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Swati, Kumar B, Pandey HK, Kaur R, Mishra S, Kalam MA. Phytochemical profiling, antioxidant capacity, acute toxicity, and gastroprotective potential of Angelica glauca root: A promising high-altitude medicinal herb. Fitoterapia 2025; 183:106565. [PMID: 40274199 DOI: 10.1016/j.fitote.2025.106565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 04/15/2025] [Accepted: 04/21/2025] [Indexed: 04/26/2025]
Abstract
Angelica glauca, a therapeutic and aromatic herb native to the Himalayas, has been traditionally used for culinary purposes and to treat various ailments including rheumatism, asthma, bronchitis, reproductive, and gastrointestinal disorders. This study provides the first comprehensive analysis of phytochemical profiling of the root extract of A. glauca, its antioxidant potential, acute oral toxicity, and gastroprotective effects. Phytochemical quantification of A. glauca revealed significant levels of phenols, flavonoids, and tannins in the hydroalcoholic extract, with major bioactive compounds such as ligustilide, butylidenephthalides, β-bisabolene, and p-hydroxyphenethyl trans-ferulate identified via LC-TOF-MS. Extract exhibited potent antioxidant activity (68 μg/mL) and was non-toxic in acute oral toxicity tests in rats. In ethanol-induced gastric ulcer models, the extract (500 mg/kg) significantly reduced the ulcer-index, enhanced gastric pH, and reduced pepsin levels. Histological analysis confirmed protection against mucosal lesions and necrosis. SOD, CAT, GSH and LPO levels were 173 U/g, 78 U/g, 195 μM GSH/g and 194 nM MDA/g of tissue, respectively at 500 mg/kg dose. This treatment restored the antioxidant systems and reduced the MDA level, indicating its ability to counter oxidative stress. The IL-6 and TNF-α were significantly reduced. Level of IL-6 was reduced by 31.2 % and 57.1 % at 500 mg/Kg and 250 mg/Kg dose, respectively while TNF-α concentration was reduced by 32 % and 60 %, respectively. These findings highlight the gastroprotective efficacy of root extract due to its antioxidant and anti-inflammatory properties. This study establishes the herb's potential as source of bioactive compounds for developing novel therapy against gastric ulcers and other gastrointestinal disorders.
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Affiliation(s)
- Swati
- SGT College of Pharmacy, SGT University, Gurugram, Haryana 122505, India
| | - Bhavna Kumar
- Faculty of Pharmacy, DIT University, Dehradun, 248009, Uttarakhand, India.
| | - H K Pandey
- Defence Institute of Bio-Energy Research, DRDO, Haldwani, Uttarakhand 263139, India
| | - Ramandeep Kaur
- SGT College of Pharmacy, SGT University, Gurugram, Haryana 122505, India
| | - Shweta Mishra
- SGT College of Pharmacy, SGT University, Gurugram, Haryana 122505, India
| | - Mohd Abul Kalam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
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Vagin O, Tokhtaeva E, Larauche M, Davood J, Marcus EA. Helicobacter pylori-Induced Decrease in Membrane Expression of Na,K-ATPase Leads to Gastric Injury. Biomolecules 2024; 14:772. [PMID: 39062486 PMCID: PMC11274427 DOI: 10.3390/biom14070772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 06/12/2024] [Accepted: 06/26/2024] [Indexed: 07/28/2024] Open
Abstract
Helicobacter pylori is a highly prevalent human gastric pathogen that causes gastritis, ulcer disease, and gastric cancer. It is not yet fully understood how H. pylori injures the gastric epithelium. The Na,K-ATPase, an essential transporter found in virtually all mammalian cells, has been shown to be important for maintaining the barrier function of lung and kidney epithelia. H. pylori decreases levels of Na,K-ATPase in the plasma membrane of gastric epithelial cells, and the aim of this study was to demonstrate that this reduction led to gastric injury by impairing the epithelial barrier. Similar to H. pylori infection, the inhibition of Na,K-ATPase with ouabain decreased transepithelial electrical resistance and increased paracellular permeability in cell monolayers of human gastric cultured cells, 2D human gastric organoids, and gastric epithelium isolated from gerbils. Similar effects were caused by a partial shRNA silencing of Na,K-ATPase in human gastric organoids. Both H. pylori infection and ouabain exposure disrupted organization of adherens junctions in human gastric epithelia as demonstrated by E-cadherin immunofluorescence. Functional and structural impairment of epithelial integrity with a decrease in Na,K-ATPase amount or activity provides evidence that the H. pylori-induced downregulation of Na,K-ATPase plays a role in the complex mechanism of gastric disease induced by the bacteria.
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Affiliation(s)
- Olga Vagin
- Department of Pediatrics, DGSOM at UCLA, 10833 LeConte Ave., 12-383 MDCC, Los Angeles, CA 90095, USA; (O.V.); (E.T.)
- VA GLAHS 11301 Wilshire Blvd, Bldg 113, Rm 324, Los Angeles, CA 90073, USA; (M.L.); (J.D.)
| | - Elmira Tokhtaeva
- Department of Pediatrics, DGSOM at UCLA, 10833 LeConte Ave., 12-383 MDCC, Los Angeles, CA 90095, USA; (O.V.); (E.T.)
- VA GLAHS 11301 Wilshire Blvd, Bldg 113, Rm 324, Los Angeles, CA 90073, USA; (M.L.); (J.D.)
| | - Muriel Larauche
- VA GLAHS 11301 Wilshire Blvd, Bldg 113, Rm 324, Los Angeles, CA 90073, USA; (M.L.); (J.D.)
- Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, DGSOM at UCLA, 650 Charles E Young Dr. S., CHS 43-276, Los Angeles, CA 90095, USA
| | - Joshua Davood
- VA GLAHS 11301 Wilshire Blvd, Bldg 113, Rm 324, Los Angeles, CA 90073, USA; (M.L.); (J.D.)
- Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, DGSOM at UCLA, 650 Charles E Young Dr. S., CHS 43-276, Los Angeles, CA 90095, USA
| | - Elizabeth A. Marcus
- Department of Pediatrics, DGSOM at UCLA, 10833 LeConte Ave., 12-383 MDCC, Los Angeles, CA 90095, USA; (O.V.); (E.T.)
- VA GLAHS 11301 Wilshire Blvd, Bldg 113, Rm 324, Los Angeles, CA 90073, USA; (M.L.); (J.D.)
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Ju M, Deng T, Jia X, Gong M, Li Y, Liu F, Yin Y. The causal relationship between anti-diabetic drugs and gastrointestinal disorders: a drug-targeted mendelian randomization study. Diabetol Metab Syndr 2024; 16:141. [PMID: 38918852 PMCID: PMC11201305 DOI: 10.1186/s13098-024-01359-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 05/24/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND The incidence of diabetic gastrointestinal diseases is increasing year by year. This study aimed to investigate the causal relationship between antidiabetic medications and gastrointestinal disorders, with the goal of reducing the incidence of diabetes-related gastrointestinal diseases and exploring the potential repurposing of antidiabetic drugs. METHODS We employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn's disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control. RESULTS Sulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10- 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10- 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10- 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10- 2). CONCLUSIONS The results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases.
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Affiliation(s)
- Mingyan Ju
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Tingting Deng
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xuemin Jia
- Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Menglin Gong
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuying Li
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Fanjie Liu
- Bone Biomechanics Engineering Laboratory of Shandong Province, Shandong Medicinal Biotechnology Center (School of Biomedical Sciences), Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
| | - Ying Yin
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
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Kim DU, Na JY, Paik SS, Jee S, Lee YH, Kim YJ. Mucosal distribution of somatostatin-secreting gastric Delta cells in children with gastrointestinal reflux diseases. Front Pediatr 2023; 11:1275842. [PMID: 37928353 PMCID: PMC10623155 DOI: 10.3389/fped.2023.1275842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 10/09/2023] [Indexed: 11/07/2023] Open
Abstract
Introduction Gastric delta cells (D-cells) secrete somatostatin, which is the primary paracrine suppressor of acid secretion. The number and distribution of D-cells were investigated in children exhibiting endoscopic findings of duodenogastric and gastroesophageal reflux. This study aimed to determine whether the number of D-cells in the gastric body differs from that in the gastric antrum in children using endoscopic findings. Methods We retrospectively used immunohistochemical assessments to determine the number of D-cells in the gastric body and antrum in 102 children who presented with abdominal symptoms. The number and distribution of D-cells were investigated according to symptoms, endoscopic findings of gastroesophageal reflux and duodenogastric reflux, and Helicobacter pylori infection status. Results The average age of the patients was 13.3 ± 3.3 years, and the male-to-female ratio was 1:1.68. The mean number of D-cells per high-power field in the antrum and body did not significantly differ by symptoms. However, these values were significantly lower in the gastric body than in the antrum for all symptoms (p < 0.05). Children with reflux had a higher mean number of D-cells (9.6 ± 8.8) in the gastric body than did those without reflux (4.3 ± 3.4) (p = 0.007). Furthermore, the number of D-cells in the gastric body was marginally significantly lower in Helicobacter pylori-positive children (4.9 ± 6.5) than in Helicobacter pylori-negative children (8.5 ± 8.2) (p = 0.053). Conclusion The number of D-cells in the gastric body decreased in Helicobacter pylori-positive children but significantly increased in children with duodenogastric reflux. Therefore, somatostatin peptide secretion by D-cells may be a major pathophysiological pathway in gastrointestinal reflux disease.
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Affiliation(s)
- Dong-Uk Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Seoul, Republic of Korea
| | - Jae Yoon Na
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Seung Sam Paik
- Department of Pathology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Seungyun Jee
- Department of Pathology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Young Ho Lee
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Yong Joo Kim
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Republic of Korea
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Preparation and Evaluation of Dual–release Esomeprazole Magnesium Pulsed Capsules Filled with Two Kinds of Enteric-coated Pellets. J Pharm Innov 2022. [DOI: 10.1007/s12247-022-09683-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Shipa SJ, Khandokar L, Bari MS, Qais N, Rashid MA, Haque MA, Mohamed IN. An insight into the anti-ulcerogenic potentials of medicinal herbs and their bioactive metabolites. JOURNAL OF ETHNOPHARMACOLOGY 2022; 293:115245. [PMID: 35367330 DOI: 10.1016/j.jep.2022.115245] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/12/2022] [Accepted: 03/27/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Peptic ulcer disease (PUD) ranks top among the most prominent gastrointestinal problems prevalent around the world. Long-term use of non-steroidal anti-inflammatory drugs, pathogenic infection by Helicobacter pylori, imbalances between gastrointestinal regulatory factors and pathological hyperacidity are major contributors towards the development of peptic ulcers. Although synthetic drugs of multiple pharmacological classes are abundantly available, inadequacy of such agents in ensuring complete recovery in not uncommon. Therefore, pharmacological explorations of herbal products including plant extracts and their respective isolated phytoconstituents, for potential gastroprotective and antiulcer properties, are regular practice among the scientific community. Moreover, the historical preferences of a significant share of world population towards herbal-based medication over modern synthetic drugs also contribute significantly to such endeavors. AIM OF THE REVIEW This review has endeavored to present ethnomedicinal and pharmacological prospects of a significant number of authenticated plant species in terms of their capacity to exert gastroprotection and antiulcer activities both in vitro and in vivo. The information delineated along the way was further subjected to critical analysis to ascertain the possible future prospects of such findings into designing plant-derived products in future for the treatment of peptic ulcer. MATERIALS AND METHODS Electronic version of prominent bibliographic databases, including Google Scholar, PubMed, Scopus, ScienceDirect, Wiley Online Library, SpringerLink, Web of Science, and MEDLINE were explored extensively for the identification and compilation of relevant information. The plant names and respective family names were verified through the Plant List (version 1.1) and World Flora Online 2021. All relevant chemical structures were verified through PubChem and SciFinder databases and illustrated with ChemDraw Ultra 12.0. RESULTS A colossal number of 97 plant species categorized under 58 diverse plant families have been discussed in the review for their gastroprotective and antiulcer properties. In vivo illustrations of the pharmacological properties were achieved for almost all the species under consideration. 29 individual phytoconstituents from these sources were also characterized with similar pharmacological potentials. Majority of the plant extracts as well as their constituents were found to exert their gastroprotective effects through antioxidative pathway featuring both enzymatic and nonenzymatic mechanism. Moreover, active inhibition of acid secretion, upregulation of gastroprotective mediators and downregulation of pro-inflammatory cytokines, were also associated with a prominent number of plants or products thereof. CONCLUSIONS Comparative evaluations of the plant sources for their antiulcer activities, both as individual and as combination formulations, are necessary to be conducted in human subjects under properly regulated clinical conditions. Moreover, the efficacy and safety of such products should also be evaluated against those of the currently available treatment options. This will further facilitate in ascertaining their suitability and superiority, if any, in the treatment of peptic ulcer diseases. Implementation of these endeavors may eventually lead to development of more efficient treatment options in the future.
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Affiliation(s)
- Sowkat Jahan Shipa
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Labony Khandokar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Md Sazzadul Bari
- Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA
| | - Nazmul Qais
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.
| | - Mohammad Abdur Rashid
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.
| | - Md Areeful Haque
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh.
| | - Isa Naina Mohamed
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia
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Protective Effect and Potential Mechanism of the Traditional Chinese Medicine Shaoyao-Gancao Decoction on Ethanol-Induced Gastric Ulcers in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3069089. [PMID: 35449820 PMCID: PMC9017495 DOI: 10.1155/2022/3069089] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 02/27/2022] [Accepted: 03/30/2022] [Indexed: 11/17/2022]
Abstract
Background Shaoyao-Gancao decoction (SGD) is a classic prescription in traditional Chinese medicine. SGD is effective in the treatment of gastric and duodenal ulcers. However, the biological activity and possible mechanisms of SGD in the treatment of gastric ulcers have not been fully elucidated. The purpose of this study was to scientifically evaluate the protective effect and potential mechanism of SGD against ethanol-induced gastric ulcers in rats. Methods A single gavage of 10 mL/kg of 75% ethanol was used to establish a rat gastric ulcer model. A histopathological examination of the gastric tissue was performed. The levels of TNF-α, EGF, PGE2, SOD, and TBARS in gastric tissue were measured by ELISA. Cellular apoptosis in gastric tissues was assessed by TUNEL assay. The expression levels of caspase-3 and Bcl-2 were determined by immunohistochemistry. The potential mechanism of SGD in treating gastric ulcers was further studied using a network pharmacology research method. Results The gastric tissue of rats with ethanol-induced gastric ulcers had obvious injury throughout the mucosal layer, which was significantly weakened in rats treated with SGD. Furthermore, treatment with SGD significantly increased the levels of EGF, PGE2, SOD, and Bcl-2 and decreased the levels of TNF-α, TBARS, and caspase-3 in the gastric tissue of rats with ethanol-induced gastric ulcers. SGD reduced ethanol-induced cell apoptosis in gastric tissue from rats with gastric ulcers. A traditional Chinese medicine-based network pharmacology study revealed that SGD exerts its anti-gastric ulcer effect by acting on multiple pathways. Conclusions The above results indicate that SGD can improve gastric ulcers induced by ethanol. Moreover, this study demonstrated multicomponent, multitarget, and multipathway characteristics of SGD in the treatment of gastric ulcers and provided a foundation for further drug development research.
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Mišak Z, Hojsak I. Helicobacter Pylori Gastritis and Peptic Ulcer Disease. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:169-184. [DOI: 10.1007/978-3-030-80068-0_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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OKKAY IF, OKKAY U, KARATAS O. Effects of Rhodiola rosea on indomethacin-induced gastric injury. DICLE MEDICAL JOURNAL 2021. [DOI: 10.5798/dicletip.1037590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Bayraktar N, Güler İ, Bayraktar M, Koyuncu I. Investigation the levels of endotoxin and 8-hydroxy-2'-deoxyguanosine in sera of patients with Helicobacter pylori-positive peptic ulcer. Int J Clin Pract 2021; 75:e14501. [PMID: 34117680 DOI: 10.1111/ijcp.14501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 06/10/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Peptic ulcer is considered an important public health problem and generally associated with complicated conditions such as bleeding and perforation. The aim of this study is to reflect the rate of oxidative damage in the body among dyspeptic patients with Helicobacter pylori-positive peptic ulcer by measuring 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in serum samples and its association with the level of bacterial endotoxin. METHODS Patients referred to Harran University Gastroenterology Outpatient Clinic with dyspeptic complaints were enrolled in this study. According to gastrointestinal endoscopy findings, 43 dyspeptic patients with H pylori-positive peptic ulcer patients and 43 healthy volunteers were included in this study. Infection with H pylori was diagnosed by H pylori urea breath and stool antigen tests. Serum 8-OHdG and endotoxins were measured by ELISA. RESULTS A total of 43 dyspeptic patients with peptic ulcer (13 women and 30 men) and 43 healthy individuals (16 women and 27 men) were enrolled in the study. In biopsies taken endoscopically, H pylori severity was mild in 19 patients (43.9%), moderate in 21 patients (48.5%) and severe in 3 patients (7.6%). 8-OHdG was compared with the healthy and patient group. It was observed that there was a statistically significant difference (P < .01). In addition, a weak correlation was found between OHdG and bacterial endotoxin. CONCLUSION Serum 8-OHdG and endotoxin levels are only weakly associated implying that they reflect specific aspects of oxidative damage. Helicobacter pylori and its endotoxin have a significant role in peptic ulcer pathogenesis. The detection of serum 8-OHdG in dyspeptic patients may be used as a biomarker for the presence of peptic ulcers.
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Affiliation(s)
- Nihayet Bayraktar
- Department of Medical Biochemistry, Faculty of Medicine, Harran University, Şanlıurfa, Turkey
| | - İslim Güler
- Department of Medical Biochemistry, Faculty of Medicine, Harran University, Şanlıurfa, Turkey
| | - Mehmet Bayraktar
- Department of Medical Microbiology, Faculty of Medicine, Harran University, Şanlıurfa, Turkey
| | - Ismail Koyuncu
- Department of Medical Biochemistry, Faculty of Medicine, Harran University, Şanlıurfa, Turkey
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Spósito L, Fortunato GC, de Camargo BAF, Ramos MADS, Souza MPCD, Meneguin AB, Bauab TM, Chorilli M. Exploiting drug delivery systems for oral route in the peptic ulcer disease treatment. J Drug Target 2021; 29:1029-1047. [PMID: 33729081 DOI: 10.1080/1061186x.2021.1904249] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Peptic ulcer disease (PUD) is a common condition that is induced by acid and pepsin causing lesions in the mucosa of the duodenum and stomach. The pathogenesis of PUD is a many-sided scenario, which involves an imbalance between protective factors, such as prostaglandins, blood flow, and cell renewal, and aggressive ones, like alcohol abuse, smoking, Helicobacter pylori colonisation, and the use of non-steroidal anti-inflammatory drugs. The standard oral treatment is well established; however, several problems can decrease the success of this therapy, such as drug degradation in the gastric environment, low oral bioavailability, and lack of vectorisation to the target site. In this way, the use of strategies to improve the effectiveness of these conventional drugs becomes interesting. Currently, the use of drug delivery systems is being explored as an option to improve the drug therapy limitations, such as antimicrobial resistance, low bioavailability, molecule degradation in an acid environment, and low concentration of the drug at the site of action. This article provides a review of oral drug delivery systems looking for improving the treatment of PUD.
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Affiliation(s)
- Larissa Spósito
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Giovanna Capaldi Fortunato
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Bruna Almeida Furquim de Camargo
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | | | | | - Andréia Bagliotti Meneguin
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Taís Maria Bauab
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Marlus Chorilli
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
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Hossen MA, Reza ASMA, Ahmed AMA, Islam MK, Jahan I, Hossain R, Khan MF, Maruf MRA, Haque MA, Rahman MA. Pretreatment of Blumea lacera leaves ameliorate acute ulcer and oxidative stress in ethanol-induced Long-Evan rat: A combined experimental and chemico-biological interaction. Biomed Pharmacother 2021; 135:111211. [PMID: 33421733 DOI: 10.1016/j.biopha.2020.111211] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/14/2020] [Accepted: 12/26/2020] [Indexed: 12/17/2022] Open
Abstract
Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p < 0.001) inhibited gastric lesions and malondealdehyde (MDA) levels and upregulated antioxidant enzymes level. Furthermore, nine compounds were documented as bioactive, displayed good binding affinities to against gastric H+-K+ATPase enzyme while these compounds illustrated inhibitory effect. From these studies, it is established MEBLL has ulcer healing property as unveiled by in vivo and in silico studies.
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Affiliation(s)
- Md Amjad Hossen
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | - A S M Ali Reza
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh; Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, 4331, Bangladesh
| | - A M Abu Ahmed
- Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, 4331, Bangladesh; Department of Genetic Engineering and Biotechnology, University of Chittagong, Chittagong, 4331, Bangladesh
| | - Md Kamrul Islam
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | - Israt Jahan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | - Rahni Hossain
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | - Mohammad Forhad Khan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | | | - Md Areeful Haque
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh; Drug & Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia
| | - Md Atiar Rahman
- Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, 4331, Bangladesh.
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Junren C, Xiaofang X, Mengting L, Qiuyun X, Gangmin L, Huiqiong Z, Guanru C, Xin X, Yanpeng Y, Fu P, Cheng P. Pharmacological activities and mechanisms of action of Pogostemon cablin Benth: a review. Chin Med 2021; 16:5. [PMID: 33413544 PMCID: PMC7791836 DOI: 10.1186/s13020-020-00413-y] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 11/18/2020] [Accepted: 12/11/2020] [Indexed: 02/07/2023] Open
Abstract
Patchouli ("Guanghuoxiang") or scientifically known as Pogostemon cablin Benth, belonging to the family Lamiaceae, has been used in traditional Chinse medicine (TCM) since the time of the Eastern Han dynasty. In TCM theory, patchouli can treat colds, nausea, fever, headache, and diarrhea. Various bioactive compounds have been identified in patchouli, including terpenoids, phytosterols, flavonoids, organic acids, lignins, glycosides, alcohols, pyrone, and aldehydes. Among the numerous compounds, patchouli alcohol, β-patchoulene, patchoulene epoxide, pogostone, and pachypodol are of great importance. The pharmacological impacts of these compounds include anti-peptic ulcer effect, antimicrobial effect, anti-oxidative effect, anti-inflammatory effect, effect on ischemia/reperfusion injury, analgesic effect, antitumor effect, antidiabetic effect, anti-hypertensive effect, immunoregulatory effect, and others.For this review, we examined publications from the previous five years collected from PubMed, Web of Science, Springer, and the Chinese National Knowledge Infrastructure databases. This review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies focused on clinical applications of this important plant extract.
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Affiliation(s)
- Chen Junren
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xie Xiaofang
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Li Mengting
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xiong Qiuyun
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Li Gangmin
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Zhang Huiqiong
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Chen Guanru
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xu Xin
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Yin Yanpeng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Peng Fu
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China.
- West China School of Pharmacy, Sichuan University, 17 South Renmin Rd, 610065, Chengdu, China.
| | - Peng Cheng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China.
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 37 Shierqiao Road, Jinniu District, Chengdu, 611137, China.
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Serafim C, Araruna ME, Júnior EA, Diniz M, Hiruma-Lima C, Batista L. A Review of the Role of Flavonoids in Peptic Ulcer (2010-2020). Molecules 2020; 25:molecules25225431. [PMID: 33233494 PMCID: PMC7699562 DOI: 10.3390/molecules25225431] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/15/2020] [Accepted: 09/16/2020] [Indexed: 02/07/2023] Open
Abstract
Peptic ulcers are characterized by erosions on the mucosa of the gastrointestinal tract that may reach the muscle layer. Their etiology is multifactorial and occurs when the balance between offensive and protective factors of the mucosa is disturbed. Peptic ulcers represent a global health problem, affecting millions of people worldwide and showing high rates of recurrence. Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most important predisposing factors for the development of peptic ulcers. Therefore, new approaches to complementary treatments are needed to prevent the development of ulcers and their recurrence. Natural products such as medicinal plants and their isolated compounds have been widely used in experimental models of peptic ulcers. Flavonoids are among the molecules of greatest interest in biological assays due to their anti-inflammatory and antioxidant properties. The present study is a literature review of flavonoids that have been reported to show peptic ulcer activity in experimental models. Studies published from January 2010 to January 2020 were selected from reference databases. This review refers to a collection of flavonoids with antiulcer activity in vivo and in vitro models.
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Affiliation(s)
- Catarina Serafim
- Postgraduate Program in Natural Products and Bioactive Synthetic, Health Sciences Center, Federal University of Paraiba, João Pessoa 58051900, Paraiba, Brazil; (C.S.); (M.E.A.); (E.A.J.)
| | - Maria Elaine Araruna
- Postgraduate Program in Natural Products and Bioactive Synthetic, Health Sciences Center, Federal University of Paraiba, João Pessoa 58051900, Paraiba, Brazil; (C.S.); (M.E.A.); (E.A.J.)
| | - Edvaldo Alves Júnior
- Postgraduate Program in Natural Products and Bioactive Synthetic, Health Sciences Center, Federal University of Paraiba, João Pessoa 58051900, Paraiba, Brazil; (C.S.); (M.E.A.); (E.A.J.)
| | - Margareth Diniz
- Department of Pharmacy, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051900, Paraiba, Brazil;
| | - Clélia Hiruma-Lima
- Department of Structural and Functional Biology (Physiology), Institute of Biosciences, São Paulo State University, Botucatu 18618970, São Paulo, Brazil;
| | - Leônia Batista
- Department of Pharmacy, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051900, Paraiba, Brazil;
- Correspondence: ; Tel.: +55-83-32167003; Fax: +55-83-32167502
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15
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de Mendonça MAA, Ribeiro ARS, de Lima AK, Bezerra GB, Pinheiro MS, de Albuquerque-Júnior RLC, Gomes MZ, Padilha FF, Thomazzi SM, Novellino E, Santini A, Severino P, B. Souto E, Cardoso JC. Red Propolis and Its Dyslipidemic Regulator Formononetin: Evaluation of Antioxidant Activity and Gastroprotective Effects in Rat Model of Gastric Ulcer. Nutrients 2020; 12:nu12102951. [PMID: 32993069 PMCID: PMC7600383 DOI: 10.3390/nu12102951] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/23/2020] [Accepted: 09/24/2020] [Indexed: 12/12/2022] Open
Abstract
Propolis has various pharmacological properties of clinical interest, and is also considered a functional food. In particular, hydroalcoholic extracts of red propolis (HERP), together with its isoflavonoid formononetin, have recognized antioxidant and anti-inflammatory properties, with known added value against dyslipidemia. In this study, we report the gastroprotective effects of HERP (50–500 mg/kg, p.o.) and formononetin (10 mg/kg, p.o.) in ethanol and non-steroidal anti-inflammatory drug-induced models of rat ulcer. The volume, pH, and total acidity were the evaluated gastric secretion parameters using the pylorus ligature model, together with the assessment of gastric mucus contents. The anti-Helicobacter pylori activities of HERP were evaluated using the agar-well diffusion method. In our experiments, HERP (250 and 500 mg/kg) and formononetin (10 mg/kg) reduced (p < 0.001) total lesion areas in the ethanol-induced rat ulcer model, and reduced (p < 0.05) ulcer indices in the indomethacin-induced rat ulcer model. Administration of HERP and formononetin to pylorus ligature models significantly decreased (p < 0.01) gastric secretion volumes and increased (p < 0.05) mucus production. We have also shown the antioxidant and anti-Helicobacter pylori activities of HERP. The obtained results indicate that HERP and formononetin are gastroprotective in acute ulcer models, suggesting a prominent role of formononetin in the effects of HERP.
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Affiliation(s)
- Marcio A. A. de Mendonça
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
| | - Ana R. S. Ribeiro
- Departament of Physiology, Federal University of Sergipe, Av. Marechal Rondon, Cidade Universitária, São Cristóvão CEP 49100-000, Sergipe, Brazil; (A.R.S.R.); (S.M.T.)
| | - Adriana K. de Lima
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
| | - Gislaine B. Bezerra
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
| | - Malone S. Pinheiro
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
| | - Ricardo L. C. de Albuquerque-Júnior
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
- Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil
| | - Margarete Z. Gomes
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
- Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil
| | - Francine F. Padilha
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
- Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil
| | - Sara M. Thomazzi
- Departament of Physiology, Federal University of Sergipe, Av. Marechal Rondon, Cidade Universitária, São Cristóvão CEP 49100-000, Sergipe, Brazil; (A.R.S.R.); (S.M.T.)
| | - Ettore Novellino
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy;
| | - Antonello Santini
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy;
- Correspondence: (A.S.); (E.B.S.); (J.C.C.); Tel.: +39-81-253-9317 (A.S.); +351-239-488-400 (E.B.S.); +55-79-3218-2190 (J.C.C.)
| | - Patricia Severino
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
- Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil
- Tiradentes Institute, 150 Mt Vernon St, Dorchester, MA 02125, USA
| | - Eliana B. Souto
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
- Correspondence: (A.S.); (E.B.S.); (J.C.C.); Tel.: +39-81-253-9317 (A.S.); +351-239-488-400 (E.B.S.); +55-79-3218-2190 (J.C.C.)
| | - Juliana C. Cardoso
- University of Tiradentes, Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil; (M.A.A.d.M.); (A.K.d.L.); (G.B.B.); (M.S.P.); (R.L.C.d.A.-J.); (M.Z.G.); (F.F.P.); (P.S.)
- Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, Aracaju CEP 49032-490, Sergipe, Brazil
- Correspondence: (A.S.); (E.B.S.); (J.C.C.); Tel.: +39-81-253-9317 (A.S.); +351-239-488-400 (E.B.S.); +55-79-3218-2190 (J.C.C.)
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16
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Marcus EA, Tokhtaeva E, Jimenez JL, Wen Y, Naini BV, Heard AN, Kim S, Capri J, Cohn W, Whitelegge JP, Vagin O. Helicobacter pylori infection impairs chaperone-assisted maturation of Na-K-ATPase in gastric epithelium. Am J Physiol Gastrointest Liver Physiol 2020; 318:G931-G945. [PMID: 32174134 PMCID: PMC7272721 DOI: 10.1152/ajpgi.00266.2019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 03/06/2020] [Accepted: 03/10/2020] [Indexed: 01/31/2023]
Abstract
Helicobacter pylori infection always induces gastritis, which may progress to ulcer disease or cancer. The mechanisms underlying mucosal injury by the bacteria are incompletely understood. Here, we identify a novel pathway for H. pylori-induced gastric injury, the impairment of maturation of the essential transport enzyme and cell adhesion molecule, Na-K-ATPase. Na-K-ATPase comprises α- and β-subunits that assemble in the endoplasmic reticulum (ER) before trafficking to the plasma membrane. Attachment of H. pylori to gastric epithelial cells increased Na-K-ATPase ubiquitylation, decreased its surface and total levels, and impaired ion balance. H. pylori did not alter degradation of plasmalemma-resident Na-K-ATPase subunits or their mRNA levels. Infection decreased association of α- and β-subunits with ER chaperone BiP and impaired assembly of α/β-heterodimers, as was revealed by quantitative mass spectrometry and immunoblotting of immunoprecipitated complexes. The total level of BiP was not altered, and the decrease in interaction with BiP was not observed for other BiP client proteins. The H. pylori-induced decrease in Na-K-ATPase was prevented by BiP overexpression, stopping protein synthesis, or inhibiting proteasomal, but not lysosomal, protein degradation. The results indicate that H. pylori impairs chaperone-assisted maturation of newly made Na-K-ATPase subunits in the ER independently of a generalized ER stress and induces their ubiquitylation and proteasomal degradation. The decrease in Na-K-ATPase levels is also seen in vivo in the stomachs of gerbils and chronically infected children. Further understanding of H. pylori-induced Na-K-ATPase degradation will provide insights for protection against advanced disease.NEW & NOTEWORTHY This work provides evidence that Helicobacter pylori decreases levels of Na-K-ATPase, a vital transport enzyme, in gastric epithelia, both in acutely infected cultured cells and in chronically infected patients and animals. The bacteria interfere with BiP-assisted folding of newly-made Na-K-ATPase subunits in the endoplasmic reticulum, accelerating their ubiquitylation and proteasomal degradation and decreasing efficiency of the assembly of native enzyme. Decreased Na-K-ATPase expression contributes to H. pylori-induced gastric injury.
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Affiliation(s)
- Elizabeth A Marcus
- Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
| | - Elmira Tokhtaeva
- Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
| | - Jossue L Jimenez
- Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
| | - Yi Wen
- Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
| | - Bita V Naini
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Ashley N Heard
- Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
| | - Samuel Kim
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
| | - Joseph Capri
- Pasarow Mass Spectrometry Laboratory, The Neuropsychiatric Insititute-Semel Institute, University of California, Los Angeles, California
| | - Whitaker Cohn
- Pasarow Mass Spectrometry Laboratory, The Neuropsychiatric Insititute-Semel Institute, University of California, Los Angeles, California
| | - Julian P Whitelegge
- Pasarow Mass Spectrometry Laboratory, The Neuropsychiatric Insititute-Semel Institute, University of California, Los Angeles, California
| | - Olga Vagin
- Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
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17
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Kim DU, Moon JH, Lee YH, Paik SS, Kim Y, Kim YJ. Analysis of Somatostatin-Secreting Gastric Delta Cells according to Upper Abdominal Symptoms and Helicobacter pylori Infection in Children. Pediatr Gastroenterol Hepatol Nutr 2020; 23:243-250. [PMID: 32483545 PMCID: PMC7231749 DOI: 10.5223/pghn.2020.23.3.243] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 11/08/2019] [Accepted: 11/28/2019] [Indexed: 11/26/2022] Open
Abstract
PURPOSE Gastric delta cells (D-cells), which are somatostatin-secreting cells, are the main paracrine inhibitor of acid secretion. The number of D-cells was studied in children presenting with upper gastrointestinal (UGI) disease. METHODS We retrospectively investigated the number of D-cells in the gastric body and antrum through immunofluorescence examinations according to symptoms, endoscopic findings, and Helicobacter pylori infection in 75 children who visited Hanyang University Hospital Pediatrics. RESULTS The mean patient age was 12.2±3.3 years. The male-to-female ratio was 1:1.4. The mean D-cell number per high-power field in the antrum and body was 20.5 and 12 in children with substernal pain, 18.3 and 10.3 in vomiting, 22.3 and 6 in diarrhea, and 9.3 and 6 in abdominal pain, respectively (p>0.05). According to endoscopic findings, the mean D-cell number in the antrum and body was 14.3 and 6 with gastritis, 14 and 9.3 with reflux esophagitis, 16.7 and 8.7 with duodeno-gastric reflux, 19.3 and 12.7 with gastric ulcer, 16 and 13.7 with duodenitis, and 12.3 and 4 with duodenal ulcer, respectively (p>0.05). The D-cell number in the gastric body was 2.7 and 8.7 in children with current H. pylori infection and non-infected children, respectively (p=0.01), while those in the antrum were 15.5 and 14, respectively, with no statistical significance. CONCLUSION The D-cell number was lower in the gastric body of children with current H. pylori infection. Further studies concerning peptide-secreting cells with a control group would provide information about the pathogenic pathways of UGI disorder.
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Affiliation(s)
- Dong-Uk Kim
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Jin-Hwa Moon
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Young-Ho Lee
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Sam Paik
- Department of Pathology, Hanyang University College of Medicine, Seoul, Korea
| | - Yeseul Kim
- Department of Pathology, Hanyang University College of Medicine, Seoul, Korea
| | - Yong Joo Kim
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
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Abstract
Mucus selectively controls the transport of molecules, particulate matter, and microorganisms to the underlying epithelial layer. It may be desirable to weaken the mucus barrier to enable effective delivery of drug carriers. Alternatively, the mucus barrier can be strengthened to prevent epithelial interaction with pathogenic microbes or other exogenous materials. The dynamic mucus layer can undergo changes in structure (e.g., pore size) and/or composition (e.g., protein concentrations, mucin glycosylation) in response to stimuli that occur naturally or are purposely administered, thus altering its barrier function. This review outlines mechanisms by which mucus provides a selective barrier and methods to engineer the mucus layer from the perspective of strengthening or weakening its barrier properties. In addition, we discuss strategic design of drug carriers and dosing formulation properties for efficient delivery across the mucus barrier.
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Affiliation(s)
- T L Carlson
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, USA;
| | - J Y Lock
- Department of Bioengineering, Northeastern University, Boston, Massachusetts 02115, USA
| | - R L Carrier
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, USA; .,Department of Bioengineering, Northeastern University, Boston, Massachusetts 02115, USA
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19
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Ugwah MO, Ugwah-Oguejiofor CJ, Etuk EU, Bello SO, Aliero AA. Evaluation of the antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca L Delile in Wistar rats. JOURNAL OF ETHNOPHARMACOLOGY 2019; 239:111931. [PMID: 31055003 DOI: 10.1016/j.jep.2019.111931] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 04/30/2019] [Accepted: 05/01/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Balanites aegyptiaca L. Delile (Zygophyllaceae) is a perennial tree that is mostly found in Africa, south Asia and most desert environments. Decoctions of its stem barks are used in northern Nigeria for the treatment of ulcers and stomach issues. Other folkloric uses include treatment of wounds, malaria, dysentery, asthma, and fever. AIM OF THE STUDY The present study evaluated the antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca in Wistar rats. MATERIALS AND METHODS The antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca (125, 250 and 500 mg/kg, p.o.) was evaluated in ethanol, indomethacin, pylorus ligation and acetic acid-induced ulcer models in rats. Parameters such as mean ulcer indices and percentage ulcer inhibition were assessed in ethanol, indomethacin and acetic acid-induced ulcer models while gastric volume, pH, and titratable acidity were evaluated in the pylorus ligation ulcer model. RESULTS The extract at the doses of 125, 250 and 500 mg/kg caused a significant (p < 0.01), dose dependent reduction in mean ulcer indices in the ethanol and indomethacin ulcer models. A significant dose dependent reduction in mean ulcer indices were also observed after three (p < 0.01) and seven (p < 0.001) days of treatment with the extract in acetic acid-induced ulcer model. In pylorus ligation model, the gastric secretion parameters (gastric volume, pH, and titratable acidity) showed no alteration in the different doses of the extract when compared to the control. CONCLUSION Our study showed that the aqueous stem bark extract of Balanites aegyptiaca possesses gastroprotective and ulcer healing properties and therefore not only provides scientific evidence for its folkloric use in the treatment of ulcers but also showed evidence that it may be used in the development of a new phytotherapeutic formulation for the treatment of peptic ulcer.
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Affiliation(s)
- Michael O Ugwah
- Department of Pharmacy, Usmanu Danfodiyo University Teaching Hospital, P.M.B., 2370, Sokoto, Nigeria.
| | - Chinenye J Ugwah-Oguejiofor
- Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B, 2346, Sokoto, Nigeria.
| | - Emmanuel U Etuk
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2346, Sokoto, Nigeria.
| | - Shaibu O Bello
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2346, Sokoto, Nigeria.
| | - Adamu A Aliero
- Department of Botany, Faculty of Biological Sciences, Usmanu Danfodiyo University, P.M.B, 2346, Sokoto, Nigeria.
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20
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Protective Effects of Dioscorea batatas Flesh and Peel Extracts against Ethanol-Induced Gastric Ulcer in Mice. Nutrients 2018; 10:nu10111680. [PMID: 30400615 PMCID: PMC6266015 DOI: 10.3390/nu10111680] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 10/24/2018] [Accepted: 11/02/2018] [Indexed: 02/07/2023] Open
Abstract
Gastric ulcer is a major digestive disorder and provoked by multifactorial etiologies, including excessive alcohol consumption. In this study, we examined the gastroprotective effect of aqueous and ethanolic extracts of Dioscorea batatas Decne (DBD; commonly called Chinese yam) flesh or peel against acidified ethanol-induced acute gastric damage in mice. Our findings demonstrated that oral supplementation of aqueous or ethanolic extracts of DBD flesh or peel before ulcer induction was significantly effective in macroscopically and histologically alleviating ethanol-induced pathological lesions in gastric mucosa, decreasing the plasma levels of inflammatory mediators, such as nitric oxide and interleukin-6, attenuating the gastric expression of cyclooxygenase-2, and increasing the gastric content of prostaglandin E2. In particular, pretreatment with the flesh extract prepared in 60% ethanol prominently decreased the expression of biomarkers of oxidative stress, including the plasma levels of 8-hydroxy-2-guanosine and malondialdehyde, and restored heme oxygenase-1 expression and superoxide dismutase activity in the stomach. Overall, these findings suggest that the oral supplementation with DBD extract, especially flesh ethanol extract, prior to excessive alcohol consumption, may exert a protective effect against ethanol-induced gastric mucosal damage in vivo, presumably through the activation of the antioxidant system and suppression of the inflammatory response.
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Sharifi-Rad M, Fokou PVT, Sharopov F, Martorell M, Ademiluyi AO, Rajkovic J, Salehi B, Martins N, Iriti M, Sharifi-Rad J. Antiulcer Agents: From Plant Extracts to Phytochemicals in Healing Promotion. Molecules 2018; 23:E1751. [PMID: 30018251 PMCID: PMC6100067 DOI: 10.3390/molecules23071751] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 07/12/2018] [Accepted: 07/14/2018] [Indexed: 12/12/2022] Open
Abstract
In this narrative review, we have comprehensively reviewed the plant sources used as antiulcer agents. From traditional uses as herbal remedies, we have moved on to preclinical evidence, critically discussing the in vitro and in vivo studies focusing on plant extracts and even isolated phytochemicals with antiulcerogenic potential. A particular emphasis was also paid to Helicobacter pylori activity, with emphasis on involved mechanisms of action. Lastly, the issue of safety profile of these plant products has also been addressed.
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Affiliation(s)
- Mehdi Sharifi-Rad
- Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol 61663335, Iran.
| | | | - Farukh Sharopov
- Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Rudaki 139, Dushanbe 734003, Tajikistan.
| | - Miquel Martorell
- Nutrition and Dietetics Department, School of Pharmacy, University of Concepción, Concepción 4070386, VIII⁻Bio Bio Region, Chile.
| | - Adedayo Oluwaseun Ademiluyi
- Functional Foods, Nutraceuticals and Phytomedicine Unit, Department of Biochemistry, Federal University of Technology, Akure 340001, Nigeria.
| | - Jovana Rajkovic
- Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Belgrade 11129, Serbia.
| | - Bahare Salehi
- Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran 88777539, Iran.
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran 22439789, Iran.
| | - Natália Martins
- Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal.
- Institute for Research and Innovation in Health (i3S), University of Porto⁻Portugal, Porto 4200-135, Portugal.
| | - Marcello Iriti
- Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, Milan 20133, Italy.
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 11369, Iran.
- Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada.
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Secretion expression of human neutrophil peptide 1 (HNP1) in Pichia pastoris and its functional analysis against antibiotic-resistant Helicobacter pylori. Appl Microbiol Biotechnol 2018; 102:4817-4827. [DOI: 10.1007/s00253-018-8982-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 03/22/2018] [Accepted: 04/02/2018] [Indexed: 12/22/2022]
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Liang J, Dou Y, Wu X, Li H, Wu J, Huang Q, Luo D, Yi T, Liu Y, Su Z, Chen J. Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis. Chem Biol Interact 2018; 283:30-37. [PMID: 29339218 DOI: 10.1016/j.cbi.2018.01.014] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 01/08/2018] [Accepted: 01/11/2018] [Indexed: 12/13/2022]
Abstract
Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.
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Affiliation(s)
- Jiali Liang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Yaoxing Dou
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Xue Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Huilin Li
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
| | - Jiazhen Wu
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Qionghui Huang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Dandan Luo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Tiegang Yi
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
| | - Yuhong Liu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Ziren Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, China.
| | - Jianping Chen
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
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Smith D, Roeser M, Naranjo J, Carr JA. The natural history of perforated foregut ulcers after repair by omental patching or primary closure. Eur J Trauma Emerg Surg 2017; 44:273-277. [PMID: 28756513 DOI: 10.1007/s00068-017-0825-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 07/25/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND The treatment of perforated foregut ulcers by omental patching (OP) or primary closure has mostly replaced vagotomy and pyloroplasty/antrectomy (VPA). We sought to determine the natural history and recurrence rate of ulceration in patients treated by omental patching or primary closure. STUDY DESIGN An 11-year retrospective study. RESULTS From 2004 through 2015, 94 patients had perforated foregut ulcers, 53 gastric, and 41 duodenal. 77 (82%) were treated by OP alone (study group) and 17 (18%) were treated with VPA (comparison group). All OP patients were discharged on PPIs, but only 86% took the drugs for a median of 22 months (1-192, SD 40). Endoscopy in the OP group showed recurrent ulcers in nine (12% recurrence rate) and gastritis in three (4%) This group also had three later recurrent perforations. Another recurrent ulcer hemorrhaged causing death (3% late mortality). Two other patients required non-emergent re-do ulcer operations for recurrent disease/symptoms (surgical re-intervention rate 4%). Total length of follow-up was median 44 months (1-192, SD 40) and was complete in 82 (87%). 18 (23%) patients in the OP group developed recurrent abdominal pain attributed to ulcer disease during follow-up, compared to 2 (12%) in the VPA group (p = 0.15). No patient in the VPA group had an endoscopic recurrence or re-intervention. CONCLUSION Omental patching does not correct the underlying disease process which causes foregut perforation, and has a 12% endoscopically proven recurrent ulceration rate and a 23% incidence of recurrent symptoms within 44 months. Patients tend to stop taking PPIs after 22 months at which time their risk increases.
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Affiliation(s)
- D Smith
- Department of Surgery, Henry Ford Allegiance Health, 205 N East Avenue, Jackson, MI, 49201, USA
| | - M Roeser
- Department of Surgery, Henry Ford Allegiance Health, 205 N East Avenue, Jackson, MI, 49201, USA
| | - J Naranjo
- Department of Statistics, Western Michigan University, 3304 Everett Tower, Mail Stop 5152, Kalamazoo, MI, 49008, USA
| | - J A Carr
- Department of Surgery, Henry Ford Allegiance Health, 205 N East Avenue, Jackson, MI, 49201, USA.
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Bagheri N, Shirzad H, Elahi S, Azadegan-Dehkordi F, Rahimian G, Shafigh M, Rashidii R, Sarafnejad A, Rafieian-Kopaei M, Faridani R, Tahmasbi K, Kheiri S, Razavi A. Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection. Microb Pathog 2017; 110:165-175. [PMID: 28666843 DOI: 10.1016/j.micpath.2017.06.040] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Revised: 06/24/2017] [Accepted: 06/26/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. METHODS AND MATERIALS A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-β1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). RESULTS The numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-β1, FOXP3, INF-γ and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4+ T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3+ T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3+ T cells and the expression of IL-10, TGF-β1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4+ T cells and the expression of IL-17A and INF-γ was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-β1, FOXP3 and INF-γ were positively correlated with the degree of H. pylori density and chronic inflammation. CONCLUSION Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease.
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Affiliation(s)
- Nader Bagheri
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Hedayatollah Shirzad
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Shokrollah Elahi
- Department of Dentistry, Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Fatemeh Azadegan-Dehkordi
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Ghorbanali Rahimian
- Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammedhadi Shafigh
- Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Reza Rashidii
- Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Abdulfatah Sarafnejad
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Rafieian-Kopaei
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Rana Faridani
- Department of Pathology, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Kamran Tahmasbi
- Department of Pathology, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Soleiman Kheiri
- Department of Epidemiology and Biostatistics, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Alireza Razavi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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da Silva LM, Boeing T, Somensi LB, Cury BJ, Steimbach VMB, Silveria ACDO, Niero R, Cechinel Filho V, Santin JR, de Andrade SF. Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: In vitro and in vivo studies. JOURNAL OF ETHNOPHARMACOLOGY 2015; 175:75-85. [PMID: 26364940 DOI: 10.1016/j.jep.2015.09.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 08/31/2015] [Accepted: 09/05/2015] [Indexed: 05/02/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Maytenus robusta Reissek (Celastraceae) is traditionally used in Brazilian folk medicine to treat gastric ulcer, as a substitute for M. ilicifolia, which is almost extinct. The gastroprotective properties of M. robusta were demonstrated previously using only preventive approaches, such as acute gastric ulcer models. However, the healing effect of M. robusta in gastric ulcers remains unclear. AIM OF THE STUDY The current study was carried out to investigate the healing effectiveness of M. robusta hydroalcoholic extract (HEMR) from aerial parts in the acetic acid-induced chronic ulcer model and to determine its effect on cell proliferation, scavenging free radicals, and inflammatory and oxidative damage. MATERIAL AND METHODS To evaluate the healing properties of HEMR in vivo, chronic gastric ulcer was induced in rats by 80% acid acetic. Next, different groups of animals (n=6) were treated orally with vehicle (water plus 1% tween, 1 ml/kg), omeprazole (20mg/kg), or HEMR (1-10mg/kg), twice daily for 7 days. At the end of the treatment, the total ulcer area (mm(2)) was measured and a sample of gastric tissue was taken for histological and histochemical analysis. Evaluation of GSH and LOOH levels, GST, SOD, CAT and MPO activity was also performed at the site of the lesion. In parallel, radical scavenging activity, cytoprotective effect, and cell proliferation activity in fibroblasts (L929 cells) were determined by in vitro trials. The antisecretory properties were evaluated using the pylorus ligature model in rats, and the anti-Helicobacter pylori activity was determined in vitro. Acute toxicity was evaluated by relative organ weight and biochemical parameters in serum. The prokinetic properties were also evaluated in mice. RESULTS Oral administration of HEMR (10mg/kg) reduced the gastric ulcer area by 53%, compared to the vehicle group (120.0 ± 8.3mm(2)), the regeneration of gastric mucosa was evidenced in histological analysis. Moreover, HEMR treatment increased gastric mucin content and reduced oxidative stress and inflammatory parameters at the site of the ulcer. In vitro, HEMR (1-1000 µg/ml) was able to scavenge free radical DPPH and promote cytoprotection against H2O2 in fibroblasts at 0.1-100 µg/ml. Moreover, HEMR healing properties also were confirmed by enhancement of proliferation and coverage of scratched wounds in fibroblast monolayer. However, HEMR (10mg/kg) by the intraduodenal route did not promote changes in volume, pH, total acidity or pepsin activity in the pylorus ligature model, and HEMR up to 2000 µg/ml also did not present considerable activity against H. pylori. In relation to gastrointestinal motility, HEMR (10mg/kg, p.o) did not provoke alterations. It is also important to mention that oral administration of HEMR did not produce any sign of acute toxicity in animals. CONCLUSIONS The data here obtained show that M. robusta has evident ulcer healing potential, mainly through the strengthening of protective factors of gastric mucosa, such as mucus layer, antioxidant defenses and cell proliferation. Taking into account the advantages of cultivation and harvesting of M. robusta compared to M. ilicifolia, and the evidence presented here, it is plausible to conclude that hydroalcoholic extract obtained from aerial parts of M. robusta is an interesting source for the development of a phytotherapeutic formulation to treat gastric ulcer.
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Affiliation(s)
- Luisa Mota da Silva
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil.
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Benhur Judah Cury
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | | | | | - Rivaldo Niero
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Valdir Cechinel Filho
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - José Roberto Santin
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
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Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: Is the end coming? World J Gastrointest Pharmacol Ther 2015; 6:183-198. [PMID: 26558152 PMCID: PMC4635158 DOI: 10.4292/wjgpt.v6.i4.183] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/01/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.
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Kojima Y, Takeuchi T, Ota K, Harada S, Edogawa S, Narabayashi K, Nouda S, Okada T, Kakimoto K, Kuramoto T, Inoue T, Higuchi K. Effect of long-term proton pump inhibitor therapy and healing effect of irsogladine on nonsteroidal anti-inflammatory drug-induced small-intestinal lesions in healthy volunteers. J Clin Biochem Nutr 2015; 57:60-5. [PMID: 26236102 PMCID: PMC4512901 DOI: 10.3164/jcbn.15-32] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 03/23/2015] [Indexed: 12/19/2022] Open
Abstract
This study assessed time-course changes of the small intestinal lesions during long-term treatment with diclofenac sodium plus omeprazole and the effects of irsogladine on such lesions. Thirty two healthy volunteers were treated with diclofenac sodium (75 mg/day) plus omeprazole (10 mg/day) for 6 weeks, with irsogladine (4 mg/day) added from weeks 6 to 10 (Group A) or with diclofenac sodium plus irsogladine for 6 weeks (Group B). Five volunteers received diclofenac sodium plus omeprazole for 10 weeks (Group C). Subjects underwent capsule endoscopy at each time. In Group A, the number of lesions remarkably increased at week 2, but the worse was not found at week 6 compared with week 2, whereas no exacerbation of lesions was observed in Group B. Additional treatment with irsogladine from weeks 6 to 10 in Group A significantly decreased the number of lesions at weeks 10 compared with Group C. In Group C, no significant change in lesions was observed since weeks 2. In conclusions, a PPI did not prevent the occurrence of small intestinal damage. However such lesions were not aggravated since weeks 2. These suggested mucosal adaptation may occur in the small intestine. Irsogladine was effective in both preventing and healing such lesions.
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Affiliation(s)
- Yuichi Kojima
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Toshihisa Takeuchi
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Kazuhiro Ota
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Satoshi Harada
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Shoko Edogawa
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Ken Narabayashi
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Sadaharu Nouda
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Toshihiko Okada
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Kazuki Kakimoto
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Takanori Kuramoto
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Takuya Inoue
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
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Polymorphisms of the IL-6, IL-8 and IL-10 genes and the risk of gastric pathology in patients infected with Helicobacter pylori. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2015; 50:153-159. [PMID: 25888319 DOI: 10.1016/j.jmii.2015.03.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Revised: 02/04/2015] [Accepted: 03/05/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND/PURPOSE Helicobacter pylori-induced gastric mucosal inflammation is mediated by proinflammatory and anti-inflammatory cytokines. Polymorphisms in genes that code cytokines influence cytokine secretion levels and appear to contribute to the risk of gastric diseases. In this sense, we performed this study to identify the polymorphisms in the IL-6, IL-8, and IL-10 genes and their associations with H. pylori infection and gastric pathologies. METHODS Gastric biopsy samples of 151 patients infected with H. pylori and 76 uninfected individuals were used. Helicobacter pylori infection was diagnosed by histological examination and the detection of the ureA and glmM genes. The polymorphisms in the IL-6 (at position -174), IL-8 (at position -251), and IL-10 (at position -819) were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS Among the genetic polymorphisms studied, we observed that only the presence of the A allele at position -251 of the IL-8 gene was significantly associated with H. pylori infection. In addition, patient carriers of the A/A genotype at position -251 of the IL-8 gene and carriers of the T allele at position -819 of the IL-10 gene had an increased risk of peptic ulcer disease in the presence of H. pylori infection. We did not find a correlation between polymorphisms in the IL-6, IL-8, and IL-10 genes and a higher risk of gastric carcinoma. CONCLUSION We demonstrated that polymorphisms in the IL-8 gene was significantly associated with H. pylori infection. Furthermore, polymorphisms in the IL-8 and IL-10 genes were associated with an enhanced risk of peptic ulcer disease in H. pylori-positive patients.
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dos Santos AA, Carvalho AA. Pharmacological therapy used in the elimination of Helicobacter pylori infection: A review. World J Gastroenterol 2015; 21:139-154. [PMID: 25574087 PMCID: PMC4284330 DOI: 10.3748/wjg.v21.i1.139] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Revised: 08/16/2014] [Accepted: 09/19/2014] [Indexed: 02/06/2023] Open
Abstract
The optimal therapy for Helicobacter pylori (H. pylori) infection should combine a high cure rate and a short treatment duration with a favorable side-effect profile and should maintain a low cost. Several strategies have been proposed to increase the H. pylori eradication rate, including the extension of the treatment duration to 14 d, the use of a four-drug regimen (quadruple, sequential, and concomitant treatments), and the use of novel antibiotics, such as levofloxacin. However, triple therapy remains the most widely accepted first-line treatment regimen in Brazil and the United States and throughout Europe. Because this therapy is limited by resistance to clarithromycin, other therapeutic regimens have been investigated worldwide. This review describes the current literature involving studies directly comparing these different therapies and their efficacies.
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Coblijn UK, Goucham AB, Lagarde SM, Kuiken SD, van Wagensveld BA. Development of ulcer disease after Roux-en-Y gastric bypass, incidence, risk factors, and patient presentation: a systematic review. Obes Surg 2014; 24:299-309. [PMID: 24234733 DOI: 10.1007/s11695-013-1118-5] [Citation(s) in RCA: 143] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the gold standard in bariatric surgery. A long-term complication can be marginal ulceration (MU) at the gastrojejunostomy. The mechanism of development is unclear and symptoms vary. Management and prevention is a continuous subject of debate. The aim was to assess the incidence, mechanism, symptoms, and management of MU after LRYGB by means of a systematic review. Forty-one studies with a total of 16,987 patients were included, 787 (4.6%) developed MU. The incidence of MU varied between 0.6 and 25%. The position and size of the pouch, smoking, and nonsteroidal inflammatory drugs usage are associated with the formation of MU. In most cases, MU is adequately treated with proton pump inhibitors, sometimes reoperation is required. Laparoscopic approach is safe and effective.
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Geraniol—a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa. Naunyn Schmiedebergs Arch Pharmacol 2013; 387:355-65. [DOI: 10.1007/s00210-013-0947-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Accepted: 12/02/2013] [Indexed: 10/25/2022]
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Marcus EA, Vagin O, Tokhtaeva E, Sachs G, Scott DR. Helicobacter pylori impedes acid-induced tightening of gastric epithelial junctions. Am J Physiol Gastrointest Liver Physiol 2013; 305:G731-9. [PMID: 23989011 PMCID: PMC3840231 DOI: 10.1152/ajpgi.00209.2013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Gastric infection by Helicobacter pylori is the most common cause of ulcer disease and gastric cancer. The mechanism of progression from gastritis and inflammation to ulcers and cancer in a fraction of those infected is not definitively known. Significant acidity is unique to the gastric environment and is required for ulcer development. The interplay between gastric acidity and H. pylori pathogenesis is important in progression to advanced disease. The aim of this study was to characterize the impact of acid on gastric epithelial integrity and cytokine release and how H. pylori infection alters these responses. Human gastric epithelial (HGE-20) cells were grown on porous inserts, and survival, barrier function, and cytokine release were studied at various apical pH levels in the presence and absence of H. pylori. With apical acidity, gastric epithelial cells demonstrate increased barrier function, as evidenced by increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. This effect is reduced in the presence of wild-type, but not urease knockout, H. pylori. The epithelial inflammatory response is also modulated by acidity and H. pylori infection. Without H. pylori, epithelial IL-8 release decreases in acid, while IL-6 release increases. In the presence of H. pylori, acidic pH diminishes the magnitude of the previously reported increase in IL-8 and IL-6 release. H. pylori interferes with the gastric epithelial response to acid, contributing to altered barrier function and inflammatory response. H. pylori diminishes acid-induced tightening of cell junctions in a urease-dependent manner, suggesting that local pH elevation promotes barrier compromise and progression to mucosal damage.
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Affiliation(s)
- Elizabeth A. Marcus
- 1Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; ,4Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California
| | - Olga Vagin
- 2Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; ,4Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California
| | - Elmira Tokhtaeva
- 2Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; ,4Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California
| | - George Sachs
- 2Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; ,3Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; and ,4Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California
| | - David R. Scott
- 2Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; ,4Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California
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Farzaei MH, Shams-Ardekani MR, Abbasabadi Z, Rahimi R. Scientific evaluation of edible fruits and spices used for the treatment of peptic ulcer in traditional Iranian medicine. ISRN GASTROENTEROLOGY 2013; 2013:136932. [PMID: 24066235 PMCID: PMC3770045 DOI: 10.1155/2013/136932] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Accepted: 07/24/2013] [Indexed: 12/24/2022]
Abstract
In traditional Iranian medicine (TIM), several edible fruits and spices are thought to have protective and healing effects on peptic ulcer (PU). The present study was conducted to verify anti-PU activity of these remedies. For this purpose, edible fruits and spices proposed for the management of PU in TIM were collected from TIM sources, and they were searched in modern medical databases to find studies that confirmed their efficacy. Findings from modern investigations support the claims of TIM about the efficacy of many fruits and spices in PU. The fruit of Phyllanthus emblica as a beneficial remedy for PU in TIM has been demonstrated to have antioxidant, wound healing, angiogenic, anti-H. pylori, cytoprotective, antisecretory, and anti-inflammatory properties. The fruit of Vitis vinifera has been found to be anti-H. pylori, anti-inflammatory, wound healing, angiogenic, cytoprotective, and antioxidant. The fruit and aril of seed from Myristica fragrans exert their beneficial effects in PU by increasing prostaglandin, modulation of nitric oxide and inflammatory mediators, wound healing, antisecretory, antacid, antioxidant, and anti-H. pylori activities, and improving angiogenesis. Pharmacological and clinical studies for evaluation of efficacy of all TIM fruits and spices in PU and their possible mechanisms of action are recommended.
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Affiliation(s)
- Mohammad Hosein Farzaei
- Department of Traditional Pharmacy, Faculty of Traditional Medicine, Tehran University of Medical Sciences, Tehran 1417653761, Iran
| | - Mohammad Reza Shams-Ardekani
- Department of Traditional Pharmacy, Faculty of Traditional Medicine, Tehran University of Medical Sciences, Tehran 1417653761, Iran
- Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Zahra Abbasabadi
- Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Roja Rahimi
- Department of Traditional Pharmacy, Faculty of Traditional Medicine, Tehran University of Medical Sciences, Tehran 1417653761, Iran
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Protective mechanism of gallic acid and its novel derivative against ethanol-induced gastric ulcerogenesis: Involvement of immunomodulation markers, Hsp70 and Bcl-2-associated X protein. Int Immunopharmacol 2013; 16:296-305. [DOI: 10.1016/j.intimp.2013.04.005] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 03/28/2013] [Accepted: 04/04/2013] [Indexed: 12/22/2022]
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Luo XJ, Liu B, Dai Z, Yang ZC, Peng J. Stimulation of calcitonin gene-related peptide release through targeting capsaicin receptor: a potential strategy for gastric mucosal protection. Dig Dis Sci 2013; 58:320-5. [PMID: 22918689 DOI: 10.1007/s10620-012-2362-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Accepted: 08/04/2012] [Indexed: 12/27/2022]
Abstract
Calcitonin gene-related peptide (CGRP) is a predominant neurotransmitter from capsaicin-sensitive sensory nerves, which are widely distributed in the gastrointestinal system. These sensory nerves are reported to be involved in the protection of gastric mucosa against damage by various stimuli, and CGRP is a potential mediator in this process. In addition to increase in gastric mucosal blood flow, the beneficial effects of CGRP on gastric mucosa include inhibition of gastric acid secretion, prevention of cellular apoptosis and oxidative injury. The synthesis and release of CGRP is regulated by the capsaicin receptor which is known as transient receptor potential vanilloid subfamily member 1 (TRPV1) and the agonists of TRPV1 have the potential for gastric mucosal protection. So far, multiple TRPV1 agonists, including capsaicin, capsiate, anandamide and rutaecarpine are reported to exert beneficial effects on gastric mucosal injury induced by various stimuli. Therefore, the TRPV1/CGRP pathway represents a novel target for therapeutic intervention in human gastric mucosal injury.
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Affiliation(s)
- Xiu-Ju Luo
- Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, 110 Xiang-Ya Road, Changsha, 410078, China
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