Ginkgo biloba Extract Drives Gut Flora and Microbial Metabolism Variation in a Mouse Model of Alzheimer’s Disease

Author:

Yu Ting1,Xing Yueyang2,Gao Qi12ORCID,Wang Dandan2,Chen Hongzhuan3,Wang Hao145,Zhang Yongfang45

Affiliation:

1. School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

2. SPH XingLing Sci. & Tech. Pharmaceutical Co., Ltd., Shanghai 201203, China

3. Department of Clinical Pharmacy, Institute of Interdisciplinary Integrative Medicine Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

4. Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

5. Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disease. Numerous investigations have demonstrated that medications that regulate the “brain–gut” axis can ameliorate disease symptoms of AD. Studies have shown that Ginkgo biloba extract (EGb) is involved in intestinal metabolism to meet the goal of illness treatment. EGb is currently utilized extensively in the clinical prevention and treatment of cardiovascular and cerebrovascular diseases. However, the regulatory effect of EGb on intestinal flora and its metabolites in AD pathology remains largely speculative. In this study, the Morris water maze test showed a significant improvement of spatial memory in the AD mouse model (APP/PS1 mice) after EGb treatment. We next confirmed the positive effects of EGb on the gut flora and metabolites of APP/PS1 mice and further showed that EGb treatment reshaped the disturbed gut microbiome, in particular by reducing the Firmicutes/Bacteroides ratio and increasing the abundance of Bacteroidetes, Uroviricota, Streptophyta, and Spirochaetes. Meanwhile, a non-targeted metabolomics analysis showed that EGb treatment significantly reversed the dysfunction of the microbial metabolic phenotype by altering Limosilactobacillus and Parvibacte, with 300 differential metabolites modulated (131 up-regulated, 169 down-regulated). Our findings highlight the significant regulatory impact of EGb on intestinal microflora and microbial metabolism in AD mice models and provide a potential therapeutic strategy for AD.

Funder

National Natural Science Foundation of China

Key Project of Shanghai Science and Technology Commission

Research Foundation of Translational Medicine of Shanghai Jiao Tong University

NATCM’s Project of High-level Construction of Key TCM Disciplines

Publisher

MDPI AG

Subject

Pharmaceutical Science

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