Isoquinoline alkaloids reduce beta-amyloid peptide toxicity in Caenorhabditis elegans

Alzheimer's disease (AD) is a multifactorial health problem widespread over the world. Regarding the historical importance of the alkaloids in the central nervous system pharmacology they remain as promising drug candidates against AD. Seven alkaloids from Amaryllidaceae and Fabaceae were evaluated in vivo, in vitro and in silico targets related to the AD pathophysiology. Erythraline and erysodine showed the greatest potential compared to Memantine, a drug currently used in AD therapy, by delaying the A beta(1-42)-induced paralysis in the transgenic strain CL2006 Caenorhabditis elegans, an alternative model to assess the impairment of beta-amyloid peptide deposition. The in vitro inhibition of the acetylcholinesterase was observed for the first time for Erythrina alkaloids; however Lycorine was the most active. Docking simulation contributed to comprehend this potential by showing a hydrophobic interaction between acetylcholinesterase and Lycorine in the amino acid residue TRP 84 as well as hydrogen bonds with TRY 121 and ASP 72.

Automated summary

The study evaluated seven alkaloids from Amaryllidaceae and Fabaceae for their potential against Alzheimer's disease, with Erythraline and erysodine showing greater potential compared to Memantine. These alkaloids demonstrated inhibitory effects on AD pathology in in vivo, in vitro, and in silico targets.