Metformin and Cyanidin 3-O-galactoside from Aronia melanocarpa Synergistically Alleviate Cognitive Impairment in SAMP8 mice

Cyanidin 3-O-galactoside (Cy3Gal) from Aronia melanocarpa has been reported in alleviating cognitive impairment. Metformin for preventing the neurodegenerative disease is causing increasing concern. However, both of them on neuroprotective effect and promoting metabolic health are not clear. We chose the senescence accelerated mice prone 8 (SAMP8) as a model of spontaneously learning and memory impairment. This study aimed to investigate the synergistic neuroprotective effect of metformin and Cy3Gal by behavioral and histopathological assays and metabolites analysis in SAMP8 mice. The SAMR1 mice were the normal group, and the SAMP8 mice were divided into five groups, including the SAMP8 model group, the Donepezil (1 mg/kg, ig) group, the Metformin (100 mg/kg, ig) group, the Cy3Gal (25 mg/kg, ig) group, and the combination of metformin plus Cy3Gal (Met + Cy3Gal, 100 mg/kg, 25 mg/kg, ig) group. The behavior experiments showed that the SAMP8 mice treat with metformin and Cy3Gal improved spatial learning and memory compared to SAMP8 model group. The number of neurons in Met + Cy3Gal group were significantly higher than SAMP8 group and Met + Cy3Gal group significantly reduced the Aβ aggregation in the brain, which were elevated in SAMP8 mice. Compared with SAMP8 mice, Met + Cy3Gal group decreased the indole, methyl esters and ketones and increased the short-chain fatty acids and alcohols in feces and urine by regulating the fatty acid biosynthesis and degradation. This study confirmed the neuroprotective effects of coadministration of metformin and cyanidin 3-O-galactoside in the SAMP8 mice, and suggested its positive effect to postpone the progression of Alzheimer’s disease.