Abstract

The large molecular weight of polysaccharides limits their absorption and utilization by organisms, affecting their biological activities. In this study, we purified α-1,6-galactan from Cantharellus cibarius Fr. (chanterelle) and reduced its molecular weight from approximately 20 kDa to 5 kDa (named CCP) to increase its solubility and absorption. In APP/PS1 mice, CCP improved both spatial and non-spatial memory loss in Alzheimer's disease (AD) mice, as confirmed by the Morris water maze, step-down, step-through, and novel object recognition tests, and dampened the deposition of amyloid-β plaques, as assessed by immunohistochemical analysis. Proteomic analysis suggested that the neuroprotective effects of CCP are related to anti-neuroinflammation. Immunofluorescence analysis and western blotting confirmed that CCP attenuated AD-like symptoms partly by inhibiting neuroinflammation, which was related to the blocking of complement component 3. Our study provides theoretical support and experimental evidence for the future application of chanterelle-extracted polysaccharides in AD treatment, promoting the modern development of traditional medicines originating from natural polysaccharides.

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