title: Acetylcholineestarase-inhibiting alkaloids from Lycoris radiata delay paralysis of amyloid beta-expressing transgenic C. elegans CL4176.
abstract: The limited symptom relief and side effects of current Alzheimer's disease (AD) medications warrant urgent discovery and study of new anti-AD agents. The "cholinergic hypothesis" of AD prompts us to search for plant-derived acetylcholineesterase (AChE) inhibitors such as galanthamine that has been licensed in Europe for AD treatment. We used the unique amyloid β-expressing transgenic C. elegans CL4176, which exhibits paralysis when human Aβ1-42 is induced, to study two natural benzylphenethylamine alkaloids isolated from Lycoris radiata (L' Her.) Herb, galanthamine and haemanthidine, and their synthetic derivatives 1,2-Di-O-acetyllycorine and 1-O-acetyllycorine for their anti-paralysis effects. Our data indicate that these Lycoris compounds effectively delay the paralysis of CL4176 worms upon temperature up-shift, and prolong the lives of these transgenic worms. Lycoris compounds were shown to significantly inhibit the gene expression of ace-1 and ace-2. Additionally, the Lycoris compounds may modulate inflammatory and stress-related gene expressions to combat the Aβ-toxicity in C. elegans.
authors.affiliation: College of Life and Environmental Sciences, Minzu University of China, Beijing, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xin
authors.forename: Ritupriya
authors.initials: R
authors.lastname: Yamujala
authors.forename: Yuehu
authors.initials: Y
authors.lastname: Wang
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Wen-Hsuan
authors.initials: WH
authors.lastname: Wu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lawton
authors.forename: Chunlin
authors.initials: C
authors.lastname: Long
authors.forename: Rong
authors.initials: R
authors.lastname: Di
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D047151:Amaryllidaceae Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D005702:Galantamine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D008136:Longevity / Q000187:drug effects; D031426:Lycoris / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010243:Paralysis / Q000517:prevention & control*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D010617:Phenanthridines / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D047151:Amaryllidaceae Alkaloids; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D010446:Peptide Fragments; D010617:Phenanthridines; C075222:amyloid beta-protein (1-42); D005702:Galantamine; C083906:hemanthidine; D000110:Acetylcholinesterase