Anti-inflammatory activity of lipophilic coffee constituents: βN-alkanoyl-5-hydroxytryptamines and diterpenes in THP-1 monocytes and HCEC-1CT intestinal cells

Lipophilic coffee compounds are present in coffee beverages and may also be found in coffee by-products, whose underutilized fractions contain molecules such as βN-alkanoyl-5-hydroxytryptamines (Cn-5HTs) and diterpenes. Although members of these groups show anti-inflammatory potential, their combined effects remain unexplored. In this study, Cn-5HTs, cafestol, kahweol, and caffeine were tested individually and in mixtures in THP-1 Lucia™ monocytes using an NF-κB reporter gene assay to evaluate additive or synergistic interactions. The most active combinations were further assessed in HCEC-1CT intestinal epithelial cells for effects on TNF-α, IL-6, IL-8, and IL- 10 expression and secretion. C18-5HT, C20-5HT, cafestol, and kahweol reduced NF-κB activation at non-cytotoxic concentrations, while caffeine and longer-chain amides were inactive. C18-5HT and kahweol were the most potent, and their co-treatment (3 μM +40 μM) produced the strongest inhibition, suggesting synergy. In HCEC- 1CT cells, treatments lowered pro-inflammatory cytokine mRNA and protein levels, supporting the bioactivity of coffee lipophilic compounds.