title: Taraxerol inhibits LPS-induced inflammatory responses through suppression of TAK1 and Akt activation.
abstract: Taraxerol, a triterpenoid compound, has potent anti-inflammatory effects. However, the molecular mechanisms are not clear. In the study, taraxerol concentration dependently inhibited nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels and these inhibitions decreased the production of nitric oxide (NO), prostaglandin 2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β induced by LPS. Furthermore, we found that taraxerol suppressed translocation of nuclear factor-κB (NF-κB), phosphorylation of IκBα, blocked the IκBα degradation as well as IKK and mitogen-activated protein kinase (MAPK) activation by inactivation of TGF-β-activated kinase-1 (TAK1) and Akt. In addition, taraxerol significantly inhibited the formation of TAK1/TAK-binding protein1 (TAB1), which was accompanied by inducing degradation of TAK1, decreasing LPS-induced polyubiquitination of TAK1 as well as TAK1 phosphorylation. Taken together, our data suggest that taraxerol downregulates the expression of proinflammatory mediators in macrophages by interfering with the activation of TAK1 and Akt, thus preventing NF-κB activation.
authors: Department of Biology and Food Engineering, Bengbu College, Bengbu, PR China. leeyxy@gmail.com
authors: Xiangyang
authors: X
authors: Yao
authors: Guilan
authors: G
authors: Li
authors: Qin
authors: Q
authors: Bai
authors: Hui
authors: H
authors: Xu
authors: Chaotian
authors: C
authors: Lü
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000819:agonists*; D012333:RNA, Messenger / Q000032:analysis; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051546:Cyclooxygenase 2; D016207:Cytokines; D015232:Dinoprostone; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009828:Oleanolic Acid; D051058:Oncogene Protein v-akt; D012333:RNA, Messenger; D000099151:MAP Kinase Kinase Kinase 7; C005802:taraxerol