Narirutin Attenuates Cerebral Ischemia-Reperfusion Injury by Suppressing the TXNIP/NLRP3 Pathway

Neurochem Res. 2024 Mar;49(3):692-705. doi: 10.1007/s11064-023-04062-z. Epub 2023 Dec 4.

Abstract

Narirutin (Nar) is a flavonoid that is abundantly present in citrus fruits and has attracted considerable attention because of its diverse pharmacological activities and low toxicity. Here, we evaluated the preventive effects of Nar in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice and oxygen-glucose deprivation/reperfusion (OGD/R)-injured bEnd.3 cells. Pretreatment with Nar (150 mg/kg) for 7 days effectively reduced infarct volume, improved neurological deficits, and significantly inhibited neuronal death in the hippocampus and cortex in MCAO/R-injured mice. Moreover, anti-apoptotic effects of Nar (50 µM) were observed in OGD/R-injured bEnd.3 cells. In addition, Nar pre-administration regulated blood-brain barrier function by increasing tight junction-related protein expression after MCAO/R and OGD/R injury. Nar also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation by reducing the expression of thioredoxin-interacting protein (TXNIP) in vivo and in vitro. Taken together, these results provide new evidence for the use of Nar in the prevention and treatment of ischemic stroke.

Keywords: Blood-brain barrier; Cerebral ischemic-reperfusion injury; Inflammation; NOD-like receptor protein 3 inflammasome; Narirutin; Thioredoxin interacting protein.

MeSH terms

  • Animals
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Brain Ischemia* / prevention & control
  • Cell Cycle Proteins
  • Disaccharides*
  • Endothelial Cells / metabolism
  • Flavanones*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Inflammasomes / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • NLR Proteins
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / prevention & control

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • narirutin
  • NLR Proteins
  • Inflammasomes
  • TXNIP protein, rat
  • Cell Cycle Proteins
  • Disaccharides
  • Flavanones