Wang_2025_Phytomedicine_149_157561

BACKGROUND: Mild cognitive impairment (MCI) refers to the impairment and difficulty of spatial cognition, understanding, communication, behavioral decision-making, and language expression in the brain. As it is an intermediate stage between normal cognitive decline and dementia, it is considered a precursor to dementia. Polysaccharides (PS) are extracted from various biological materials, such as plants, animals, and microorganisms, and have immunomodulatory, anti-inflammatory, and antioxidant effects and promote neuronal growth. The main objective of this systematic review and meta-analysis was to comprehensively evaluate existing research on PS extracts in the context of MCI. METHOD: As of April 2025, detailed searches were conducted on electronic databases such as PubMed, Web of Science, Cochrane Library, Embase, and MEDLINE. The research focused on comparing the improvement in behavioral ability and biochemical indicators in a mouse model of MCI induced by PS extracts. Intergroup heterogeneity was evaluated through a random effects model by following the Cochrane systematic review and PRISMA criteria. RESULTS: Our systematic review and meta-analysis included 84 studies involving 9 mouse strains, more than 40 types of PS, and 6 types of PS mechanisms of action. Through behavioral testing and biochemical indicator detection, comparisons were made between the groups that received PS treatment and the control group that did not receive any treatment. The results revealed significant differences between the PS and control groups in the three behavioral testing processes: the Morris water maze test (MWMT) (SMD=-2.19, 95% CI=-2.57 to -1.81, p<0.0001), the Y-maze test (SMD=0.12, 95% CI=0.07 to 0.16, p<0.0001), and the new object recognition test (NORT) (SMD=0.2, 95% CI=0.16 to 0.24, p<0.0001). The effect on acetylcholinesterase (AChE) activity was significantly different between the PS group and the untreated MCI group (SMD=-0.86, 95% CI=-2.34 to 0.61, p=0.08). Regarding oxidative stress, the PS intervention group and the untreated MCI model group exhibited significant differences in the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) (SMD=4.87, 95% CI=3.62 to 6.13, p<0.0001) (SMD=-4.59, 95% CI=-5.67 to -3.50, p<0.0001). A significant difference in anti-inflammatory effects was noted between the PS group and the untreated MCI group (SMD=-3.34, 95% CI=-4.30 to -2.38, p<0.0001). CONCLUSION: Our research revealed that PS extracts can improve the learning and cognitive abilities of MCI animal models through various mechanisms, such as promoting neuronal regeneration and exerting anti-inflammatory, antioxidant, and anti-protein-aggregation effects.