Honokiol Attenuates Oligomeric Amyloid beta(1-42)-Induced Alzheimer's Disease in Mice Through Attenuating Mitochondrial Apoptosis and Inhibiting the Nuclear Factor Kappa-B Signaling Pathway

Background: Increasing evidence indicates that amyloid beta oligomer (A beta O) is toxic to neurons in Alzheimer's disease (AD) brain. The aim of the present study is to evaluate the effects of honokiol on A beta O-induced learning and memory dysfunction in mice. Methods: AD mice model was established by A beta O intrahippocampal injection. The cognitive function was evaluated using Morris water maze (MWM). Nissl staining was used to examine the hippocampal neuron damage. Primary hippocampal neurons were exposed to A beta O. The apoptosis in the hippocampal tissues and primary neurons was assessed using terminal dexynucleotidyl transferase-mediated dUTP nick end labeling-neuronal nuclei (NeuN) and Hoechst staining, respectively. The mitochondrial membrane potential and radical oxygen species were detected using standard methods. Western blotting assay was used to check the expression levels of apoptotic and nuclear factor kappa-B (NF-kappa B) signaling-associated proteins and electrophoretic mobility shift assay was used to detect NF-kappa B-DNA binding. Results: Honokiol increased the time spend in the target zone of the AD mice in the MWM. In addition, honokiol dose-dependently attenuated A beta O-induced hippocampal neuronal apoptosis, reactive oxygen species production and loss of mitochondrial membrane potential. Furthermore, A beta O-induced NF-kappa B activation was inhibited by honokiol, as well as the upregulated amyloid precursor protein and beta-secretase. Conclusion: Honokiol attenuates A beta O-induced learning and memory dysfunction in mice and it may be a potential candidate in AD therapy. (C) 2017 The Author(s) Published by S. Karger AG, Basel