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He JY, Li J, Zhang YY, He HB, He YM, Xu DX, Wang X, Wu HY, Zhang JH, Jahid H, Sadia A, Yu HF, Wang JZ, Zou K. Tormentic acid, a triterpenoid isolated from the fruits of Chaenomeles speciose, protected indomethacin-induced gastric mucosal lesion via modulating miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho a/MLC pathway. PHARMACEUTICAL BIOLOGY 2023; 61:1343-1363. [PMID: 37623313 PMCID: PMC10461523 DOI: 10.1080/13880209.2023.2249526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 07/31/2023] [Accepted: 08/14/2023] [Indexed: 08/26/2023]
Abstract
CONTEXT Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. OBJECTIVE To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. MATERIALS AND METHODS TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. RESULTS TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. DISCUSSION AND CONCLUSIONS TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.
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Affiliation(s)
- Jun-Yu He
- Department of Clinical Medicine, College of Basic Medical Science, China Three Gorges University, Yichang, P.R. China
| | - Jie Li
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Yuan-Yuan Zhang
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Hai-Bo He
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
- Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Shiyan, P.R. China
| | - Yu-Min He
- Department of Clinical Medicine, College of Basic Medical Science, China Three Gorges University, Yichang, P.R. China
| | - Dao-Xiang Xu
- Department of Gastroenterology, Seventh People’s Hospital of Wenzhou, Wenzhou, P.R. China
| | - Xiao Wang
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Hao-Yang Wu
- Department of Clinical Medicine, College of Basic Medical Science, China Three Gorges University, Yichang, P.R. China
| | - Ji-Hong Zhang
- Department of Gastroenterology, Chinese Medicine Clinical Medical College & Hubei Clinical Research Center for Functional Digestive Diseases of Traditional Chinese Medicine, China Three Gorges University, Yichang, P.R. China
| | - Hasan Jahid
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Akter Sadia
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Hui-Fan Yu
- Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Shiyan, P.R. China
| | - Jun-Zhi Wang
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Kun Zou
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
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Zhou G, Sun S, Yuan Q, Zhang R, Jiang P, Li G, Wang Y, Li X. Multiple-Tissue and Multilevel Analysis on Differentially Expressed Genes and Differentially Correlated Gene Pairs for HFpEF. Front Genet 2021; 12:668702. [PMID: 34306013 PMCID: PMC8296822 DOI: 10.3389/fgene.2021.668702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 05/12/2021] [Indexed: 11/15/2022] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a complex disease characterized by dysfunctions in the heart, adipose tissue, and cerebral arteries. The elucidation of the interactions between these three tissues in HFpEF will improve our understanding of the mechanism of HFpEF. In this study, we propose a multilevel comparative framework based on differentially expressed genes (DEGs) and differentially correlated gene pairs (DCGs) to investigate the shared and unique pathological features among the three tissues in HFpEF. At the network level, functional enrichment analysis revealed that the networks of the heart, adipose tissue, and cerebral arteries were enriched in the cell cycle and immune response. The networks of the heart and adipose tissues were enriched in hemostasis, G-protein coupled receptor (GPCR) ligand, and cancer-related pathway. The heart-specific networks were enriched in the inflammatory response and cardiac hypertrophy, while the adipose-tissue-specific networks were enriched in the response to peptides and regulation of cell adhesion. The cerebral-artery-specific networks were enriched in gene expression (transcription). At the module and gene levels, 5 housekeeping DEGs, 2 housekeeping DCGs, 6 modules of merged protein–protein interaction network, 5 tissue-specific hub genes, and 20 shared hub genes were identified through comparative analysis of tissue pairs. Furthermore, the therapeutic drugs for HFpEF-targeting these genes were examined using molecular docking. The combination of multitissue and multilevel comparative frameworks is a potential strategy for the discovery of effective therapy and personalized medicine for HFpEF.
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Affiliation(s)
- Guofeng Zhou
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shaoyan Sun
- School of Mathematics and Statistics, Ludong University, Yantai, China
| | - Qiuyue Yuan
- CEMS, NCMIS, MDIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.,School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Run Zhang
- School of Mathematics and Statistics, Ludong University, Yantai, China
| | - Ping Jiang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Guangyu Li
- CEMS, NCMIS, MDIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China
| | - Yong Wang
- CEMS, NCMIS, MDIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.,School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xiao Li
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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Effectiveness of fibrin sealant as hemostatic technique in accelerating ESD-induced ulcer healing: a retrospective study. Surg Endosc 2019; 34:1191-1199. [PMID: 31236721 DOI: 10.1007/s00464-019-06872-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 05/20/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Healing of gastric endoscopic submucosal dissection (ESD)-induced ulcer is critical for patient recovery. During ESD treatment, submucosal incisions are made with an electrosurgical knife to accomplish en bloc resections of superficial lesions. Nevertheless, excess electrocoagulation may decrease the blood supply of ESD-induced ulcer and delay the ulcer healing. The aim of this retrospective study was to evaluate the effectiveness of conservative electrocoagulation followed by porcine fibrin sealant (FS) as a wound microvessels-protective hemostatic technique in promoting the healing of ESD-induced ulcer. METHODS A total of 332 patients with early gastric cancer (EGCs), or gastric precancerous lesion and gastric adenoma were retrospectively analyzed. Propensity score matching was used to compensate for the differences in age, gender, tumor location, resected specimen area, and pathology. One-month ulcer healing rates and delayed bleeding were compared between two matched groups (combined hemostats group and electrocautery group). RESULTS A total of 115 matched pairs were created after propensity score matching. There was no difference in tumor location, specimen surface area, tumor differentiation and invasion depth between groups. The completed healing rate 1 month after ESD was 44.3% in combined hemostats group and 30.4% in electrocautery group (P = 0.004). There was no difference in delayed massive bleeding rate between two groups (P = 0.300). In addition, based on the multivariate regression analysis for ulcer healing rate, the use of FS (OR, 0.348, 95% CI 0.196 - 0.617, P = 0.000) and larger specimen size (OR, 2.640, 95% CI 2.015-3.458, P = 0.000) were associated with nonhealing ulcer 1 month after ESD. CONCLUSION Applying conservative electrocoagulation followed by porcine FS as a wound microvessels-protective hemostatic technique can promote ESD-induced ulcer healing without increasing delayed bleeding.
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Otsuka T, Sugimoto M, Ban H, Nakata T, Murata M, Nishida A, Inatomi O, Bamba S, Andoh A. Severity of gastric mucosal atrophy affects the healing speed of post-endoscopic submucosal dissection ulcers. World J Gastrointest Endosc 2018; 10:83-92. [PMID: 29774087 PMCID: PMC5955726 DOI: 10.4253/wjge.v10.i5.83] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/04/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate factors associated with the healing of endoscopic submucosal dissection (ESD)-induced ulcers. METHODS We enrolled 132 patients with gastric tumors scheduled for ESD. Following ESD, patients were treated with daily lansoprazole 30 mg or vonoprazan 20 mg. Ulcer size was endoscopically measured on the day after ESD and at 4 and 8 wk. The gastric mucosa was endoscopically graded according to the Kyoto gastritis scoring system. We assessed the number of patients with and without a 90% reduction in ulcer area at 4 wk post-ESD and scar formation at 8 wk, and looked for risk factors for slower healing. RESULTS The mean size of gastric tumors and post-ESD ulcers was 17.4 ± 12.1 mm and 32.9 ± 13.0 mm. The mean reduction rates in ulcer area were 90.4% ± 0.8% at 4 wk and 99.8% ± 0.1% at 8 wk. The reduction rate was associated with the Kyoto grade of gastric atrophy at 4 wk (A0: 97.9% ± 0.6%, A1: 93.4% ± 4.1%, and A2: 89.7% ± 1.0%, respectively). In multivariate analysis, the factor predicting 90% reduction at 4 wk was gastric atrophy (Odds ratio: 5.678, 95%CI: 1.190-27.085, P = 0.029). CONCLUSION The healing speed of post-ESD ulcers was associated with the degree of gastric mucosal atrophy, and Helicobacter pylori eradication therapy is required to perform at younger age.
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Affiliation(s)
- Taketo Otsuka
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Hiromitsu Ban
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Toshiro Nakata
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Masaki Murata
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Atsushi Nishida
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Osamu Inatomi
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Shigeki Bamba
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
| | - Akira Andoh
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
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Sato T, Amano H, Ito Y, Eshima K, Minamino T, Ae T, Katada C, Ohno T, Hosono K, Suzuki T, Shibuya M, Koizumi W, Majima M. Vascular endothelial growth factor receptor 1 signaling facilitates gastric ulcer healing and angiogenesis through the upregulation of epidermal growth factor expression on VEGFR1+CXCR4 + cells recruited from bone marrow. J Gastroenterol 2014; 49:455-69. [PMID: 23982810 DOI: 10.1007/s00535-013-0869-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Accepted: 08/01/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Angiogenesis is essential for gastric ulcer healing. Recent results suggest that vascular endothelial growth factor receptor 1 (VEGFR1), which binds to VEGF, promotes angiogenesis. In the present study, we investigated the role of VEGFR1 signaling in gastric ulcer healing and angiogenesis. METHODS Gastric ulcers were induced by serosal application of 100 % acetic acid in wild-type (WT) and tyrosine kinase-deficient VEGFR1 mice (VEGFR1 TK(-/-)). Bone marrow transplantation into irradiated WT mice was carried out using bone marrow cells isolated from WT and VEGFR1 TK(-/-) mice. RESULTS Ulcer healing was delayed in VEGFR1 TK(-/-) mice compared to WT mice and this was accompanied by decreased angiogenesis, as evidenced by reduced mRNA levels of CD31 and decreased microvessel density. Recruitment of cells expressing VEGFR1 and C-X-C chemokine receptor type 4 (CXCR4) was suppressed and epidermal growth factor (EGF) expression in ulcer granulation tissue was attenuated. Treatment of WT mice with neutralizing antibodies against VEGF or CXCR4 also delayed ulcer healing. In WT mice transplanted with bone marrow cells from VEGFR1 TK(-/-) mice, ulcer healing and angiogenesis were suppressed, and this was associated with reduced recruitment of bone marrow cells to ulcer granulation tissue. VEGFR1 TK(-/-) bone marrow chimeras also exhibited downregulation of EGF expression on CXCR4(+)VEGFR1(+) cells recruited from the bone marrow into ulcer lesions. CONCLUSION VEGFR1-mediated signaling plays a critical role in gastric ulcer healing and angiogenesis through enhanced EGF expression on VEGFR1(+)CXCR4(+) cells recruited from the bone marrow into ulcer granulation tissue.
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Affiliation(s)
- Takehito Sato
- Department of Pharmacology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa, 252-0374, Japan
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Moraes TM, Rozza AL, Kushima H, Pellizzon CH, Rocha LRM, Hiruma-Lima CA. Healing Actions of Essential Oils from Citrus aurantium and d-Limonene in the Gastric Mucosa: The Roles of VEGF, PCNA, and COX-2 in Cell Proliferation. J Med Food 2013; 16:1162-7. [DOI: 10.1089/jmf.2012.0259] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Thiago Mello Moraes
- Department of Physiology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Ariane Leite Rozza
- Department of Morphology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Hélio Kushima
- Department of Physiology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Claudia Helena Pellizzon
- Department of Morphology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Lucia Regina Machado Rocha
- Department of Physiology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Clélia Akiko Hiruma-Lima
- Department of Physiology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
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Park HJ, Kim HS, Kim BR, Park SY, Hong JH, Jo KW, Kim JW. Half-dose rabeprazole has an equal efficacy to standard-dose rabeprazole on endoscopic submucosal dissection-induced ulcer. Dig Dis Sci 2013; 58:1054-61. [PMID: 23065090 DOI: 10.1007/s10620-012-2436-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Accepted: 09/21/2012] [Indexed: 02/15/2023]
Abstract
BACKGROUND Although endoscopic submucosal dissection (ESD)-induced ulcers heal faster and recur less often than non-iatrogenic gastric ulcers, the optimal dosage and duration of proton pump inhibitor treatment for ESD-induced ulcers remain unclear. AIMS To evaluate the efficacy of half-dose rabeprazole on endoscopic submucosal dissection-induced ulcer compared with standard dose rabeprazole. METHODS The study was a prospective randomized controlled double-blind trial at a single tertiary hospital. A total of 80 patients who underwent ESD for gastric neoplasia were enrolled. Of these patients, 10 were not followed to completion. Final analysis included the remaining 70 patients. Rabeprazole 20 or 10 mg, depending on randomization, was given orally for 4 weeks after ESD. RESULTS Of the 70 patients, 45 (64 %) were men, and the median age was 65.2 ± 9.7 years. The mean ESD-induced ulcer area was 673 mm(2). No significant differences in ulcer area reduction ratio (p = 0.49) or ulcer-related symptoms (p = 0.91) were observed between the two groups at 4 weeks after ESD. CONCLUSION For ESD-induced ulcers, treatment with 10 mg of rabeprazole daily produces a similar outcome as 20 mg of rabeprazole with regard to healing efficacy and symptom resolution.
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Affiliation(s)
- Hong Jun Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Institute of Lifelong Health, Wonju College of Medicine, Yonsei University, 162, Ilsan-dong, Gangwon-do, Wonju 220-701, Korea
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Effects of the Ethyl Acetate Fraction of Alchornea triplinervia on Healing Gastric Ulcer in Rats. Pharmaceuticals (Basel) 2011; 4:1423-33. [PMID: 26791640 PMCID: PMC4060132 DOI: 10.3390/ph4111423] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Accepted: 10/17/2011] [Indexed: 12/20/2022] Open
Abstract
Alchornea triplinervia (Spreng.) Muell. Arg (Euphorbiaceae) is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. We previously described the gastroprotective action of methanolic extract (ME) of Alchornea triplinervia and the ethyl acetate fraction (EAF) in increasing of prostaglandin E2 (PGE2) gastric levels in the mucosa. In this work we evaluated the effect of EAF in promoting the healing process in rats with acetic acid-induced gastric ulcers. In addition, toxicity was investigated during treatment with EAF. After 14 days of treatment with EAF, the potent stimulator of gastric cell proliferation contributed to the acceleration of gastric ulcer healing. Upon immunohistochemical analysis, we observed a pronounced expression of COX-2, mainly in the submucosal layer. The 14-day EAF treatment also significantly increased the number of neutrophils in the gastric mucosa regeneration area. The EAF induced angiogenesis on gastric mucosa, observed as an increase of the number of blood vessels supplying the stomach in rats treated with EAF. Oral administration for 14 days of the ethyl acetate fraction from Alchornea triplinervia accelerated the healing of gastric ulcers in rats by promoting epithelial cell proliferation, increasing the number of neutrophils and stimulation of mucus production. This fraction, which contained mainly phenolic compounds, contributed to gastric mucosa healing.
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Vasconcelos PCP, Andreo MA, Vilegas W, Hiruma-Lima CA, Pellizzon CH. Effect of Mouriri pusa tannins and flavonoids on prevention and treatment against experimental gastric ulcer. JOURNAL OF ETHNOPHARMACOLOGY 2010; 131:146-53. [PMID: 20600773 DOI: 10.1016/j.jep.2010.06.017] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2010] [Revised: 06/07/2010] [Accepted: 06/11/2010] [Indexed: 05/16/2023]
Abstract
AIM OF THE STUDY Mouriri pusa, popularly known as "manapuçá" or "jaboticaba do mato", is a plant from Brazilian cerrado that has been found to be commonly used in the treatment of gastrointestinal disturbs in its native region. The present work was carried out to investigate the effect of tannins (TF) and flavonoids (FF) fractions from Mouriri pusa leaves methanolic extract on the prevention and cicatrisation process of gastric ulcers, and also evaluate possible toxic effects. MATERIALS AND METHODS The following protocols were taken in rats: acute assay, in which ulcers were induced by oral ethanol after pre-treatment with the fractions; and 14 days treatment assay, in which ulcers were treated for 14 days after induction by local injection of acetic acid. RESULTS In the acute model, treatment with either, TF (25mg/kg) or FF (50mg/kg), was able to reduce lesion area, showing gastroprotective effect. In addition, FF proved itself anti-inflammatory by reducing COX-2 levels. In acetic acid model, both fractions exhibited larger ulcers' regenerative mucosa, indicating cicatrisation enhancement. FF group also showed augmented cell proliferation, anti-inflammatory action and enhanced angiogenesis as well as increased mucus secretion. Moreover, concerning the toxicity parameters analyzed, no alteration in the fractions groups was observed. CONCLUSIONS Tannins and flavonoids from Mouriri pusa provide beneficial effects against gastric ulcers with relative safety.
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Affiliation(s)
- P C P Vasconcelos
- Botucatu Institute of Biosciences, UNESP - São Paulo State University, Botucatu, SP, Brazil
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Kim YG, Jang BI, Kim TN. A matched case-control study of a novel Acid-pump antagonist and proton-pump inhibitor for the treatment of iatrogenic ulcers caused by endoscopic submucosal dissection. Gut Liver 2010; 4:25-30. [PMID: 20479909 DOI: 10.5009/gnl.2010.4.1.25] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2009] [Accepted: 11/21/2009] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND/AIMS Revaprazan, a novel acid-pump antagonist, and proton-pump inhibitors (PPIs) have pH-independent effects on ulcer healing. The addition of a PPI promotes the cell restitution rate as well as vessel regeneration and maturation for ulcer repair. Revaprazan is known to protect the mucosa by increasing the prostaglandin concentration. METHODS We reviewed the medical records of patients who underwent endoscopic submucosal dissection (ESD) for gastric neoplasia at Yeungnam University Hospital between January 2008 and May 2009. We conducted a matched case-control study to compare the healing rates effected by revaprazan and rabeprazole. RESULTS Each group consisted of 30 patients. The baseline characteristics did not differ significantly between the two groups. Stage S1 disease was observed in 97% and 100% of patients after 8 weeks of treatment in the revaprazan and rabeprazole groups, respectively. In the revaprazan group, only one patient had stage H2 disease: a 54-year-old man with a 5.5-cm lesion after ESD of the ulcer, type IIa early gastric cancer, and adenocarcinoma. No serious adverse effects occurred during the treatment period in either group. CONCLUSIONS The safety and efficacy profiles of revaprazan and rabeprazole are similar for the treatment of ESD-induced ulcers.
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Affiliation(s)
- Yong Gil Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
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Carvalho RR, Pellizzon CH, Justulin L, Felisbino SL, Vilegas W, Bruni F, Lopes-Ferreira M, Hiruma-Lima CA. Effect of mangiferin on the development of periodontal disease: Involvement of lipoxin A4, anti-chemotaxic action in leukocyte rolling. Chem Biol Interact 2009; 179:344-50. [DOI: 10.1016/j.cbi.2008.10.041] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2008] [Revised: 10/23/2008] [Accepted: 10/24/2008] [Indexed: 12/18/2022]
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Hansson M, Hermansson M, Svensson H, Elfvin A, Hansson LE, Johnsson E, Sjöling A, Quiding-Järbrink M. CCL28 is increased in human Helicobacter pylori-induced gastritis and mediates recruitment of gastric immunoglobulin A-secreting cells. Infect Immun 2008; 76:3304-11. [PMID: 18426876 PMCID: PMC2446710 DOI: 10.1128/iai.00041-08] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2008] [Revised: 02/23/2008] [Accepted: 04/13/2008] [Indexed: 01/28/2023] Open
Abstract
Human Helicobacter pylori infection gives rise to an active chronic gastritis and is a major risk factor for the development of duodenal ulcer disease and gastric adenocarcinoma. The infection is accompanied by a large accumulation of immunoglobulin A (IgA)-secreting cells in the gastric mucosa, and following mucosal immunization only H. pylori-infected volunteers mounted a B-cell response in the gastric mucosa. To identify the signals for recruitment of gastric IgA-secreting cells, we investigated the gastric production of CCL28 (mucosa-associated epithelial chemokine) and CCL25 (thymus-expressed chemokine) in H. pylori-infected and uninfected individuals and the potential of gastric B-cell populations to migrate toward these chemokines. Gastric tissue from H. pylori-infected individuals contained significantly more CCL28 protein and mRNA than that from uninfected individuals, while CCL25 levels remained unchanged. Chemokine-induced migration of gastric lamina propria lymphocytes isolated from patients undergoing gastric resection was then assessed using the Transwell system. IgA-secreting cells and IgA(+) memory B cells from H. pylori-infected tissues migrated toward CCL28 but not CCL25, while the corresponding cells from uninfected patients did not. Furthermore, IgG-secreting cells from H. pylori-infected patients did not migrate to CCL28 but instead to CXCL12 (SDF-1alpha). However, chemokine receptor expression did not correlate to the migratory pattern of the different B-cell populations. These studies are the first to show increased CCL28 production during gastrointestinal infection in humans and provide an explanation for the large influx of IgA-secreting cells to the gastric mucosa in H. pylori-infected individuals.
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Affiliation(s)
- Malin Hansson
- Department of Microbiology and Immunology, Institute of Biomedicine, and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Box 435, 405 30 Göteborg, Sweden
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Okazaki M, Shimizu I, Ishikawa M, Fujiwara S, Yamamoto H, Shiraishi T, Horie T, Iuchi A, Ito S. Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine. THE JOURNAL OF MEDICAL INVESTIGATION 2007; 54:83-90. [PMID: 17380018 DOI: 10.2152/jmi.54.83] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
AIM Prostaglandins (PGs) and leukotrienes (LTs) are major factors involved in the defense of the gastric mucosa against ulcer formation. However, little is still known about the gastromucosa-protecting action of proton pump inhibitors (PPIs) and histamine H(2) receptor antagonists (H(2) blockers) in patients with gastric ulcer. We therefore examined the effectiveness of a PPI in protecting the gastric mucosa. METHODS We compared the PGE(2) and LTB(4) levels and the expression levels of cyclooxygenase (COX)-1 and COX-2 mRNA in the gastric mucosa in gastric ulcer patients between the group treated for 8 weeks with a PPI, rabeprazole (PPI group; n=5), and the group treated for 8 weeks with an H(2) blocker, ranitidine (H(2) blocker group; n=6), as well as in nonulcer subjects (control group; n=5). RESULTS The mucosal levels of PGE(2) and COX-2 mRNA expression were significantly lower in the ulcer patients than those in the nonulcer patients, whereas the LTB(4) level was significantly higher in the ulcer patients than that in the nonulcer patients, and it was also significantly lower in the ulcerated mucosa than that in the nonulcerated mucosa. The PPI group had a significantly increased PGE(2) and decreased LTB(4) levels in comparison to the H(2) blocker group during the ulcer-healing stage. The COX-1 mRNA expression showed no difference among the PPI and H(2) blocker groups or between before and after the treatment. However, the COX-2 mRNA expression increased in the PPI group more than that in the H(2) blocker group during the ulcer-healing stage. CONCLUSION These findings demonstrated the significant gastric-mucosa-protecting effect of PPI by increasing the PGE(2) production and reducing the LTB(4) production.
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Affiliation(s)
- Michiyo Okazaki
- Department of Gastroenterology, Kochi Red Cross Hospital, Kochi, Japan
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Akimoto M, Hashimoto H, Shigemoto M, Maeda A, Yamashita K. Effects of antisecretory agents on angiogenesis during healing of gastric ulcers. J Gastroenterol 2005; 40:685-9. [PMID: 16082584 DOI: 10.1007/s00535-005-1611-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2004] [Accepted: 03/04/2006] [Indexed: 02/04/2023]
Abstract
BACKGROUND We studied the effects of a proton pump inhibitor (PPI) and an H2-receptor antagonist (H2-blocker) on angiogenesis during gastric ulcer healing, by examining stromal cell-derived factor (SDF-1) and CXC chemokine receptor 4 (CXCR4) expression in the gastric mucosa. METHODS Patients with gastric ulcers were allocated to an untreated control group, consisting of patients with active ulcers (GA), healing ulcers (GH), and ulcer scars (GS) or a PPI group (P; given rabeprazole at 20 mg/day), or an H2-blocker group (H; given nizatidine at 800 mg/day). Frozen sections of biopsy specimens were examined by reverse transcription-polymerase chain reaction (RT-PCR) to analyze SDF-1 and CXCR4 mRNA. RESULTS CXCR4 mRNA levels were elevated in the control (GH and GS patients) group and the H2-blocker group. CXCR4 was significantly elevated in the P-GA subgroup of the PPI group (P<0.01), but its level decreased with time. CONCLUSIONS In the PPI group, CXCR4 levels were increased in the early phase of ulcer healing and returned to a level similar to that in the control group during the scar phase. These results suggest that PPIs increase the expression of CXCR4 mRNA and thus promote vessel regeneration and maturation, facilitating ulcer healing.
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Affiliation(s)
- Masumi Akimoto
- Institute of Geriatrics, Tokyo Women's Medical University, 2-15-1 Shibuya, Shibuya-ku, Tokyo, 150-0002, Japan
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