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Javamide‐I found in coffee is a potent p38 MAP kinase inhibitor suppressing MCP‐1 expression significantly in LPS‐stimulated monocytic THP‐1 cells

Monocyte chemotactic protein‐1 (MCP‐1) is an inflammatory cytokine, profoundly implicated in pathogeneses of several chronic diseases such as rheumatoid arthritis, atherosclerosis, CVD and CKD. Coffee is one of most consumed drinks worldwide with potential health effects. Javamide‐I (N‐coumaroyltryptophan) is a phenolic amides found in coffee, which is believed to contain some important biological activities including anti‐inflammatory activity. However, its anti‐inflammatory actions have not been fully investigated related to MCP‐1. Interestingly, p38 MAP kinase plays a crucial role in regulating the production of several pro‐inflammatory cytokines including MCP‐1. Therefore, blocking p38 kinase may offer an effective therapy for treating many inflammatory diseases. Therefore, in this study, potential effects of javamide‐I on p38 MAP kinase and the production of MCP‐1expression were investigated in LPS‐stimulated monocytic THP‐1 cells. Javamide‐I was able to inhibit p38 MAP kinase, and also showed noncompetitive inhibition of p38 MAP kinase against ATP. In supporting the inhibition, a docking simulation showed stronger binding pose of javamide‐I to p38 MAP kinase than SB‐203580. Additionally, javamide‐I decreased ATF‐2 phosphorylation in LPS‐stimulated monocytic THP cells. Consequently, the treatment of javamide‐I (1–20 μM) showed significant decrease not only in the expression of MCP‐1 mRNA but also the production of MCP‐1 protein in the stimulated cells (P < 0.05). In addition, in this study, potential effects of javamide‐I on NF‐kB and other MAP kinases will be also discussed related to MCP‐1 expression.