We explored the effect of
phlorizin against
cholinergic memory impairment and
dysbacteriosis in
D-galactose induced ICR mice. The control (CON) group,
D-galactose model (DGM) group, and three groups (DG-PL, DG-PM, DG-PH) treated with
phlorizin at 0.01%, 0.02%, and 0.04% (w/w) in diets were raised for 12 weeks. Supplementing with
phlorizin reversed the loss of organ coefficient and
body weight caused by
D-galactose. The functional abilities of
phlorizin on hippocampal-dependent spatial learning and memory, anti-oxidation, anti-
inflammation were also observed. Meanwhile,
phlorizin intervention upregulated the gene expression of Nrf2, GSH-PX, SOD1, decreased the gene expression of NF-κB, TLR-4, TNF-α, and IL-1β in the hippocampus, while enhanced the gene expression of JAM-A, Mucin2,
Occludin in the caecum. Furthermore, a
neurotransmitter of
acetylcholine (ACh) was enhanced, while
acetylcholinesterase (AChE) activity was inhibited by
phlorizin administration. Moreover,
phlorizin administration increased
short-chain fatty acids (SCFAs) content, and reduced
lipopolysaccharides (LPS) levels, which may relate to the rebuilding of gut microbiota homeostasis. Treatment with
phlorizin may be an effective intervention for alleviating
cognitive decline and gut microbiota
dysbiosis.