Apigenin attenuates copper-mediated β-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model

Apigenin, belonging to a less toxic and non-mutagenic flavone subclass of flavonoids, has been reported to possess numerous biological activities beneficial to health. Although evidence has shown apigenin might exert its protective effects by reducing the toxicity induced by amyloid-beta peptides (A beta), the precise mechanism is unclear. In the present study, we investigated the in vitro neuroprotective activity of apigenin interrelated with amyloid toxicity and mental homeostasis in an Alzheimer's disease (AD) cell model and explored its potential signal transduction. Our results showed that apigenin protected neurons against A beta-mediated toxicity induced by copper, which was characterized by increasing neuronal viability and relieving mitochondrial membrane dissipation and neuronal nuclear condensation. Further, we demonstrated that apigenin did not provide sufficient effect on decreasing beta-amyloid precursor protein (A beta PP) expression and lowering A beta(1-42) secretion, but conserved redox balance by increasing intracellular glutathione levels and enhancing cellular superoxide dismutase and glutathione peroxidase activities, reduced intracellular reactive oxygen species (ROS) generation, blocked ROS-induced p38 mitogen-activated protein kinases (p38 MAPK)- MAPKAP kinase-2 (MK2)-heat shock protein 27 (Hsp27) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways, preserved mitochondrial function, and then regulated apoptotic pathways. In conclusion, apigenin could exert neuroprotection against A beta-induced toxicity in the presence of copper mainly through the mechanisms that regulate redox imbalance, preserve mitochondrial function, inhibit MAPK pathways, and depress neuronal apoptosis. (C) 2012 Elsevier B.V. All rights reserved.