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Betula utilis extract prolongs life expectancy, protects against amyloid-β toxicity and reduces Alpha Synuclien in Caenorhabditis elegans via DAF-16 and SKN-1.
Comparative Biochemistry and Physiology C: Toxicology & Pharmacology ( IF 3.9 ) Pub Date : 2019-10-25 , DOI: 10.1016/j.cbpc.2019.108647
Swapnil Pandey 1 , Suresh Chandra Phulara 2 , Shashank Kumar Mishra 3 , Rajesh Bajpai 4 , Anil Kumar 5 , Abhishek Niranjan 5 , Alok Lehri 6 , Dalip Kumar Upreti 7 , Puneet Singh Chauhan 1
Affiliation  

Betula utilis (BU), an important medicinal plant that grows in high altitudes of the Himalayan region, has been utilized traditionally due to it's antibacterial, hepatoprotective, and anti-tumor properties. Here, we demonstrated the longevity and amyloid-β toxicity attenuating activity of B. utilis ethanolic extract (BUE) in Caenorhabditis elegans. Lifespan of the worms was observed under both the standard laboratory and stress (oxidative and thermal) conditions. Effect of BUE was also observed on the attenuation of age-dependent physiological parameters. Further, gene-specific mutants and green fluorescent protein (GFP)-tagged strains were used to investigate the molecular mechanism underlying the beneficial effects mediated by BUE supplementation. Our results showed that BUE (50 μg/ml) extended the mean lifespan of C. elegans by 35.99% and increased its survival under stress conditions. The BUE also reduced the levels of intracellular reactive oxygen species (ROS) by 22.47%. A delayed amyloid-β induced paralyses was observed in CL4176 transgenic worms. Interestingly, the BUE supplementation was also able to reduce the α-synuclein aggregation in NL5901 transgenic strain. Gene-specific mutant studies suggested that the BUE-mediated lifespan extension was dependent on daf-16, hsf-1, and skn-1 but not on sir-2.1 gene. Furthermore, transgenic reporter gene expression assay showed that BUE treatment enhanced the expression of stress-protective genes such as sod-3 and gst-4. Present findings suggested that ROS scavenging activity, together with multiple longevity mechanisms, were involved in BUE-mediated lifespan extension. Thus, BUE might have potential to increase the lifespan and to attenuate neuro-related disease progression.

中文翻译:

桦木提取物可延长寿命,防止淀粉样β毒性,并通过DAF-16和SKN-1减少秀丽隐杆线虫中的Alpha Synuclien。

桦木(BU)是一种重要的药用植物,在喜马拉雅地区的高海拔地区生长,由于其具有抗菌,保肝和抗肿瘤的特性,因此一直在传统上得到利用。在这里,我们证明了秀丽隐杆线虫中的B. utilis乙醇提取物(BUE)的寿命和淀粉样β毒性减弱活性。在标准实验室和压力(氧化和热)条件下均可观察到蠕虫的寿命。还观察到BUE对衰减年龄依赖性生理参数的影响。此外,使用基因特异性突变体和带有绿色荧光蛋白(GFP)标签的菌株研究了BUE补充介导的有益作用的分子机制。我们的结果表明,BUE(50μg/ ml)将秀丽隐杆线虫的平均寿命延长了35岁。99%并增加了在压力条件下的存活率。BUE还使细胞内活性氧(ROS)的水平降低了22.47%。在CL4176转基因蠕虫中观察到延迟的淀粉样β诱导的麻痹。有趣的是,补充BUE还能够减少NL5901转基因菌株中的α-突触核蛋白聚集。基因特异性突变研究表明,BUE介导的寿命延长取决于daf-16,hsf-1和skn-1,而不取决于sir-2.1基因。此外,转基因报道基因表达测定表明,BUE处理增强了胁迫保护基因例如sod-3和gst-4的表达。目前的发现表明,ROS清除活性以及多种长寿机制参与了BUE介导的寿命延长。因此,
更新日期:2019-10-25
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