Effects of SKI306X on arachidonate metabolism and other inflammatory mediators.
SKI306X was previously reported to have good anti-inflammatory and analgesic efficacy in various studies. To determine its mode of action, an investigation was carried out for some representative mediators. Arachidonic acid metabolism and its products are particularly important in inflammation and pain. The pro-inflammatory cytokines, especially interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha), and induced nitric oxide (NO) appear to be most involved in the inflammatory process such as osteoarthritis (OA). Thus SKI306X was tested to determine the effects on enzymes related to arachidonic acid metabolism and the release or synthesis of inflammatory mediators. SKI306X did inhibit the expression of cyclooxygenase-2 (COX-2) enzyme without affecting COX-1 and COX-2 activity. Leukotriene B4 (LTB4) production also was inhibited by SKI306X (IC50 = 98.7+/-4.26 microg/ml). SKI306X inhibited significantly TNF-alpha release (IC50 = 97.6+/-17.8 microg/ml) and NO production (IC50 = 280+/-17.8 microg/ml). But IL-1alpha release was not attenuated by SKI306X. This study suggests that inhibition of these mediators by SKI306X may be one of the mechanisms responsible for its anti-inflammatory effects.
Kim
Joo-Hyon
JH
Life Science Research Center, SK Chemicals, Suwon-Si, Kyungki-Do, Korea.
Ryu
Keun-Ho
KH
Jung
Ki-Won
KW
Han
Chang-Kyun
CK
Kwak
Wie-Jong
WJ
Cho
Yong-Baik
YB
D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D007476:Ionophores; D008565:Membrane Proteins; D010936:Plant Extracts; C460104:SKI 306X; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D016718:Arachidonic Acid; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D003474:Curcumin; D015232:Dinoprostone