Protective Effect of Ginkgolide B against Cognitive Impairment in Mice via Regulation of Gut Microbiota

Ginkgolide B (GB) is one of the main bioactive components of Ginkgo biloba leaf extracts with neuroprotective activity. However, the neuroprotective mechanism link between the anti-Alzheimer's disease (AD) efficiency of GB and gut microbiota have remained elusive. Here, we elucidated the effect and possible mechanism of GB against cognitive impairment in mice. Male mice were induced with d-galactose and aluminum chloride to establish an AD animal model, and then intragastrically treated with GB. Cognitive function was assessed by an object recognition test and an open-field test. Amyloid deposition and neuropathological change were detected. The levels of receptor for advanced glycation end products (RAGE), Bcl-2, and Bax were detected. Moreover, microbial compositions were measured by 16s rRNA sequencing. Our results showed that GB significantly alleviated cognitive dysfunction, neurodegeneration, and neuropathological changes in AD model mice. Moreover, GB treatment remarkably reduced the levels of RAGE and Bax and increased the level of Bcl-2 in AD model mice. GB treatment reversed the decreased abundance of Lactobacillus and the increased abundance of Bacteroidales, Muribaculaceae, and Alloprevotella, which led to reconstruction of gut microbiota. These findings demonstrated the neuroprotective effects of GB in AD mice, which were partly mediated by modulating gut dysbiosis, indicating that GB might be a potentially active supplement to alleviate AD.