Abstract
Background and AimWe 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.Methods and ResultsWe 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.ConclusionsThis 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.
Highlights
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC), are chronic autoimmune inflammatory disorders of the gastrointestinal tract [1,2]
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-aminosalicylic acid (5-ASA)
We believe that the oral administration of zonarol might offer a better treatment for human inflammatory bowel disease (IBD) than 5-ASA, or may be useful as an alternative/additive therapeutic strategy against UC, without any evidence of side effects
Summary
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC), are chronic autoimmune inflammatory disorders of the gastrointestinal tract [1,2]. UC is a complex disease orchestrated by multiple factors, and its etiology/pathogenesis is poorly understood, it is likely that immune dysregulation, mucosal barrier dysfunction and/or a loss of immunological tolerance to commensal microbiota, lead to imbalanced and elevated inflammatory cells and aberrant cytokine production [1,2,3,4,5,6]. Inflammatory cytokines, such as tumor necrosis factor (TNF)-a or interleukin (IL)-1b, have been implicated in the pathogenesis of UC [3,4,5,6]. Our goal is to establish a safe and effective cure for inflammatory bowel disease (IBD) using zonarol
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