taraxerol (cas 127-22-0) inhibits LPS-induced inflammatory responses through suppression of TAK1 and Akt activation

Add time:09/24/2019    Source:sciencedirect.com

taraxerol (cas 127-22-0), 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.

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