title: In vitro and in vivo anti-inflammatory activities of Polygonum hydropiper methanol extract.
abstract: BACKGROUND
  Polygonum hydropiper L. (Polygonaceae) has been traditionally used to treat various inflammatory diseases such as rheumatoid arthritis. However, no systematic studies on the anti-inflammatory actions of Polygonum hydropiper and its inhibitory mechanisms have been reported. This study is therefore aimed at exploring the anti-inflammatory effects of 99% methanol extracts (Ph-ME) of this plant.
  
  
  METHODS
  The effects of Ph-ME on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages were investigated. Molecular mechanisms underlying the effects, especially inhibitory effects, were elucidated by analyzing the activation of transcription factors and their upstream signalling, and by evaluating the kinase activities of target enzymes. Additionally, a dextran sulphate sodium (DSS)-induced colitis model was employed to see whether this extract can be used as an orally available drug.
  
  
  RESULTS
  Ph-ME dose-dependently suppressed the release of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin (PG)E(2), in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ph-ME inhibited mRNA expression of pro-inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by suppressing the activation of nuclear factor (NF)-κB, activator protein (AP-1), and cAMP responsive element binding protein (CREB), and simultaneously inhibited its upstream inflammatory signalling cascades, including cascades involving Syk, Src, and IRAK1. Consistent with these findings, the extract strongly suppressed the kinase activities of Src and Syk. Based on HPLC analysis, quercetin, which inhibits NO and PGE(2) activities, was found as one of the active ingredients in Ph-ME.
  
  
  CONCLUSIONS
  Ph-ME exerts strong anti-inflammatory activity by suppressing Src/Syk/NF-κB and IRAK/AP-1/CREB pathways, which contribute to its major ethno-pharmacological role as an anti-gastritis remedy.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Jang
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Byeon
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Song
authors.forename: Byoung-Hee
authors.initials: BH
authors.lastname: Lee
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D000432:Methanol / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D028502:Polygonum / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry*; D000072377:Syk Kinase; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D017362:Cyclic AMP Response Element-Binding Protein; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012997:Solvents; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D000432:Methanol