Antineuroinflammatory Effect of SMTP-7 in Ischemic Mice

J Stroke Cerebrovasc Dis. 2018 Nov;27(11):3084-3094. doi: 10.1016/j.jstrokecerebrovasdis.2018.06.039. Epub 2018 Aug 3.

Abstract

Background: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both potentials of thrombolytic and neuroprotective effects, but its detailed neuroprotective mechanisms in ischemic stroke are still unclear. Here, we assessed the neuroprotective effects of SMTP-7 for anti-inflammatory and antiapoptosis mechanisms after 60 minutes of transient middle cerebral artery occlusion (tMCAO) in mice.

Methods: After 60minutes of tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA+SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24hours after reperfusion. We histologically assessed the antineuroinflammatory effect of SMTP-7 on the expressive changes of inflammatory markers in ischemic mouse brains.

Results: Compared with the vehicle and tPA groups, SMTP-7 treatment significantly improved clinical scores and decreased the infarct volume and the numbers of TNF-α, nuclear factor-κB (NF-κB), nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), and cleaved caspase-3-positive cells in the brain of mice at 24hours after tMCAO but not p62-positive cells. However, tPA+SMTP-7 treatment did not show such effects.

Conclusions: The present study suggested that SMTP-7 provides a therapeutic benefit for ischemic stroke mice through anti-inflammatory and antiapoptotic effects but not antiautophagic effect.

Keywords: Apoptosis—Inflammation—Ischemic stroke—tPA—SMTP-7.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects
  • Benzopyrans / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Inflammation Mediators / metabolism
  • Male
  • Mice, Inbred ICR
  • Neuroprotective Agents / pharmacology*
  • Pyrrolidinones / pharmacology*
  • Time Factors
  • Tissue Plasminogen Activator / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Apoptosis Regulatory Proteins
  • Benzopyrans
  • Cytokines
  • Inflammation Mediators
  • Neuroprotective Agents
  • Pyrrolidinones
  • SMTP 7
  • Tissue Plasminogen Activator