5-O-dicaffeoyl-3-O-(4-malic acid methyl ester)-quinic acid; D017304:Annexin A5; D002109:Caffeic Acids; D018690:Excitatory Amino Acid Agonists; D008293:Malates; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C099798:caffeoylmalic acid; D002726:Chlorogenic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3; D053453:Caspase 9; D002118:Calcium
keywords: Apoptosis; Caffeoylquinic acid; Excitotoxicity; N-methyl-d-aspartate (NMDA); Neuroprotection