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      Gastroprotection of Suaveolol, Isolated from Hyptis suaveolens, against Ethanol-Induced Gastric Lesions in Wistar Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryls

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          Abstract

          Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced gastric ulcer experimental model in rats. The results show that the hexane extract had protective activity (close to 70% when using doses between 10 and 100 mg/kg), and that the compound suaveolol, isolated from this extract, was one of the active gastroprotective agents. This is the first report about the gastroprotective activity of suaveolol. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 12.6, 21.3, 39.6 and 70.2% gastroprotection respectively. The effect elicited by suaveolol (at 100 mg/kg) was attenuated by pretreatment with either N G-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of this compound involves NO, prostaglandins and sulfhydryl groups.

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          Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006.

          Despite progress in diagnosis and treatment, peptic ulcer disease (PUD) remains a common reason for hospitalization and operation. The purpose of this study was to quantify the time trends of hospitalizations and operations for PUD in the United States (US) since 1993. The Healthcare Cost and Utilization Project Nationwide Inpatient Sample is a 20% stratified sample of all hospitalizations in the United States. It was used to study hospitalizations with PUD as the principal diagnosis during 1993 to 2006, including details on ulcer site, complications, procedures, and mortality. Statistical methods included the chi test and multivariate logistic regression. The national estimate of hospitalizations for PUD decreased significantly from 222,601 in 1993 to 156,108 in 2006 (-29.9%), with a larger reduction in duodenal ulcers (95,552 in 1993 vs. 60,029 in 2006, -37.2%) than gastric ulcers (106,987 in 1993 vs. 86,064 in 2006, -19.6%). The inpatient mortality rate of PUD decreased from 3.8% to 2.7% during 1993 to 2006 (P < 0.001). Hemorrhage remained the most common complication (71.6% in 1993; 73.3% in 2006) but perforation had the highest mortality (15.1% in 1993; 10.6% in 2006). In comparison to 1993, patients hospitalized for PUD in 2006 more frequently had endoscopic treatment to control bleeding (12.9% vs. 22.2%, P < 0.001), similar use of surgical oversewing of ulcer (7.6% vs. 7.4%), less use of gastrectomy (4.4% vs. 2.1%, P < 0.001), and less use of vagotomy (5.7% vs. 1.7%, P < 0.001). In multivariate logistic regressions, the determinants of mortality were similar in 1993 and 2006. Hospitalizations for PUD decreased in the United States from 1993 to 2006, suggesting a decrease in the prevalence and/or severity of ulcer complications over this recent time period. Despite increased patient age and comorbidities, there has been a significant decrease in PUD mortality, a significant increase in the use of therapeutic endoscopy for bleeding ulcer, and a significant decrease in the use of definitive surgery (vagotomy or resection) for ulcer complications.
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            Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins.

            This study investigated the possible mechanisms underlying the gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats. Rats were randomly assigned to vehicle-, simvastatin-, simvastatin+L-arginine- and simvastatin+N(G)-nitro-L-arginine methyl ester (L-NAME)-pretreated groups for two weeks. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Gastric juice parameters (total acid output, pepsin activity and mucin concentration) were determined. The stomachs tissues were used for determination of gastric mucosal lipid peroxides, superoxide dismutase, catalase, total nitrites and prostaglandin E(2) levels. Pretreatment with simvastatin (10 mg/kg, orally, for 2 weeks) caused significant reduction in gastric mucosal lesions and lipid peroxides associated with a significant increase in gastric juice mucin concentration. Simvastatin significantly increased the gastric mucosal total nitrite and prostaglandin E(2) levels. Additionally, simvastatin attenuated the elevations in gastric mucosal superoxide dismutase observed with indomethacin. The gastroprotective effect afforded by simvastatin was significantly augmented by coadministration with L-arginine (a nitric oxide precursor) and inhibited by coadministration with L-NAME (a nitric oxide synthase inhibitor). Results confirm a gastroprotective effect for simvastatin, and indicate that the anti-ulcer effect of simvastatin is mediated by scavenging free radicals, increasing nitric oxide and prostaglandin E(2) levels, and increasing gastric juice mucin production. We conclude that simvastatin represents a more suitable antihyperlipidemic therapy for patients who are at risk of gastric ulcers that were induced by the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
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              Gastroprotective and ulcer healing effects of essential oil from Hyptis spicigera Lam. (Lamiaceae).

              Hyptis Jacq. (Lamiaceae) is being used in traditional medicine to treat fever, inflammation and gastric disturbances. Hyptis spicigera Lam. is a native plant distributed across the central region of Brazil. The essential oil extracted from this plant is used in folk medicine as antipyretic. The effects of the essential oil obtained from the aerial parts of Hyptis spicigera (OEH) were evaluated for their gastroprotective and healing activities. OEH chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The gastroprotective action of the OEH was evaluated in rodent experimental models (ethanol and NSAID). To elucidate mechanisms of action, the antisecretory action and involvements of NO, SH, mucus and PGE2 were evaluated. The acetic acid-induced gastric ulcer model and Western Blot assay (COX-2 and EGF) were also used to evaluate the OEH healing capacity. GC-MS analysis of OEH indicated three monoterpenes as major compounds: alpha-pinene (50.8%), cineole (20.3%) and beta-pinene (18.3%) and, at the dose of 100 mg/Kg, p.o., OEH provided effective gastroprotection against lesions induced by absolute ethanol (97%) and NSAID (84%) in rats. OEH do not interfere with H+ secretion in gastric mucosa and its gastric protection does not depend on nitric oxide (NO) and sulfhydryl compounds (SH). The gastroprotective action of OEH occurs due to an increase in the gastric mucus production (28%) induced by PGE2 levels. Furthermore, OEH demonstrated a great healing capacity with 87% of reduction in ulcerative lesion area. It accelerated the healing of acetic acid-induced gastric lesions due to an increase in COX-2 (75%) and EGF (115%) expression in gastric mucosa. No sign of toxicity was observed in this study, considering the analyzed parameters. All these results suggest the efficacy and safety of Hyptis spicigera in combating and healing gastric ulcer. Considering the results, it is suggested that the OEH could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                26 July 2012
                August 2012
                : 17
                : 8
                : 8917-8927
                Affiliations
                [1 ]Superior Medicine School, National Polytechnic Institute, Plan de San Luis y Díaz Mirón, Colonia Santo Tomás, Delegación Miguel Hidalgo, Mexico City, 11340, Mexico; Email: cvarzave@ 123456gmail.com (C.V.-A.); jearrval@ 123456yahoo.com.mx (J.A.); gerardocruz2282@ 123456hotmail.com (G.C.-H.)
                [2 ]Zaragoza Faculty of Higher Studies, Batalla del 5 de Mayo Esquina Fuerte de Loreto, Ejército de Oriente, Mexico City, 09230, Mexico; Email: letycruza@ 123456yahoo.com.mx (L.C.A.); adelfo@ 123456puma2.zaragoza.unam.mx (A.R.-R.)
                [3 ]Technological University of the Jungle, Entronque Toniná Carretera Ocosingo-Altamirano, Ocosingo, State of Chiapas, 29950, Mexico; Email: antoniomagdielv@ 123456yahoo.com
                Author notes
                [* ] Author to whom correspondence should be addressed; Email: mesmendoza@ 123456hotmail.com ; Tel.: +55-5729-6300 (ext. 62827); Fax: +55-5622-5329.
                Article
                molecules-17-08917
                10.3390/molecules17088917
                6268582
                22836211
                09c4e113-7042-4749-8812-0e968f2d193c
                © 2012 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 13 June 2012
                : 20 July 2012
                : 23 July 2012
                Categories
                Article

                hyptis suaveolens,suaveolol,gastroprotection,medicinal plants

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