Spices as Alternative Agents for Gastric Ulcer Prevention and Treatment

1.1 Important aspects on ulcer pathogenesis World-wide, peptic Ulcer disease (PUD) is considered as a common gastrointestinal disorder. It develops as a result of altered balance between offensive and defensive factors. Offensive (aggressive) factors disrupt normal mucosal integrity and allow H+ back diffusion with a subsequent cellular injury. Helicobacter pylori (H. pylori) and nonsteroidal antiinflammatory drugs (NSAID) represent the major aggressive factors associated with PUD. Experimentally induced gastric ulcer has expanded our knowledge on ulcer pathogenesis. Indomethacine, 80% ethanol and pyloric ligation are the methods commonly applied in experimental ulcer models. Other universally accepted experimental ulcer models include 0.2 mol/L NaOH, 25% NaCl, stress induced by swimming (1), acetylsalicylic acid (2), coldrestraint (3) and hypothermic restraint (4). A major event in the pathogenesis of NSAID induced gastric ulcer is represented by inhibition of prostaglandin (PG) synthesis, enhancement of gastric acid secretion, suppression of bicarbonate secretion, glutathione (GSH) levels, mucosal circulation, cell proliferation and growth as well as alteration of gastric mucosal barrier integrity. Inhibition of PG biosynthesis enhances generation of leukotrienes and other products of the 5lipoxygenase pathway (5). These products disrupt the mucosal barrier with subsequent enhancement of gastric mucosal permeability for H + ions and Na+ ions and reduction of transmucosal potential difference (6, 7). Furthermore, NSAID uncouple mitochondrial oxidative phosphorylation, affect mitochondrial morphology, reduce the intracellular ATP levels and alter the normal regulatory cellular function (8). These processes promote erosions and ulcer formation. In addition, generation of reactive oxygen species (ROS) is also considered as a major factor contributing to ulcer pathogenesis. Another, prostaglandin-independent pathway of gastric ulcer pathogenesis is induced by enhanced endothelial adhesion, activation of polymorphonuclear cells (PMN) with subsequent release of oxidative byproducts (9, 10). PMN activation induces depletion of GSH and sulfhydryl compounds (SH) in tissue with enhanced mucosal myeloperoxidase (MPO) and malondialdehyde (MDA) concentration (11). Myeloperoxidase is considered as a marker of oxidative process induced by PMN tissue infiltration. Similarly, in ethanol-induced gastric mucosal injury there is enough evidence to suggest the role of oxidative burst. Ethanol-induced oxidative damage is commonly associated with