| Objective Gastric ulcer (GU) is a worldwide illness that affects billions of people in the globe. There is no drug that can treat GU thoroughly because of the complex pathogenesis and unknown etiology. At present, the drugs used in the patients with GU mainly include antiacids, drugs reducing gastric acid secretion, anti- -helicobacter pyloridis drugs, and mucosal protective agents. However, these single-active drugs are usually used in combination of each orther in the clinical practice, and ulcers easily relapse after drugs withdrawal. Pomegranate bark is the dry peel of pomegranate, the essential component of which is tannin. Recently, it has been shown that tanin has effects of antiulcer on some of experimental gastric ulcer models in animal models. So far, there was no research paper about effects of the acetone extract obtained from pomegranate bark (POM) on GU. Thus, here we systematically studied the antiulcer effects of acetone extract obtained from pomegranate peel, antiulcer mechanism, and its acute toxicity. Methods (1) Using acetone to obtain the extractive from pomegranate peel. Detecting the content of tanin by complexometry. (2) The antiulcer effects of POM were evaluated using 3 experimental gastric ulcer models that were established by water-immersion stress, intragastric ethanol and pylorus ligation, respectively. (3) The effects of POM administrated previously on gastric secretion in rats with pylorus ligation were observed. (4) Using pathomorphology technique, the protective effects of POM given previously on gastric ulcers induced by alcohol in rats were further observed. Furtheremore, the contents of nitric oxide (NO), malondialdehyde (MDA), the activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) from rats gastric mucosa were measured so as to explore the interrelation between therapeutic effects of POM and these factors. (5) The effects of POM on the expressions of nervous nitrogen monoxide synthase (nNOS), endothelial nitrogen monoxide synthase (eNOS), and induced nitrogen monoxide synthase (iNOS) in rat gastric mucosa damaged by alcohol were analysed using immunohistochemical method. (6) The effects of POM on the the levels of PGE2 and 6-keto—PGF1αin gastric mucosa were studied with radioimmunoassay. (7) Evaluate the acute toxicity of POM in mice after oral administration.Results (1) The content of tanin in POM was 73%. (2) POM significantly inhibited ulcerative formation induced by both water- -immersion stress and pylorus ligation, obviously antagonized the gastric mucosa damages induced by intragastric ethanol, in dose-dependent manner. The antiulcer activity of POM was similar to that of Colloidal Bismuth Subcitrate(CBS). (3) POM significantly increased the secretion of adherent mucus and free mucus,but did not affect elevation of the free acidity, total acidity, and total acid output, gastric juice volume, gastric pepsin activity induced by pylorus ligation. The antiulcer activity of POM (500mg/kg) was superior to that of cimetidine (Cim 100 mg/kg). (4) POM significantly inhibited elevation of MDA and decrease of NO level,as well as the activities of both SOD and GHS-PX from gastric mucosa induced by absolute alcohol . (5) POM given previously orally significantly suppressed alcohol -induced decreasing expression of nNOS and eNOS as well as elevatiing expression of iNOS from rats gastric mucosa. (6) POM given previously orally significantly increased the levels of PGE2 and 6-keto—PGF1αin gastric mucosa. (7) The LD50 and 95% confidence limit of POM (oral administration) were 8469.28 mg/kg and (8469.28±1216.58) mg/kg, respectively. However, it was found that a hepatic injury could be caused when high doses of the POM were used during the periods of acute toxic assay.Conclusion (1)POM has a protective role against gastric ulcer. The essential component of POM is tanin that plays an important role. (2) It is suggested that POM shows its antiulcer effects via direct local action. (3) It seems that the antiulcer mechanisms of POM involve in the following aspects. Firstly, POM increases secretion of adherent mucus and free mucus from the stomach wall. Secondly, POM inhibits generation of oxygen-derived free radicals, decreases the consumption of GSH-PX and SOD, and maintains content of NO at normal level. Thirdly, POM inhibits decreasing expression of nNOS and eNOS as well as elevating expression of iNOS from gastric mucosa to maintain content of NO in normal level. Finally,POM increases the levels of gastric mucosa PGE2 and 6-keto—PGF1α。(4) The maximal therapeutical dose (500mg/kg) of POM we used is safe to mice.
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