Alantolactone and Isoalantolactone Prevent Amyloid 25-35-induced Toxicity in Mouse Cortical Neurons and Scopolamine-induced Cognitive Impairment in Mice

Given the evidence for detoxifying/antioxidant enzyme-inducing activities by alantolactone (AL) and isoalantolactone (IAL), the purpose of this study was to investigate the effects of AL and IAL on A(25-35)-induced cell death in mouse cortical neuron cells and to determine their effects on scopolamine-induced amnesia in mice. Our data demonstrated that both compounds effectively attenuated the cytotoxicity of A(25-35) (10M) in neuronal cells derived from the mouse cerebral cortex. It was also found that the production of intracellular reactive oxygen species, including superoxide anion induced by A(25-35), was inhibited. Moreover, the administration of the sesquiterpenes reversed scopolamine-induced cognitive impairments as assessed by Morris water, Y-maze, and the passive avoidance tests, and the compounds decreased acetylcholinesterase (AChE) activities in a dose-dependent manner. Interestingly, AL and IAL did not improve scopolamine-induced cognitive deficit in Nrf2(-/-) mice, suggesting that memory improvement by sesquiterpenes was mediated not only by the activation of the Nrf2 signaling pathway but also by their inhibitory activity against AChE. In conclusion, our results showed that AL and IAL had neuroprotective effects and reversed cognitive impairments induced by scopolamine in a mouse model. Therefore, AL and IAL deserve further study as potential therapeutic agents for reactive oxygen species-related neurodegenerative diseases. Copyright (c) 2017 John Wiley & Sons, Ltd.