Hispidulin Protects Against Focal Cerebral Ischemia Reperfusion Injury in Rats

J Mol Neurosci. 2018 Jun;65(2):203-212. doi: 10.1007/s12031-018-1086-2. Epub 2018 May 24.

Abstract

Focal cerebral ischemia is associated with ischemia/reperfusion (I/R) injury. Hispidulin is a flavonoid compound with a variety of pharmacological properties. The neuroprotective effects of hispidulin have not been fully elucidated. Herein, we demonstrated that pretreatment of animals with hispidulin improved the neurological outcomes and decreased the infarct size and brain edema in the cerebral focal I/R model. Mechanistically, we showed in vivo and in vitro that hispidulin exerted a protective effect against I/R injury by inducing the Nrf2 antioxidant pathway through modulation of AMPK/GSK3β signaling. Taken together, our results suggest that hispidulin may be a useful neuroprotective agent against ischemia/reperfusion (I/R) injury.

Keywords: AMPK/GSK3β; Hispidulin; Ischemia/reperfusion (I/R) injury; Nrf2.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Animals
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Brain / blood supply
  • Brain / drug effects
  • Brain / metabolism
  • Brain Ischemia* / drug therapy
  • Cell Line, Tumor
  • Flavones* / pharmacology
  • Flavones* / therapeutic use
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Male
  • NF-E2-Related Factor 2
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury* / drug therapy
  • Signal Transduction

Substances

  • AMP-Activated Protein Kinase Kinases
  • Antioxidants
  • Flavones
  • Glycogen Synthase Kinase 3 beta
  • hispidulin
  • Neuroprotective Agents
  • Protein Kinases
  • NF-E2-Related Factor 2