Attenuation of antigen-specific T helper 1 immunity by and its derived terpenoids.

Background: T cells play a pivotal role in the adaptive immunity that participates in a wide range of immune responses through a complicated cytokine network. Imbalance of T-cell responses is involved in several immune disorders. species, one of the biggest genera in the family Lauraceae, have been employed widely as folk medicines for a long time in Asia. Previous phytochemical investigations revealed the abundance of terpenes in the leaves of , an endemic in Taiwan, and demonstrated anti-inflammatory activities. However, the effect of on the functionality of immune cells, especially T cells, is still unclear. In this study, we utilize and approaches to characterize the effects of leaves of and its terpenoids on adaptive immune responses.

Methods: Dried leaves of were extracted three times with cold methanol to prepare crude extracts and to isolate its secondary metabolites. The ovalbumin (OVA)-sensitized BALB/c mice were administrated with extracts (5-20 mg/kg). The serum and splenocytes of treated mice were collected to evaluate the immunomodulatory effects of on the production of OVA-specific antibodies and cytokines. To further identify the derived compounds with immunomodulatory potentials, OVA-primed splenocytes were treated with compounds isolated from by determining the cell viability, cytokine productions, and mRNA expression in the presence of OVA .

Results: Crude extracts of leaves of significantly inhibited IL-12, IFN-, and IL-2 cytokine productions as well as the serum levels of antigen-specific IgM and IgG. Two of fourteen selected terpenoids and one diterpenoid derived from the leaves of suppressed IFN-. In addition, -caryophyllene oxide attenuated the expression of IFN-, T-bet, and IL-12R2 in a dose-dependent manner. derived -caryophyllene oxide inhibited several aspects of adaptive immune responses, including T-cell differentiation, IFN- production, and Th1-assocaited genes.

Conclusion: As IFN- is the key cytokine secreted by T helper-1 cells and plays a pivotal role in Th1 immune responses, our results suggested that the and its terpenoids may possess potential therapeutic effects on Th1-mediated immune disorders.