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Ivashkin KV, Izatullaev EA, Korneeva VR. Gastric Cytoprotection as Basis of Gastrointestinal Mucosa Protection and Repair in Erosive Ulcerative Lesions of Various Aetiologies. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2020; 30:7-17. [DOI: 10.22416/1382-4376-2020-30-7-17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Aim.Assessment of efficacy and the mechanism of action of gastrointestinal mucosa (GM) protection in current treatment settings with methylmethionine-sulfonium chloride (vitamin U) to illustrate its applicability in erosive ulcerative lesions of various aetiologies.Key points.Aside to damage prevention in exposure to aggressive agents, gastroprotection implies healing promotion under the preserved level of hydrochloric acid secretion. Prostaglandins (PG) and SH-antioxidants are key mediators of gastroprotection in acute and chronic damage. SH-containing endogenous substances (L-cysteine, D,L-methionine, GSH) and exogenous molecules (methylmethionine-sulfonium chloride (MMSC), N-acetylcysteine) prevent damage due to the ability to absorb/neutralise free radicals released in xenobiotic-triggered cell damage, inhibit TNF-α expression, reduce the aspirin-induced leukocyte-endothelium adhesion and stimulate mucin release. In experiment, MMSC prevented the ethanol-induced GM damage, stimulated mucin release and its redistribution on the GM surface; in clinical trials, MMSC effectively facilitated remission in duodenal ulcer.Conclusion.Preparations exerting a protective effect on gastroduodenal mucosa, such as methylmethionine-sulfonium chloride (vitamin U), may improve basic treatment settings and facilitate remission in erosive ulcerative lesions of upper gastrointestinal tract.
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Affiliation(s)
- K. V. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | - V. R. Korneeva
- Sechenov First Moscow State Medical University (Sechenov University)
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Zakaria ZA, Balan T, Mamat SS, Mohtarrudin N, Kek TL, Salleh MZ. Mechanisms of gastroprotection of methanol extract of Melastoma malabathricum leaves. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 15:135. [PMID: 25927982 PMCID: PMC4487837 DOI: 10.1186/s12906-015-0638-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Accepted: 03/30/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Melastoma malabathricum L. (Melastomaceae) is a small shrub with various medicinal uses. The present study was carried out to determine the gastroprotective mechanisms of methanol extract of M. malabathricum leaves (MEMM) in rats. METHODS The extract's mechanisms of gastroprotection (50, 250, 500 mg/kg) were studied using the pylorus-ligation in rat model wherein volume, pH, free and total acidity of gastric juice, and gastric wall mucus content were determined. The involvement of endogenous nitric oxide (NO) and sulfhydryl (SH) compounds in the gastroprotective effect of MEMM were also measured. MEMM was subjected to the antioxidant, anti-inflammatory and phytochemical analysis and HPLC profiling. RESULTS MEMM contained various phyto-constituents with quercitrin being identified as part of them. MEMM and quercitrin: i) significantly (p < 0.05) reduced the volume and acidity of gastric juice while increasing the pH and gastric wall mucus content.; ii) significantly (p < 0.05) increased the level of SOD, GTP and GTR while significantly (p < 0.05) reduced the level of CAT, MPO and TBARS activities.; iii) exerted gastroprotective activity when assessed using the ethanol-induced gastric ulcer assay, which was reversed by N(G)-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase) and N-ethylmaleimide (NEM; a sulfhydryl (SH) blocker). MEMM inhibited the lipoxygenase (LOX) and xanthine oxidase (XO) activities with the highest affinity for the former while quercitrin showed high affinity for XO activity. CONCLUSIONS MEMM exhibited a gastroprotective activity due partly to the presence of quercitrin, its antioxidant and anti-inflammatory activities, and via the modulation of NO and SH groups.
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Affiliation(s)
- Zainul Amiruddin Zakaria
- Halal Product Research Institute, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
- Integrative Pharmacogenomics Institute (iPROMISE), Faculty of Pharmacy, Universiti Teknologi MARA, Shah Alam, Selangor, Malaysia.
| | - Tavamani Balan
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Serdang, Selangor, Malaysia.
| | - Siti Syariah Mamat
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Serdang, Selangor, Malaysia.
| | - Norhafizah Mohtarrudin
- Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Serdang, Selangor, Malaysia.
| | - Teh Lay Kek
- Integrative Pharmacogenomics Institute (iPROMISE), Faculty of Pharmacy, Universiti Teknologi MARA, Shah Alam, Selangor, Malaysia.
| | - Mohd Zaki Salleh
- Integrative Pharmacogenomics Institute (iPROMISE), Faculty of Pharmacy, Universiti Teknologi MARA, Shah Alam, Selangor, Malaysia.
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de Morais Lima GR, de Albuquerque Montenegro C, de Sousa Falcão H, de Jesus NZT, Cabral AGS, Gomes IF, Agra MDF, Tavares JF, Batista LM. Gastroprotective activity of the ethanolic extract and hexane phase of Combretum duarteanum Cambess. (Combretaceae). J Nat Med 2012; 67:492-502. [PMID: 22983657 DOI: 10.1007/s11418-012-0706-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2011] [Accepted: 08/21/2012] [Indexed: 02/06/2023]
Abstract
Combretum duarteanum Cambess. is found in South America, particularly in Bolivia, Paraguay, and Brazil. In Paraiba state (Brazil), the species usually occurs in the Caatinga biome. It is popularly known as mofumbo, cipiúba, or cipaúba. This work aims to evaluate the gastroprotective activity and the cytoprotective mechanisms of the ethanolic extract (Cd-EtOHE) and hexane phase (Cd-HexP) obtained from the leaves of C. duarteanum. Doses at 62.5, 125, 250, and 500 mg/kg of Cd-EtOHE and Cd-HexP were tested in models of gastric ulcers induced by HCl/ethanol, absolute ethanol, stress, non-steroidal anti-inflammatory drugs, and pylorus ligation in male rats or mice. Cd-EtOHE and Cd-HexP significantly reduced gastric injuries induced in all models. Cd-EtOHE and Cd-HexP did not alter gastric juice parameters such as pH, [H(+)], or volume after pylorus ligation. Cytoprotective mechanisms of Cd-EtOHE and Cd-HexP in relation to mucus, nitric oxide (NO), and sulfhydryl (SH) groups were evaluated. Neither product increased the mucus, and they both showed dependence on NO and SH groups to prevent gastric ulcer. Both Cd-EtOHE and Cd-HexP demonstrated gastroprotective activity.
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Affiliation(s)
- Gedson Rodrigues de Morais Lima
- Departamento de Ciências Farmacêuticas, Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa, PB, 58051-970, Brazil
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Morphologic and pharmacological investigations in the epicatechin gastroprotective effect. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:708156. [PMID: 22666296 PMCID: PMC3359827 DOI: 10.1155/2012/708156] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2012] [Accepted: 02/29/2012] [Indexed: 12/18/2022]
Abstract
Previous studies of the gastroprotective activity of plants have highlighted the importance of the polyphenolic compound epicatechin (EC) in the treatment of gastric ulcers. This paper aimed to evaluate and characterize the gastroprotective mechanism of action of EC using male rats. The gastroprotective action of EC was analyzed in gastric ulcers induced by ethanol or indomethacin. The involvement of sulfhydryl (SH) groups, K+ATP channels, α2 adrenoceptors, gastric antisecretory activity, and the amount of mucus in the development of gastric ulcers were investigated. The lowest effective dose of EC providing gastroprotective effects was 50 mg/kg in the ethanol-induced gastric ulcers and 25 mg/kg in the indomethacin-induced gastric ulcers. The gastroprotection seen upon treatment with EC was significantly decreased in rats pretreated with a SH compound reagent or an α2-receptor antagonist, but not with a K+ATP channel blocker. Furthermore, oral treatment with EC increased mucus production and decreased H+ secretion. Immunohistochemistry demonstrated the involvement of superoxide dismutase (SOD), nitric oxide (NO), and heat shock protein-70 (HSP-70) in the gastroprotection. These results demonstrate that EC provides gastroprotection through reinforcement of the mucus barrier and neutralization of gastric juice and this protection occurs through the involvement of SH compounds, α2-adrenoceptors, NO, SOD, and HSP-70.
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Rozza AL, Moraes TDM, Kushima H, Tanimoto A, Marques MOM, Bauab TM, Hiruma-Lima CA, Pellizzon CH. Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene: Involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E2. Chem Biol Interact 2011; 189:82-9. [DOI: 10.1016/j.cbi.2010.09.031] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2010] [Revised: 09/28/2010] [Accepted: 09/30/2010] [Indexed: 12/16/2022]
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Arruda APCCBN, Coelho RG, Honda NK, Ferrazoli C, Pott A, Hiruma-Lima CA. Gastroprotective Effect of Serjania erecta Radlk (Sapindaceae): Involvement of Sensory Neurons, Endogenous Nonprotein Sulfhydryls, and Nitric Oxide. J Med Food 2009; 12:1411-5. [DOI: 10.1089/jmf.2008.0269] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
| | - Roberta Gomes Coelho
- Chemistry Department, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
| | - Neli Kika Honda
- Chemistry Department, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
| | - Catharine Ferrazoli
- Physiology Department, Biosciences Institute, São Paulo State University-UNESP, Botucatu, São Paulo
| | - Arnildo Pott
- Biology Department, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
| | - Clélia Akiko Hiruma-Lima
- Physiology Department, Biosciences Institute, São Paulo State University-UNESP, Botucatu, São Paulo
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de Paula Ferreira M, Nishijima CM, Seito LN, Dokkedal AL, Lopes-Ferreira M, Di Stasi LC, Vilegas W, Hiruma-Lima CA. Gastroprotective effect of Cissus sicyoides (Vitaceae): involvement of microcirculation, endogenous sulfhydryls and nitric oxide. JOURNAL OF ETHNOPHARMACOLOGY 2008; 117:170-174. [PMID: 18304768 DOI: 10.1016/j.jep.2008.01.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2007] [Revised: 01/04/2008] [Accepted: 01/12/2008] [Indexed: 05/26/2023]
Abstract
AIM OF THE STUDY Cissus sicyoides L. is a medicinal plant popularly known in Brazil against various diseases and the research interest in this plant is justifiable because of its potential medicinal value in stomachache and gastric ulcer. MATERIALS AND METHODS The methanolic extract obtained from the leaves of Cissus sicyoides (Cc) was evaluated for the ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH, absolute ethanol, piroxicam and pylorus ligature) in rodents. We also evaluated microcirculation, antioxidant action and participation of NO (nitric oxide) and sulfhydryls (SH) groups in the Cc gastroprotective action. RESULTS Administration of Cc significantly reduced gastric lesions induced by different ulcerogenic agents in rodents. This extract administered by oral route significantly increased gastric volume without exerting antisecretory effect. The Cc effect involved an increase of the defense mechanism of the gastrointestinal mucosa such as NO and SH groups that prevent and attenuate the ulcer process. The Cc also has antioxidant property against oxidative stress but does not modify microcirculation response in gastric mucosa. CONCLUSIONS These results confirmed the traditional use of Cissus sicyoides for the treatment of gastric ulcer.
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Affiliation(s)
- Mariana de Paula Ferreira
- Physiology Department, Biosciences Institute, CP 510,UNESP-São Paulo State University, 18618-000 Botucatu, SP, Brazil
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Andreo MA, Ballesteros KVR, Hiruma-Lima CA, Machado da Rocha LR, Souza Brito ARM, Vilegas W. Effect of Mouriri pusa extracts on experimentally induced gastric lesions in rodents: role of endogenous sulfhydryls compounds and nitric oxide in gastroprotection. JOURNAL OF ETHNOPHARMACOLOGY 2006; 107:431-41. [PMID: 16698206 DOI: 10.1016/j.jep.2006.04.001] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2005] [Revised: 03/20/2006] [Accepted: 04/03/2006] [Indexed: 05/09/2023]
Abstract
Several plants are used in folk medicine to treat gastrointestinal disorders. Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used in the central region of Brazil against gastric ulcer. Two organic extracts methanolic (MeOH) and dichloromethane (DCM) obtained by sequential extraction from the leaves of Mouriri pusa were evaluated for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3M HCl/60% EtOH, absolute ethanol, non-steroidal anti-inflammatory drug, stress and pylorus ligature) in mice and rats. The best results were obtained after pretreatment with MeOH extract whereas the DCM extract did not show the same significant antiulcerogenic activity. No acute toxicity was observed in animals treated with 5 g/kg, p.o. of MeOH extract. The mechanism involving the antiulcerogenic action of MeOH extract seemed to be related to NO generation and also suggested the effective participation of endogenous sulfhydryl group in the gastroprotective action. Phytochemical investigation of the MeOH extract of Mouriri pusa yielded tannins, flavonoids and (-)-epicatechin. The presence of these phenolic compounds probably would explain the antiulcerogenic effect of the polar extract of Mouriri pusa leaves.
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Affiliation(s)
- Marcio Adriano Andreo
- Departamento de Química Orgânica, Instituto de Química, CP 355, CEP 14801-970, UNESP, São Paulo State University, Araraquara, SP, Brasil
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Chen SH, Liang YC, Chao JCJ, Tsai LH, Chang CC, Wang CC, Pan S. Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats. World J Gastroenterol 2005; 11:3746-50. [PMID: 15968732 PMCID: PMC4316028 DOI: 10.3748/wjg.v11.i24.3746] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats.
METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured.
RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats.
CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis.
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Affiliation(s)
- Sheng-Hsuan Chen
- Department and Research Center of Gastroenterology, Taipei Medical University Hospital, Taipei 110, Taiwan, China.
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Watanabe T, Ohara S, Ichikawa T, Saigenji K, Hotta K. Mechanisms for cytoprotection by vitamin U from ethanol-induced gastric mucosal damage in rats. Dig Dis Sci 1996; 41:49-54. [PMID: 8565766 DOI: 10.1007/bf02208583] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A comparison was made of the effects of a nonsulfhydryl compound, vitamin U (methylmethioninesulfonium chloride, MMSC), and a sulfhydryl compound, cysteine (Cys), with regard to the inducement of acute gastric mucosal damage in the presence and absence of N-ethylmaleimide (NEM), a sulfhydryl-blocking reagent. The effects of MMSC, Cys, or NEM on gastric mucin content were examined using a newly developed biochemical method. MMSC and Cys inhibited mucosal damage due to 50% ethanol. The preinjection of NEM had no effect on cytoprotection of prostaglandins, but prevented the effects of Cys and MMSC. MMSC and Cys increased surface mucin content but lessened that of deep mucin. NEM decreased surface mucin and increased deep mucin. It thus follows that sulfhydryl compounds accelerate the secretion of deep mucin and accumulate surface mucin. The cytoprotective mechanism of MMSC may thus be mediated by sulfhydryl compounds, and the increase in surface mucosal mucin may possibly be related to cytoprotection.
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Affiliation(s)
- T Watanabe
- Department of Internal Medicine, School of Medicine, Kitasato University, Kanagawa, Japan
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