title: Otophylloside B Protects Against Aβ Toxicity in Caenorhabditis elegans Models of Alzheimer's Disease.
abstract: 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.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.|The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Qin-Li
authors.initials: QL
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China. luohuairong@mail.kib.ac.cn.|Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China. luohuairong@mail.kib.ac.cn.
authors.forename: Huai-Rong
authors.initials: HR
authors.lastname: Luo
keywords: Alzheimer’s disease; Caenorhabditis elegans; HSF-1; Otophylloside B; β-Amyloid peptide