整合生物学期刊网

应用天然产物 ›› 2017, Vol. 7 ›› Issue (2): 207-214.DOI: 10.1007/s13659-017-0122-1

• Original article • 上一篇    下一篇

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

Jie Yang1,2,3, Xiao-Bing Huang4, Qin-Li Wan1,2, Ai-Jun Ding1,2, Zhong-Lin Yang1,2, Ming-Hua Qiu1, Hua-Ying Sun1, Shu-Hua Qi5, Huai-Rong Luo1,4   

  1. 1. 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;
    2. University of Chinese Academy of Sciences, Beijing 100049, China;
    3. The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan, China;
    4. Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China;
    5. Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
  • 收稿日期:2016-12-22 修回日期:2017-02-01 出版日期:2017-04-24 发布日期:2018-02-06
  • 通讯作者: Huai-Rong Luo,e-mail:luohuairong@mail.kib.ac.cn
  • 基金资助:
    This work was partially supported by the Natural Science Foundation of China (81671405 and 81370453),Natural Science Foundation of Yunnan province (2013FA045 and 2015FB172),and Open Funds of Guangdong Key Laboratory of Marine Materia Medica (LMM2016-1).

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

Jie Yang1,2,3, Xiao-Bing Huang4, Qin-Li Wan1,2, Ai-Jun Ding1,2, Zhong-Lin Yang1,2, Ming-Hua Qiu1, Hua-Ying Sun1, Shu-Hua Qi5, Huai-Rong Luo1,4   

  1. 1. 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;
    2. University of Chinese Academy of Sciences, Beijing 100049, China;
    3. The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan, China;
    4. Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China;
    5. Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
  • Received:2016-12-22 Revised:2017-02-01 Online:2017-04-24 Published:2018-02-06
  • Supported by:
    This work was partially supported by the Natural Science Foundation of China (81671405 and 81370453),Natural Science Foundation of Yunnan province (2013FA045 and 2015FB172),and Open Funds of Guangdong Key Laboratory of Marine Materia Medica (LMM2016-1).

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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. 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.

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.

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