Amaryllidaceae alkaloids from Lycoris suppress amyloid β-induced neurodegeneration in transgenic Caenorhabditis elegans CL2355

Alzheimer's disease (AD) accounts for 60-80 % of dementia cases worldwide and has no effective treatment currently, presenting a pressing need to search for new anti-AD agents. One of the AD therapeutic options is to improve the cognitive impairment by restoring the characteristic cholinergic deficiency with acetylcholinesterase (AChE) inhibitors. It has been previously shown that the natural Amaryllidaceae alkaloids galanthamine and haemanthidine from Lycoris radiata inhibit the ace-2 gene expression in transgenic CL4176 C. elegans. The aim of this project was to screen and characterize the Amaryllidaceae alkaloids extracted from twelve Lycoris species. Different type of alkaloids were tentatively identified by UPLC-QTOF-MS method. Three alkaloids lycorine, lycoramine and galanthamine were quantified in these species. These Lycoris alkaloids were shown to reduce the toxicity and the neurodegeneration induced by the neuronal expression of amyloid beta in transgenic CL2355 C. elegans by a serotonin assay and to collectively inhibit the ace-2 gene expression by both qRT-PCR and BLItz (TM) analyses. The active species includes L. chinensis, L. caldwellii, L. squamigera and L. incarnate. The alkaloid metabolite profiling results indicate that these active species are rich in different alkaloids, which are potential markers for anti-Alzheimer disease.

Automated summary

This study screened and characterized Amaryllidaceae alkaloids from various Lycoris species and found that galanthamine, one of these alkaloids, has potential therapeutic effects against Alzheimer's disease. Galanthamine reduced toxicity and neurodegeneration caused by amyloid beta and inhibited the expression of related genes.