Paeonol attenuates microglia-mediated inflammation and oxidative stress-induced neurotoxicity in rat primary microglia and cortical neurons.

Abstract

Inflammation and oxidative stress play important roles in the pathogenesis of neurodegenerative disorders such as stroke, traumatic injury, Parkinson disease, and Alzheimer disease. Paeonol, a natural compound extracted from Moutan cortex, is a potent anti-inflammatory and antioxidative agent. The aim of this study was to investigate the neuroprotective mechanisms of paeonol on lipopolysaccharide (LPS)-induced inflammation in rat primary microglia and 6-hydroxydopamine-induced oxidative damage in cortical neurons. In LPS-treated microglia, paeonol attenuated the overexpression of inducible nitric oxide synthase and cyclooxygenase 2, leading to the decrease in nitric oxide and prostaglandin E2 production, respectively. Paeonol also suppressed LPS-induced phosphorylation of extracellular signal-regulated kinase and Jun N-terminal kinase. In addition, LPS-stimulated NADPH oxidase activation and reactive oxygen species production were attenuated by paeonol. Paeonol-induced upregulation of heme oxygenase 1 was also observed. Moreover, paeonol attenuated LPS-treated microglia culture medium-induced neuron cells death. Posttreatment with paeonol also reduced inflammatory responses in LPS-activated microglia and increased cell viability in LPS-treated microglia culture medium-treated neurons. Furthermore, in 6-hydroxydopamine-treated cortical neurons, paeonol not only decreased reactive oxygen species production but also increased cell viability, superoxide dismutase activity, and the antiapoptotic protein B-cell lymphoma 2 expression. Taken together, the present results suggest that paeonol might be a potential neuroprotective agent via inhibiting microglia-mediated inflammation and oxidative stress-induced neuronal damage.

• Authors: Yu-Ting Tseng, Ya-Yun Hsu, Yu-Tzu Shih, Yi-Ching Lo
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 37 Issue 3 Pg. 312-8 (Mar 2012) ISSN: 1540-0514 [Electronic] United States
• PMID: 22089194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Anti-Inflammatory Agents
• Inflammation Mediators
• Lipopolysaccharides
• Neuroprotective Agents
• Reactive Oxygen Species
• paeonol
• Oxidopamine
• Nitric Oxide Synthase Type II
• Heme Oxygenase-1
• Cyclooxygenase 2
• Superoxide Dismutase
• Mitogen-Activated Protein Kinases

Topics

• Acetophenones (pharmacology)
• Animals
• Animals, Newborn
• Anti-Inflammatory Agents (pharmacology)
• Cell Survival (drug effects)
• Cells, Cultured
• Cerebral Cortex (cytology)
• Cyclooxygenase 2 (metabolism)
• Female
• Heme Oxygenase-1 (biosynthesis)
• Inflammation (prevention & control)
• Inflammation Mediators (metabolism)
• Lipopolysaccharides (antagonists & inhibitors)
• Microglia (drug effects, physiology)
• Mitogen-Activated Protein Kinases (metabolism)
• Neurodegenerative Diseases (prevention & control)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide Synthase Type II (biosynthesis)
• Oxidative Stress (drug effects)
• Oxidopamine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (antagonists & inhibitors)