Elucidating the Role of Protandim and 6-Gingerol in Protection Against Osteoarthritis
Elucidating the Role of Protandim and 6-Gingerol in Protection Against Osteoarthritis
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DOI：
10.1002/jcb.25659
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发表时间：
2017-05-01
影响因子：
4
通讯作者：
Benderdour, Mohamed
中科院分区：
文献类型：
--
作者：
Abusarah, Jamilah;Benabdoune, Houda;Benderdour, Mohamed
Protandim和6-gingerol是两种有效的营养保健品，已被证明可以通过增强内源性抗氧化酶来减少自由基的产生。在这项研究中，我们评估了这些产品对骨关节炎（OA）过程中不同因子表达的影响。用1ng/ml IL-1处理人OA软骨细胞，同时加入或不加入protandim （0-10g/ml）或6-姜辣素（0-10M）。通过内侧半月板失稳（DMM）手术诱导小鼠骨关节炎。动物每周关节内注射10l载药或protandim (10g/ml)，连续8周。假手术小鼠作为对照。在体外，我们证明了protandim和6-姜辣素可以保持细胞活力和线粒体代谢，并防止4-羟基壬烯醛（HNE）诱导的细胞死亡。它们激活Nrf2转录因子，消除IL-1诱导的NO、PGE(2)、MMP-13和HNE的产生，以及IL-诱导的GSTA4-4下调。Nrf2过表达可降低il -1诱导的HNE和MMP-13以及il -1诱导的GSTA4-4下调。转染siRNA后，Nrf2敲低可消除蛋白对氧化应激和分解代谢的保护作用。IL-1对MAPK和NF-B的激活不受6-姜辣素的影响。在体内，我们观察到Nrf2和GSTA4-4在人和小鼠OA软骨中的表达明显低于正常对照组。有趣的是，给药可降低DMM小鼠的OA评分。总之，我们的数据表明，protandim和6-姜辣素在保护软骨和消除一些已知参与OA发病机制的因素方面是必不可少的。j .细胞。中国生物医学工程学报，2016,33(2):391 - 391。(c) 2016 Wiley Periodicals, Inc.；
Protandim and 6-gingerol, two potent nutraceuticals, have been shown to decrease free radicals production through enhancing endogenous antioxidant enzymes. In this study, we evaluated the effects of these products on the expression of different factors involved in osteoarthritis (OA) process. Human OA chondrocytes were treated with 1ng/ml IL-1 in the presence or absence of protandim (0-10g/ml) or 6-gingerol (0-10M). OA was induced surgically in mice by destabilization of the medial meniscus (DMM). The animals were treated weekly with an intraarticular injection of 10l of vehicle or protandim (10g/ml) for 8 weeks. Sham-operated mice served as controls. In vitro, we demonstrated that protandim and 6-gingerol preserve cell viability and mitochondrial metabolism and prevented 4-hydroxynonenal (HNE)-induced cell mortality. They activated Nrf2 transcription factor, abolished IL-1-induced NO, PGE(2), MMP-13, and HNE production as well as IL--induced GSTA4-4 down-regulation. Nrf2 overexpression reduced IL-1-induced HNE and MMP-13 as well as IL-1-induced GSTA4-4 down-regulation. Nrf2 knockdown following siRNA transfection abolished protandim protection against oxidative stress and catabolism. The activation of MAPK and NF-B by IL-1 was not affected by 6-gingerol. In vivo, we observed that Nrf2 and GSTA4-4 expression was significantly lower in OA cartilage from humans and mice compared to normal controls. Interestingly, protandim administration reduced OA score in DMM mice. Altogether, our data indicate that protandim and 6-gingerol are essential in preserving cartilage and abolishing a number of factors known to be involved in OA pathogenesis. J. Cell. Biochem. 118: 1003-1013, 2017. (c) 2016 Wiley Periodicals, Inc.