Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen-glucose deprivation and reoxygenation

Int J Nanomedicine. 2017 Jun 22:12:4563-4578. doi: 10.2147/IJN.S138178. eCollection 2017.

Abstract

Recently, environment-friendly synthesis of gold nanoparticles (GNPs) has been extensively explored by biologists and chemists. However, significant research is still required to determine whether "eco-friendly" GNPs are beneficial to human health and to elucidate the molecular mechanisms of their effects on human cells. We used human neuronal SH-SY5Y cells to show that treatment with Kalopanacis Cortex extract-capped GNPs (KC-GNs), prepared via an eco-friendly, fast, one-pot synthetic route, protected neuronal cells against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced damage. To prepare GNPs, Kalopanacis Cortex was used without any chemical reducing and stabilizing agents. Ultraviolet-visible spectroscopy showed maximum absorbance at 526 nm owing to KC-GN surface plasmon resonance. Hydrodynamic size (54.02±2.19 nm) and zeta potential (-20.3±0.04 mV) were determined by dynamic light scattering. The average diameter (41.07±3.05 nm) was determined by high-resolution transmission electron microscopy. Energy-dispersive X-ray diffraction spectroscopy and X-ray diffraction confirmed the presence of assembled GNPs. Fourier transform infrared analysis suggested that functional groups such as O-H, C-C, and C-N participated in KC-GN formation. Cell viability assays indicated that KC-GNs restored the viability of OGD/R-treated SH-SY5Y cells. Flow cytometry demonstrated that KC-GNs inhibited the OGD/R-induced reactive oxygen species production and mitochondrial membrane potential disruption. KC-GNs also inhibited the apoptosis of OGD/R-exposed cells. Western blot analysis indicated that the OGD/R-induced cellular apoptosis and simultaneous increases in the expression of cleaved caspase-3, p53, p21, and B-cell lymphoma 2-associated X protein were reversed by KC-GNs. The KC-GN-mediated protection against OGD/R-induced neurotoxicity was diminished by NRF2 and heme oxygenase-1 gene knockdowns. Collectively, these results suggested that KC-GNs exerted strong neuroprotective effects on human neuronal cells, which might be attributed to the attenuation of OGD/R-induced neuronal cell injury through the NRF2 signaling pathway.

Keywords: Kalopanacis Cortex; NRF2; gold nanoparticle; neuroprotection; oxygen–glucose deprivation.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Glucose / metabolism
  • Gold / chemistry
  • Gold / pharmacology
  • Green Chemistry Technology
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Kalopanax / chemistry*
  • Membrane Potential, Mitochondrial / drug effects
  • NF-E2-Related Factor 2 / metabolism*
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Oxygen / metabolism
  • Plant Extracts / chemical synthesis
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Spectrometry, X-Ray Emission
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Neuroprotective Agents
  • Plant Extracts
  • Reactive Oxygen Species
  • Gold
  • Heme Oxygenase-1
  • Glucose
  • Oxygen