Prolonged Dietary Curcumin Supplementation Augments Nrf2 Nuclear Translocation and Attenuates Oxidative Stress in Skeletal Muscle of Aging Rats
Prolonged Dietary Curcumin Supplementation Augments Nrf2 Nuclear Translocation and Attenuates Oxidative Stress in Skeletal Muscle of Aging Rats
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DOI：
10.1096/fasebj.2018.32.1_supplement.856.14
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
Candace N. Receno;Chen Liang;Donna L. Korol;K. Deruisseau
中科院分区：
文献类型：
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作者：
Candace N. Receno;Chen Liang;Donna L. Korol;K. Deruisseau
肌肉减少症是一种与衰老有关的肌肉质量、功能和质量的丧失，它的发展可以归因于无数的因素。氧化应激作为肌少症发生的一个关键因素受到了特别的关注，它可能是抗氧化储备减少和活性氧（ROS）产生增加的结果。有趣的是，核因子红细胞2相关因子2 (Nrf2)，一种负责激活抗氧化反应元件（ARE）的转录因子，显示出随着年龄的增长核激活减少。姜黄素是香料姜黄中的活性成分，具有通过激活Nrf2增加抗氧化能力和直接抑制ROS的特性。姜黄素的这些有益特性在许多研究中都有记载，这些研究都是通过口服给药来补充的。因此，通过饮食补充姜黄素可能有利于改变肌肉的氧化还原状态并减轻肌肉减少症。本研究检测了4个月饮食中姜黄素暴露对氧化应激、Nrf2激活和衰老骨骼肌模型中抗氧化反应的影响。给32月龄雄性f344 × bn大鼠（n=54）提供纯化AIN - 93M饲料，每食物重量添加或不添加0.2%姜黄素，为期4个月。一组饲喂自由支配的对照饲粮（CON, n=18），另一组饲喂含有0.2%姜黄素的相同饲粮（CUR, n=18）。第三组接受对照纯化饮食，但与CUR动物食用的量相同（PAIR, n=18），以解释由于姜黄素的适口性而导致的食物摄入变化。在4个月的补充期后，对植物肌肉进行体内力测量，并收集后肢肌肉组织进行生化和功能分析。采用单因素方差分析分析体重、肌肉质量、收缩力、氧化损伤、抗氧化表达/活性和Nrf2核激活。所有数值均以平均值±SEM报告。CUR组动物比CON组动物消耗的食物少，因此CON组和PAIR组之间也存在差异（p 0.05）。然而，Nrf2核水平（p < 0.01）、氧化损伤测量包括3‐硝基酪氨酸（3NT; 1.16±0.226 vs. 0.337±0.108 od; p < 0.05）和蛋白质羰基（2.29±0.195 vs. 1.43±0.328 od; p < 0.05）在PAIR组和CUR组之间分别有显著差异。因此，本研究表明，当动物受到食物限制时，补充姜黄素对衰老肌肉有有利的影响，包括氧化应激和肌肉质量和功能的变化。
The development of sarcopenia, which is the aging‐related loss of muscle mass, function and quality, can be attributed to a myriad of factors. Oxidative stress has received particular attention as a key factor in the development of sarcopenia and can collectively be a result of a decreased antioxidant reserve and increased production of reactive oxygen species (ROS). Interestingly, nuclear factor erythroid‐2‐related factor 2 (Nrf2), a transcription factor responsible for activating the antioxidant response element (ARE), has shown decreased nuclear activation with age. Curcumin, the active ingredient in the spice turmeric, has properties that can both increase antioxidant capacity through the activation of Nrf2 and directly quench ROS. These beneficial traits of curcumin were documented in numerous studies that implemented an oral administration method of supplementation. Hence, it is possible that curcumin supplementation through the diet can favorably alter the redox status of muscle and attenuate sarcopenia. This study examined the effects of 4‐months of dietary curcumin exposure on oxidative stress, Nrf2 activation, and the antioxidant response in a rodent model of aging skeletal muscle. Thirty‐two‐month‐old male F344xBN rats (n=54) were provided a purified AIN‐93M diet with or without 0.2% curcumin per food weight for a period of 4 months. One group received the control diet ad libitum (CON, n=18) and another received the same diet containing 0.2% curcumin (CUR, n=18). A third group received the control purified diet, but in equal amounts to those consumed by the CUR animals (PAIR, n=18) to account for any changes in food consumption due to curcumin palatability. After the 4‐month supplementation period, plantaris muscle was tested in vivo for force measures and hindlimb muscle tissue was harvested for biochemical and functional analyses. Body mass, muscle mass, contractile force, measures of oxidative damage, antioxidant expression/activity, and Nrf2 nuclear activation were analyzed using 1‐way ANOVA. All values are reported as mean ± SEM. CUR animals consumed less food than CON rats, and thus a difference between the CON and PAIR groups was also observed (p 0.05). However, Nrf2 nuclear levels (p < 0.01), and measures of oxidative damage including 3‐nitrotyrosine (3NT; 1.16 ± 0.226 vs. 0.337 ± 0.108 O.D.; p < 0.05), and protein carbonyls (2.29 ± 0.195 vs. 1.43 ± 0.328 O.D.; p < 0.05) were significantly different between the PAIR and CUR groups, respectively. Thus, this study suggests that curcumin supplementation exerts favorable effects on aging muscle that include changes in oxidative stress and muscle mass and function when animals are subjected to food restriction.