1. Introduction
Since ancient times, humans have obtained pharmacological compounds from natural products derived from plants and bacteria. Phytochemicals, which are produced in plants to resist various stresses, including UV and insect pests, exhibit beneficial effects, such as antioxidant, anticancer, and anti-inflammatory effects, on humans and mammals. Because some phytochemicals are scenting and are used as flavors and flagrances, we expected that unidentified immunomodulators could be found in aroma compounds.
Dendritic cells (DCs), the most typical antigen presenting cells (APCs), contribute to both innate and adaptive immunity. Activation of DCs by pathogens leads to the release of cytokines and chemokines from DCs, and DC-mediated expansion of antigen-specific T cell clones. Therefore, DC activation is essential for host defense against infection, but hyper and/or lasting activation of DC-mediated immunoresponses causes inflammation and autoimmune diseases.
A number of studies regarding the immunomodulatory effects of phytochemicals have been reported 1. Resveratrol is the most well-known polyphenolic stilbenoid 2,3 and exhibits effects on the prevention of inflammation-related diseases by suppressing TLR signaling-induced expression of proinflammatory genes4. Regarding scent phytochemicals, several food ingredients, including curcumin 5 and menthol6, are expected to possess therapeutic potential.
In the current study, we first performed screening to find novel immunomodulators by analyzing the effect on APC-dependent T cell activation and selected β-damascone, a major ingredient of rose fragrance, from approximately 150 kinds of aroma compounds. Next, we investigated the molecular mechanisms by which β-damascone regulates antigen (Ag)-dependent T cell proliferation and found that β-damascone suppressed DC-mediated immunoresponses and that activation of the transcription factor NF-E2-related factor 2 (NRF2)-pathway in DCs by β-damascone is one of the causes. Finally, we confirmed the effect of β-damascone on immunoresponses in vivo using a contact hypersensitivity (CHS) mouse model. Taken together, these results indicate that β-damascone, which suppresses immunoresponses mainly targeting DCs, exhibits beneficial effects on the prevention and/or treatment of immunorelated diseases.