title: Attenuation of antigen-specific T helper 1 immunity byNeolitsea hiiranensisand its derived terpenoids.
abstract: 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.Neolitseaspecies, 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 ofN. hiiranensis, an endemicNeolitseain Taiwan, and demonstrated anti-inflammatory activities. However, the effect ofN. hiiranensison the functionality of immune cells, especially T cells, is still unclear. In this study, we utilizein vitroandin vivoapproaches to characterize the effects of leaves ofN. hiiranensisand its terpenoids on adaptive immune responses.
  
  
  METHODS
  Dried leaves ofN. hiiranensiswere 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 withN. hiiranensisextracts (5-20 mg/kg). The serum and splenocytes of treated mice were collected to evaluate the immunomodulatory effects ofN. hiiranensison the production of OVA-specific antibodies and cytokines. To further identify theN. hiiranensis-derived compounds with immunomodulatory potentials, OVA-primed splenocytes were treated with compounds isolated fromN. hiiranensisby determining the cell viability, cytokine productions, and mRNA expression in the presence of OVAin vitro.
  
  
  RESULTS
  Crude extracts of leaves ofN. hiiranensissignificantly inhibited IL-12, IFN-γ, and IL-2 cytokine productions as well as the serum levels of antigen-specific IgM and IgG2ain vivo. Two of fourteen selected terpenoids and one diterpenoid derived from the leaves ofN. hiiranensissuppressed IFN-γ in vitro. In addition,β-caryophyllene oxide attenuated the expression of IFN-γ, T-bet, and IL-12Rβ2 in a dose-dependent manner.N. hiiranensis-derivedβ-caryophyllene oxide inhibited several aspects of adaptive immune responses, including T-cell differentiation, IFN-γproduction, and Th1-assocaited genes.
  
  
  CONCLUSIONS
  As IFN-γis the key cytokine secreted by T helper-1 cells and plays a pivotal role in Th1 immune responses, our results suggested that theN. hiiranensisand its terpenoids may possess potential therapeutic effects on Th1-mediated immune disorders.
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan.
authors.forename: Yin-Hua
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: School of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan.
authors.forename: Ih-Sheng
authors.initials: IS
authors.lastname: Chen
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Tung
authors.affiliation: School of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan.
authors.forename: Hsun-Shuo
authors.initials: HS
authors.lastname: Chang
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
keywords: IFN-γ; Neolitsea; T-bet; Terpenoids; Th1 cells; β-caryophyllene oxide