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Abstract：
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.
摘要：
Withanolides是一类通常在植物提取物中发现的化合物，是一种有吸引力的老年保护药物设计起点。我们使用果蝇模型评估了体内WithaferinA（WA）的老年保护特性。实验组用营养培养基补充苍蝇，其中含有WA（溶解在乙醇中的浓度为1、10或100μM），对照组则为30μM乙醇。在10和100μM浓度下的WA处理使黑腹D.melanogaster的男性的中位寿命分别延长了7.7％、9.6％，最大寿命（死亡年龄90％的个体）延长了11.1％。另外，在1、10和100μM的WA处理改善了老年果蝇的肠屏障通透性，并影响了参与抗氧化防御（PrxV）的基因表达，识别DNA损伤（Gadd45），热休克蛋白（Hsp68，Hsp83），和修复双链断裂(Ku80)。WA还显示出对果蝇对促氧化剂百草枯（氧化应激）和33°C高温（热休克）的抵抗力具有多向影响。WA治疗在4周龄和7周龄时增加了男性对氧化应激的抵抗力，在6周龄时降低了。它在2、4和7周龄时增加了男性对高热的抵抗力，在3、5和8周龄时降低了。WA治疗降低了1、2和3周龄女性对高温的抵抗力，而不影响其对氧化应激的抵抗力。
