Tangeretin synergistically enhances odorant-induced increases in cAMP and calcium levels and CREB phosphorylation in non-neuronal 3T3-L1 cells

Tangeretin is a natural flavone found mainly in citrus peels. Although emerging evidence suggests the beneficial health effects of tangeretin, little is known about the biological role of tangeretin in the odorant-induced signal transduction pathway. In this study, the effects of tangeretin on odorant-stimulated non-neuronal 3T3-L1 cells were evaluated. Here, we present the first evidence that an olfactory receptor for lyral, an odorant, is expressed in 3T3-L1 cells and that it responds to its ligand. Stimulation with lyral increased the cyclic adenosine monophosphate (cAMP) and Ca2+ levels as well as the phosphorylation of cAMP response element binding protein (CREB). Pretreatment with tangeretin synergistically enhanced the effects of stimulation with lyral: up-regulation of cAMP and Ca2+ levels and CREB phosphorylation. These data collectively suggest that tangeretin synergistically enhances the odorant-induced signaling pathway through modulation of cAMP and CREB signal transduction in non-chemosensory cells.