title: Water extract of Cynanchi atrati Radix regulates inflammation and apoptotic cell death through suppression of IKK-mediated NF-κB signaling.
abstract: BACKGROUND
  Cynanchi atrati Radix has been traditionally used as an anti-inflammatory agent to treat febrile diseases, acute urinary infection or subcutaneous pyogenic infection with invasion of the pathogenic factors.
  
  
  OBJECTIVE
  Nuclear factor (NF)-κB is a pleiotropic transcriptional factor of many genes involved in inflammatory and anti-apoptotic responses. To identify a novel, potent inhibitor of NF-κB signaling pathway, a plant extract library of traditional oriental medicine was screened for the capability to block the NF-κB activity in cells overexpressing toll-like receptor 4 (TLR4), and then evaluated the anti-inflammatory and pro-apoptotic functions of water extract of Cynanchi atrati Radix (WECR) in macrophages and cancer cells, respectively.
  
  
  METHODS
  The effect of WECR on the proinflammatory mediators (inducible NO synthase [iNOS], cyclooxygenase [COX]-2), IκB-α degradation, RelA/p65 phosphorylation and caspase cleavages were measured by immunblotting. NF-κB transcriptional activity, IκB kinase (IKK) activity and nitric oxide (NO) production was measured using the luciferase assay, in vitro kinase assay and Griess reaction.
  
  
  RESULTS
  WECR efficiently inhibited LPS-induced expression of proinflammatory mediators including iNOS and COX-2. IKK kinase activity, IκB-α degradation, nuclear translocation of RelA/p65 and NF-κB transcriptional activity induced by LPS were suppressed by WECR. Furthermore, WECR dramatically enhances the apoptotic response, as evident by the combination with tumor necrosis factor (TNF) was able to induce the cytotoxic action through caspase-dependent pathway.
  
  
  CONCLUSIONS
  These results indicate that WECR has a potential to inhibit IKK-mediated NF-κB activation, and is a valuable compound for modulating inflammatory or cancerous conditions.
authors: Department of Pharmacology, Research Institute for Medical Science, Daejeon Regional Cancer Center, College of Medicine, Chungnam National University, Daejeon 301-131, Republic of Korea.
authors: Juhee
authors: J
authors: Jeon
authors: Kyeong Ah
authors: KA
authors: Park
authors: Hyunji
authors: H
authors: Lee
authors: Sanghee
authors: S
authors: Shin
authors: Tiejun
authors: T
authors: Zhang
authors: Minho
authors: M
authors: Won
authors: Hyun Kyung
authors: HK
authors: Yoon
authors: Min Kyung
authors: MK
authors: Choi
authors: Hyeong Geug
authors: HG
authors: Kim
authors: Chang Gue
authors: CG
authors: Son
authors: Jang Hee
authors: JH
authors: Hong
authors: Gang Min
authors: GM
authors: Hur
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029062:Apocynaceae / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012997:Solvents / Q000737:chemistry*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014867:Water / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D017472:Receptors, Interleukin-1; D012997:Solvents; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase