Protective Role of Corilagin on A25-35-Induced Neurotoxicity: Suppression of NF-B Signaling Pathway

Aggregation and deposition of beta-amyloid peptides (A), a pathological hallmark of Alzheimer's disease, has been recognized as a potent activator of neuroinflammation and neuronal dysfunction. In this study, the underlying molecular mechanisms responsible for the neuroprotective effects of corilagin against A(25-35)-triggered neurotoxicity and inflammatory responses were investigated in PC12 cells. Pretreatment with corilagin effectively protected PC12 cells against A(25-35)-induced damage and apoptosis. A(25-35) induced damage in PC12 cells as revealed by increased production of reactive oxygen species, caspase-3 activity, and cell cycle arrest was attenuated by corilagin pretreatment. Corilagin not only significantly suppressed the production of neurotoxic inflammatory mediators such as tumor necrosis factor-, nitric oxide, and prostaglandin E-2 but also downregulated cyclooxygenase-2 and inducible nitric oxide synthase expression in PC12 cells. It also exerted a beneficial effect by suppressing the degradation of inhibitor of B (IB)- and subsequent activation of transcription factor nuclear factor B (NF-B), mostly through inhibition of extracellular signal-regulated kinase activity in comparison to c-Jun N-terminal kinase and p38 MAP kinase (p38) mitogen-activated protein kinase activity. These findings suggest that attenuation of A(25-35)-induced inflammatory responses by downregulating the NF-B signaling pathway might be a valuable strategy for both Alzheimer's disease prevention and/or treatment.