In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa.
We investigated in vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone from Saussurea lappa, on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) release, and lymphocyte proliferation. Cynaropicrin strongly inhibited TNF-alpha release from lipopolysaccharide-stimulated murine macrophage, RAW264.7 cells, and differentiated human macrophage, U937 cells, proved to produce notable amount of TNF-alpha. It also potently attenuated the accumulation of NO released from lipopolysaccharide- and interferon-gamma-stimulated RAW264.7 cells in a dose-dependent manner. In addition, the immunosuppressive effects of the compound on lymphocyte proliferation in response to mitogenic stimuli were examined. Cynaropicrin also dose-dependently suppressed the proliferation of lymphocytes from splenocytes and interleukin-2-sensitive cytotoxic T lymphocyte, CTLL-2 cells, stimulated by lipopolysaccharide, concanavalin A, phytohemagglutinin and interleukin-2. However, treatment with sulphydryl compound, L-cysteine, abrogated all these inhibitory effects. These results suggest that cynaropicrin may participate in the inflammatory response by inhibiting the production of inflammatory mediators and the proliferation of lymphocytes and its inhibitory effect is mediated through conjugation with sulphydryl groups of target protein(s).
Cho
J Y
JY
Department of Inflammation, Allergy and Autoimmune Diseases, R&D Center, Daewoong Pharmaceutical Co. Ltd, 462-120, Sungnam, South Korea.jae.cho@ucl.ac.uk
Baik
K U
KU
Jung
J H
JH
Park
M H
MH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D003603:Cytotoxins; D007783:Lactones; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C075687:cynaropicrin