title: Marine hydroquinone zonarol prevents inflammation and apoptosis in dextran sulfate sodium-induced mice ulcerative colitis.
abstract: OBJECTIVE
  We previously identified an anti-inflammatory compound, zonarol, a hydroquinone isolated from the brown algae Dictyopteris undulata as a marine natural product. To ascertain the in vivo functions of zonarol, we examined the pharmacological effects of zonarol administration on dextran sulfate sodium (DSS)-induced inflammation in a mouse model of ulcerative colitis (UC). Our goal is to establish a safe and effective cure for inflammatory bowel disease (IBD) using zonarol.
  
  
  RESULTS
  We subjected Slc:ICR mice to the administration of 2% DSS in drinking water for 14 days. At the same time, 5-aminosalicylic acid (5-ASA) at a dose of 50 mg/kg (positive control) and zonarol at doses of 10 and 20 mg/kg, were given orally once a day. DSS-treated animals developed symptoms similar to those of human UC, such as severe bloody diarrhea, which were evaluated by the disease activity index (DAI). Treatment with 20 mg/kg of zonarol, as well as 5-ASA, significantly suppressed the DAI score, and also led to a reduced colonic ulcer length and/or mucosal inflammatory infiltration by various immune cells, especially macrophages. Zonarol treatment significantly reduced the expression of pro-inflammatory signaling molecules, and prevented the apoptosis of intestinal epithelial cells. Finally, zonarol protected against in vitro lipopolysaccharide (LPS)-induced activation in the RAW264.7 mouse macrophage cell line.
  
  
  CONCLUSIONS
  This is the first report that a marine bioproduct protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazine, a well-known prodrug that releases 5-ASA. We believe that the oral administration of zonarol might offer a better treatment for human IBDs than 5-ASA, or may be useful as an alternative/additive therapeutic strategy against UC, without any evidence of side effects.
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Laboratory of Nutraceuticals and Functional Foods Science, Graduate School of Marine Science and Technology, Tokyo 108-8477, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Laboratory of Nutraceuticals and Functional Foods Science, Graduate School of Marine Science and Technology, Tokyo 108-8477, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka 020-8551, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kitsuyama
authors.affiliation: Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka 020-8551, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Shared-Use Research Center, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Nawata
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Laboratory of Pathology, Fukuoka Wajiro Hospital, Fukuoka 811-0213, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.affiliation: Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka 020-8551, Japan; Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, Hachioji 192-0982, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Satoh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D000459:Phaeophyceae / Q000737:chemistry / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D006873:Hydroquinones; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C000603465:Zonarol; D019804:Mesalamine; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C031927:hydroquinone