Oleic acid ameliorates Aβ-induced inflammation by downregulation of COX-2 and iNOS via NFκB signaling pathway

Beta-amyloid peptide (Aβ) damage is one of major potential causes of Alzheimer's disease (AD) and its modulation has emerged as a promising approach to control the onset of AD. In the present study, the effects of oleic acid (OA) against Aβ25-35-stimulated neurotoxicity, inflammatory responses, and further molecular mechanism underlying the neuroprotective properties of OA in PC12 cells were investigated. Pre-treatment of OA significantly decreased Aβ25-35-mediated cytotoxicity by increasing cell viability through the attenuation of intracellular reactive oxygen species (ROS) level and downregulation of pro-apoptotic activated caspase-3, thereby mitigating apoptotic morphological alterations. Improper up-regulation of both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by Aβ25-35 was significantly suppressed by preconditioning of OA through repression of the inhibitory unit I-κB degradation, which impedes subsequent nuclear translocation of the functionally active subunit of transcription factor nuclear factor-kappa B (NF-κB). OA noticeably attenuated Aβ25-35-stimulated phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK1/2), and c-Jun-N-terminal kinase (JNK). Taken together, these findings suggest that the mechanisms responsible for anti-apoptotic and anti-inflammatory properties of OA in Aβ25-35-mediated neuronal damage is associated with COX-2 and iNOS downregulation through activation of NF-κB mediated by upstream kinases including JNK, ERK and p38 MAPK.