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      The Effects of Methanolic Extract of Melissa officinalis on Experimental Gastric Ulcers in Rats

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          Abstract

          Background

          Melissa officinalis (MO) has potent antioxidant activity. Recent research has demonstrated the anti-ulcer properties of some medicinal plants through their antioxidant properties.

          Objectives

          The aim of this study was to evaluate the effects of methanolic extracts of MO on experimental gastric ulcers in rats.

          Materials and Methods

          Male Wistar rats (200 - 250 g) were starved for 24 hours prior to the induction of gastric ulceration by either indomethacin (48 mg/kg/oral) or water immersion restraint (WIR) stress. Experimental rats received either ranitidine (25 mg/kg) or MO extract (150, 300 and 450mg/kg) orally 2 hours prior to WIR stress or indomethacin treatment, for the evaluation of their gastroprotective effects. The control group received the same volume of saline. Gastric lesions were scored according to the surface of lesions on the ulcer index. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) were determined as measures of antioxidant defense, and malondialdehyde (MDA) was determined to measure tissue oxidation.

          Results

          MO extract (150 and 300 mg/kg) significantly decreased the ulcer index in both the indomethacin (1.3 ± 0.09 and 1.5 ± 0.19, respectively) and WIR stress groups (1.5 ± 0.17 and 1.5 ± 0.22, respectively), as compared to the control rats (2.5 ± 0.28) (P < 0.01). MO extract (450 mg/kg) significantly reduced ulcer index readings in WIR stress rats (1.8 ± 0.31 vs. 2.4 ± 0.15 in the WIR group), however, MO extract at a dose of 450 mg/kg did not prevent indomethacin-induced gastric ulceration (2.4 ± 0.26). There was no significant difference in the ulcer index for MO extract- (150 and 300 mg/kg) and ranitidine-treated rats (P > 0.05). Also, MO extract (150 and 300 mg/kg) significantly reduced MDA serum levels (0.69 ± 0.6 µmol/L and 0.85 ± 0.24 µmol/L, respectively, vs. 4.5 ± 1.9 µmol/L in the saline group) and significantly increased antioxidants’ SOD activities (296.3 ± 146.4 U/mL and 561.4 ± 120 U/mL, respectively, vs. 190.2 ± 63.8U/mL in the control group) and GPX levels (8273 ± 3049 U/mL and 14574 ± 5012 U/mL, respectively), compared to the control (3236 ± 1699 U/mL).

          Conclusions

          Our results showed that MO extract may have a gastroprotective effect against experimental gastric ulcers in rats. The exact mechanism has not yet been determined, but it may be due to enhancing enzymatic antioxidant defenses and inhibiting lipid peroxidation.

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          Most cited references33

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          Systematic Review of the Epidemiology of Complicated Peptic Ulcer Disease: Incidence, Recurrence, Risk Factors and Mortality

          Background/Aims: The incidence of uncomplicated peptic ulcer has decreased in recent years. It is unclear what the impact of this has been on the epidemiology of peptic ulcer complications. This systematic review aimed to determine the incidence, recurrence and mortality of complicated peptic ulcer and the risk factors associated with these events. Methods: Systematic PubMed searches. Results: Overall, 93 studies were identified. Annual incidence estimates of peptic ulcer hemorrhage and perforation were 19.4–57.0 and 3.8–14 per 100,000 individuals, respectively. The average 7-day recurrence of hemorrhage was 13.9% (95% CI: 8.4–19.4), and the average long-term recurrence of perforation was 12.2% (95% CI: 2.5–21.9). Risk factors for peptic ulcer complications and their recurrence included nonsteroidal anti-inflammatory drug and/or acetylsalicylic acid use, Helicobacter pylori infection and ulcer size ≧1 cm. Proton pump inhibitor use reduced the risk of peptic ulcer hemorrhage. Average 30-day mortality was 8.6% (95% CI: 5.8–11.4) after hemorrhage and 23.5% (95% CI: 15.5–31.0) after perforation. Older age, comorbidity, shock and delayed treatment were associated with increased mortality. Conclusions: Complicated peptic ulcer remains a substantial healthcare problem which places patients at a high risk of recurrent complications and death.
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            Flavonoids with Gastroprotective Activity

            Peptic ulcers are a common disorder of the entire gastrointestinal tract that occurs mainly in the stomach and the proximal duodenum. This disease is multifactorial and its treatment faces great difficulties due to the limited effectiveness and severe side effects of the currently available drugs. The use of natural products for the prevention and treatment of different pathologies is continuously expanding throughout the world. This is particularly true with regards to flavonoids, which represent a highly diverse class of secondary metabolites with potentially beneficial human health effects that is widely distributed in the plant kingdom and currently consumed in large amounts in the diet. They display several pharmacological properties in the gastroprotective area, acting as anti-secretory, cytoprotective and antioxidant agents. Besides their action as gastroprotectives, flavonoids also act in healing of gastric ulcers and additionally these polyphenolic compounds can be new alternatives for suppression or modulation of peptic ulcers associated with H. pylori. In this review, we have summarized the literature on ninety-five flavonoids with varying degrees of antiulcerogenic activity, confirming that flavonoids have a therapeutic potential for the more effective treatment of peptic ulcers.
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              Effects of reactive oxygen species action on gastric mucosa in various models of mucosal injury.

              The exposure of gastric mucosa to damaging factors, such as ethanol, water restraint stress, or ischemia followed by reperfusion, produces pathological changes: inflammatory process, hemorrhagic erosions, even acute ulcers. The base of these changes is a disturbance of protective mechanisms and disrupture of gastric mucosal barrier. Previous studies pointed out the role of disturbances of gastric blood flow, mucus secretion and involvement of prostaglandins and nitric oxide formation in the pathomechanism of gastric mucosa lesions. The role of reactive oxygen species (ROS) in these processes has been little studied. The purpose of our present investigations is to explain the participation of ROS in acute gastric mucosal damage by various irritants. Experiments were carrying out on 80 male Wistar rats. To assess gastric blood flow (GBF) laser Doppler flowmeter was used. The area of gastric lesions was established by planimetry. The levels of proinflammatory cytokines were measured by ELISA technique. The colorimetric assays were used to determine of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) as well as superoxide dismutase (SOD) activity. We demonstrated that 3.5 h of water immersion and restraint stress (WRS), 30 min of gastric ischemia followed by 60 min of reperfusion or intragastric administration of 100% ethanol, all resulted in appearance of acute gastric mucosal lesions accompanied by a significant decrease of gastric blood flow. These lesions are also accompanied by the significant increase of proinflammatory cytokines including interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) plasma level. Biological effects of ROS were estimated by measuring tissue level of MDA and 4-HNE, the products of lipid peroxydation by ROS, as well as the activity of SOD, the scavanger of ROS. It was established that 3.5 h of WRS, ischemia-reperfusion and 100% ethanol lead to significant increase of MDA and 4-HNE mucosal level, accompanied by a decrease of SOD activity (significant in WRS and ethanol application). The pathogenesis of experimental mucosal damage in rat stomach includes the generation of ROS that seem to play an important role, namely due to generation of lipid peroxides, accompanied by impairment of antioxidative enzyme activity of cells.
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                Author and article information

                Journal
                Iran Red Crescent Med J
                Iran Red Crescent Med J
                10.5812/ircmj
                Kowsar
                Iranian Red Crescent Medical Journal
                Kowsar
                2074-1804
                2074-1812
                15 May 2016
                July 2016
                : 18
                : 7
                : e24271
                Affiliations
                [1 ]Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IR Iran
                [2 ]Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IR Iran
                [3 ]Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, IR Iran
                [4 ]Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, IR Iran
                Author notes
                [* ]Corresponding Author: Gholamreza Sepehri, Professor of Pharmacology, Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IR Iran. Tel/Fax: +98-3433220081, E-mail: gsepehri@ 123456yahoo.com
                Article
                10.5812/ircmj.24271
                5020425
                27651945
                f25cba97-6433-44b7-b9ea-f761bc908803
                Copyright © 2016, Iranian Red Crescent Medical Journal

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

                History
                : 21 October 2014
                : 15 March 2015
                : 11 April 2015
                Categories
                Research Article

                Medicine
                anti-ulcer,ulcer index,gastroprotective,antioxidant,water immersion restraint stress,indomethacin,melissa officinalis

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