Caffeoylquinic Acid Derivatives Protect SH-SY5Y Neuroblastoma Cells from Hydrogen Peroxide-Induced Injury Through Modulating Oxidative Status

Cell Mol Neurobiol. 2017 Apr;37(3):499-509. doi: 10.1007/s10571-016-0387-7. Epub 2016 Jun 2.

Abstract

Oxidative stress has been confirmed as a contribution to the pathogenesis and pathophysiology of many neurological disorders such as Alzheimer's disease and Parkinson's disease. Caffeoylquinic acids (CQAs) are considered to have anti-oxidative stress ability in a previous study, but the structure-activity relationships (SARs) of CQAs in neuroprotective effects are still unclear. In the present study, we primarily expound the SARs of CQAs in counteracting H2O2-induced injury in SH-SY5Y cells. We found that CQAs (1-10) represented the protection of SH-SY5Y cells against H2O2-induced injury in varying degrees and malonyl groups could obviously increase the anti-oxidative stress ability of CQAs. Intensive studies of 4,5-O-dicaffeoyl-1-O-(malic acid methyl ester)-quinic acid (MDCQA) indicated that the mechanisms could potentially involve activation of endogenous antioxidant enzymes and the regulation of the phosphorylation of MAPKs and AKT. In conclusion, MDCQA could serve as a neuroprotective agent with a potential to attenuate oxidative stress.

Keywords: Caffeoylquinic acid; MDCQA; Neuroprotection; ROS; SH-SY5Y.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glutathione Peroxidase / metabolism
  • Humans
  • Hydrogen Peroxide / toxicity*
  • Malondialdehyde / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Neuroblastoma / enzymology
  • Neuroblastoma / pathology*
  • Neuroprotection / drug effects*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quinic Acid / analogs & derivatives*
  • Quinic Acid / chemistry
  • Quinic Acid / pharmacology
  • Superoxide Dismutase / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 4,5-o-dicaffeoylquinic acid methyl ester
  • Neuroprotective Agents
  • caffeoylquinic acid
  • Quinic Acid
  • Malondialdehyde
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases