Metformin and cyanidin 3-O-galactoside from Aronia melanocarpa synergistically alleviate cognitive impairment in SAMP8 mice

Abstract

Cyanidin 3-O-galactoside (Cy3Gal) from Aronia melanocarpa has been reported to alleviate cognitive impairment. Metformin for preventing the neurodegenerative disease is attracting increasing attention. However, the neuroprotective and metabolic health promoting both of their effects are not clear. We chose the senescence accelerated mouse prone 8 (SAMP8) as a model of spontaneous learning and memory impairment. This study aimed to investigate the synergistic neuroprotective effect of metformin and Cy3Gal by behavioral and histopathological assays and metabolite 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⁻¹, ig) group, the metformin (100 mg kg⁻¹, ig) group, the Cy3Gal (25 mg kg⁻¹, ig) group, and the combination of metformin plus Cy3Gal (Met + Cy3Gal, 100 mg kg⁻¹, 25 mg kg⁻¹, ig) group. The behavior experiments showed that the SAMP8 mice treated with metformin and Cy3Gal showed improved spatial learning and memory compared to the SAMP8 model group. The number of neurons in the Met + Cy3Gal group was significantly higher than that in the SAMP8 group and the Met + Cy3Gal group showed significantly reduced Aβ aggregation in the brain, which was elevated in SAMP8 mice. Compared with SAMP8 mice, the Met + Cy3Gal group showed decreased indole, methyl esters and ketones and increased 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 on postponing the progression of Alzheimer's disease.