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一种天然化合物抗氧化活性和 SIRT1 调节的体外比较研究。

An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds.

机构信息

Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Department of Translational Research and New Technologies in Medicine and Surgery, Pharmacology, Medical School, University of Pisa, Italy.

出版信息

Biomed Pharmacother. 2018 May;101:805-819. doi: 10.1016/j.biopha.2018.03.006. Epub 2018 Mar 22.

Abstract

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation.

摘要

氧化应激是由于自由基的产生和抗氧化防御之间的失衡引起的。一些研究表明,膳食抗氧化剂(如多酚和黄连素)可能通过 Sirtuin 1/腺苷单磷酸激活蛋白激酶(SIRT1/AMPK)途径来抵抗氧化应激。本研究旨在评估一些天然化合物的直接和特定抗氧化活性,以及它们调节 SIRT1 表达和 AMPK 激活的能力。使用 TOSC 测定法评估槲皮素、酪醇、阿魏酸、儿茶素、黄连素和姜黄素的特异性和直接抗氧化活性。通过免疫印迹测定法评估它们对 SIRT1 和 AMPK 的调节能力,通过 CellTiter-Blue 细胞活力测定法评估它们的细胞毒性。用天然化合物刺激后,未发现活细胞数量有统计学显著下降(p > 0.05)。槲皮素对过氧自由基和过亚硝酸盐衍生物表现出最高的抗氧化活性,而姜黄素相对于其他化合物,更重要的是相对于参考抗氧化剂,表现出最好的抗羟自由基活性。最后,所有测试的化合物都显著增加了 SIRT1 的表达和 AMPK 的激活。我们的结果清楚地揭示了这些天然化合物的特定抗氧化活性及其增加 SIRT1 表达和 AMPK 激活的能力。

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