The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China.
Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
Br J Pharmacol. 2022 May;179(9):1825-1838. doi: 10.1111/bph.15410. Epub 2021 Feb 27.
Ageing is associated with progressive metabolic dysregulation. Rutin is a metabolic regulator with a poor solubility. Using soluble sodium rutin we investigating the effect and mechanisms of rutin in ageing process.
Wild type male mice were treated with or without sodium rutin ( 0.2 mg·ml in drinking water from 8-month-old until end of life. Kaplan-Meier survival curve was used for lifespan assay, ageing-related histopathology analysis and metabolic analysis were performed to determine the effects of chronic sodium rutin on the longevity. Serological test, liver tissue metabolomics and transcriptomics were used for liver function assay. SiRNA knockdown Angptl8 and autophagy flux assay in HepG2 cell lines explored the mechanism through which sodium rutin might impact the function of hepatocyte.
Sodium rutin treatment extends the lifespan of mice by 10%. Sodium rutin supplementation alleviates ageing-related pathological changes and promotes behaviour performance in ageing mice. Sodium rutin supplementation altered the whole-body metabolism in mice, which exhibited increased energy expenditure and lower respiratory quotient. Transcriptomics analysis showed that Sodium rutin affected the expression of metabolic genes. Metabolomics analysis showed that Sodium rutin reduced liver steatosis through increased lipid β-oxidation. Sodium rutin treatment increased the autophagy level both in vivo and in vitro. The inhibition of autophagy partially abolished the sodium rutin-mediated effect on lipolysis in HepG2 cells.
Sodium rutin treatment extends the lifespan and health span of mice with beneficial effects on metabolism, which were achieved by enhancing the autophagy activity in hepatocytes.
This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.
衰老与代谢失调的进行性发展有关。芦丁是一种代谢调节剂，但溶解度较差。本研究使用可溶的芦丁钠来研究芦丁在衰老过程中的作用和机制。
从 8 月龄开始，雄性野生型小鼠通过饮用水（含 0.2mg·ml 的芦丁钠）处理或不处理，直至生命结束。采用 Kaplan-Meier 生存曲线进行寿命测定，进行衰老相关组织病理学分析和代谢分析，以确定慢性芦丁钠对长寿的影响。血清学检测、肝组织代谢组学和转录组学用于肝功能检测。在 HepG2 细胞系中，使用 siRNA 敲低 Angptl8 和自噬流测定来探索芦丁可能影响肝细胞功能的机制。
芦丁钠处理可使小鼠的寿命延长 10%。芦丁钠补充可减轻衰老相关的病理变化，并促进衰老小鼠的行为表现。芦丁钠补充改变了小鼠的全身代谢，表现为能量消耗增加和呼吸商降低。转录组学分析表明，芦丁钠影响代谢基因的表达。代谢组学分析表明，芦丁钠通过增加脂质β-氧化来减少肝脏脂肪变性。芦丁钠处理在体内和体外均增加自噬水平。自噬的抑制部分消除了芦丁钠对 HepG2 细胞中脂肪分解的作用。
芦丁钠处理可延长小鼠的寿命和健康寿命，对代谢有益，这是通过增强肝细胞的自噬活性实现的。
本文是炎症、修复和衰老专题的一部分。要查看该部分的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.
