N-benzylcinnamide protects rat cultured cortical neurons from β-amyloid peptide-induced neurotoxicity.

Abstract

The pathogenesis of Alzheimer's disease involves an amyloid β-peptide (Aβ)-induced cascade of elevated oxidative damage and inflammation. The present study investigates the protective effects and the underlying mechanisms of N-benzylcinnamide (PT-3), purified from Piper submultinerve. Against Aβ-induced oxidative stress and inflammation in rat primary cortical cell cultures. Pre-treatment with 10-00nM PT-3 significantly attenuated neuronal cell death induced by 10μM Aβ1-42. PT-3 was found to enhance cell viability through a significant reduction in the level of reactive oxygen species, down-regulated expression of pro-apoptotic activated caspase-3 and Bax, increased expression of anti-apoptotic Bcl-2, and mitigation of Aβ-induced morphological alterations. Regarding its effects on inflammatory responses, PT-3 pre-treatment decreased the expression of pro-inflammatory cytokines IL-1β and IL-6. The mechanisms of PT-3 neuronal protection against inflammation may be associated with the mitogen-activated protein kinases (MAPK) pathway. Aβ1-42-induced phosphorylation of JNK and p38 MAPK was inhibited by pretreatment with PT-3 in a dose-dependent manner. However, phosphorylation of ERK1/2 was not affected by either PT-3 or Aβ1-42. PT-3 did not stimulate Akt phosphorylation, which was inhibited by Aβ1-42. These findings suggest that PT-3 protects neurons from Aβ1-42-induced neurotoxicity through its anti-apoptotic, anti-oxidative, and anti-inflammatory properties with inhibition of JNK and p38 MAPK phosphorylation as the potential underlying mechanism.

• Authors: Wipawan Thangnipon, Nicha Puangmalai, Vorapin Chinchalongporn, Chanati Jantrachotechatchawan, Narisorn Kitiyanant, Rungtip Soi-Ampornkul, Patoomratana Tuchinda, Saksit Nobsathian
• Journal: Neuroscience letters (Neurosci Lett) Vol. 556 Pg. 20-5 (Nov 27 2013) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 24120429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Cinnamates
• N-benzylcinnamide
• Neuroprotective Agents
• Peptide Fragments
• Reactive Oxygen Species
• amyloid beta-protein (1-42)
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cells, Cultured
• Cerebral Cortex (cytology)
• Cinnamates (pharmacology)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Neurons (cytology, drug effects)
• Neuroprotective Agents (pharmacology)
• Peptide Fragments (toxicity)
• Phosphorylation
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)