Effects of chrysophanol on hippocampal damage and mitochondrial autophagy in mice with cerebral ischemia reperfusion

Int J Neurosci. 2022 Jun;132(6):613-620. doi: 10.1080/00207454.2020.1830085. Epub 2020 Oct 20.

Abstract

Objective: The cerebral ischemia-reperfusion (I/R) model is crucial for the study of cerebral stroke. Chrysophanol (Chry) can protect nerve damage of mice in cerebral ischemia-reperfusion injury. This study aimed at investigating the neuroprotective effects of chrysophanol through mitochondrial autophagy in mice with ischemia-reperfusion injury.

Materials and methods: Adult mice were stochastically divided into five groups: sham, I/R (solvent), I/R+Chry (dose, 10.0ml/kg), I/R+Chry (dose, 1.0ml/kg), and I/R+Chry (dose, 0.1ml/kg). The cerebral ischemia-reperfusion model was made in I/R and I/R+Chry groups. The changes in hippocampal formation were observed by hematoxylin and eosin (H&E) staining. The expressions of LC3B-II and LC3B-I protein in hippocampus were demonstrated by western blot (WB). The fluorescence intensities of NIX, LC3B, and mitochondria were detected by immunohistochemistry fluorescent (IF).

Results: Comparing with the I/R group, the I/R+Chry groups showed improvements in reducing the damage on the hippocampus, indicated by the reduced ratio of LC3B-II and LC3B-I protein, decreased fluorescence intensity of NIX and LC3B, and increased intensity of mitochondrial fluorescence.

Conclusion: Our study showed that chrysophanol may regulate mitochondrial autophagy through NIX protein and alleviate the damage of hippocampus through decreasing the level of mitochondrial autophagy.

Keywords: Chrysophanol; LC3B; cerebral ischemia-reperfusion injury; hippocampus; mitochondrial autophagy.

MeSH terms

  • Animals
  • Anthraquinones
  • Autophagy
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Cerebral Infarction
  • Hippocampus / metabolism
  • Mice
  • Mitochondria / metabolism
  • Reperfusion
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism

Substances

  • Anthraquinones
  • chrysophanic acid