Flavonoids from Ficus pandurate var. angustifolia W.C. Cheng Restore Cognitive Impairment and Regulate the Gut Microbiota in Sleep-Deprived Mice.

Sleep deprivation (SD) induces cognitive impairment associated with gut microbiota dysbiosis, making it crucial to explore natural remedies targeting the microbiota-gut-brain axis. This study aims to investigate whether Ficus pandurata var. angustifolia W.C. Cheng (a traditional medicine-food plant rich in flavonoids) can mitigate cognitive impairment caused by SD by modulating the gut microbiota. The sleep-deprived mouse model was established using the multiple platform water environment method. This study investigated the effects of F. pandurata var. angustifolia flavonoids (FCFs) via behavioral tests, 16S rRNA sequencing, and biochemical analyses to assess cognitive function, gut microbiota, and related pathways. FCF alleviated SD-induced cognitive deficits, reversed gut microbiota dysbiosis (increased beneficial bacteria like Lactobacillus, reduced harmful ones like Desulfovibrio), promoted short-chain fatty acids production, improved colonic histopathology and intestinal barrier function, reduced serum lipopolysaccharide, inhibited glial cell activation and TLR4/NF-κB signaling, and regulated neurotransmitters. In conclusion, FCF ameliorates SD-induced cognitive impairment through regulating gut microbiota, enhancing intestinal barrier, and suppressing neuroinflammation via the microbiota-gut-brain axis, providing a theoretical basis for its application.