Effect of rutin on spinal cord injury through inhibition of the expression of MIP-2 and activation of MMP-9, and downregulation of Akt phosphorylation

Mol Med Rep. 2015 Nov;12(5):7554-60. doi: 10.3892/mmr.2015.4357.

Abstract

Rutin has extensive pharmacological activities, including antibacterial and anti-inflammatory activities, cooling of the blood to inhibit bleeding, reducing capillary wall fragility and anti-influenza activities. However, whether rutin can ameliorate neuropathic function in spinal cord injury (SCI) in constriction-induced peripheral nerve injury remains to be elucidated. In the present study, the potential protective effects of rutin on SCI rats were investigated. Neurological function was examined using the Basso, Beattie and Bresnahan (BBB) scoring system and by measuring the water content of the spinal cord tissue in SCI rats. SCI-induced programmed cell death was measured using hematoxylin and eosin staining. In addition, the expression of macrophage inflammatory protein-2 (MIP-2) and the activation of matrix metalloproteinase-9 (MMP-9) in the SCI rats were evaluated using ELISA assay kits and zymographic analysis, respectively. The phosphorylation of protein kinase B (p-Akt) was analyzed using a western blot assay. The results demonstrated that administrating rutin began to increase BBB scores and attenuate the spinal cord water content of the SCI rats. Administrating rutin prevented SCI-induced programmed cell death. The SCI rats of in the rutin-treated group were found to exhibit lower expression levels of MIP-2 and p-Akt, reduced MMP-9 activation, compared with the SCI model rats. In conclusion, rutin was demonstrated as a potential protective agent in SCI and enhances the neurotrophic effect by inhibiting the expression of MIP-2 and activation of MMP-9, and downregulating the expression of p-Akt.

MeSH terms

  • Animals
  • Apoptosis
  • Chemokine CXCL2 / metabolism*
  • Down-Regulation
  • Drug Evaluation, Preclinical
  • Enzyme Activation
  • Gene Silencing / drug effects
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats, Sprague-Dawley
  • Rutin / pharmacology*
  • Rutin / therapeutic use
  • Spinal Cord Injuries / drug therapy*

Substances

  • Chemokine CXCL2
  • Cxcl2 protein, rat
  • Rutin
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat