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Molecular mechanisms of anti-oxidant and anti-aging effects induced by convallatoxin in Caenorhabditis elegans.

Abstract
Convallatoxin is widely used as a cardiac glycoside in acute and chronic congestive heart-failure and paroxysmal tachycardia, with many effects and underlying protective mechanisms on inflammation and cellular proliferation. However, convallatoxin has not been investigated in its antioxidant effects and lifespan extension in Caenorhabditis elegans. In this study, we found that convallatoxin (20 μM) could significantly prolong the lifespan of wild-type C. elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased thermotolerance and resistance to paraquat-induced oxidative stress. Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin accumulation and reactive oxygen species levels in C. elegans, which were attributed to hormesis, free radical-scavenging effects in vivo, and up-regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1. Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to contribute to the stress-resistance effect of convallatoxin. In summary, this study demonstrates that convallatoxin can protect against heat and oxidative stress and extend the lifespan of C. elegans, pointing it as a potential novel drug for retarding the aging process in humans.
AuthorsJia Xu, Youming Guo, Tianzhuo Sui, Qifei Wang, Yue Zhang, Ruining Zhang, Mingyang Wang, Shuwen Guan, Liping Wang
JournalFree radical research (Free Radic Res) Vol. 51 Issue 5 Pg. 529-544 (May 2017) ISSN: 1029-2470 [Electronic] England
PMID28503972 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Reactive Oxygen Species
  • Strophanthins
  • daf-16 protein, C elegans
  • convallatoxin
  • Paraquat
Topics
  • Aging (drug effects)
  • Animals
  • Antioxidants (pharmacology)
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins (metabolism)
  • Drug Evaluation, Preclinical
  • Forkhead Transcription Factors (metabolism)
  • Oxidative Stress
  • Paraquat (toxicity)
  • Protein Transport
  • Reactive Oxygen Species (metabolism)
  • Strophanthins (pharmacology)

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