Crocin Ameliorates Cognitive Impairment and Pathological Changes in Alzheimer's Disease Model Mice by Regulating Gut...

Alzheimer's disease (AD), a primary cause of dementia, places a significant strain on both patients and society due to the absence of effective treatments. Recent research suggests that the gut microbiota may play a role in the development of AD. Crocin, a compound derived from traditional medicine, has demonstrated potential in alleviating neurological disorders and influencing gut microbiota, yet its specific mechanisms in AD remain unclear. In this study, we administered Crocin or saline to 5xFAD mice and wild-type controls. We discovered that Crocin treatment led to notable improvements in cognitive function, as measured by the Morris water maze test, reduced beta-amyloid (Aβ) accumulation, and decreased neuroinflammation, as indicated by reduced microglial and astrocyte activation. Metagenomic sequencing revealed a significant increase in the gut microbiota diversity, specifically the abundance of Firmicutes, Verrucomicrobiota, and Akkermansia. Additionally, Crocin enhanced intestinal barrier function by upregulating tight junction proteins and Secretory immunoglobulin A, while improving the structure of the jejunal mucosa. These results suggest that Crocin may alleviate cognitive deficits and neuropathological changes in 5xFAD mice, possibly through modulation of the gut microbiota and strengthening the gut barrier, presenting it as a promising therapeutic approach for AD.