Mulberry Fruit Extract Alleviates Cognitive Impairment by Promoting the Clearance of Amyloid-beta and Inhibiting Neuroinflammation in Alzheimer's Disease Mice

摘要

Alzheimer's disease (AD) is a common neurodegenerative disease, always clinically manifesting with memory loss and other cognitive abilities serious enough to interfere with daily life. Over the past decade, the extensive accumulation of A beta plaques and the related neuroinflammation such as the activation of glial cells have been frequently demonstrated to contribute to the pathogenesis of AD. However, drugs promoting A beta plaques degradation and modulating the neuroinflammation remain undeveloped for AD treatment. Mulberry (or Morus alba Linn.) fruit, a common folk medicine, has been demonstrated to exhibit a considerable neuroprotective effect such as promoting memory impairment and enhancing cognitive ability on Parkinson's-disease-related animal models. Whether mulberry fruit can treat or alleviate AD-related symptoms are unclear so far. In the present study, we estimated the neuroprotective effects of mulberry fruit ethanol extract (MFE) using APP/PS1 transgenic mice, a widely used AD animal model. We found that daily oral MFE (100 mg/kg body weight, for 1.5-3 weeks) remarkably improved the spatial memory and learning ability of APP/PS1 mice, determined by behavioral tests including the Rotarod, Elevated plus maze and Morris water maze test. In histological, we observed that MFE reduced A beta plaques and neuron apoptosis both in the cortex and hippocampus tissues of APP/PS1 mice. Moreover, MFE treatment noticeably alleviated the neuroinflammation, indicated by the decreased number of astrocytes in the cortex and hippocampus of APP/PS1 mice. These results were further confirmed by the elevation of anti-inflammatory cytokines (IL-4) and reduction of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) in the cortex and hippocampus tissues of MFE-treated APP/PS1 mice. Collectively, our findings demonstrate that MFE exhibits a good neuroprotective effect on APP/PS1 mice. Therefore, MFE may be a promising therapeutic drug in the treatment of neurodegenerative disorders, especially like AD.