In vitro neuroprotective effects of naringenin nanoemulsion against β-amyloid toxicity through the regulation of amyloidogenesis and tau phosphorylation

Int J Biol Macromol. 2018 Oct 15;118(Pt A):1211-1219. doi: 10.1016/j.ijbiomac.2018.06.190. Epub 2018 Jul 3.

Abstract

Alzheimer's disease (AD) is an increasingly prevalent neurological disorder of the central nervous system. There is growing evidence that amyloidogenesis is a pathological hallmark for AD; this leads to the formation of senile plaques. Naringenin is a bioflavonoid which has neuroprotective effects through its antioxidant and anti-inflammatory properties. However, its clinical usage is limited due to its inefficient transport across biological membranes. In the present study, a naringenin nanoemulsion was prepared and its neuroprotective effects were tested against β-amyloid induced neurotoxicity in a human neuroblastoma cell line (SH-SY5Y). The optimised, naringenin-loaded nanoemulsion formulation had a droplet size of 113.83 ± 3.35 nm and around 50 nm, as assessed respectively by photon correlation spectroscopy and transmission electron microscopy. The preparation showed a low polydispersity index (0.312 ± 0.003), a high zeta potential (12.4 ± 1.05) and a high percentage transmittance (97.01%). The neuroprotective activity of naringenin nanoemulsions was determined by assessing their ability to protect SH-SY5Y neuroblastoma cells against the neurotoxic effect of beta amyloid (Aβ). Aβ-induced production of reactive oxygen species (ROS), amyloid precursor protein (APP), β-secretase (BACE), total tau and phosphorylated tau (pT231) was also determined. The naringenin loaded nanoemulsion significantly alleviated the direct neurotoxic effects of Aβ on SH-SY5Y cells; this was associated with a down-regulation of APP and BACE expression, indicating reduced amyloidogenesis. Furthermore, it decreased the levels of phosphorylated tau in SH-SY5Y cells exposed to Aβ. These results suggest that a naringenin-loaded nanoemulsion could be a promising agent for the treatment of Alzheimer's disease.

Keywords: Alzheimer disease (AD); Nanoemulsion (NE); Naringenin (NRG); Oxidative stress; pTau; β-Amyloid.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Cell Line, Tumor
  • Emulsions
  • Flavanones / pharmacology*
  • Humans
  • Phosphorylation / drug effects
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Emulsions
  • Flavanones
  • MAPT protein, human
  • tau Proteins
  • naringenin