title: Atractylenolide I inhibits lipopolysaccharide-induced inflammatory responses via mitogen-activated protein kinase pathways in RAW264.7 cells.
abstract: Atractylenolide I (ATL-I) is a bioactive component of Rhizoma Atractylodis macrocephalae. Although increasing evidence shows that ATL-I has an anti-inflammatory effect, the anti-inflammatory molecular mechanism of ATL-I is still unknown. In this study, we investigated the effect of ATL-I on cell viability by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and the level of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay (ELISA) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further, we examined the effect of ATL-I on the activation of nuclear factor-kappaB (NF-κB) and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38) by Western blot. We also investigated the effect of ATL-I on the expression of myeloid differentiation protein-2 (MD-2), CD14, complement receptor 3 (CR3), scavenger receptor class A (SR-A), toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). We found that ATL-I showed no inhibitory effect on cell viability at concentrations ranging from 1 µM to 100 µM and markedly reduced the release of IL-6 and TNF-α at a concentrate-dependent manner. In addition, ATL-I suppressed the activity of nuclear NF-κB and the phosphorylation of ERK1/2 and p38 in LPS-treated RAW264.7 cells. Further analysis showed that ATL-I inhibited the expression of MD-2, CD14, SR-A, TLR4 and MyD88, but the expression of CR3 was unaffected. These data suggest that ATL-I shows an anti-inflammatory effect by inhibiting TNF-α and IL-6 production. The anti-inflammatory effects of ATL-I may be associated with the inhibition of the NF-κB, ERK1/2 and p38 signaling pathways.
authors.affiliation: College of Light Industry and Food Sciences, South China University of Technology , Guangzhou , China and.
authors.forename: Guangquan
authors.initials: G
authors.lastname: Ji
authors.forename: Renqiong
authors.initials: R
authors.lastname: Chen
authors.forename: Jianxian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D012717:Sesquiterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D007783:Lactones; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C424804:atractylenolide I
keywords: Atractylenolide I; MAPK; NF-κB; macrophage; tumor necrosis factor alpha