Salvianolic Acids for Injection (SAFI) suppresses inflammatory responses in activated microglia to attenuate brain damage in focal cerebral ischemia

J Ethnopharmacol. 2017 Feb 23:198:194-204. doi: 10.1016/j.jep.2016.11.052. Epub 2017 Jan 10.

Abstract

Background: Inflammatory reactions induced by microglia in the brain play crucial roles in ischemia/reperfusion (I/R) cerebral injuries. Microglia activation has been shown to be closely related to TLR4/NF-κB signal pathways. Salvianolic acids for injection (SAFI) have been used in clinical practice to treat ischemic stroke with reported neuroprotective effects; however, the underlying mechanisms are still uncertain.

Objective and methods: First, we studied the effect of SAFI on inflammatory responses in LPS-stimulated BV-2 microglia. Then, to discover whether the beneficial in vitro effects of SAFI lead to in vivo therapeutic effects, an MCAO (Middle cerebral artery occlusion) rat model was further employed to elucidate the probable mechanism of SAFI in treating ischemic stroke. Rats in the SAFI group were given SAFI (23 or 46mg/kg) before I/R injury.

Results: The results showed that SAFI treatment significantly decreased neuroinflammation and the infarction volume compared with the vehicle group. Activation of microglia cells was reduced, and TLR4/NF-κB signals, which were markedly inhibited by SAFI treatment in ischemic hemisphere, were accompanied by reduced expression and release of cytokines IL-1β and IL-6.

Conclusion: This study provides evidence that SAFI effectively protects the brain after cerebral ischemia, which may be caused by attenuating inflammation in microglia.

Keywords: Inflammatory reaction; Ischemia/Reperfusion cerebral injury; Microglia; Salvianolic Acids for Injection; TLR4/NF-κB signals.

MeSH terms

  • Alkenes / administration & dosage
  • Alkenes / pharmacology*
  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Infarction, Middle Cerebral Artery
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Microglia / drug effects
  • NF-kappa B / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Polyphenols / administration & dosage
  • Polyphenols / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / complications
  • Reperfusion Injury / drug therapy
  • Signal Transduction / drug effects
  • Stroke / drug therapy*
  • Stroke / pathology
  • Toll-Like Receptor 4 / metabolism

Substances

  • Alkenes
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Neuroprotective Agents
  • Polyphenols
  • Toll-Like Receptor 4
  • salvianolic acid