Secondary metabolites of Galactomyces geotrichum from Laminaria japonica ameliorate cognitive deficits and brain oxidative stress in D-galactose induced Alzheimer’s disease mouse model

Abstract

Accumulating evidences have shown the beneficial effects of natural products for Alzheimer’s disease (AD) treatment. The present study was designed to investigate the neuroprotective effects of secondary metabolites of Galactomyces geotrichum (SMGG) on D-galactose induced AD mice. SMGG was extracted and its toxicological evaluation was conducted. To explore the neuroprotective mechanism responsible for anti-AD activity of SMGG, spatial learning and memory behavioral, oxidative stress levels, acetylcholinesterase and choline acetyltransferase activity assays were employed. The AD mice received SMGG treatment exhibited significant improvement in cognitive performance, enhanced antioxidant capacity, decreased acetylcholinesterase activity and increased choline acetyltransferase activity. Meanwhile, SMGG had no toxicity and seven compounds were separated from it: 7,8-dimethyl-iso-alloxazine, 1-methyl-3-benzyl-6-(4-hydroxybenzyl)-2,5-piperzainedione, cyclo-(Phe-Pro), cyclo-(Leu-Pro), cyclo-(Pro-Gly), cyclo-(Gly-Leu) and uracil, respectively. Overall, these data suggested that SMGG protects the brain against D-galactose induced cognitive impairment, oxidative damages and acetylcholine content decrease in AD mice.

Graphical Abstract

KEYWORDS:

• Galactomyces geotrichum
• secondary metabolites
• Alzheimer’s disease
• cognitive deficits
• oxidative damages
• toxicological evaluation

Disclosure statement

No potential conflict of interest was reported by all authors.

Additional information

Funding

The work was supported by Natural Science Foundation of Shandong Province of China (No. ZR2015BM016) and Major Basic Program of Natural Science Foundation of Shandong Province of China (No. ZR2018ZC0945).