Combinatorial chemistry & high throughput screening · 2026
Therapeutic Effects of the Traditional Chinese Formula Qifuyin on Cognition, Lipid Metabolism, and Gut Microbiota in ApoE4 Mice.
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Yu Ying, Zhao Hongwei, He Yun, Zhao Junqi, Yang Xiuzhao, Liu Xijian, Cheng Xiaorui
Аннотация
INTRODUCTION: Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Qifuyin is a promising herbal formula used clinically for cognitive decline, but its effects on ApoE4-associated cognitive and systemic phenotypes remain unclear. This study aimed to evaluate the effects of Qifuyin on cognitive performance in ApoE4 transgenic mice and to preliminarily explore its associations with lipid metabolism and gut microbiota alterations.
METHODS: Ten-month-old ApoE4 transgenic mice were treated with Qifuyin by gavage for 321 days, once daily for the first 123 days and once every two days thereafter. Cognitive function was assessed using the step-down test, novel object recognition test (NORT), and Morris water maze test (MWM). Aging- and frailty-related phenotypes were evaluated using senescence grading scores. Serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) levels were measured to assess lipid metabolism. Gut microbiota composition and functional profiles were analyzed by 16S rRNA and metagenomic sequencing.
RESULTS: Qifuyin treatment significantly reduced error counts and prolonged latency in the stepdown test, increased the 24h preference index in the NORT, shortened escape latency, and increased platform crossings in the MWM in ApoE4 transgenic mice. High-dose Qifuyin reduced aging scores in males and in all doses in females and in the pooled dataset. Qifuyin decreased serum TG and ApoB levels, and increased serum HDL-C levels. 16S rRNA sequencing indicated that Qifuyin increased alpha diversity and shifted beta diversity toward the control profile. At the phylum level, Qifuyin altered the relative abundances of Firmicutes, Bacteroidota, Cyanobacteria, and Synergistota. At the family and genus levels, Qifuyin treatment was associated with increased abundances of Helicobacteraceae, Bacteroidaceae, Helicobacter, and Bacteroides, and a reduced abundance of Ruminococcaceae. Metagenomic annotation analysis showed altered abundances of K02003, K06147, COG1961, CBM37, and GH35-related features.
DISCUSSION: These findings suggest that Qifuyin may benefit ApoE4-associated cognitive and systemic dysfunction through its integrated effects on lipid metabolism and gut microbiota alterations. The microbiota-related changes observed in this study may provide a potential link between peripheral metabolic regulation and cognitive improvement, although their mechanistic significance requires further validation.
CONCLUSIONS: Qifuyin improved cognitive performance and lipid metabolism, and was associated with alterations in gut microbiota composition in ApoE4 transgenic mice. These findings suggest that Qifuyin may exert beneficial effects on cognitive and systemic phenotypes in this model, while the biological significance of specific microbial changes warrants further investigation.
METHODS: Ten-month-old ApoE4 transgenic mice were treated with Qifuyin by gavage for 321 days, once daily for the first 123 days and once every two days thereafter. Cognitive function was assessed using the step-down test, novel object recognition test (NORT), and Morris water maze test (MWM). Aging- and frailty-related phenotypes were evaluated using senescence grading scores. Serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) levels were measured to assess lipid metabolism. Gut microbiota composition and functional profiles were analyzed by 16S rRNA and metagenomic sequencing.
RESULTS: Qifuyin treatment significantly reduced error counts and prolonged latency in the stepdown test, increased the 24h preference index in the NORT, shortened escape latency, and increased platform crossings in the MWM in ApoE4 transgenic mice. High-dose Qifuyin reduced aging scores in males and in all doses in females and in the pooled dataset. Qifuyin decreased serum TG and ApoB levels, and increased serum HDL-C levels. 16S rRNA sequencing indicated that Qifuyin increased alpha diversity and shifted beta diversity toward the control profile. At the phylum level, Qifuyin altered the relative abundances of Firmicutes, Bacteroidota, Cyanobacteria, and Synergistota. At the family and genus levels, Qifuyin treatment was associated with increased abundances of Helicobacteraceae, Bacteroidaceae, Helicobacter, and Bacteroides, and a reduced abundance of Ruminococcaceae. Metagenomic annotation analysis showed altered abundances of K02003, K06147, COG1961, CBM37, and GH35-related features.
DISCUSSION: These findings suggest that Qifuyin may benefit ApoE4-associated cognitive and systemic dysfunction through its integrated effects on lipid metabolism and gut microbiota alterations. The microbiota-related changes observed in this study may provide a potential link between peripheral metabolic regulation and cognitive improvement, although their mechanistic significance requires further validation.
CONCLUSIONS: Qifuyin improved cognitive performance and lipid metabolism, and was associated with alterations in gut microbiota composition in ApoE4 transgenic mice. These findings suggest that Qifuyin may exert beneficial effects on cognitive and systemic phenotypes in this model, while the biological significance of specific microbial changes warrants further investigation.