Ferulic acid delayed amyloid β-induced pathological symptoms by autophagy pathway via a fasting-like effect in Caenorhabditis elegans

The amyloid β (Aβ) generation or aggregation plays a crucial role in Alzheimer's disease (AD). Autophagy agonists, which function as the clearance of Aβ, could be the potential drug candidates against AD. In staple food crops, ferulic acid (FA) is an enormously copious and almost ubiquitous phenolic antioxidant. In the present study, FA significantly inhibited Aβ-induced pathological symptoms of paralysis and hypersensitivity to exogenous serotonin, meanwhile restrained Aβ monomers, oligomers, and deposits in AD C. elegans. FA increased the expression of autophagy reporter LGG-1 and enhanced autophagy flux. However, the autophagy inhibitors abolished the restrictive action of FA on the worm paralysis phenotype. According to these results, FA triggered autophagy and ameliorated Aβ-induced pathological symptoms by the autophagy pathway. Moreover, FA activated the HLH-30 transcription factor to nuclear localization, which acts upstream of autophagy in fasted animals, reduced the level of lipids, but affected nor the growth of E. coli OP50, neither animal food intake behavior. These suggest that FA induced a fasting-like effect to activate the autophagy pathway. Additionally, FA ameliorated poly Q aggregations in Huntington's disease worm. Thus, FA could not only affect AD, broadly but also neurodegenerative diseases characterized by misfolded or aggregated proteins. [Display omitted] •Ferulic acid effectively repectively delayed AD-like symptoms of paralysis and hypersensitivity to exogenous 5-HT in worms.•Ferulic acid reduced Aβ deposits and lowered the level of Aβ oligomers and monomers.•Ferulic acid exerted anti-AD action by inducing autophay.•Ferulic acid activated HLH-30 transcription factor to nuclear localization and reduced the level of lipids.•Ferulic acid did not affect the growth of worm food resource of E.coli OP50 or animal food intake behavior.•Ferulic acid also ameliorated poly Q aggregations in Huntington’s disease worm characterized by misfolded or aggregated proteins.