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

  • Nat Prod Bioprospect. 2017 Apr;7(2):207-214. doi: 10.1007/s13659-017-0122-1.
Jie Yang  1  2  3 ,  Xiao-Bing Huang  4 ,  Qin-Li Wan  1  2 ,  Ai-Jun Ding  1  2 ,  Zhong-Lin Yang  1  2 ,  Ming-Hua Qiu  1 ,  Hua-Ying Sun  1 ,  Shu-Hua Qi  5 ,  Huai-Rong Luo  6  7
Affiliations
  • 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.
  • 6. 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. [email protected].
  • 7. Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China. [email protected].
PMID: 28194725 DOI: 10.1007/s13659-017-0122-1
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.

Keywords
Alzheimer’s disease; Caenorhabditis elegans; HSF-1; Otophylloside B; β-Amyloid peptide.
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