Effects of isosakuranetin on cerebral infarction and blood brain barrier damage from cerebral ischemia/reperfusion injury in a rat model

J Biomol Struct Dyn. 2024 Jan-Feb;42(2):1064-1071. doi: 10.1080/07391102.2023.2205940. Epub 2023 Apr 28.

Abstract

This study investigated the effects of isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) on cerebral infarction and blood brain barrier (BBB) damage in cerebral ischemia and reperfusion (I/R) in a rat model. The right middle cerebral artery was occluded for 2 h followed by reperfusion. The experimental rats were divided into five groups: a sham, or control group; vehicle group; and 5 mg/kg, 10 mg/kg, and 20 mg/kg bodyweight isosakuranetin-treated I/R groups. After 24 h of reperfusion, the rats were tested using a six-point neurological function score. The percentage of cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. BBB leakage was determined by Evan Blue injection assay and brain morphology changes were observed under light microscopy following staining with hematoxylin and eosin (H&E). The results of neurological function score revealed that isosakuranetin reduced the severity of neurological damage. A dose of 10 and 20 mg/kg bodyweight of isosakuranetin significantly decreased the infarct volume. All three doses of isosakuranetin significantly decreased Evan Blue leakage. The penumbra area of the I/R brains revealed the characteristics of apoptotic cell death. Therefore, isosakuranetin-treated I/R attenuated the brain damage from cerebral I/R injury and further investigation of the mechanisms warrant further investigation to assist in the development of protective strategies against cerebral I/R injury in clinical trials.Communicated by Ramaswamy H. Sarma.

Keywords: Isosakuranetin; blood brain barrier; cerebral infarction; ischemic/ reperfusion; middle cerebral artery occlusion.

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Cerebral Infarction / drug therapy
  • Cerebral Infarction / metabolism
  • Evans Blue / metabolism
  • Evans Blue / pharmacology
  • Evans Blue / therapeutic use
  • Flavonoids*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism

Substances

  • isosakuranetin
  • Evans Blue
  • Flavonoids