Effects of rikkunshito supplementation on mice: analysis of oxidative stress resistance and lifespan

Effects of rikkunshito supplementation on mice: analysis of oxidative stress resistance and lifespan
复制标题

六君子补充剂对小鼠的影响:氧化应激抵抗力和寿命分析

DOI:
10.1111/ggi.13848
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发表时间:
2020
影响因子:
3.3
通讯作者:
Chiba T
Chiba T
中科院分区:
医学3区
文献类型:
--
作者:
Wang Z;Komatsu T;Ohata Y;Watanabe Y;Yuan Y;Yoshii Y;Park S;Mori R;Satou M;Kondo Y;Shimokawa I;Chiba T

文献摘要

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目的限制热量摄入(CR),将各种实验动物的热量摄入限制在随意(AL)量的60-70%,延缓衰老并延长寿命。我们以前表明,神经肽Y(NPY)是一种食欲刺激肽,对于CR的抗氧化和延长寿命作用至关重要。在这里,我们调查了日本传统草药,rikkunshito(RKT),诱导NPY激活,是否具有CR样的延长寿命的effects.MethodsFirst,我们评估了延长寿命的活性RKT通过检查长期RKT管理野生型和NPY敲除小鼠的效果。此外,我们测试了RKT是否在AL条件下使用正常饮食和在轻度CR条件下使用高脂肪饮食增强CR介导的有益作用。然后,我们使用3-硝基丙酸或阿霉素诱导氧化应激,并分析各组之间的存活率,体重减轻,基因表达和细胞氧化损伤的差异。在氧化应激模型中,RKT治疗上调了肝脏中的抗氧化基因表达。此外,与单独的CR条件相比,RKT给药减少了肝脏中的氧化损伤。然而,在3-硝基丙酸或多柔比星诱导氧化应激时,RKT给药并不影响存活率。结论这些结果表明,RKT给药仅在细胞水平上部分模拟CR的作用,但在生物体水平上不能延长小鼠的寿命。Geriatr Gerontol Int 2019; ··:··-··。
AimCaloric restriction (CR), which limits the caloric intake to 60–70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite‐stimulating peptide, is essential for the anti‐oxidative and life‐extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR‐like life‐extending effects.MethodsFirst, we evaluated the life‐extending activity of RKT by examining the effect of long‐term RKT administration on wild‐type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR‐mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high‐fat diet. We then used 3‐nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups.ResultsRKT administration did not extend the lifespan of wild‐type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti‐oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3‐nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate.ConclusionsThese results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice.Geriatr Gerontol Int 2019; ••: ••–••.