Longan Aril polysaccharides ameliorate cognitive impairment in AD mice via restoration of the immune phagocytosis of microglia

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) belongs to the category of "forgetfulness" or "dementia" in traditional Chinese medicine, and is often caused by deficiency of five zang-viscera. Longan Aril (the aril of Dimocarpus longan Lour., LA) possesses properties beneficial for heart and spleen health, blood nourishment, and mind tranquility, suggesting its potential as a treatment for AD. This study aimed to investigate the therapeutic effects of Longan Aril polysaccharides (LAPs), a primary active constituent of LA, on lipopolysaccharides (LPS) and amyloid β-peptide (Aβ) induced immune tolerance in AD mice. Further, BV2 cells were employed to explore the mechanism of LAPs in improving immune tolerance. MATERIAL AND METHODS: . The LAPs group mice received LAPs (1.4 g/kg) daily for 40 days. The anti-AD efficacy and mechanism of LAPs in vivo was evaluated by the Y maze, Morris water maze, Degenerating Neurons Stain (FJC staining), hematoxylin-eosin (H&E) staining, Nissl staining, measurements of lactate, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) secretion levels, immunofluorescence and western blot. Furthermore, the mechanism of LAPs in improving the function of immune-tolerant BV2 cells was explored in vitro using lactic acid kits, ELISA kits, and western blot. The phagocytic function of BV2 cells was evaluated by the fluorescent dye Alexa Fluor 488 labeled Aβ (AF448-Aβ). RESULTS: LAPs contained five monosaccharides. LAPs improved cognitive function and increased the number of Nissl bodies, lactate secretion, the IL-10 content, the relative fluorescence intensity of the IBA1 and AXL proteins, and the protein expression levels of AXL, Mertk, Glut1, HK2, PI3K, p-Akt/Akt, p-mTOR/mTOR and HIF-1α of immune-tolerant AD mice. LAPs also reduced the TNF-α content, and the protein expression level of CD68 in immune-tolerant AD mice. In vitro, LAPs elevated the IL-10 content and protein expression levels of PI3K, Akt, p-Akt, and HIF-1α, while reducing lactate secretion and the TNF-α content in immune-tolerant BV2 cells. LAPs promoted the phagocytic activity of BV2 cells, and their effects are completely inhibited by 2-DG and partially inhibited by BAY and Rapa. CONCLUSIONS: LAPs can enhance the cognitive abilities of immune-tolerant AD mice and diminish their pathological damage. The mechanism involves the regulation of glycolysis and the PI3K/Akt/mTOR/HIF-1α signaling pathway to promote microglial immune phagocytosis.