Protection by silibinin against experimental ischemic stroke: up-regulated pAkt, pmTOR, HIF-1α and Bcl-2, down-regulated Bax, NF-κB expression

Neurosci Lett. 2012 Oct 31;529(1):45-50. doi: 10.1016/j.neulet.2012.08.078. Epub 2012 Sep 19.

Abstract

Inflammation and apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Silibinin has been proved to elicit a variety of biological effects through its anti-inflammatory and anti-apoptotic properties in hepatotoxic, cancer and carcinogenic events. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigated the potential protective role of silibinin in ischemic stroke and the underlying mechanisms. Silibinin was administered intragastric 30 min before permanent middle cerebral artery occlusion (pMCAO). We found that silibinin significantly alleviated neurological deficit, reduced infarct volume, and suppressed brain edema, which were accompanied with upregulation of pAkt, pmTOR, HIF-1α, Bcl-2 and downregulation of Bax, NF-κB in ischemic brain tissue after stroke. Our results show that silibinin might exert anti-inflammatory and anti-apoptotic effects in ischemic brain through activating Akt/mTOR signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain Ischemia
  • Down-Regulation
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Infarction, Middle Cerebral Artery / diagnosis
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / metabolism*
  • Male
  • NF-kappa B / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Neuroprotective Agents / administration & dosage*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Silybin
  • Silymarin / administration & dosage*
  • Stroke
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein

Substances

  • Bax protein, rat
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NF-kappa B
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Silymarin
  • bcl-2-Associated X Protein
  • Silybin
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases