Cur2004-8, a synthetic curcumin derivative, extends lifespan and modulates age-related physiological changes in Caenorhabditis elegans

Drug Discov Ther. 2019;13(4):198-206. doi: 10.5582/ddt.2019.01057.

Abstract

Curcumin, a compound found in Indian yellow curry, is known to possess various biological activities, including anti-oxidant, anti-inflammatory, and anti-cancer activities. Cur2004-8 is a synthetic curcumin derivative having symmetrical bis-alkynyl pyridines that shows a strong anti-angiogenic activity. In the present study, we examined the effect of dietary supplementation with Cur2004-8 on response to environmental stresses and aging using Caenorhabditis elegans as a model system. Dietary intervention with Cur2004-8 significantly increased resistance of C. elegans to oxidative stress. Its anti-oxidative-stress effect was greater than curcumin. However, response of C. elegans to heat stress or ultraviolet irradiation was not significantly affected by Cur2004-8. Next, we examined the effect of Cur2004-8 on aging. Cur2004-8 significantly extended both mean and maximum lifespan, accompanying a shift in time-course distribution of progeny production. Age-related decline in motility was also delayed by supplementation with Cur2004-8. In addition, Cur2004-8 prevented amyloid-beta-induced toxicity in Alzheimer's disease model animals which required a forkhead box (FOXO) transcription factor DAF-16. Dietary supplementation with Cur2004-8 also reversed the increase of mortality observed in worms treated with high-glucose-diet. These results suggest that Cur2004-8 has higher anti-oxidant and anti-aging activities than curcumin. It can be used for the development of novel anti-aging product.

Keywords: Caenorhabditis elegans; Cur2004-8; Curcumin; aging; oxidative stress.

Publication types

  • Comparative Study

MeSH terms

  • Aging / drug effects*
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Caenorhabditis elegans
  • Catechols / administration & dosage*
  • Catechols / chemistry
  • Catechols / pharmacology
  • Curcumin / administration & dosage
  • Curcumin / analogs & derivatives*
  • Curcumin / pharmacology
  • Dietary Supplements
  • Disease Models, Animal
  • Longevity / drug effects*
  • Molecular Structure
  • Oxidative Stress / drug effects

Substances

  • Amyloid beta-Peptides
  • Catechols
  • Curcumin