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

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.

The Algal Meroterpene 11-Hydroxy-1′-O-Methylamentadione Ameloriates Dextran Sulfate Sodium-Induced Colitis in Mice

“…In the present study, the administration of AMT-E potently down-regulated the expression of these pro-inflammatory cytokines. Our results on the anti-inflammatory capacity of AMT-E are related to previous findings for zonarol, which has also been shown to inhibit the production of the pro-inflammatory cytokine TNF-α in DSS mice [28], and bolinaquinone, which was found to reduce the levels of IL-1β in the TNBS model of intestinal damage [27]. Concerning IL-10, this cytokine is an essential immune component in the intestinal tract, down-regulating the inflammatory process and helping to restore tissue homeostasis [38].…”

Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells

“…Interestingly, the protection afforded by PA, OAA, and AKG was totally different than that of NRF2 activators such as carnosic acid [19,20], zonarol [21,22], and tert-butyl hydroquinone [23]. These activators can protect cells against a high concentration of Glu, but not against H 2 O 2 .…”

Zonarol, a sesquiterpene from the brown algae Dictyopteris undulata , provides neuroprotection by activating the Nrf2/ARE pathway

“…Subsequently, the chemical structure of the hydroquinone was elucidated in 1986 [6]. In a prior study, we described the protective role of ZO against dextran sodium sulfate-induced colon injury in young male Slc:ICR mice, representing a murine model of the inflammatory bowel disease, ulcerative colitis [7]. However, actions on the brain of ZO and its intracellular signaling pathways remain largely unknown.…”

“…Previously, we have shown that electrophilic compounds, such as the hydroquinone product of carnosic acid (CA) from the herb rosemary, manifest a significant advantage over other antioxidant molecules in mediating cytoprotection against oxidative damage because their actions are sustained and amplified by transcriptionmediated signaling pathways [7–12]. Electrophiles can induce the expression of a series of antioxidant enzymes, called “phase-2 enzymes”, including NADPH quinone oxidoreductase 1 (NQO1), glutathione S-tranferase, heme oxygenase-1 (HO-1), and peroxiredoxin 4 (PRDX4), all of which provide efficient cytoprotection by regulating intracellular redox state [13,14].…”