The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice

2013 ◽  
Vol 304 (2) ◽  
pp. G193-G202 ◽  
Author(s):  
Jung Mogg Kim ◽  
Su Hyun Kim ◽  
Su Hyuk Ko ◽  
Jireh Jung ◽  
Jaeyoung Chun ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Mucosal Inflammation ◽  
Histological Evaluation ◽  
Dependent Manner ◽  
Gastric Epithelial Cells ◽  
Gastric Mucosal Lesions ◽  
Tnf Α ◽  
Mucosal Lesions

Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.

scholarly journals Comparison of the Effects of Pantoprazole Enantiomers on Gastric Mucosal Lesions and Gastric Epithelial Cells in Rats

2004 ◽  
Vol 50 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Hong Cao ◽  
Minwei Wang ◽  
Jianhui Jia ◽  
Qinghe Wang ◽  
Maosheng Cheng
Keyword(s):  
Epithelial Cells ◽  
Gastric Epithelial Cells ◽  
Gastric Mucosal Lesions ◽  
Mucosal Lesions

Protective effect of endogenous PPARγ against acute gastric mucosal lesions associated with ischemia-reperfusion

2004 ◽  
Vol 287 (2) ◽  
pp. G452-G458 ◽  
Author(s):  
Koichiro Wada ◽  
Atsushi Nakajima ◽  
Hirokazu Takahashi ◽  
Masato Yoneda ◽  
Nobutaka Fujisawa ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Gastric Mucosal Lesions ◽  
Tnf Α ◽  
Mucosal Lesions ◽  
Nuclear Receptor Family ◽  
Oxide Synthase

Acute gastric mucosal lesions (AGMLs) are an important cause of gastrointestinal bleeding. Herein, we demonstrate that peroxisome proliferator-activated receptor-γ (PPARγ), a member of a nuclear receptor family, functions as an endogenous anti-inflammatory pathway in a murine model of AGML induced by ischemia-reperfusion (I/R). Treatment with specific PPARγ ligands such as BRL-49653, pioglitazone, or troglitazone was examined in a model of AGML induced by I/R. PPARγ-deficient and wild-type mice were also examined for their response to I/R in stomach. Specific PPARγ ligands exhibited dramatic and rapid protection against AGML formation associated with I/R in mice in a dose-dependent manner. In contrast, the AGML induced by I/R in PPARγ-deficient mice was more severe than that observed in wild-type mice. Administration of the PPARγ ligand significantly inhibited the upregulation of TNF-α, ICAM-1, inducible nitric oxide synthase, apoptosis, and nitrotyrosine formation induced by I/R in the stomach. These data indicate that an endogenous pathway associated with PPARγ plays an important role in the pathogenesis of I/R-associated injury in the stomach.

scholarly journals Protective Effect of Pyrus ussuriensis Maxim. Extract against Ethanol-Induced Gastritis in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 439
Author(s):  
Naila Boby ◽  
Muhammad Aleem Abbas ◽  
Eon-Bee Lee ◽  
Zi-Eum Im ◽  
Walter H. Hsu ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Adenosine Monophosphate ◽  
Ethanol Ingestion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Gastric Mucosal Lesions ◽  
Cellular Degeneration ◽  
Mucosal Lesions ◽  
Pyrus Ussuriensis Maxim

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (P < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.

Effect of sialoadenectomy on ethanol-induced gastric mucosal damage in the rat: role of neutrophils

1990 ◽  
Vol 68 (2) ◽  
pp. 207-210 ◽  
Author(s):  
B. L. Tepperman ◽  
B. D. Soper
Keyword(s):  
Growth Factor ◽  
Gastric Mucosa ◽  
Epidermal Growth Factor ◽  
Salivary Glands ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Mucosal Inflammation ◽  
Prostaglandin E ◽  
Epidermal Growth ◽  
Extent Of Damage

We have observed that removal of the salivary glands is associated with an increase in the susceptibility to gastric mucosal damage in the rat. In the present study, we have examined the effect of sialoadenectomy on ethanol-induced mucosal hemorrhagic damage and myeloperoxidase (MPO) activity. Hemorrhagic damage and MPO activity in response to intragastric 50% w/v ethanol were greater in sialoadenectomized rats when compared with sham-operated animals. Pretreatment with 16,16-dimethylprostaglandin E2 (0.3 μg/kg s.c.) reduced damage and MPO activity in both sialoadenectomized and sham control rats receiving 50% ethanol. The reduction in these parameters was greater in control than in sialoadenectomized rats. Pretreatment with epidermal growth factor (5 μg/kg s.c.) significantly reduced MPO activity but did not significantly affect the extent of damage. These data suggest that sialoadenectomy is associated with an increase in mucosal inflammation in animals given ethanol. However, in some situations tissue inflammation (as indicated by MPO activity) was reduced, while the proportion of gastric mucosa exhibiting hemorrhagic damage was not changed.Key words: salivary glands, gastric mucosa, neutrophils, prostaglandin E2, epidermal growth factor.

scholarly journals Role of Activated Protein C in Helicobacter pylori-Associated Gastritis

2000 ◽  
Vol 68 (5) ◽  
pp. 2863-2869 ◽  
Author(s):  
Satoko Oka ◽  
Esteban Cesar Gabazza ◽  
Yukiko Taguchi ◽  
Michihiko Yamaguchi ◽  
Shigehito Nakashima ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Protein C ◽  
Activated Protein C ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Gastric Corpus ◽  
H Pylori

ABSTRACT The protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients with Helicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), andH. pylori lipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients with H. pylori-associated gastritis as compared to H. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-α) induced by H. pylori LPS. Overall, these results suggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-α secretion may serve to protect H. pylori-induced gastric mucosal damage.

Effects of IL-1β, TNF-α, and TGF-β on Proliferation of Human Nasal Epithelial Cells in Vitro

1998 ◽  
Vol 12 (4) ◽  
pp. 279-282 ◽  
Author(s):  
Yang-Gi Min ◽  
Chae-Seo Rhee ◽  
Sam-Hyun Kwon ◽  
Kang Soo Lee ◽  
Ja Bock Yun
Keyword(s):  
Epithelial Cells ◽  
Collagen Gel ◽  
Time Dependent ◽  
Dependent Manner ◽  
Primary Cells ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Tnf Α ◽  
Collagen Gel Matrix

Previous reports suggest that cytokines may be involved in proliferation of the epithelium. The aim of this study was to determine the effects of cytokines, IL-1β, TNF-α, and TGF-β on proliferation of human nasal epithelial cells (HNECs) in vitro. Primary cells were cultured from HNECs on collagen gel matrix. Subcultured HNECs were incubated in a medium with recombinant human (rh) cytokines, rhIL-1β, rhTNF-a, and rhTGF-β at different concentrations of 0.01 ng/mL, 0.1 ng/mL, 1 ng/mL, 10 ng/mL, and 100 ng/mL. After 2-day incubation with these cytokines, daily cell proliferation was measured by MTT assay for 6 days. While rhIL-1β inhibited proliferation of HNECs in concentration-dependent and time-dependent manners, rhTNF-a stimulated HNEC growth at concentrations ranging from 0.01 ng/mL to 10 ng/mL in concentration-dependent and time-dependent manner. In contrast, rhTGF-b inhibited HNEC growth irrespective of concentration and incubation time. This study suggests that IL-1β, TNF-α, and TGF-β may have an important role in the repair of the nasal mucosa by regulating proliferation of the nasal epithelium.

scholarly journals Helicobacter pylori induces intracellular galectin-8 aggregation around damaged lysosomes within gastric epithelial cells in a host O-glycan-dependent manner

Glycobiology ◽  
2018 ◽  
Vol 29 (2) ◽  
pp. 151-162 ◽  
Author(s):  
Fang-Yen Li ◽  
I-Chun Weng ◽  
Chun-Hung Lin ◽  
Mou-Chieh Kao ◽  
Ming-Shiang Wu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Rhesus Macaques ◽  
Dependent Manner ◽  
Gastric Epithelial Cells ◽  
Vacuolating Cytotoxin ◽  
Infected Cells ◽  
H Pylori ◽  
Autophagy Activity ◽  
Binding Lectin

Abstract Galectin-8, a beta-galactoside-binding lectin, is upregulated in the gastric tissues of rhesus macaques infected with Helicobacter pylori. In this study, we found that H. pylori infection triggers intracellular galectin-8 aggregation in human-derived AGS gastric epithelial cells, and that these aggregates colocalize with lysosomes. Notably, this aggregation is markedly reduced following the attenuation of host O-glycan processing. This indicates that H. pylori infection induces lysosomal damage, which in turn results in the accumulation of cytosolic galectin-8 around damaged lysosomes through the recognition of exposed vacuolar host O-glycans. H. pylori-induced galectin-8 aggregates also colocalize with autophagosomes, and galectin-8 ablation reduces the activation of autophagy by H. pylori. This suggests that galectin-8 aggregates may enhance autophagy activity in infected cells. We also observed that both autophagy and NDP52, an autophagy adapter, contribute to the augmentation of galectin-8 aggregation by H. pylori. Additionally, vacuolating cytotoxin A, a secreted H. pylori cytotoxin, may contribute to the increased galectin-8 aggregation and elevated autophagy response in infected cells. Collectively, these results suggest that H. pylori promotes intracellular galectin-8 aggregation, and that galectin-8 aggregation and autophagy may reciprocally regulate each other during infection.

scholarly journals Effect of Cuttlebone on Healing of Indomethacin-Induced Acute Gastric Mucosal Lesions in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Lifeng Qiu ◽  
Lingya Yao ◽  
Yanfei Fang ◽  
Lan Wang ◽  
Meng Xue ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Gastric Ulcers ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Gastric Lesions ◽  
Gastric Mucosal Lesions ◽  
Antioxidant Parameters ◽  
Epidermal Growth ◽  
Mucosal Lesions ◽  
Underlying Mechanisms

The continuing use of nonsteroidal anti-inflammatory drugs (NSAIDs) usually increases the side effects such as peptic ulcer and acute gastric lesions in the gastrointestinal tract. Cuttlebone (CB), isolated from Sepiella maindroni de Rochebrune, was reported to have antioxidant activities, but its role in the treatment of indomethacin-induced gastric lesions has not yet been confirmed. In this research, we investigate the protective effect of cuttlebone on indomethacin-related ulcers in rats and possible mechanisms. Here, gastric ulcers were induced by oral administration of indomethacin, and then the rats were treated with omeprazole (4 mg/kg) or different doses (750, 1500, and 3000 mg/kg of body weight) of cuttlebone. We evaluated lesion index, inflammation score, and a series of oxidant/antioxidant parameters. The data demonstrated that cuttlebone could protect against gastric ulcers induced by indomethacin in a dose-dependent manner (positive correlation). Also, these effects were associated with attenuating the expression of malonaldehyde (MDA) and increasing the levels of some protective ingredients like epidermal growth factor (EGF), prostaglandin E2 (PGE2), and superoxide dismutase (SOD). Thus, considering its ability to protect indomethacin-induced acute gastric mucosal lesions and the underlying mechanisms, CB might be a potential candidate for treating gastric damage caused by NSAIDs.

Bauhinia Protease Inhibitors Attenuate Gastric Ulcer by Blocking Neutrophil Enzymes

Planta Medica ◽  
2020 ◽  
Author(s):  
Mayara Vioto Valois ◽  
Cleide de Oliveira ◽  
Antonio José Lapa ◽  
Caden Souccar ◽  
Maria Luiza Vilela Oliva
Keyword(s):  
Protease Inhibitors ◽  
Trypsin Inhibitor ◽  
Cysteine Proteases ◽  
Mucosal Damage ◽  
Cathepsin G ◽  
Human Neutrophil Elastase ◽  
Therapeutic Success ◽  
Gastric Mucosal Lesions ◽  
Elastase Inhibitor ◽  
Mucosal Lesions

AbstractProteases play a pivotal role in many signaling pathways; inhibitors of well-established proteases have shown a substantial therapeutic success. This study aimed to examine the in vivo effects of 3 protease inhibitors isolated from Bauhinia species: i) Bauhinia mollis elastase inhibitor, which blocks human neutrophil elastase (Kiapp 2.8 nM) and cathepsin G (Kiapp 1.0 nM) activities; ii) Bauhinia mollis trypsin inhibitor, a trypsin inhibitor (Kiapp 5.0 nM); and iii) Bauhinia bauhinioides cruzipain inhibitor, which inhibits elastase (Kiapp 2.6 nM), cathepsin G (Kiapp 160.0 nM), and the cysteine proteases cathepsin L (Kiapp 0.2 nM). Bauhinia bauhinioides cruzipain inhibitor, Bauhinia mollis elastase inhibitor, and Bauhinia mollis trypsin inhibitor were isolated using acetone and ammonium sulfate fractionations, DEAE-Sephadex, trypsin-Sepharose, and Resource-Q chromatographies. Mice and rats were treated intraperitoneally with 1 dose of inhibitor; gastric mucosal lesions were induced by cold-restraint stress. Oral pretreatment of mice with Bauhinia mollis elastase inhibitor or Bauhinia mollis trypsin inhibitor (1 – 10 mg/kg) did not show anti-ulcer effect, while Bauhinia bauhinioides cruzipain inhibitor (0.1 – 1.0 mg/kg) produced a similar reduction of the index of mucosal damage at all effective doses (30 to 33% < control). In rats at doses lower than those used in mice, Bauhinia mollis elastase inhibitor and Bauhinia bauhinioides cruzipain inhibitor reduced the index of mucosal damage by 66% and 54% of controls, respectively. The results indicate a protective effect against gastric mucosal lesions associated with elastase inhibition but not inhibition of trypsin activities. Moreover, the lack of Bauhinia mollis elastase inhibitor efficacy observed in mice may possibly be related to the reported structural differences of elastase in mice and rats.

Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells

2005 ◽  
Vol 289 (4) ◽  
pp. G731-G738 ◽  
Author(s):  
Maria J. Redlak ◽  
Jacinda J. Power ◽  
Thomas A. Miller
Keyword(s):  
Epithelial Cells ◽  
Complex Formation ◽  
Oxidative Phosphorylation ◽  
Caspase 8 ◽  
Mucosal Cell ◽  
Dependent Manner ◽  
Gastric Epithelial Cells ◽  
Caspase 9 ◽  
Mitochondrial Fractions ◽  
Induced Apoptosis

This study was undertaken to determine whether the Bcl-2 family proteins and Smac are regulators of aspirin-mediated apoptosis in a gastric mucosal cell line known as AGS cells. Cells were incubated with varying concentrations of acetylsalicylic acid (ASA; 2–40 mM), with or without preincubation of caspase inhibitors. Apoptosis was characterized by Hoechst staining and DNA-histone-associated complex formation. Antiapoptotic Bcl-2, proapoptotic Bax and Bid, Smac, and cytochrome- c oxidase (COX IV) were analyzed by Western blot analyses from cytosol and mitochondrial fractions. ASA downregulated Bcl-2 protein expression and induced Bax translocation into the mitochondria and cleavage of Bid. In contrast, expression of Smac was significantly decreased in mitochondrial fractions of ASA-treated cells. Bax and Bid involvement in apoptosis regulation was dependent on caspase activation, because caspase-8 inhibition suppressed Bax translocation and Bid processing. Caspase-9 inhibition prevented Smac release from mitochondria. Additionally, increased expression of the oxidative phosphorylation enzyme COX IV was observed in mitochondrial fractions exposed to ASA at concentrations >5 mM. Although caspase-8 inhibition had no effect on aspirin-induced apoptosis and DNA-histone complex formation, caspase-9 inhibition significantly decreased both of these events. We conclude that Bcl-2 protein family members and Smac regulate the apoptotic pathway in a caspase-dependent manner. Our results indicate also that mitochondrial integration and oxidative phosphorylation play a critical role in the pathogenesis of apoptosis in human gastric epithelial cells.

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