Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses

PLoS One. 2012;7(11):e49701. doi: 10.1371/journal.pone.0049701. Epub 2012 Nov 14.

Abstract

Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX(2) and 5-LOX) in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Benzoates / administration & dosage
  • Benzoates / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism*
  • Bridged-Ring Compounds / administration & dosage
  • Bridged-Ring Compounds / pharmacology*
  • Cerebral Infarction / drug therapy
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / pathology
  • Cyclooxygenase 2 / metabolism
  • Cytochromes c / genetics
  • Cytochromes c / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Glucosides / administration & dosage
  • Glucosides / pharmacology*
  • Hippocampus / drug effects
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics
  • Lipoxygenase / metabolism
  • Male
  • Microglia / drug effects
  • Microglia / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Monoterpenes
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzoates
  • Bridged-Ring Compounds
  • Glucosides
  • Interleukin-1beta
  • Monoterpenes
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • peoniflorin
  • Cytochromes c
  • Lipoxygenase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81273495), Major Porject of Jiangsu Provincial Department of Education (No. 12KJA310002), National Key Basic Research Program of China (No. 2009CB521906) and Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. JX10131801042). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.