title: Anti-inflammatory activity of atractylenolide III through inhibition of nuclear factor-κB and mitogen-activated protein kinase pathways in mouse macrophages.
abstract: To elucidate the anti-inflammatory mechanisms involved, we investigated the effects of atractylenolide III (ATL-III) on cytokine expression, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 mitogen-activated protein kinase (p38), C-Jun-N-terminal protein kinase1/2 (JNK1/2) and nuclear factor-κB (NF-κB) pathways in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages. Macrophages were incubated with various concentrations (0, 25, 50, 100 μM) of ATL-III and/or LPS (1 μg/mL) for 24 h. The production of nitric oxide (NO) was determined by the Greiss reagent. The production of tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) and interleukin 6 (IL-6) was determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, macrophages were treated with ATL-III (0, 25, 100 μM) for 1 h and then stimulated by LPS. NF-κB, p38, JNK1/2 and ERK1/2 were determined by western blotting. We found ATL-III showed no inhibitory effect on cell proliferation at concentrations ranging from 1 μM to 100 μM. In addition, ATL-III decreased the release of NO, TNF-α, PGE2 and IL-6 in a dose-dependent manner and showed statistically significant at concentrations of 50 μM and 100 μM as well as cyclooxygenase-2 (COX-2) expression. Furthermore, ATL-III suppressed the transcriptional activity of NF-κB. ATL-III also inhibited the activation of ERK1/2, p38 and JNK1/2 in LPS-treated macrophages and showed statistically significant at concentrations of 25 μM and 100 μM. These data suggest that ATL-III shows an anti-inflammatory effect by suppressing the release of NO, PGE2, TNF-α and IL-6 related to the NF-κB- and MAPK-signaling pathways.
authors.affiliation: a Department of Science and Technology , Lianyungang First People's Hospital , Lianyungang , China .
authors.forename: Guang-Quan
authors.initials: GQ
authors.lastname: Ji
authors.affiliation: b Department of Dermatology , Lianyungang First People's Hospital , Lianyungang , China , and.
authors.forename: Ren-Qiong
authors.initials: RQ
authors.lastname: Chen
authors.affiliation: c Department of Dermatology , Changshu First People's Hospital , Changshu , China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C424802:atractylenolide III; D009569:Nitric Oxide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Atractylenolide III; MAPK; TNF-α; nuclear factor-κB