Nonivamide, a capsaicin analogue, exhibits anti-inflammatory properties in peripheral blood mononuclear cells and U-937 macrophages

Scope: Inflammation-related diseases are a worldwide problem. The counteraction of inflammation with compounds activating the trigeminal nerve is one strategy to fight these diseases. Known trigeminally active compounds found in black or red pepper are the tingling t-pellitorine, the pungent capsaicin, and the less pungent nonivamide. The presented study compares the anti-inflammatory potential of nonivamide to the two known anti-inflammatory compounds, elucidating the mechanism of action and the role of transient receptor protein (TRP) channels. Methods and results: Primary peripheral blood mononuclear cells (PBMCs) and U-937 macrophages were stimulated with 1 μg/mL LPS from Escherichia coli (EC-LPS) to induce inflammation. Nonivamide attenuated the EC-LPS induced release of IL-6 and TNF-α in PBMCs and U-937 macrophages determined by magnetic bead kit analysis. This anti-inflammatory mechanism was independent from nuclear factor-kappa B pathway but mitogen-activated protein kinase (MAPK) pathway may be involved. In addition, cotreatment of U-937 with the trigeminally active compound and an antagonist of TRPV1 or TRPA1 abolished the anti-inflammatory activity. Conclusions: Nonivamide possessed similar anti-inflammatory potential as capsaicin and t-pellitorine. In U-937 macrophages, the tested compounds exploited an anti-inflammatory effect by inhibiting the EC-LPS induced activation of the MAPK pathway. In addition, the TRP channel activation plays a role in the anti-inflammatory capacity of capsaicin and nonivamide.