Sesamin and sesamolin reduce amyloid-beta toxicity in a transgenic Caenorhabditis elegans

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (A beta) plaques in the brain. At the present, there is no approved drug with a proven disease-modifying effect. Sesame seed (Sesame indicum) has long been known as a healthy food in Southeast Asian countries. Sesame lignans obtained from sesame seed possess antioxidant property that exhibit a variety of beneficial effects in various models. The objective of this study was to investigate the protective effects of sesame lignans including sesamin, sesamolin, and sesamol against A beta toxicity in Caenorhabditis elegans (C. elegans) model of A beta toxicity and to address whether these sesame lignans have a positive effect on lifespan extension. A transgenic C. elegans expressing human A beta was used to investigate protective effects of sesame lignans against A beta toxicity. Sesamin and sesamolin significantly alleviated A beta-induced paralysis. The real-time PCR revealed that both sesamin and sesamolin did not affect the expression of A beta transgene. However, we found that only sesamin inhibited A beta oligomerization. These findings demonstrated that, among three sesame lignans tested, sesamin protected against A beta toxicity by reducing toxic A beta oligomers. Sesamin and sesamolin also significantly improved A beta-induced defect in chemotaxis behavior and reversed the defect to normal. Moreover, sesamin prolonged median and mean lifespan of the wild type worm. On the other hand, sesamolin and sesamol failed to extend lifespan. These results offer valuable evidence for the future use of sesamin in the development of agents for the treatment of AD. It is also worth investigating the structure-activity relationship of lignan-related structures and their anti-A beta toxicity activities in the future.