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.