title: Effective suppression of pro-inflammatory molecules by DHCA via IKK-NF-κB pathway, in vitro and in vivo.
abstract: OBJECTIVE
  Dehydrodiconiferyl alcohol (DHCA), a lignan compound isolated from Cucurbita moschata, has previously been shown to contain anti-adipogenic and antilipogenic effects on 3T3-L1 cells and mouse embryonic fibroblasts. As some of phytochemicals derived from natural plants show anti-inflammatory or antioxidative activities, we determined whether DHCA affects the production of pro-inflammatory mediators and also investigated its underlying mechanisms.
  
  
  METHODS
  Raw264.7, a murine macrophage cell line, and primary murine macrophages derived from bone marrow cells were treated with LPS in the presence of DHCA. Furthermore, cells were treated with LPS and palmitate in the presence of DHCA to examine its effect on inflammasomes. The production of various pro-inflammatory mediators was examined and the underlying mechanisms investigated using a variety of molecular biological techniques. To test whether DHCA exhibits anti-inflammatory effects in vivo, mouse dextran sodium sulfate (DSS)-induced colitis model was used.
  
  
  RESULTS
  DHCA reduced the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β and CCL2) and mediators (iNOS, COX-2 and ROS) by down-regulating the activity of I-κB kinase and, subsequently, the DNA binding activity of NF-κB. Moreover, DHCA effectively suppressed the palmitate-mediated activation of inflammasomes, which resulted in decreased production of IL-1β. DHCA also showed therapeutic effects in the mouse DSS-induced colitis model by suppressing the production of TNF-α and IL-1β and thus preventing weight loss and colon shrinkage.
  
  
  CONCLUSIONS
  Our data suggest that DHCA is a novel phytochemical that by regulating key molecules involved in inflammation and oxidative stress might exert a broad range of anti-inflammatory activities.
authors: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors: Junghun
authors: J
authors: Lee
authors: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors: Jinyong
authors: J
authors: Choi
authors: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors: Sunyoung
authors: S
authors: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010636:Phenols; D017382:Reactive Oxygen Species; C080686:dehydrodiconiferyl alcohol; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D015232:Dinoprostone