Abstract
Gastric ulcer is sores that form in the stomach mucosal layer because of erosion caused by high acid secretion and excessive use of non-steroidal anti-inflammatory drugs. Prodigiosins (PdGs) are red-pigmented secondary metabolites produced by bacteria, including actinomycetes. Butylcycloheptylprodigiosin (1) and undecylprodigiosin (2) were identified and isolated from a crude extract of the actinomycete RA2 isolated from the Red Sea Sponge Spheciospongia mastoidea. Chemical structure of 1 and 2 was determined by NMR and mass spectroscopy. Although their antioxidant and anti-inflammatory properties are known, their effect on gastric lesion is unknown. Therefore, this study aimed to investigate gastroprotective effects of PdGs against HCl/ethanol-induced gastric lesion in rats. Oral pretreatment with PdGs (100, 200, and 300 mg/kg) attenuated severity of HCl/ethanol-induced gastric mucosal injury, as evidenced by decreases in gastric lesion index scores, ulceration area, histopathologic abnormality, and neutrophil infiltration. These effects were comparable to those of omeprazole, a standard anti-gastric ulcer agent. HCl/ethanol-induced gastric erosions was associated with tremendous increases in lipid peroxidation, nitric oxide, and pro-inflammatory cytokines and mediators (myeloperoxidase, interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2), and with significant decreases in enzymatic and non-enzymatic antioxidant activities. However, PdGs ameliorated gastric inflammation and oxidative stress by downregulating nuclear factor kappa B and inducible nitric oxide synthase expression and upregulating heme oxygenase-1 expression. PdGs prevented gastric mucosal apoptosis by downregulating Bax and caspase-3 expression and upregulating Bcl-2 expression, thereby increasing prostaglandin E2 production. Our results suggested that PdGs exerted gastroprotective effects by decreasing the levels of inflammatory mediators, apoptotic markers, and antioxidants.
Highlights
Gastric ulcer is a lesion that penetrates the mucosal muscularis layer characterized by inflammation, irritation, and cell loss in the gastric mucosa, can advance to gastric cancer [1]
By using the Dictionary of Natural Products (DNP) as a reference, we identified 1 as butylcycloheptylprodigiosin
One study reported that low expression of NF-κB causes failure of cytokine production and neutrophil recruitment in the gastric mucosa of children and adults infected with H. pylori [35]
Summary
Gastric ulcer is a lesion that penetrates the mucosal muscularis layer characterized by inflammation, irritation, and cell loss in the gastric mucosa, can advance to gastric cancer [1]. Common causes of gastric ulcer include Helicobacter pylori infection and excessive use of non-steroidal anti-inflammatory drugs. Inflammation and oxidative damage are commonly associated with gastric ulcer [3]. Oxidative damage is a serious problem in gastric ulcer [4]. Excessive production of reactive oxygen species (ROS) stimulates pro-inflammatory cytokine production, induces cellular protein damage, and disrupts the stomach lining, thereby causing further injury to the gastric mucosa [2]. Alternative therapies with antioxidants have been studied to minimize the risk of gastric ulcer and stomach cancer
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