Marine Hydroquinone Zonarol Prevents Inflammation and Apoptosis in Dextran Sulfate Sodium-Induced Mice Ulcerative Colitis

• Published in: PloS one Vol. 9; no. 11; p. e113509
• Main Authors: Yamada, Sohsuke, Koyama, Tomoyuki, Noguchi, Hirotsugu, Ueda, Yuki, Kitsuyama, Ryo, Shimizu, Hiroya, Tanimoto, Akihide, Wang, Ke-Yong, Nawata, Aya, Nakayama, Toshiyuki, Sasaguri, Yasuyuki, Satoh, Takumi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.11.2014; Public Library of Science (PLoS)
• Subjects: Administration, Oral; Algae; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Biology and Life Sciences; Cell activation; Cell Line; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Colon; Colon - pathology; Dextran; Dextran sulfate; Dextran Sulfate - toxicity; Diarrhea; Dictyopteris undulata; Disease Models, Animal; Drinking water; Epithelial cells; Hydroquinone; Hydroquinones - chemistry; Hydroquinones - pharmacology; Hydroquinones - therapeutic use; Immune system; Infiltration; Inflammation - prevention & control; Inflammatory bowel diseases; Interleukin-6 - analysis; Interleukin-6 - genetics; Intestine; Lipopolysaccharides; Lipopolysaccharides - toxicity; Macrophages; Male; Medical treatment; Medicine and Health Sciences; Mesalamine - therapeutic use; Mice; Mice, Inbred ICR; Mucosa; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Oral administration; Phaeophyceae - chemistry; Phaeophyceae - metabolism; Pharmacology; Polyphenols; Rodents; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Side effects; Signaling; Sodium; Sulfasalazine; Sulfate; Sulfates; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - genetics; Ulcerative colitis; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113509

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. 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. 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.