title: Monascin from Monascus-Fermented Products Reduces Oxidative Stress and Amyloid-β Toxicity via DAF-16/FOXO in Caenorhabditis elegans.
abstract: Amyloid-β (Aβ)-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, Aβ 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 Aβ-induced paralysis phenotype and Aβ deposits in the transgenic strains CL4176 and CL2006 of C. elegans, which expresses human muscle-specific Aβ1-42 in the cytoplasm of body wall muscle cells. In addition, mRNA levels of strain CL4176 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 Aβ toxicity via DAF-16 in C. elegans, suggesting that MS can be used for the prevention of AD-associated oxidative stress complications.
authors.affiliation: Department of Bioenvironmental Systems Engineering and ‡Department of Biochemical Science and Technology, National Taiwan University , No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Yeu-Ching
authors.initials: YC
authors.lastname: Shi
authors.affiliation: Department of Bioenvironmental Systems Engineering and ‡Department of Biochemical Science and Technology, National Taiwan University , No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
authors.affiliation: Department of Bioenvironmental Systems Engineering and ‡Department of Biochemical Science and Technology, National Taiwan University , No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Vivian Hsiu-Chuan
authors.initials: VH
authors.lastname: Liao
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005285:Fermentation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D032741:Monascus / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000099156:Superoxide Dismutase 2
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D006575:Heterocyclic Compounds, 3-Ring; D010446:Peptide Fragments; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C075222:amyloid beta-protein (1-42); C108831:daf-16 protein, C elegans; C108431:hsp-16.2 protein, C elegans; C587809:Sod-1 protein, C elegans; C525107:Sod-3 protein, C elegans; C517880:monascin
keywords: Alzheimer’s disease (AD); Caenorhabditis elegans; DAF-16; amyloid-β; fungus secondary metabolite; monascin; oxidative stress