CA-30,an active fraction derived from Liuwei Dihuang Decoction,ameliorates cognitive deterioration via intestinal microbiome

Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chinese medicine(TCM)prescription,has long been used to treat various diseases,including dementia.A great number of pharmacological studies have showed that LW and its active fractions had beneficial effects on AD associated cognitive impairments.Our recent study found that LW,especially its oligosaccharide fraction CA-30,could improve the gastrointestinal microbiota dysbiosis in senescence-accelerated mouse prone 8(SAMP8),an AD mouse model.Here,we sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in SAMP8 mice.Administration with CA-30 decreased the degree of senescence,increased the nest building and locomotor activity,ameliorated the impairments in object recognition,spatial learningand memory behavour,and decreased the active avoidance response in SAMP8 mice.Meanwhile,CA-30 improvedthe cytokine and hormone secretion and lymphocyte subset dysregulation in SAMP8 mice.Moreover,we found that CA-30 altered the abundance of 4 genera and 10 newborn genera.Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment,especially GH85,were also noted.We further found that 7 genera were significantly correlated with the NIM network and cognitive performance.CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels.CA-30 ameliorated the intestinal microbiome,rebalanced the NIM network,improved the AD-like cognitive impairments in SAMP8,and might thus be a potential therapeutic agent for AD.