Protective effects of crocin against endogenous Aβ-induced neurotoxicity in N2a/APP695swe cells

Psychopharmacology (Berl). 2021 Oct;238(10):2839-2847. doi: 10.1007/s00213-021-05899-4. Epub 2021 Jun 30.

Abstract

Alzheimer's disease (AD) is a most common neurodegenerative disorder worldwide. Because of its complex pathogenesis, the prevention and therapies of AD still are a severe challenge. Evidence suggested that crocin, the major component of saffron, exhibited neuroprotective effects in AD. As such, in this study, N2a/APP695swe cells were enrolled to investigate the effects of crocin on endogenous Aβ-induced neurotoxicity. Crocin (100 and 200 μM) could ameliorate cytotoxicity according to CCK-8 assay and reduce apoptosis in line with Hoechst 33,342 staining and Annexin V-FITC/PI double staining in N2a/APP695swe cells. Reduced ROS generation and elevated MMP were found in N2a/APP695swe cells treated with crocin (100 and 200 μM). Additionally, crocin at concentrations of 100 and 200 μM inhibited the release of cytochrome and attenuated caspases-3 activity in N2a/APP695swe cells. Furthermore, succinylation, crotonylation, 2-hydroxyisobutyrylation, malonylation, and phosphorylation were significantly reduced, while a slight increase of acetylation was found in 100-μM crocin treated N2a/APP695swe cells. Taken together, crocin may be a promising natural product candidate for the effective cure of AD.

Keywords: Alzheimer’s disease; Apoptosis; Crocin; Post-translational modifications.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Amyloid beta-Peptides / toxicity
  • Apoptosis
  • Carotenoids / pharmacology
  • Carotenoids / therapeutic use
  • Humans
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Phosphorylation

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Carotenoids
  • crocin