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.