Effects of KB-5492, a New Anti-Ulcer Agent, on Ethanol- and Acidified Aspirin-Induced Gastric Mucosal Damage In Vivo and In Vitro

Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.

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Gastroprotective effects of Nelumbinis Rhizomatis Nodus carbonisata-derived carbon dots on ethanol-induced gastric ulcers in rats

10.21203/rs.3.rs-101143/v1 ◽

2020 ◽

Author(s):

Juan Luo ◽

Jie Hu ◽

Meiling Zhang ◽

Yue Zhang ◽

Jiashu Wu ◽

...

Keyword(s):

Carbon Dots ◽

Average Diameter ◽

Mucosal Damage ◽

In Vitro Cytotoxicity ◽

Gastric Mucosal Damage ◽

Gastric Ulcers ◽

Necrosis Factor Alpha ◽

In Vivo Experiments

Abstract BackgroundGastric ulcers is a common gastrointestinal digestive system disease. Considering the frequency of human gastric ulcers, the side effects and cost of some existing synthetic drugs, the use of natural products is an important choice for many people. The aim of present study was to explore gastroprotective effects of nelumbinis rhizomatis nodus carbonisata carbon dots (NRNC-CDs) on ethanol-induced gastric ulcers in rats.MethodsThe NRNC-CDs were synthesized via high temperature calcinations treatment at 350 ℃ for 1 h were characterized by various spectroscopic and electron microscopy techniques for their structural, morphological, and optical properties. In vitro cytotoxicity of CDs for the human gastric epithelial cells line (GES-1 cells) was assessed by the CCK-8 assay. Furthermore, the study evaluated gastroprotective effects of NRNC-CDs on ethanol-induced gastric ulcers in rats, followed by a preliminary study on the possible mechanisms of gastroprotection.ResultesNRNC-CDs with a quantum yield of 1.38% have an average diameter of 2.89±0.82nm and the lattice spacing of 0.29 nm , and exerted low toxicity to GES-1 cells by CCK-8 test. In vivo experiments showed that NRNC-CDs remarkably reduced gastric mucosal damage and significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px). In addition, NRNC-CDs also significantly inhibited tumor necrosis factor-alpha (TNF-a) and pro-inflammatory interleukin-6 (IL-6) level in gastric tissues. Histological findings demonstrated that NRNC-CDs exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer.ConclussionThe potent gastroprotective effect of NRNC-CDs were thus attributed to its anti-inflammatory and antioxidant effects. This discovery provides guidance for further research the effect of CDs in gastrointestinal digestive diseases.

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Curcumin: A Potent Protectant against Esophageal and Gastric Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms20061477 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1477 ◽

Cited By ~ 9

Author(s):

Slawomir Kwiecien ◽

Marcin Magierowski ◽

Jolanta Majka ◽

Agata Ptak-Belowska ◽

Dagmara Wojcik ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Curcuma Longa ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Gastric Cancer Cells ◽

Wide Range ◽

Anti Inflammatory ◽

Pleiotropic Properties

Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett’s esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.

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Nonprotein sulfhydryl compounds in canine gastric mucosa: effects of PGE2 and ethanol

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1985.249.1.g137 ◽

1985 ◽

Vol 249 (1) ◽

pp. G137-G144 ◽

Cited By ~ 5

Author(s):

T. A. Miller ◽

D. Li ◽

Y. J. Kuo ◽

K. L. Schmidt ◽

L. L. Shanbour

Keyword(s):

Gastric Mucosa ◽

Low Dose ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

High Dose ◽

Mucosal Protection ◽

Gastric Mucosal Protection ◽

Sulfhydryl Compounds ◽

Mild Irritants

By use of an in vivo canine chambered stomach preparation in which the gastric mucosa was partitioned into two equal halves, the effect of topical 16,16-dimethyl PGE2 (DMPGE2) (1 microgram/ml of perfusate) and 8% and 40% ethanol on tissue levels of nonprotein sulfhydryl compounds was assessed. Both DMPGE2 and 8% ethanol significantly increased (P less than 0.005) mucosal levels of nonprotein sulfhydryls when compared with corresponding mucosa bathed with saline alone. In contrast, mucosa bathed with 40% ethanol showed significantly decreased levels. If mucosa was bathed with DMPGE2 or 8% ethanol prior to exposing the stomach to 40% ethanol, this depletion in sulfhydryl compounds was not observed. Since other experimental observations have shown that exogenously administered prostaglandins and mild irritants (such as low-dose alcohol) can prevent gastric mucosal damage by necrotizing agents (such as high-dose alcohol), our findings are consistent with the hypothesis that nonprotein sulfhydryls may play a role in mediating gastric mucosal protection.

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A new in vitro model for ethanol-induced gastric mucosal damage

Journal of Pharmacological and Toxicological Methods ◽

10.1016/s1056-8719(99)00038-6 ◽

1999 ◽

Vol 41 (4) ◽

pp. 167-172 ◽

Cited By ~ 11

Author(s):

Yassir M.Al-Mulla Hummadi ◽

Rafid A Najim ◽

Imad B Farjou

Keyword(s):

In Vitro Model ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Vitro Model

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Role of Activated Protein C in Helicobacter pylori-Associated Gastritis

Infection and Immunity ◽

10.1128/iai.68.5.2863-2869.2000 ◽

2000 ◽

Vol 68 (5) ◽

pp. 2863-2869 ◽

Cited By ~ 14

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.

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Therapeutic effects of Zuojin Pill on Helicobacter pylori-induced chronic atrophic gastritis through JMJD2B/COX-2/VEGF signaling axis

10.21203/rs.3.rs-20652/v2 ◽

2020 ◽

Author(s):

Shihua Wu ◽

Chunmei Bao ◽

Ruilin Wang ◽

Xiaomei Zhang ◽

Sijia Gao ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cell Viability ◽

Atrophic Gastritis ◽

Chronic Atrophic Gastritis ◽

Gastric Mucosal Damage ◽

Therapeutic Effects ◽

Cox 2 ◽

H Pylori

Abstract Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG. Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.

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Pancreatic spasmolytic polypeptide protects the gastric mucosa but does not inhibit acid secretion or motility

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.273.1.g112 ◽

1997 ◽

Vol 273 (1) ◽

pp. G112-G117 ◽

Cited By ~ 1

Author(s):

C. McKenzie ◽

T. Marchbank ◽

R. J. Playford ◽

W. Otto ◽

L. Thim ◽

...

Keyword(s):

Acid Secretion ◽

Mucosal Damage ◽

Inhibitory Effect ◽

Gastric Mucosal Damage ◽

Conscious Rat ◽

Immature Rat ◽

Trefoil Peptide ◽

Spasmolytic Polypeptide ◽

Evoked Contractions

The objectives of these studies were to examine whether the trefoil peptide porcine pancreatic spasmolytic polypeptide (PSP) had gastric mucosal protectant properties similar to its human equivalent human spasmolytic polypeptide (hSP) and to confirm the antisecretory and antimotility action of the peptide. PSP and recombinant hSP reduced gastric mucosal damage caused by a combination of subcutaneous indomethacin and restraint stress in the conscious rat. At a dose of 500 micrograms/kg bolus plus 500 micrograms.kg-1.h-1 sc, PSP significantly reduced the total area of damage by 58%. PSP at a dose of 150 micrograms/kg iv had no inhibitory effect on pentagastrin-stimulated gastric acid secretion in the perfused stomachs of anesthetized rats. This lack of antisecretory activity was confirmed in vitro using an isolated stomach preparation from the immature rat. PSP and hSP at concentrations up to 800 nM did not inhibit electrically or chemically evoked contractions of the guinea pig ileum and duodenum in vitro. Thus antisecretory and antimotility actions do not underlie the mucosal protectant properties of PSP. PSP did, however, stimulate cell migration, and this may, at least in part, account for its protectant properties.

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Drugs acting at the GABAA receptor attenuate ethanol-induced gastric mucosal damage in vitro*

Clinical and Experimental Pharmacology and Physiology ◽

10.1046/j.1440-1681.2003.03866.x ◽

2003 ◽

Vol 30 (7) ◽

pp. 495-500 ◽

Cited By ~ 4

Author(s):

Rafid A Najim ◽

Hiwa K Saaed

Keyword(s):

Gabaa Receptor ◽

Mucosal Damage ◽

Gastric Mucosal Damage

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Gastroprotective Effect of Ethanol Extracts from Bark of Magnolia officinalis on Ethanol-Induced Gastric Mucosal Damage in Rats

BioMed Research International ◽

10.1155/2021/6688414 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xiao Wang ◽

Shu Fu ◽

Chen Zhang ◽

Xin Nie ◽

Wan Liao ◽

...

Keyword(s):

Gastric Ulcer ◽

Periodic Acid ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Gastric Injury ◽

Dependent Manner ◽

Gastroprotective Effect ◽

Ethanol Extracts ◽

Magnolia Officinalis

Background. Magnolia officinalis Rehd. and Wils. is widely used in Asian countries because of its multiple pharmacological effects. This study investigated the gastroprotective effect and mechanisms of the ethanol extracts from the bark of Magnolia officinalis (MOE) against ethanol-induced gastric mucosal damage in rats. Methods. MOE was prepared by reflux extraction with 70% ethanol, and its main compounds were analyzed by UPLC-Q-Exactive Orbitrap-MS. DPPH, ABTS, and FRAP methods were used to evaluate the antioxidant capacity of MOE in vitro. The gastroprotective effects of MOE were evaluated by the area of gastric injury, H&E (hematoxylin-eosin), and PAS (periodic acid-Schiff). The mechanism was explored by measuring the levels of cytokines and protein in the NF-κB signaling pathway. Results. 30 compounds were identified from MOE, mainly including lignans and alkaloids. MOE presented a high antioxidant activity in several oxidant in vitro systems. Gastric ulcer index and histological examination showed that MOE reduced ethanol-induced gastric mucosal injury in a dose-dependent manner. MOE pretreatment significantly restored the depleted activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzymes, reduced malondialdehyde (MDA), and prostaglandin E2 (PGE2) levels in the gastric tissue in rats. In addition, MOE also inhibited the activation of nuclear factor kappa B (NF-κB) pathway and decreased the production of proinflammatory cytokines. Conclusions. The gastroprotective effect of MOE was attributed to the inhibition of oxidative stress and the NF-κB inflammatory pathway. The results provided substantial evidence that MOE could be a promising phytomedicine for gastric ulcer prevention.

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