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

Autor: Zhong-Lin Yang, Jie Yang, Hua-Ying Sun, Ai-Jun Ding, Huai-Rong Luo, Shu-Hua Qi, Ming-Hua Qiu, Qin-Li Wan, Xiao-Bing Huang
Rok vydání: 2017
Předmět:
Zdroj: Natural Products and Bioprospecting
ISSN: 2192-2209
2192-2195
Popis: 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. elegans 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 that Ot B protects against Aβ toxicity. Further mechanistic studies revealed that Ot B decreased Aβ deposition by decreasing the expression of Aβ at 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 Aβ toxicity. Graphical Abstract Electronic supplementary material The online version of this article (doi:10.1007/s13659-017-0122-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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