Otophylloside B Protects Against AβToxicity in Caenorhabditis elegans Models of Alzheimer’s Disease

摘要

Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.