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Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/10/2018 Publication Date: 7/5/2018 Citation: Park, J.B. 2018. Javamide-II found in coffee suppresses TNF-alpha production more effectively than caffeine in PMA/PHA-treated lymphocytic Jurkat cells. Journal of Agricultural and Food Chemistry. 66(26):6782-6789. https://doi.org/10.1021/acs.jafc.8b01885. DOI: https://doi.org/10.1021/acs.jafc.8b01885 Interpretive Summary: There is accumulating information suggesting that diet components can play significant roles in regulating immune functions, especially those related to inflammation. Coffee is one of most consumed drinks worldwide. Several studies suggest that the consumption of coffee protects against Fatty liver disease, diabetes, and degenerative disease, possibly by inhibiting inflammation-related processes. For years, caffeine in coffee has been considered to be a major contributing component in suppressing inflammation. However, its use as an anti-inflammation agent has been challenged by relatively high-dose requirements and potential adverse effects. Therefore, there have been on-going research efforts to find other bio-active compounds in coffee, responsible for inhibiting inflammation-related molecules such as TNF-alpha. Javamide-II is a phenolic amide found in coffee, with several biological activities including anti-inflammation activity. Our study showed that javamide-II may be a stronger anti-inflammatory compound than caffeine, responsible for inhibiting the production of TNF-alpha significantly in the cells. This study provided new information about the strong anti-inflammatory property of javamide-II in coffee and its potential usability. Technical Abstract: Several recent studies have suggested positive health effects of coffee consumption on inflammation. TNF-alpha is a major inflammatory cytokine involved in the initiation/progression of several chronic diseases such as liver diseases and diabetes. Interestingly, some studies suggested that javamide-II found in coffee may have greater anti-inflammation activity than caffeine. Therefore, in this study, the potential effects of javamide-II on TNF-alpha were investigated in PMA/PHA-treated lymphocytic Jurkat cells. At the concentration of 5 µM, javamide-II, not caffeine, inhibited the production of TNF-alpha significantly (more than 30%) in the Jurkat cells (P > 0.05). In addition, javamide-II (1-10 µM) was found to increase cAMP production significantly in the cells compared to caffeine (P > 0.05), and the increase was not suppressed by MT agonists in the Jurkat cells, suggesting that the cAMP production is independent of MT receptors present on Jurkat cells. To elucidate cellular effects of cAMP on TNF-alpha production, the phosphorylation of three MAP kinases (ERK, JNK and p38 MAPK) were investigated in PMA/PHA-treated Jurkat cells. The data showed that phospho-ERK was decreased (not phospho-JNK or phospho-p38 MAPK) with the elevated cAMP production by javamide-II in the cells, suggesting that the suppression of ERK phosphorylation may down-regulate TNF-alpha mRNA production in the Jurkat cells. As expected, javamide-II (5-20 µM) was found to decrease TNF-alpha mRNA production in PMA/PHA-treated Jurkat cells. Altogether, javamide-II is more effective than caffeine in suppressing the production of TNF-alpha mRNA and protein significantly by inhibiting ERK phosphorylation in PMA/PHA-treated Jurkat cells. |
