Location: Diet, Genomics and Immunology LaboratoryTitle: N-caffeoyltryptomine, a potent anti-inflammatory phenolic amide, suppressed MCP-1 expression in LPS-stimulated THP-1 cells and rats fed with a high fat diet Author
Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/2017
Publication Date: 5/27/2017
Citation: Park, J.B. 2017. N-caffeoyltryptomine, a potent anti-inflammatory phenolic amide, suppressed MCP-1 expression in LPS-stimulated THP-1 cells and rats fed with a high fat diet. International Journal of Molecular Sciences. 18(6). pii:E1148.. https://doi.org/10.3390/jms18061148.
DOI: https://doi.org/10.3390/jms18061148 Interpretive Summary: Cardiovascular disease (CVD) is one of the major causes for human deaths worldwide. Particularly, chronic cardiovascular inflammation is critically involved in initiating and developing atherosclerotic CVD, suggesting a significant connection between systemic cardiac inflammation and atherosclerosis. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is a potent mononuclear chemokine that regulates monocyte/macrophage migration and infiltration, critically involved in multiple stages in atherosclerosis. N-caffeoyltryptamine is a phenolic amide belonging to a group of tryptophan-derived phenylpropenoid amides found in plants. In this study, the potential effects of N-caffeoyltryptamine on MCP-1 expression were investigated as a p38 MAP kinase inhibitor in vitro and in vivo. N-caffeoyltryptamine significantly inhibited p38 MAP kinase alpha, beta, gamma, and delta greatly. Also, the pretreatment with N-caffeoyltryptamine led to the suppression of MCP-1 production in THP-1 cells. Furthermore, N-caffeoyltryptamine could lower plasma MCP-1 levels significantly. This study provides new information about N-caffeoyltryptamine to suppress MCP-1 expressionmin vitro and in vivo, which could be utilized in systemic cardiac inflammation-related cardiovascular diseases.
Technical Abstract: Monocyte chemoattractant protein-1 (MCP-1) is a well-known chemokine critically involved in the pathophysiological progression of cardiovascular diseases such as arthrosclerosis. N-caffeoyltryptamine is a phenolic amide with strong anti-inflammatory effects. Therefore, in this paper, the potential effect of N-caffeoyltryptamine on MCP-1 expression was investigated as a p38 MAP kinase inhibitor in vitro and in vivo. At the concentration of 20 µM, N-caffeoyltryptamine significantly inhibited p38 MAP kinase alpha, beta, gamma and delta by 15-50% (P < 0.05), particularly p38 MAP kinase alpha (IC50 = 19.2 µM) and beta (IC50 =19.5 µM). Because N-caffeoyltryptamine was able to inhibit the p38 MAP kinases, its effect on MCP-1 expression was investigated in monocytic THP-1 cells stimulated with LPS. The pretreatment of the THP-1 cells with N-caffeoyltryptamine (10, 20 and 40 µM) led to significant suppression of MCP-1 production by 10-45% (P < 0.05) in the cells. On the basis of this strong inhibition in vitro, we conducted an animal study to verify this inhibitory effect in vivo. For this study, rats were divided into three groups (n=8): a normal control diet (C), a high fat diet (HF), or a high fat diet supplemented with N-caffeoyltryptamine (2 mg per day) (HFS). After 16 weeks, blood samples were collected from the rats in each group, and MCP-1 levels were determined in plasma with other atherogenic markers (C-reactive protein and sE-selectin). As expected, the average MCP-1 levels of the HF group were found to be higher than those of the C group (P < 0.05). However, the MCP-1 levels of the HFS group were significantly lower than those of the HF group (P < 0.05), suggesting that N-caffeoyltryptamine may decrease MCP-1 expression via inhibiting p38 MAP kinase. However, we could not find any significant difference in the levels of other atherogenic markers, such as C-reactive protein and sE-selectin, between the HFS and HF groups. These data suggest that N-caffeoyltryptamine may specifically suppress MCP-1 expression in vitro and in vivo, possibly by inhibiting p38 MAP kinase.