INHIBITORY EFFECT OF SESQUITERPENE LACTONES FROM SAUSSUREA-LAPPA ON TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION IN MURINE MACROPHAGE-LIKE CELLS

Total methanol extract of Saussurea lappa radix (Compositae) showed po tent inhibitory effect on the production of tumor necrosis factor-alph a (TNF-alpha), a proinflammatory cytokine, in murine macrophage-like c ell (RAW264.7 cells) in our previous screening studies on 120 Korean m edicinal plants. The activity-guided purification of the plant resulte d in the isolation of three components. The chemical structures of the components isolated were established by spectroscopic analyses as ses quiterpene lactones [cynaropicrin (1), reynosin (2), and santamarine ( 3)]. These three compounds inhibited TNF-alpha production in a dose-de pendent manner. The molar concentrations of cynaropicrin, reynosin, an d santamarine producing 50 % inhibition (ICS,) of TNF-alpha production were 2.86 mu g/ml (8.24 mu M), 21.7 mu g/ml (87.4 mu M), and 26.2 mu g/ml (105 mu M), respectively. However, treatment with sulphydryl (SH) compounds such as L-cysteine, dithiothreitol, and 2-mercaptoethanol a brogated the inhibitory effect of cynaropicrin on TNF-alpha production . Therefore, we conclude that the principal inhibitory component of Sa ussurea lappa is cynaropicrin and its inhibitory effect is mediated th rough conjugation with SH-groups of target proteins.