scholarly journals Codonopsis Decoction Inhibits Aspirin-Induced Gastric Mucosal Injury in Rats by Regulating COX, COX-1, COX-2, TNF-α, IL-6 and TGF-α

2021 ◽  
Vol 34 (5) ◽  
Author(s):  
Bo Feng
Keyword(s):  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Tnf Α ◽  
Cox 2 ◽  
Cox 1

Tumor necrosis factor-α stimulates gastric epithelial cell proliferation

2005 ◽  
Vol 288 (1) ◽  
pp. G32-G38 ◽  
Author(s):  
Jiing Chyuan Luo ◽  
Vivian Yvonne Shin ◽  
Ying Hua Yang ◽  
William Ka Kei Wu ◽  
Yi Ni Ye ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Epithelial Cell Line ◽  
Epithelial Cell Proliferation ◽  
Protein Levels ◽  
Tnf Α ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Factor Α

TNF-α is a cytokine produced during gastric mucosal injury. We examined whether TNF-α could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-α treatment (1–10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-α treatment significantly increased cytosolic phospholipase A2 and cyclooxygenase-2 (COX-2) protein expression and PGE2 level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-α on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE2 level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-5H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-α on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE2 significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-α plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-α receptor and activation of the arachidonic acid/PG pathway.

Mucositis in cancer patients: Prototypic semi-mechanistic kinetic model

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19617-19617
Author(s):  
D. E. Peterson ◽  
R. V. Lalla ◽  
R. Srivastava ◽  
L. M. Loew
Keyword(s):  
Molecular Mechanisms ◽  
Mucosal Injury ◽  
Study Data ◽  
Tissue Samples ◽  
Hematopoietic Stem ◽  
Software Packages ◽  
Before And After ◽  
Cox 2 ◽  
Berkeley Madonna ◽  
Cox 1

19617 Background: Recent research advances have helped (i) define pathobiology of alimentary tract mucosal injury secondary to cancer therapy and (ii) link molecular mechanisms with clinically important outcomes. Recently-developed computational biology modeling may further enhance these advances. Semi-mechanistic (SM) modeling allows one to approach quantitative analysis of a biochemical system that is incompletely determined. In this study, data from sequential oral mucosal biopsies in 3 patients developing oral mucositis secondary to hematopoietic stem cell transplantation (HSCT) conditioning were utilized to establish a prototypic computational model for this toxicity. Methods: Plasma and oral mucosal biopsy specimens were obtained from 3 autologous HSCT patients before and after administration of conditioning chemotherapy: Day -10, +10, +28 and +100; Day 0 was day of transplant. Full-thickness tissue samples were measured by RT- PCR for COX-1, COX-2, IL-1β and TNF-a. Plasma samples were measured by ELISA for PGE2 and PGI2, markers of COX-2 activity. The SM model was implemented as a system of 6 ordinary differential equations with 15 parameters. Parameter estimation and simulations were conducted based on experimental results, using a combination of Mathematica, Berkeley Madonna and Virtual Cell software packages. Results: The SM model captured the behavior of COX-1, IL-1β and PGE2 dynamics, predicting an exponential decay for each of these species. Half-lives relative to average steady-state values were found to be 9.7 days, 8.7 days and 9.3 days for COX-1, IL-1β and PGE2 respectively. Correlation ratios for each of these species were calculated to be 0.62, 0.61 and 0.90 respectively. Conclusions: This prototypic model provides a basis for development of a detailed mathematical model for quantifying relevant components of the mucositis pathway. This combination of modeling and experiment could also identify gaps in the pathway that would be important targets for new hypotheses, including possible feedback mechanisms relative to inflammatory cytokines. No significant financial relationships to disclose.

Protective role of adiponectin against ethanol-induced gastric injury in mice

2012 ◽  
Vol 302 (8) ◽  
pp. G773-G780 ◽  
Author(s):  
Shunsuke Yamamoto ◽  
Kenji Watabe ◽  
Hiroshi Araki ◽  
Yoshihiro Kamada ◽  
Motohiko Kato ◽  
...  
Keyword(s):  
Wound Repair ◽  
Mucosal Injury ◽  
Protective Role ◽  
Gastric Mucosal Injury ◽  
Serum Adiponectin ◽  
Gastric Injury ◽  
Prostaglandin E ◽  
Ethanol Treatment ◽  
Cox 2

Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin concentrations are reduced in obesity. We previously reported that gastric erosion occurs in association with obesity and low serum adiponectin levels. In the present study, we examined adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin E2 (PGE2) were detected in the injured stomach. We next assessed the effect of adiponectin on the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). Adiponectin induced the expression of PGE2 and cyclooxygenase 2 (COX-2) in ethanol-treated RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE2 expression in the presence of adiponectin. Coadministration of adiponectin with celecoxib, a COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a protective role against ethanol-induced gastric mucosal injury in mice. This effect may be partially mediated by the efficient wound repair of epithelial cells via increased PGE2 expression.

Role of endogenous nitric oxide synthase inhibitor in gastric mucosal injury

2008 ◽  
Vol 86 (3) ◽  
pp. 97-104 ◽  
Author(s):  
Li Wang ◽  
Yuan Zhou ◽  
Jun Peng ◽  
Zhe Zhang ◽  
De-Jian Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Epithelial Cell Line ◽  
Tnf Α ◽  
Endogenous Nitric Oxide ◽  
Injury Models ◽  
Oxide Synthase

To explore the role of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in gastric mucosal injury, 3 models of gastric mucosal injury induced by ethanol, indomethacin, or cold stress were used in rats. The cultured human gastric mucosal epithelial cell line GES-1 infected by Helicobacter pylori (Hp) was selected to mimic human gastric mucosal injury. Gastric mucosal ulcer index (UI), levels of ADMA and NO, and activity of dimethylarginine dimethylaminohydrolase (DDAH) were determined in the mucosal injury models; in Hp-infected or ADMA-treated GES-1 cells, levels of ADMA, NO, and TNF-α and activity of DDAH were measured. The results showed that UI and levels of ADMA were markedly increased and accompanied by significantly decreased DDAH activity in the mucosal injury models. Incubation of GES-1 cells with Hp increased levels of TNF-α and ADMA and decreased activity of DDAH. Administration of ADMA also increased levels of TNF-α. The results suggest that ADMA plays an important role in facilitating gastric mucosal injury, an effect which is associated with inhibiting NO synthesis and inducing inflammatory reaction.

scholarly journals Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An In Silico, In Vitro and In Vivo Approach

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 825
Author(s):  
Mohammad Khalid ◽  
Mohammed H. Alqarni ◽  
Ambreen Shoaib ◽  
Muhammad Arif ◽  
Ahmed I. Foudah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Arthritis Score ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract’s ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.

scholarly journals Rapid and transient induction of cyclo-oxygenase 2 by epidermal growth factor in human amnion-derived WISH cells

1997 ◽  
Vol 321 (3) ◽  
pp. 677-681 ◽  
Author(s):  
Douglas J. PERKINS ◽  
Douglas A. KNISS
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Protein Expression ◽  
De Novo ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Epidermal Growth ◽  
Cox 2 ◽  
Dose Dependent ◽  
Cox 1

The central enzyme in the prostaglandin (PG) biosynthetic cascade is PGH2 synthase or cyclo-oxygenase (COX). At present, two distinct isoforms of PGH2 synthase/COX have been identified: COX-1 and COX-2. In many systems, COX-1 is a constitutively expressed isoform that is responsible for normal physiological production of PGs, whereas COX-2 is an inducible isoform that responds to cytokines, endotoxin and growth factors by producing high levels of PGs. The regulation of COX-2 mRNA and protein, and the subsequent production of PGE2, were therefore examined in amnion-derived WISH cells stimulated with epidermal growth factor (EGF). Treatment of WISH cells with EGF (0.01Ő100 ng/ml) elicited dose-dependent synthesis of COX-2 mRNA and protein de novo. In addition, stimulation of WISH cells with EGF (10 ng/ml) induced steady-state levels of COX-2 mRNA and protein that appeared within 30 min and then declined rapidly to near baseline levels within 2Ő4 h. In contrast, COX-1 protein was unchanged in response to treatment with EGF. PGE2 production was also rapid and transient. Preincubation of cells with the novel COX-2 enzymic inhibitor NS-398 (10-5Ő10-10 M) completely prevented PGE2 formation in a dose-dependent manner. Preincubation of cells in dexamethasone (Dex; 0.1 ƁM), however, resulted in only a 31% decrease in PGE2 formation in response to EGF (10 ng/ml) while completely attenuating PGE2 biosynthesis in tumour necrosis factor α (TNF-α)-stimulated cells. In addition, Dex (0.1 ƁM) was only partly effective at preventing EGF-induced COX-2 mRNA and protein expression de novo, whereas Dex completely inhibited TNF-α-promoted COX-2 mRNA and protein expression. Thus the results presented here demonstrate that EGF induces the rapid but transient expression of COX-2 mRNA and protein and the subsequent production of PGE2 in WISH cells.

scholarly journals Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Sichen Ren ◽  
Ying Wei ◽  
Ruilin Wang ◽  
Shizhang Wei ◽  
Jianxia Wen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Nuclear Translocation ◽  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Mrna Levels ◽  
Immunofluorescence Analysis ◽  
Ulcer Index ◽  
Gastroprotective Effect ◽  
Tnf Α

Background: Rutaecarpine (RUT), a major quinazolino carboline alkaloid compound from the dry unripe fruit Tetradium ruticarpum (A. Juss.) T. G. Hartley, has various pharmacological effects. The aim of this present study was to investigate the potential gastroprotective effect of rutaecarpine on ethanol-induced acute gastric mucosal injury in mice and associated molecular mechanisms, such as activating Nrf2 and Bcl-2 via PI3K/AKT signaling pathway and inhibiting NF-κB.Methods: Gastric ulcer index and histopathology was carried out to determine the efficacy of RUT in gastric ulceration, and the content of SOD, GSH in serum and CAT, MDA, MPO, TNF-α, IL-6, IL-1β in tissue were measured by kits. Besides, in order to illustrate the potential inflammatory, oxidative, and apoptotic perturbations, the mRNA levels of NF-κB p65, PI3K, AKT, Nrf2, Nqo1, HO-1, Bcl-2 and Bax were analyzed. In addition, the protein expression of NF-κB p65 and Nrf2 in cytoplasm and nucleus, AKT, p-AKT, Bcl-2 Bax and Caspase 3 were analyzed for further verification. Finally, immunofluorescence analysis was performed to further verify nuclear translocation of NF-κB p65.Results: Current data strongly demonstrated that RUT alleviated the gross gastric damage, ulcer index and the histopathology damage caused by ethanol. RUT inhibited the expression and nuclear translocation of NF-κB p65 and the expression of its downstream signals, such as TNF-α, IL-6, IL-1β and MPO. Immunofluorescence analysis also verifies the result. In the context of oxidative stress, RUT improved the antioxidant milieu by remarkably upregulating the expression Nqo1 and HO-1 with activating Nrf2, and could remarkably upregulate antioxidant SOD, GSH, CAT and downregulate levels of MDA. Additionally, RUT activate the expression of Bcl-2 and inhibited the expression of downstream signals Bax and Caspase 3 to promote gastric cellular survival. These were confirmed by RUT activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K and promotion of AKT phosphorylation.Conclusion: Taken together, these results strongly demonstrated that RUT exerted a gastroprotective effect against gastric mucosal injury induced by ethanol. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis system.

Anti-ulcerogenic activity of Gum Arabic in gastric mucosal injury induced by ethanol in male albino rats

2020 ◽  
Vol 45 (7) ◽  
pp. 731-736 ◽  
Author(s):  
Mervat S. Taha ◽  
Emad. M. El-Sherbiny ◽  
Hala. F. Osman
Keyword(s):  
Drinking Water ◽  
Gastric Mucosa ◽  
Total Protein ◽  
Gum Arabic ◽  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Ethanol Administration ◽  
Albino Rats ◽  
Tnf Α ◽  
Ulcerogenic Activity

The present study was performed to evaluate the anti-ulcerogenic activity of Acacia senegal (Gum Arabic) against ethanol-induced gastric mucosal injury in rats. Thirty-six adult male albino rats were divided into 4 groups: group 1 served as a control; group 2 consisted of rats that received 15% of gum in drinking water for 2 weeks; group 3 comprised ulcerated animals administered 5 mL of ethanol/kg body weight by gavage; and group 4 consisted of rats received 15% of gum in drinking water for 2 weeks before ethanol administration. Superoxide dismutase (SOD) glutathione peroxidase (GPx), malondialdehyde (MDA), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin (IL)-B1), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, and albumin were assayed in addition to histological study. The results revealed that ethanol decreased SOD, GPx, and PGE2 in tissue and serum total protein and albumin, while increased MDA in tissue, serum TNF-α, IL-B1, PGE2, ALT, AST, and ALP. Histological findings showed less edema and leucocytes infiltration compared with ulcer group. Furthermore, gum administration elevated PGE2, SOD, and GPx and significantly reduced MDA, TNF-α, and IL-B2. In conclusion, Gum Arabic can enhance gastric protection and sustain the integrity of the gastric mucosa. Novelty The selected dose of Gum Arabic has the ability to decrease the pro-inflammatory cytokines in plasma and gastric tissue, thus enhancing gastric protection and maintaining the integrity of the gastric mucosa. Gum Arabic can compensate for the loss of antioxidants.

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