title: Inhibitory effect of sesquiterpene lactones from Saussurea lappa on tumor necrosis factor-alpha production in murine macrophage-like cells.
abstract: Total methanol extract of Saussurea lappa radix (Compositae) showed potent inhibitory effect on the production of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, in murine macrophage-like cell (RAW264.7 cells) in our previous screening studies on 120 Korean medicinal plants. The activity-guided purification of the plant resulted in the isolation of three components. The chemical structures of the components isolated were established by spectroscopic analyses as sesquiterpene lactones [cynaropicrin (1), reynosin (2), and santamarine (3)]. These three compounds inhibited TNF-alpha production in a dose-dependent manner. The molar concentrations of cynaropicrin, reynosin, and santamarine producing 50% inhibition (IC50) of TNF-alpha production were 2.86 micrograms/ml (8.24 microM), 21.7 micrograms/ml (87.4 microM), and 26.2 micrograms/ml (105 microM), respectively. However, treatment with sulphydryl (SH) compounds such as L-cysteine, dithiothreitol, and 2-mercaptoethanol abrogated the inhibitory effect of cynaropicrin on TNF-alpha production. Therefore, we conclude that the principal inhibitory component of Saussurea lappa is cynaropicrin and its inhibitory effect is mediated through conjugation with SH-groups of target proteins.
authors.affiliation: Department of Inflammation, Allergy and Autoimmune Diseases, Daewoong Pharmaceutical Co. Ltd., Sungnam, Korea. cjy0905@chollian.net
authors.forename: J Y
authors.initials: JY
authors.lastname: Cho
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: E S
authors.initials: ES
authors.lastname: Yoo
authors.forename: K U
authors.initials: KU
authors.lastname: Baik
authors.forename: J H
authors.initials: JH
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: M H
authors.initials: MH
authors.lastname: Park
mesh_terms: D000818:Animals; D002460:Cell Line; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C016722:santamarine; C075687:cynaropicrin; C016715:reynosin