Jeon Hoon, Cha Dong Seok
Department of Oriental Pharmacy, College of Pharmacy, Woosuk University, Jeonbuk 55338, Republic of Korea.
Department of Oriental Pharmacy, College of Pharmacy, Woosuk University, Jeonbuk 55338, Republic of Korea.
Chin J Nat Med. 2016 May;14(5):335-42. doi: 10.3724/SP.J.1009.2016.00335.
The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum (ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activity of ERF was determined by lifespan assay under normal culture condition. The survival rate of nematodes under various stress conditions was assessed to validate the effects of ERF on the stress tolerance. To determine the antioxidant potential of ERF, the superoxide dismutase (SOD) activities and intracellular reactive oxygen species (ROS) levels were investigated. The ERF-mediated change in SOD-3 expression was examined using GFP-expressing transgenic strain. The effects of ERF on the aging-related factors were investigated by reproduction assay and pharyngeal pumping assay. The intestinal lipofuscin levels of aged nematodes were also measured. The mechanistic studies were performed using selected mutant strains. Our results indicated that ERF showed potent lifespan extension effects on the wild-type nematode under both normal and various stress conditions. The ERF treatment also enhanced the activity and expression of superoxide dismutase (SOD) and attenuated the intracellular ROS levels. Moreover, ERF-fed nematodes showed decreased lipofuscin accumulation, indicating ERF might affect age-associated changes in C. elegans. The results of mechanistic studies indicated that there was no significant lifespan extension in ERF-treated daf-2, age-1, sir-2.1, and daf-16 null mutants, suggesting that they were involved in ERF-mediated lifespan regulation. In conclusion, R. fasciculatum confers increased longevity and stress resistance in C. elegans via SIR-2.1-mediated DAF-16 activation, dependent on the insulin/IGF signaling pathway.
本研究利用秀丽隐杆线虫模型,研究了束花醋栗乙酸乙酯馏分(ERF)对寿命和应激耐受性的影响及其潜在机制。通过在正常培养条件下的寿命测定来确定ERF的长寿活性。评估线虫在各种应激条件下的存活率,以验证ERF对应激耐受性的影响。为了确定ERF的抗氧化潜力,研究了超氧化物歧化酶(SOD)活性和细胞内活性氧(ROS)水平。使用表达绿色荧光蛋白的转基因菌株检测ERF介导的SOD-3表达变化。通过繁殖试验和咽部抽吸试验研究ERF对衰老相关因子的影响。还测量了老年线虫肠道脂褐素水平。使用选定的突变菌株进行机制研究。我们的结果表明,在正常和各种应激条件下,ERF对野生型线虫均显示出强大的寿命延长作用。ERF处理还增强了超氧化物歧化酶(SOD)的活性和表达,并降低了细胞内ROS水平。此外,用ERF喂养的线虫脂褐素积累减少,表明ERF可能影响秀丽隐杆线虫与年龄相关的变化。机制研究结果表明,在ERF处理的daf-2、age-1、sir-2.1和daf-16基因敲除突变体中,寿命没有显著延长,这表明它们参与了ERF介导的寿命调节。总之,束花醋栗通过SIR-2.1介导的DAF-16激活,依赖胰岛素/胰岛素样生长因子信号通路,赋予秀丽隐杆线虫更长的寿命和更强的抗逆性。