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

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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Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms23010416 ◽

2021 ◽

Vol 23 (1) ◽

pp. 416

Author(s):

Jingjing Liu ◽

Wenyang Zhao ◽

Chun Li ◽

Tongyu Wu ◽

Liang Han ◽

...

Keyword(s):

Gastrointestinal Disease ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Health Concern ◽

Disease Treatment ◽

Atp Production ◽

Anti Inflammation ◽

Clinical Drug

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

The Japanese Journal of Pharmacology ◽

10.1254/jjp.64.41 ◽

1994 ◽

Vol 64 (1) ◽

pp. 41-48 ◽

Cited By ~ 1

Author(s):

Yasuo Morimoto ◽

Shinya Oshima ◽

Hideaki Hara ◽

Takayuki Sukamoto

Keyword(s):

Mucosal Damage ◽

Gastric Mucosal Damage

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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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Gastric mucosal protection with chronic mild restraint: role of endogenous prostaglandins

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.2.g127 ◽

1984 ◽

Vol 247 (2) ◽

pp. G127-G132 ◽

Cited By ~ 4

Author(s):

J. L. Wallace ◽

M. M. Cohen

Keyword(s):

Chronic Stress ◽

Mucosal Injury ◽

Mucosal Damage ◽

Gastric Fundus ◽

Gastric Mucosal Damage ◽

Gastric Injury ◽

Protective Effects ◽

Endogenous Prostaglandins

The role of endogenous prostaglandins (PGs) in adaptation of the rat gastric mucosa to chronic stress was examined. After 10 days of chronic mild restraint (CMR), gastric mucosal damage induced by orally administered 40% ethanol was significantly (P less than 0.01) less extensive than that to control mucosae. When the mucosal injury was produced by oral administration of acetylsalicylic acid (250 mg/kg), there was no protection afforded by prior exposure to CMR. Pretreatment with indomethacin (1 mg/kg ip) abolished the protective effects of CMR against ethanol injury. The indomethacin blockade of CMR protection was reversed by the subsequent administration of PGE2 (75 micrograms/kg po). Fundic samples from 10-day CMR rats synthesized three times as much PGE2 (P less than 0.01) and twice as much 6-keto-PGF1alpha (P less than 0.05) as control samples. Thromboxane B2 synthesis by control and CMR samples was not significantly different. The capacity of gastric fundus and antrum to synthesize PGE2 in vitro was higher in samples from CMR rats than from controls. These results suggest that the resistance to gastric injury that develops during chronic stress is mediated by endogenous prostaglandins.

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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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