Neuroprotection of low-molecular-weight galactan obtained from Cantharellus cibarius Fr. against Alzheimer's disease

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.