title: Sesamol suppresses the inflammatory response by inhibiting NF-κB/MAPK activation and upregulating AMP kinase signaling in RAW 264.7 macrophages.
abstract: OBJECTIVE
  Sesamol is a lignan isolated from sesame seed oil. In recent years, it was found that sesamol could decrease lung inflammation and lipopolysaccharide (LPS)-induced lung injury in rats. In this study, we investigated whether sesamol exhibited anti-inflammatory activity in LPS-stimulated macrophages.
  
  
  METHODS
  RAW 264.7 cells were treated with sesamol, then treated with LPS to induce inflammation. The levels of proinflammatory cytokines were analyzed with ELISA. The gene and protein expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and nuclear factor erythroid-2-related factor 2 (Nrf2) were evaluated with real-time PCR and Western blots, respectively. We also examined inflammatory signaling pathways, including nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.
  
  
  RESULTS
  Sesamol inhibited production of nitric oxide, prostaglandin E2 (PGE2), and proinflammatory cytokines. Sesamol markedly suppressed mRNA and protein expression of iNOS and COX-2. Sesamol enhanced the protective antioxidant pathway represented by Nrf2 and HO-1. Moreover, sesamol suppressed NF-κB transport into the nucleus and decreased MAPK activation, but it promoted adenosine monophosphate-activated protein kinase (AMPK) activation.
  
  
  CONCLUSIONS
  These data suggested that sesamol ameliorated inflammatory and oxidative damage by upregulating AMPK activation and Nrf2 signaling and blocking the NF-κB and MAPK signaling pathways.
authors.affiliation: Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, 261 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Xin-Ling
authors.initials: XL
authors.lastname: Wu
authors.forename: Chian-Jiun
authors.initials: CJ
authors.lastname: Liou
authors.forename: Zih-Ying
authors.initials: ZY
authors.lastname: Li
authors.forename: Xuan-Yu
authors.initials: XY
authors.lastname: Lai
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Fang
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Huang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D052117:Benzodioxoles; D016207:Cytokines; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D010636:Phenols; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C025583:sesamol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; D015232:Dinoprostone