Anti-apoptotic effect of silymarin-loaded chitosan nanoparticles on hippocampal caspase-3 and Bcl-2 expression following cerebral ischemia/reperfusion injury

Int J Neurosci. 2022 Nov;132(11):1102-1109. doi: 10.1080/00207454.2020.1860971. Epub 2021 Jan 21.

Abstract

Background: Cerebral ischemia/reperfusion (I/R) causes memory and learning impairments and apoptosis in the hippocampus. The aim of present study aimed to investigate the anti-apoptotic effects of silymarin-loaded chitosan nanoparticles (SM-CS-NPs) on the expression of Bcl-2 and Caspase-3 genes in hippocampal neurons after I/R injury.

Material and methods: SM and SM-CS-NPs were orally administered (15 mg/kg) for 14 days, and then cerebral I/R injury was induced by the bilateral common carotid artery occlusion (BCCAO). One day after I/R induction, memory and learning impairments and various biochemical estimations were assessed.

Results: Our results indicated that SM-CS-NPs improved I/R-induced memory and learning impairments and oxidative damage in the hippocampal region. The qRT-PCR analysis indicated that SM-CS-NPs pretreatment inhibited I/R-induced neuronal apoptosis by increasing the expression of Bcl-2 and decreasing the expression of Caspase-3 in the hippocampus.

Conclusion: These findings suggest that SM-CS-NPs exert neuroprotective effects, and the neuroprotection is likely to be associated with the regulation of Bcl-2 and Caspase-3, leading to inhibition of apoptotic cell death in hippocampal neurons.

Keywords: Apoptosis; chitosan nanoparticles; hippocampus; ischemia/reperfusion injury; oxidative damage; silymarin.

MeSH terms

  • Apoptosis
  • Brain Ischemia* / metabolism
  • Caspase 3 / metabolism
  • Caspases / metabolism
  • Caspases / pharmacology
  • Chitosan* / pharmacology
  • Hippocampus / metabolism
  • Humans
  • Nanoparticles*
  • Neuroprotective Agents* / pharmacology
  • Reperfusion Injury* / metabolism
  • Silymarin* / metabolism
  • Silymarin* / pharmacology

Substances

  • Caspase 3
  • Neuroprotective Agents
  • Chitosan
  • Caspases
  • Silymarin