Isoquinoline alkaloids reduce beta-amyloid peptide toxicity in Caenorhabditis elegans

Abstract

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 Aβ_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.

Graphical Abstract

Keywords:

• Erythrina
• Hippeastrum
• Alzheimer

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) grant [445149/2014-0] awarded to R.B.G. and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) [Finance Code 001]. The authors also acnowledge the financial support by the following Brazilian agencies: Foundation of Support to Research and Innovation of Espírito Santo, Ministério de Ciência, Tecnologia, Inovação e Comunicações – MCTIC and the Instituto Nacional de Ciência e Tecnologia em Biodiversidade e Produtos Naturais - INCT BioNat.