Research Paper Volume 13, Issue 2 pp 1817—1841
Evaluation of the geroprotective effects of withaferin A in Drosophila melanogaster
- 1 Institute of Biology, Komi Science Centre, the Ural Branch of the Russian Academy of Sciences, Syktyvkar, Komi Republic, Russia
- 2 Deep Longevity Ltd, Hong Kong Science and Technology Park, Hong Kong, China
Received: November 9, 2020 Accepted: January 4, 2021 Published: January 26, 2021https://doi.org/10.18632/aging.202572
How to Cite
Copyright: © 2021 Koval et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Withanolides are a class of compounds usually found in plant extracts which are an attractive geroprotective drug design starting point. We evaluated the geroprotective properties of Withaferin A (WA) in vivo using the Drosophila model. Flies were supplemented by nutrient medium with WA (at a concentration of 1, 10, or 100 μM dissolved in ethanol) for the experiment group and 30 μM of ethanol for the control group. WA treatment at 10 and 100 μM concentrations prolong the median life span of D. melanogaster’s male by 7.7, 9.6% (respectively) and the maximum life span (the age of death 90% of individuals) by 11.1% both. Also WA treatment at 1, 10 and 100 μM improved the intestinal barrier permeability in older flies and affected an expression of genes involved in antioxidant defense (PrxV), recognition of DNA damage (Gadd45), heat shock proteins (Hsp68, Hsp83), and repair of double-strand breaks (Ku80). WA was also shown to have a multidirectional effect on the resistance of flies to the prooxidant paraquat (oxidative stress) and 33° C hyperthermia (heat shock). WA treatment increased the resistance to oxidative stress in males at 4 and 7 week old and decreased it at 6 weeks old. It increased the male’s resistance to hyperthermia at 2, 4 and 7 weeks old and decreased it at 3, 5 and 8 weeks old. WA treatment decreased the resistance to hyperthermia in females at 1, 2 and 3 weeks old and not affected on their resistance to oxidative stress.