Monascin from Monascus-Fermented Products Reduces Oxidative Stress and Amyloid-β Toxicity via DAF-16/FOXO in Caenorhabditis elegans

Amyloid-beta-(A beta)-induced oxidative-stress and toxicity are leading risk factors. for Alzheimer's disease (AD). Monascin (MS) is a novel compound proposed for antioxidative stress applications and is derived from an edible fungus secondary metabolite. This study assessed the effects of MS on oxidative stress, paralysis, A beta accumulation, and lifespan in the nematode Caenorhabditis elegans and investigated its underlying mechanisms of action. The results showed that MS increased the survival of C. elegans under juglone-induced oxidative stress and attenuated endogenous levels,of reactive oxygen species. Furthermore, MS induced a decline in A beta-induced paralysis phenotype and A beta deposits in the transgenic strains CL4176 and CL2006 of C. elegans, which expresses human muscle-specific A beta(1-42) in the cytoplasm of body wall muscle cells. In addition, mRNA levels of strain CI4176 of several antioxidant genes (sod-1, sod-2, sod-3, hsp16.2) and daf-16 were up-regulated by MS treatment when compared to the nontreated controls. Further evidence showed that MS treatment in C. elegans strains lacking DAF-16/FOXO did not affect paralysis or lifespan phenotypes. The findings indicate that MS reduces oxidative stress and A beta toxicity via DAF-16 in C. elegans, suggesting that MS can be used for the prevention of AD-associated oxidative stress complications.