Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant inCaesalpinia bonduc(Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aβ-induced toxicity and possible mechanisms in the transgenicCaenorhabditis elegansAD model. Our results showed that caesalmin C significantly alleviated the Aβ-induced paralysis phenotype in transgenic CL4176 strainC. elegans. Caesalmin C dramatically reduced the content of Aβ monomers, oligomers, and deposited spots in ADC. elegans. In addition, mRNA levels ofsod-3,gst-4, andrpt-3were up-regulated, and mRNA levels oface-1were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD inC. elegansvia the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.Keywords:caesalmin C;Alzheimer’s disease;Caenorhabditis elegans;amyloid β-protein;DAF-16