Rose flavor compound b-damascone regulates dendritic cell-mediated
immunoresponses by modulating the NRF2 pathway and ameliorates contact
hypersensitivity
Abstract
Background: Numerous pharmacologically beneficial compounds
have been isolated from natural products derived from plants; these
compounds are often characterized as phytochemicals and are used in
flavors, spices, fragrances, and colors. In the current study, we aimed
to obtain novel immunomodulators from aroma compounds. Methods:
We selected a candidate that inhibits antigen-presenting cell-mediated
activation of T cells from an aroma library. The molecular mechanisms by
which the candidate compound modulates immunoresponses were analyzed
with in vitro studies, and the biological significance of the
candidate was evaluated by using a mouse model. Results:
b-Damascone, a major ingredient of rose fragrance, was selected from an
aroma library as a candidate compound that suppresses antigen-dependent
T cell activation, through 2-step screening using OT-II splenocytes.
Investigations using flow cytometry, ELISA, and qPCR revealed that
b-damascone inhibited dendritic cell (DC)-related responses, including
DC-induced Th1 development, TLR ligand-induced transactivation and
production of inflammatory cytokines in DCs, and LPS-induced
upregulation of MHC class II and CD86 on DCs. Regarding intracellular
events, we found that b-damascone treatment increased the levels of NRF2
protein and Hmox1 mRNA in DCs. Nrf2 -/-
DCs, in which b-damascone-induced Hmox1 transcription was not
observed, possessed Th1-induction activity and higher IL-12p40
production activity even in the presence of b-damascone in comparison
with Nrf2 +/- DCs. Finally, we evaluated the
effect of orally administered b-damascone on the pathology of contact
hypersensitivity model mice and found that b-damascone intake suppressed
ear swelling. Conclusions: The rose aroma compound b-damascone,
which suppresses DC-mediated immunoresponses by activating the NRF2
pathway, could be useful to ameliorate immunorelated diseases.