Taylor Jared F, Goudarzi Ramin, Yazdi Puya G, Pedersen Brian Allen
Systomic Health, USA.
Division of Research and Development, Pharmin USA, LLC, USA.
Int J Chem. 2017;9(4):31-39. doi: 10.5539/ijc.v9n4p31.
Osteoarthritis (OA) is the most common form of arthritis. Symptomatically characterized by stiffness and pain, OA is a chronic degenerative disease of joints. Of note, there is growing interest in the potential use of plant-based compounds for symptomatic treatment of OA. Arthrocen is a plant-derived agent consisting of a one to two ratio of avocado and soy unsaponifiable extracts. In order to decipher the potential mechanisms of Arthrocen's action at the molecular level, we employed an assay using cultured human THP-1 cells (a model cell line for monocytes) to study its effects. By pairing protein arrays enriched for inflammatory markers, transcriptomic pathway analysis using RNA-Sequencing, and eicosanoid specific lipidomics, we have begun to unravel its potential mechanism of action. Specifically, we found that Arthrocen can attenuate the inflammatory response at the transcript level while inducing significant changes in numerous cytokines. Furthermore, we discovered that while Arthrocen alone did not increase IL-8 or MCP-1 levels, its presence had a synergistic effect on the observed increase in response to LPS stimulation. Additionally, this synergistic effect of Arthrocen on LPS stimulation of IL-8 and MCP-1 protein levels was also observed at the mRNA level and suggests a regulatory mechanism at the transcriptional level. Interestingly, Arthrocen induced no changes in any of the eicosanoids studied. This multi-omics approach implies that Arthrocen functions at the level of gene transcription to dampen inflammation mediated by monocytes in OA.
骨关节炎(OA)是最常见的关节炎形式。其症状表现为僵硬和疼痛,是一种关节慢性退行性疾病。值得注意的是,人们对植物性化合物用于OA症状治疗的潜在用途越来越感兴趣。Arthrocen是一种植物源制剂,由牛油果和大豆不皂化物提取物按1:2的比例组成。为了在分子水平上解读Arthrocen的潜在作用机制,我们采用了一种利用培养的人THP-1细胞(一种单核细胞模型细胞系)的检测方法来研究其效果。通过将富含炎症标志物的蛋白质阵列、使用RNA测序的转录组通路分析以及类花生酸特异性脂质组学相结合,我们已经开始揭示其潜在的作用机制。具体而言,我们发现Arthrocen可以在转录水平上减弱炎症反应,同时诱导多种细胞因子发生显著变化。此外,我们发现虽然单独使用Arthrocen不会增加IL-8或MCP-1的水平,但其存在对观察到的LPS刺激引起的增加具有协同作用。此外,Arthrocen对LPS刺激IL-8和MCP-1蛋白水平的这种协同作用在mRNA水平上也观察到了,这表明在转录水平上存在一种调节机制。有趣的是,Arthrocen在所研究的任何类花生酸中均未诱导变化。这种多组学方法表明,Arthrocen在基因转录水平上发挥作用以减轻OA中由单核细胞介导的炎症。