title: Methanol extracts of Euphorbia cooperi inhibit the production of inflammatory mediators by inhibiting the activation of c‑Jun N‑terminal kinase and p38 in murine macrophages.
abstract: Numerous Euphorbiaceae plants have been used for the treatment of diseases, including liver diseases, asthma and rheumatism. The present study evaluated the effect of methanol extracts from Euphorbia cooperi (MEC), a member of the Euphorbiaceae plant family, on the production of inflammatory cytokines interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α, nitric oxide (NO) as well as the activation of mitogen‑activated protein kinase and nuclear factor (NF)‑κB signaling. Non‑cytotoxic concentrations of MEC significantly reduced the production of NO and IL‑6, but not TNF‑α, in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophages. The decreased production of NO by MEC was due to alleviated expression of inducible NO synthase. Reporter assays with cells treated with MEC demonstrated reduced activator protein‑1 (AP-1) activity, while NF‑κB activity was not reduced. Furthermore, the phosphorylation levels of c‑Jun N‑terminal kinase (JNK) and p38 were suppressed by MEC while phosphorylation levels of inhibitor of κB were not reduced by MEC, suggesting that MEC‑mediated inactivation of JNK and p38 is the underlying regulatory mechanism for inflammatory mediators in LPS‑stimulated RAW 264.7 macrophages.
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Young-Chang
authors.initials: YC
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Huiyun
authors.initials: H
authors.lastname: Seo
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Anna
authors.initials: A
authors.lastname: Ju
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Deokkyu
authors.initials: D
authors.lastname: Youn
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Younghyun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Jaehee
authors.initials: J
authors.lastname: Choun
authors.affiliation: College of Pharmacy, Chung‑Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sayeon
authors.initials: S
authors.lastname: Cho
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D000432:Methanol / Q000737:chemistry; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D012997:Solvents / Q000737:chemistry; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007155:Immunologic Factors; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D012997:Solvents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000432:Methanol