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

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 st...

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Bibliographic Details
Published in:PloS one 2012-11, Vol.7 (11), p.e49701
Main Authors: Guo, Ruo-Bing, Wang, Guo-Feng, Zhao, An-Peng, Gu, Jun, Sun, Xiu-Lan, Hu, Gang
Format: Article
Language:English
Subjects:
Activation
Animals
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Apoptosis
Astrocytes
Astrocytes - drug effects
Astrocytes - metabolism
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
Benzoates - administration & dosage
Benzoates - pharmacology
Biology
Brain
Brain - drug effects
Brain - metabolism
Brain - pathology
Brain damage
Brain Ischemia - drug therapy
Brain Ischemia - metabolism
Brain research
Bridged-Ring Compounds - administration & dosage
Bridged-Ring Compounds - pharmacology
Carotid arteries
Cerebral blood flow
Cerebral Infarction - drug therapy
Cerebral Infarction - metabolism
Cerebral Infarction - pathology
Chinese medicine
Cyclooxygenase 2 - metabolism
Cyclooxygenase-2
Cytochromes c - genetics
Cytochromes c - metabolism
Cytokines
Disease Models, Animal
Gene Expression Regulation - drug effects
Glucosides - administration & dosage
Glucosides - pharmacology
Hippocampus - drug effects
Hypoxia
IL-1β
Inflammation
Inflammation - drug therapy
Inflammation - metabolism
Inflammatory response
Interleukin-1beta - blood
Interleukin-1beta - genetics
Ischemia
JNK protein
Kinases
Laboratory animals
Lipoxygenase - metabolism
Liquid oxygen
Male
MAP kinase
Medicine
Microglia
Microglia - drug effects
Microglia - metabolism
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Monoterpenes
Neurodegeneration
Neurons - drug effects
Neurons - metabolism
Neuroprotection
NF-kappa B - antagonists & inhibitors
NF-kappa B - metabolism
NF-κB protein
Nitric Oxide Synthase Type II - metabolism
Nitric-oxide synthase
Occlusion
Paeonia lactiflora
Pharmacology
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Rats
Rodents
Signal transduction
Signal Transduction - drug effects
Signaling
Stroke
Traditional Chinese medicine
Tumor Necrosis Factor-alpha - blood
Tumor Necrosis Factor-alpha - genetics
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Veins & arteries
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0049701