title: Ethanol Extract of Potentilla supina Linne Suppresses LPS-induced Inflammatory Responses through NF-κB and AP-1 Inactivation in Macrophages and in Endotoxic mice.
abstract: In this study, we investigated the antiinflammatory effects of ethanol extracts of Potentilla. supina Linne (EPS) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and septic mice. EPS suppressed LPS-induced nitric oxide, prostaglandin E2, TNF-α, interleukin-6 and interleukin-1β at production and mRNA levels in LPS-induced RAW 264.7 macrophages. Consistent with these observations, EPS attenuated the expressions of inducible nitric oxide synthase and cyclooxygenase-2 by downregulation of their promoter activities. Molecularly, EPS reduced the LPS-induced transcriptional activity and DNA-binding activity of nuclear factor-κB (NF-κB), and this was associated with a decrease of translocation and phosphorylation of p65 NF-κB by inhibiting the inhibitory κB-α degradation and IKK-α/β phosphorylation. Furthermore, EPS inhibited the LPS-induced activation of activator protein-1 by reducing the expression of c-Fos and c-Jun in nuclear. EPS also suppressed the phosphorylation of mitogen-activated protein kinase, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In an LPS-induced endotoxemia mouse model, pretreatment with EPS reduced the mRNA levels of inducible nitric oxide synthase, cyclooxygenase-2 and proinflammatory cytokines and increased the survival rate of mice. Collectively, these results suggest that the antiinflammatory effects of EPS were associated with the suppression of NF-κB and activator protein-1 activation and support its possible therapeutic role for the treatment of endotoxemia. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Korea.|Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Korea.
authors.forename: Hae-Jun
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Korea.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Korea.
authors.forename: Kyoung-Goo
authors.initials: KG
authors.lastname: Lee
authors.affiliation: Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Park
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Korea.|Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Young Pyo
authors.initials: YP
authors.lastname: Jang
authors.affiliation: Highland Agriculture Research Center, NICS, RDA, Pyeongchang, 232-955, Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Nam
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Korea.|Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Korea.
authors.forename: Kyung-Tae
authors.identifier: http://orcid.org/0000-0002-3141-3727
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins; D000431:Ethanol / Q000737:chemistry* / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D031987:Potentilla / Q000737:chemistry*; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D000431:Ethanol
keywords: AP-1; NF-κB; Potentilla supina L; endotoxemia; macrophage