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

Abstract

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 Aβ 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 Aβ 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 Aβ 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-1β, IL-6 and TNF-α) 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.