Institute of Biology, Komi Science Centre, the Ural Branch of the Russian Academy of Sciences, Syktyvkar, Komi Republic, Russia.
Deep Longevity Ltd, Hong Kong Science and Technology Park, Hong Kong, China.
Aging (Albany NY). 2021 Jan 26;13(2):1817-1841. doi: 10.18632/aging.202572.
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) using the 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 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 (), recognition of DNA damage (), heat shock proteins (), and repair of double-strand breaks (). 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.
醉茄内酯是一类通常存在于植物提取物中的化合物，是一种有吸引力的抗衰老药物设计起点。我们使用 模型评估了醉茄内酯 A (WA) 的抗衰老特性。实验组的雄性果蝇用含有 WA（浓度为 1、10 或 100 μM，溶于乙醇）的营养培养基补充，对照组用 30 μM 的乙醇补充。WA 处理浓度为 10 和 100 μM 时，分别将雄性的平均寿命延长了 7.7%和 9.6%，最大寿命（90%个体死亡的年龄）延长了 11.1%。此外，WA 处理浓度为 1、10 和 100 μM 改善了老年果蝇的肠道屏障通透性，并影响了参与抗氧化防御（）、DNA 损伤识别（）、热休克蛋白（）和双链断裂修复（）的基因的表达。WA 还对果蝇对促氧化剂百草枯（氧化应激）和 33°C 热应激的抗性表现出多向作用。WA 处理在 4 周和 7 周龄雄性中增加了对氧化应激的抗性，而在 6 周龄雄性中降低了其抗性。它在 2、4 和 7 周龄雄性中增加了对热应激的抗性，而在 3、5 和 8 周龄雄性中降低了其抗性。WA 处理在 1、2 和 3 周龄雌性中降低了对热应激的抗性，但对其氧化应激的抗性没有影响。
