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Polysaccharides improve cognitive impairment in mice: A meta-analysis
Xin-Chen Wang1, Chen-Liang Chu2, Yan-Lu Liu2
1Department of Pharmaceutical Engineering, College of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, China; Guangdong Provincial Key Laboratory of Environmental Health and Resource Utilization, Zhaoqing University, Zhaoqing, China; School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong SAR, China.
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.
Insights
Polysaccharide (PS) extracts significantly improved cognitive and behavioral abilities in mouse models of mild cognitive impairment (MCI). These findings highlight PS as a potential therapeutic agent for MCI by enhancing neuronal function and reducing inflammation and oxidative stress.
Area of Science:
- Neuroscience and Pharmacology
- Biochemistry and Molecular Biology
Background:
- Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia, characterized by deficits in cognition, behavior, and language.
- Polysaccharides (PS) are bioactive compounds with known immunomodulatory, anti-inflammatory, and antioxidant properties, and they can promote neuronal growth.
Purpose of the Study:
- To systematically review and meta-analyze existing research on the efficacy of polysaccharide (PS) extracts in improving cognitive and behavioral deficits in animal models of mild cognitive impairment (MCI).
- To evaluate the impact of PS extracts on behavioral performance and key biochemical indicators associated with MCI.
Main Methods:
- A comprehensive systematic search of electronic databases (PubMed, Web of Science, Cochrane Library, Embase, MEDLINE) was conducted up to April 2025.
- Included studies involved mouse models of MCI induced by various methods, comparing outcomes between PS extract treatment groups and control groups.
- Data were analyzed using a random effects model, adhering to Cochrane systematic review and PRISMA guidelines to assess intergroup heterogeneity.
Main Results:
- The meta-analysis included 84 studies across 9 mouse strains and over 40 types of PS, examining 6 mechanisms of action.
- PS treatment significantly improved performance in behavioral tests, including the Morris water maze (SMD=-2.19), Y-maze (SMD=0.12), and new object recognition test (SMD=0.2).
- Significant differences were observed in biochemical markers, with PS intervention positively affecting acetylcholinesterase activity, oxidative stress markers (superoxide dismutase and malondialdehyde), and anti-inflammatory effects compared to untreated MCI models.
Conclusions:
- Polysaccharide (PS) extracts demonstrate a significant capacity to enhance learning and cognitive functions in animal models of mild cognitive impairment (MCI).
- The therapeutic effects are attributed to multiple mechanisms, including the promotion of neuronal regeneration, and the exhibition of anti-inflammatory, antioxidant, and anti-protein aggregation properties.
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