Butterbur Leaves Attenuate Memory Impairment and Neuronal Cell Damage in Amyloid Beta-Induced Alzheimer's Disease Models

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, and is characterized by the accumulation of amyloid beta (A) as a pathological hallmark. A plays a central role in neuronal degeneration and synaptic dysfunction through the generation of excessive oxidative stress. In the present study, we explored whether leaves of Petasites japonicus (Siebold & Zucc.) Maxim. (PL), called butterbur and traditionally used in folk medicine, show neuroprotective action against A(25-35) plaque neurotoxicity in vitro and in vivo. We found that PL protected A(25-35) plaque-induced neuronal cell death and intracellular reactive oxygen species generation in HT22 cells by elevating expression levels of phosphorylated cyclic AMP response element-binding protein, heme oxygenase-1, and NAD(P)H quinine dehydrogenase 1. These neuroprotective effects of PL were also observed in A(25-35) plaque-injected AD mouse models. Moreover, administration of PL diminished A(25-35) plaque-induced synaptic dysfunction and memory impairment in mice. These findings lead us to suggest that PL can protect neurons against A(25-35) plaque-induced neurotoxicity and thus may be a potential candidate to regulate the progression of AD.