title: 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.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand. Electronic address: wipawan.tha@mahidol.ac.th.
authors.forename: Wipawan
authors.initials: W
authors.lastname: Thangnipon
authors.forename: Nicha
authors.initials: N
authors.lastname: Puangmalai
authors.forename: Vorapin
authors.initials: V
authors.lastname: Chinchalongporn
authors.forename: Chanati
authors.initials: C
authors.lastname: Jantrachotechatchawan
authors.forename: Narisorn
authors.initials: N
authors.lastname: Kitiyanant
authors.forename: Rungtip
authors.initials: R
authors.lastname: Soi-Ampornkul
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.forename: Saksit
authors.initials: S
authors.lastname: Nobsathian
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002934:Cinnamates / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002934:Cinnamates; C586180:N-benzylcinnamide; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Alzheimer's disease; Amyloid β-peptide; Anti-inflammation; Antioxidant; Apoptosis; Mechanism; N-benzylcinnamide