Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression

Neurochem Res. 2014 Aug;39(8):1405-15. doi: 10.1007/s11064-014-1326-y. Epub 2014 May 20.

Abstract

Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague-Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG's influence on blood-brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Brain Ischemia / prevention & control*
  • Claudin-5 / biosynthesis
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Nod2 Signaling Adaptor Protein / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism
  • Stroke / metabolism*
  • Stroke / pathology
  • Stroke / prevention & control*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Claudin-5
  • Cldn5 protein, rat
  • Flavanones
  • NF-kappa B
  • NOD2 protein, rat
  • Neuroprotective Agents
  • Nod2 Signaling Adaptor Protein
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • naringenin