Isoquercitrin Played a Neuroprotective Role in Rats After Cerebral Ischemia/Reperfusion Through Up-Regulating Neuroglobin and Anti-Oxidative Stress

Transplant Proc. 2023 Sep;55(7):1751-1761. doi: 10.1016/j.transproceed.2023.04.046. Epub 2023 Jun 28.

Abstract

Background: This study aims to investigate whether isoquercitrin (Iso) exerts a neuroprotective role effect after cerebral ischemia-reperfusion (CIR) via up-regulating neuroglobin (Ngb) or reducing oxidative stress.

Methods: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was constructed using Sprague Dawley rats. First, we divided 40 mice into 5 groups (n = 8): sham, MCAO/R, Low-dosed Iso (5 mg/kg Iso), Mid-dosed Iso (10 mg/kg Iso), and High-dosed Iso (20 mg/kg Iso). Then, 48 rats were separated into 6 groups (n = 8): sham, MCAO/R, Iso, artificial cerebrospinal fluid, Ngb antisense oligodeoxynucleotides (AS-ODNs), and AS-ODNs ± Iso. The effects of Iso on brain tissue injury and oxidative stress were evaluated using hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunofluorescence, western blotting, and real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and reactive oxygen species (ROS) detection.

Results: The neurologic score, infarct volume, histopathology, apoptosis rate, and ROS production were reduced in Iso dose-dependent. The Ngb expression enhanced in Iso dose-dependent. The oxidative stress-related factors SOD, GSH, CAT, Nrf2, HO-1, and HIF-1α levels also increased in Iso dose-dependent, whereas the MDA levels decreased. However, related regulation of Iso on brain tissue damage and oxidative stress were reversed after low expression of Ngb.

Conclusion: Isoquercitrin played a neuroprotective role after CIR through up-regulating of Ngb and anti-oxidative stress.

MeSH terms

  • Animals
  • Apoptosis
  • Brain Ischemia* / metabolism
  • Brain Ischemia* / pathology
  • Brain Ischemia* / prevention & control
  • Mice
  • Neuroglobin / metabolism
  • Neuroglobin / pharmacology
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Reperfusion
  • Reperfusion Injury* / pathology

Substances

  • Neuroglobin
  • Reactive Oxygen Species
  • isoquercitrin
  • Neuroprotective Agents