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衰老过程中Nrf2信号通路的沉默会导致白藜芦醇抗炎作用的减弱。

Silencing of the Nrf2 pathway in aging promotes a decrease in the anti-inflammatory effect of resveratrol.

作者信息

Franco Filipe Nogueira, Peixoto Brenda Evangelista, de Araújo Glaucy Rodrigues, Chaves Miriam Martins

机构信息

Biochemistry Laboratory of Aging and Correlated Diseases, Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Av. Antônio Carlos 6627, 30161-970, Belo Horizonte MG Brazil.

Biochemistry Laboratory of Aging and Correlated Diseases, Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Av. Antônio Carlos 6627, 30161-970, Belo Horizonte MG Brazil.

出版信息

Arch Gerontol Geriatr. 2025 Feb;129:105694. doi: 10.1016/j.archger.2024.105694. Epub 2024 Nov 10.

DOI:10.1016/j.archger.2024.105694
PMID:39541750
Abstract

During aging, in addition to increased oxidative stress, inflammation also occurs. A chronic and low-grade inflammation - called "inflammaging" - develops, which contributes to the etiology of diseases related to aging. Resveratrol (Resv.) is a polyphenol well known for its biologically active properties, such as antioxidant and anti-inflammatory properties. This balance can be regulated by Nrf2 - a transcription factor that regulates cellular defense against oxidative agents through the expression or inhibition of certain genes. The objective was to evaluate the effect of Nrf2 on the production of cytokines in leukocytes of different ages treated with resveratrol (5µm). The subjects were divided into three groups: 20-39, 40-59 and 60-80 years old. After separation of the leukocytes, a 24-hour treatment was carried out with and without ML385 inhibitor with the treatments: Control, Resv, Peroxide and Peroxide+Resv. 150 µM peroxide was set to develop an oxidative environment. Cytokines were measured by ELISA (*p < 0.05). In general, there was an increase in TNF and IL-6 in cells stimulated with peroxide compared to controls. A decrease in these two cytokines was also observed in cells treated with resveratrol, both at basal levels and in an oxidizing environment (with peroxide). The polyphenol was able to increase IL-10 only in the youngest age groups. The same profile was observed comparing the same groups when the Nrf2 pathway was inhibited with ML385. It is concluded that resveratrol may have a better effect on preventing oxidation and inflammation present in aging, especially through the antioxidant and anti-inflammatory Nrf2 pathway.

摘要

在衰老过程中,除了氧化应激增加外,炎症也会发生。一种慢性低度炎症——称为“炎症衰老”——逐渐形成,它促成了与衰老相关疾病的病因。白藜芦醇(Resv.)是一种以其生物活性特性(如抗氧化和抗炎特性)而闻名的多酚。这种平衡可由Nrf2调节——一种转录因子,它通过某些基因的表达或抑制来调节细胞对氧化因子的防御。目的是评估Nrf2对用白藜芦醇(5µm)处理的不同年龄白细胞中细胞因子产生的影响。受试者分为三组:20 - 39岁、40 - 59岁和60 - 80岁。分离白细胞后,在有和没有ML385抑制剂的情况下进行24小时处理,处理方式有:对照、Resv、过氧化物和过氧化物 + Resv。设定150µM过氧化物以形成氧化环境。通过酶联免疫吸附测定法测量细胞因子(*p < 0.05)。一般来说,与对照组相比,用过氧化物刺激的细胞中TNF和IL - 6增加。在用白藜芦醇处理的细胞中,无论是在基础水平还是在氧化环境(用过氧化物)中,这两种细胞因子也都减少。多酚仅在最年轻的年龄组中能够增加IL - 10。当用ML385抑制Nrf2途径时,在相同组中观察到相同的情况。得出的结论是,白藜芦醇可能对预防衰老中存在的氧化和炎症有更好的效果,特别是通过抗氧化和抗炎的Nrf2途径。

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