Gastric Damage Research Articles

6′-O-Galloylpaeoniflorin attenuates Helicobacter pylori-associated gastritis via modulating Nrf2 pathway

As a common disease of the digestive system, chronic gastritis is inflammation of the gastric mucosa caused by various factors. Helicobacter pylori (H. pylori) is one of the main causes of chronic gastritis, which can lead to gastric mucosal damage and gland atrophy, thereby promoting gastrocarcinogenesis. Oxidative stress and the inflammatory response are important mechanisms of H. pylori-induced gastritis. 6′-O-Galloylpaeoniflorin (GPF) is a substance isolated from peony root with antioxidant and anti-inflammatory activities. However, its role and mechanism in the pathogenesis of H. pylori-induced chronic gastritis remain unclear. This study explored the effects of GPF on H. pylori-induced gastric mucosal oxidative stress and inflammation using flow cytometry, western blotting, real-time quantitative PCR, and immunohistochemistry. We found that H. pylori infection increased oxidative stress and expression of inflammatory cytokines in vitro and in vivo and that these outcomes were inhibited by GPF. Furthermore, GPF activated nuclear factor erythroid-related factor-2 (Nrf2) and its downstream target genes in H. pylori-infected GES-1 cells and mice. The anti-inflammatory and antioxidant effects of GPF on H. pylori-infected cells were attenuated by an Nrf2 inhibitor. Taken together, these data suggest that GPF reduces H. pylori-induced gastric mucosa injury by activating Nrf2 signaling and that GPF is a potential candidate for the treatment of H. pylori-associated gastritis.

In vivo inhibition of gastric acid secretions and H+/K+- ATPase activity, and enhancement of mucin activity by Dissotis rotundifolia plant extract

Gastric H+/K+ ATPase enzyme is a central biomolecule that controls gastric secretions and its inhibition is reported to correlate with healing and symptomatic relief in both gastroesophageal reflux disease and peptic ulcers patients. The current study was done to assess the claim that Dissotis rotundifolia possesses anti-ulcer potentials. The experiment was done on Aspirin (acetylsalicylic acid)-induced gastric ulcer rats to ascertain the ability of the plant extract in protecting against gastric ulcer. Histological investigation of gastric lesions and physical examinations of the stomach lining were carried out together with evaluation of gastric secretions. There was experimental evidence in rats to support the purported effectiveness of the plant in the management of gastrointestinal ulceration. The data shows that Dissotis rotundifolia extract at 300 mg/kgbwt acts as an antiulcer agent by serving as a proton pump inhibitor that also increases mucin activity, gastric mucus content, pH but decreases titrable acidity. This was confirmed in the observation of a marked reduction in gastric mucosal damage affirmed by histology in DR-pre-treated groups compared to negative control groups.

Effect of Carrots (Daucus carota L.) on Gastric Histopathology of Piroxicam-Induced Mice as a Peptic Ulcer Prevention

Highlights:1. Carrots (Daucus carota L.) can reduce the side effects of non-steroidal anti-inflammatory drugs (NSAIDs) due to its gastroprotective components.2. Histopathological studies of the gastric inflammation signs showed that carrots can prevent NSAID-induced peptic ulcers. AbstractIntroduction: Non-steroidal anti-inflammatory drugs (NSAIDs) consumption contributes significantly to gastrointestinal morbidity, including peptic ulcers. NSAIDs cause gastric mucosal damage by inhibiting PGE2 and PGI2 secretion, increasing HCl secretion, and also causing local irritation and neutrophil adhesion. Flavonoids and chlorogenic acid are gastroprotective agents found in carrots (Daucus carota L.). Therefore, this study aimed to validate the effect of carrots on gastric histopathology of piroxicam-induced mice.Methods: This was an experimental study using a post-test-only control group design. 35 mice were divided into 5 groups and were allowed to adapt for 1 week. The negative control group received 0.25 mL aqua dest, while the positive control group received 0.104 mg famotidine. Group A, B, and C received carrot extract with each dosage was 200 mg/kgBW, 300 mg/kgBW, and 400 mg/kgBW. The mice were induced 2 hours later with 0.052 mg piroxicam. The treatments lasted 14 days. Each stomach was taken and examined on the 15th day. Afterward, histopathological preparations were made.Results: The results of the histopathological signs of inflammation using the Kruskal-Wallis method showed p = 0.000, indicating that there was an effect of the carrot extract in preventing the inflammation on the gastric histopathology (p < 0.05).Conclusion: In conclusion, this study confirmed that carrot extract is more effective in avoiding peptic ulcers due to NSAID consumption.

CHEMICAL COMPOSITION, ANTI-ULCER AND ANTI-INFLAMMATORY EFFECTS OF CAROB PODS (CERATONIA SILIQUA L.) POLYPHENOLS FROM AIN TEMOUCHENT

This research was aimed to evaluate the chemical composition by HPLC/UV, anti-inflammatory effect in vitro (hyaluronidase assay) and anti-ulcer activity in vivo against gastric ulcer. This anti-ulcer activity was explored in vivo on Wistar rats exposed to a gastric ulcer provoked with oral administration of HCl /ethanol (150 mM /60%) for one day after five days of oral treatment with 250 mg/kg of ethanolic extract of carob pods (EECp), to restore stomach ulceration. Several compounds of carob have been identified by HPLC/UV. This identification reveals the existence of phenolic compounds; flavonoids (chrysin, galangin, pinocembrin, quercetin, genistein, kaempferol, etc.) and phenolic acids (rosmarinic acid, caffeic acids, ferulic acid, etc.). Our extract showed strong inhibitory activity of hyaluronidase with (IC50 = 20.7 mg / ml). The results obtained indicated that administration of HCl /ethanol alone produced stomach ulceration in rats with very extensive and bleeding gastric lesions with 44.09% of percentage lesion and 362.26 mm2 of lesions area in the stomach mucosa. However, pretreatement of rats with EECp revealed a spectacular inhibition of gastric mucosal damage (7.46%), a significant reduction in malondialdehyde (4.86 nmol/mL) and an increase in enzymes of oxidative status (superoxide dismutase, catalase and glutathione peroxidase). The present study results can attribute to carob an antioxidant, anti-inflammatory and anti-ulcer effects.

Mitochondria-targeted hydrogen sulfide donors versus acute oxidative gastric mucosal injury.

Hydrogen sulfide (H2S) as a gaseous molecule prevents gastrointestinal (GI)-tract against various injuries. This study aimed to evaluate for the first time the detailed molecular mechanism of mitochondria-targeting H2S-prodrugs, AP39 and RT01 in gastroprotection against ischemia/reperfusion (I/R)-induced lesions. Wistar rats exposed to I/R were pretreated i.g. with vehicle, AP39 (0.004-2mg/kg), RT01 (0.1mg/kg), or with AP219 (0.1mg/kg) as structural control without ability to release H2S. AP39 was also administered with mTOR1 inhibitor, rapamycin (1mg/kg i.g.). Gastric damage area was assessed micro-/macroscopically, gastric blood flow (GBF) by laser flowmetry, mRNA level of HIF-1α, GPx, SOD1, SOD2, annexin-A1, SOCS3, IL-1RA, IL-1β, IL-1R1, IL-1R2, TNFR2, iNOS by real-time PCR. Gastric mucosal and/or serum content of IL-1β, IL-4, IL-5, IL-10, G-CSF, M-CSF, VEGFA, GRO, RANTES, MIP-1α, MCP1, TNF-α, TIMP1, FABP3, GST-α, STAT3/5 and phosphorylation of mTOR, NF-κB, ERK, Akt was evaluated by microbeads-fluorescent assay. Mitochondrial complexes activities were measured biochemically. RNA damage was assessed as 8-OHG by ELISA. AP39 and RT01 reduced micro-/macroscopic gastric I/R-injury increasing GBF. AP39-gastroprotection was accompanied by maintained activity of mitochondrial complexes, prevented RNA oxidation and enhanced mRNA/protein expression of SOCS3, IL-1RA, annexin-A1, GST-α, HIF-1α. Rapamycin reversed AP-39-gastroprotection. AP39-gastroprotection was followed by decreased NF-κB, ERK, IL-1β and enhanced Akt and mTOR proteins phosphorylation. AP39-prevented gastric mucosal damage caused by I/R-injury, partly by mitochondrial complex activity maintenance. AP39-mediated attenuation of gastric mucosal oxidation, hypoxia and inflammation involved mTOR1 and Akt pathways activity and modulation of HIF-1α, GST-α, SOCS3, IL1RA and TIMP1 molecular interplay.

Antibiotics-free nanoparticles eradicate Helicobacter pylori biofilms and intracellular bacteria.

Biofilms and intracellular survival tremendously help Helicobacter pylori (H. pylori) escape from antibacterial agents attacking, therefore issuing extreme challenges to clinical therapies. Herein, we constructed fucoidan (FU)-coated nanoparticles (FU/ML-LA/EB NPs) via simple self-assembly of biguanide derivative (metformin-linoleic acid, ML) and linoleic acid (LA), encapsulating urease inhibitor ebselen (EB) instead of antibiotics to take antibacterial effect. Negatively charged FU/ML-LA/EB NPs easily penetrated through the gastric mucus layer to arrive at infection sites, then eradicated extracellular polymeric substances (EPS) to destroy H. pylori biofilms structure. After strengthening bacterial membrane permeability, the nanoparticles could enter H. pylori and kill bacteria by inhibiting the activity of urease. FU/ML-LA/EB NPs also entered H. pylori-infected host cells through receptor-mediated internalization, in which they activated AMPK to recover lysosomal acidification for killing intracellular H. pylori. Additionally, FU/ML-LA/EB NPs alleviated oxidative stress, hence reducing gastric mucosal damage and cutting off the pathways of carcinogenesis. Notably, H. pylori burden after FU/ML-LA/EB NPs treatment was reduced to a great extent in vivo, which was significantly lower than that after treatment with clinical therapy. Antibiotics-free FU/ML-LA/EB NPs improving bacterial eradication and alleviating oxidation stress made it a powerful approach against H. pylori.

Atractylone Alleviates Ethanol-Induced Gastric Ulcer in Rat with Altered Gut Microbiota and Metabolites.

BackgroundGastric ulcer (GU) is the most common multifactor gastrointestinal disorder affecting millions of people worldwide. There is evidence that gut microbiota is closely related to the development of GU. Atractylone (ATR) has been reported to possess potential biological activities, but research on ATR alleviating GU injury is unprecedented.MethodsHelicobacter pylori (H. pylori)-induced GU model in zebrafish and ethanol-induced acute GU model in rat were established to evaluate the anti-inflammatory and ulcer inhibitory effects of ATR. Then, 16S rRNA sequencing and metabolomics analysis were performed to investigate the effect of ATR on the microbiota and metabolites in rat feces and their correlation.ResultsTherapeutically, ATR inhibited H. pylori-induced gastric mucosal injury in zebrafish. In the ulceration model of rat, ATR mitigated the gastric lesions damage caused by ethanol, decreased the ulcer area, and reduced the production of inflammatory factors. Additionally, ATR alleviated the gastric oxidative stress injury by increasing the activity of superoxide dismutase (SOD) and decreasing the level of malondialdehyde (MDA). Furthermore, ATR played a positive role in relieving ulcer through reshaping gut microbiota composition including Parabacteroides and Bacteroides and regulating the levels of metabolites including amino acids, short-chain fatty acids (SCFAs), and bile acids.ConclusionOur work sheded light on the mechanism of ATR treating GU from the perspective of the gut microbiota and explored the correlation between gut microbiota, metabolites, and host phenotype.

Phenolic Characterization Using cLC-DAD Analysis and Evaluation of In Vitro and In Vivo Pharmacological Activities of Ruta tuberculata Forssk

The perennial aromatic plant Ruta tuberculata Forssk (Rutaceae) has been traditionally used by Mediterranean peoples as folk medicine against several types of disease to treat diverse illness. The objective of this work is to evaluate the in vitro and in vivo pharmacological activities of the aqueous (RAE) and methanolic (MeOH) 80% (RME) extracts of Algerian R. tuberculata aerial parts. Antioxidant potential, neuro-protective and anti-arthritic activities were investigated in vitro using six antioxidant approaches and by determining acetyl-cholinesterase and bovine albumin denaturation inhibitory capacities, respectively. Furthermore, in vivo anti-ulcer and anti-inflammatory activities were evaluated on EtOH-induced gastric mucosal damage and carrageenan-induced paw edema models in mice. Moreover, bio-compounds’ contents were also quantified using spectrophotometric and cLC-DAD methods. Both in vivo and in vitro investigations showed remarkable antioxidant activity of Ruta tuberculata Forssk, while methanolic extract (RME) of Ruta tuberculata Forssk exhibited more significant neuro-protective and anti-inflammatory effects. However, the antiulcer activity was more pronounced with RAE of R. tuberculata, which suggests that this plant can be considered as a natural resource of potent bioactive compounds that may act as antioxidant and anti-inflammatory agents, which underlines the importance of incorporating them in therapies in order to treat various diseases linked to oxidative stress, and they may also provide crucial data for the development of new anticholinesterase drugs to improve neurodegenerative diseases, such as Alzheimer’s.

Digestion Resistance of Soybean 7S Protein and Its Implications for Reinforcing the Gastric Mucus Barrier.

Previous studies have found that soybean protein, especially soybean 7S protein (β-conglycinin), exhibits digestion resistance, but the mechanism of digestion resistance and its implications for human health are still unclear. Here, we show that the extracted soybean 7S protein contains both oligomer globulins and amyloid aggregates, while the gastric digested soybean 7S protein only contains amyloid aggregates and thus exhibits digestion resistance. An animal experiment shows that un-digestible soybean 7S protein effectively prevents aspirin-induced acute gastric mucosa damage. The impacts of un-digestible soybean 7S protein on gastric mucus barrier properties are investigated using quartz crystal microbalance with dissipation (QCM-D), Langmuir monolayer, and multiple particle tracking (MPT). Results show that these un-digestible protein aggregates can penetrate into gastric mucus, increase the viscosity and compactness of the mucin layer, and reinforce the gastric mucus barrier properties. The findings are helpful to understand that high consumption of non-fermented soybean foods is associated with a decreased risk of gastric cancer.

Purple Corn (Zea mays indurata) Ice Cream as an Immune Booster in The Pandemic Era

The COVID-19 pandemic has had an impact on public health. Immune resistance was a crucial factor in the pandemic era considering all diseases that arise as self-limiting diseases. Food as a source of nutrients had a vital role as an immunomodulator. As an agricultural country with food production commodities that were still massive, agricultural products are needed to develop food innovations, such as purple corn. One of the nutritional contents of purple corn was the flavonoid group in the form of anthocyanin compounds as a source of antioxidants to increase the body's immunity and prevent diseases caused by viruses, fungi, and bacteria, as well as prevent atherosclerosis, gastric damage, cholesterol, obesity, and others. Anthocyanin compounds in purple corn 70mg/100 grams. Anthocyanins in purple corn are processed into healthy food in ice cream with the product label "Purple Corn Ice Cream". This research aims to help people choose food innovations that can help them increase their immunity in the Covid-19 pandemic era. This ice cream product was formulated and has gone through several tests. The anthocyanin test results showed that the sample contained anthocyanins. The sensory test results stated that this product had a soft texture, milky smell, light purple colour, and sweet taste, so it was accepted and received a positive response from the community. Based on the total questionnaire assessment results, 88% of respondents. Purple Corn Ice Cream was expected to be a nutritious food innovation, popular with people regardless of age, practical, and durable with the content of flavonoid anthocyanin compounds in purple corn, which can improve the body's immune system during a pandemic.

Protective effect of active components of Eucommia ulmoides leaves on gastric ulcers in rats: Involvement of the PI3K/Akt/NF-κB pathway.

Eucommia ulmoides leaves are widely developed as food and medicines in China and Japan. Its main components have anti-inflammatory properties against gastric ulcers. The purpose of this study was to assess the protective role of an extract derived from the active components of Eucommia ulmoides leaves (EUL 50) against a gastric ulcer and analyze the underlying antiulcer mechanism. The main components of EUL 50 were identified using an ultra-performance liquid chromatography (UPLC) method. Network pharmacology and molecular docking were performed to predict the possible mechanism of action of EUL 50 in the treatment of gastric ulcers. The rats received EUL 50 intragastric administration twice a day for 3 days. Hydrochloric acid/ethanol (HCl/EtOH) was utilized to induce gastric ulcers, followed by histopathological and histochemical evaluation of the ulcer tissues and determination of the main oxidative stress parameters and inflammatory cytokines. The expression of PI3K/Akt/NF-κB pathway-related proteins was measured. Neochlorogenic acid, chlorogenic acid, rutin, and so on were identified as the major components of EUL 50 by UPLC. The prediction results identified the PI3K/Akt/NF-κB signaling pathway as the main possible protective mechanism against gastric ulcers. Furthermore, in a dose-dependent manner, EUL 50 reduced gastric tissue damage. In addition, the high dose of EUL 50 administration resulted in remarkable reductions in the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin-1β (IL-1β) by 22.64%, 42.61%, 57.78%, and 56.51%, respectively, and suppression of the phosphorylation of Akt, p65, IKKα, and IκBα by 60.87%, 67.65, 74.58%, and 59.57%, respectively, and increased the antioxidant enzyme activity. EUL 50 is rich in flavonoids and organic acids that can act on the PI3K/Akt/NF-κB signaling pathway; as a result, oxidative stress and inflammation are considerably reduced, and gastric ulcers caused by HCl/EtOH are reduced. PRACTICAL APPLICATION: As a medicinal and food substance, Eucommia ulmoides leaves are widely used in the development of health products. EUL 50, a moderately polar part of E. ulmoides leaves, was obtained by extraction and enrichment and was found to have a better protective effect against HCl/EtOH-induced gastric ulcers. This finding can enrich the traditional application of E. ulmoides leaves and provide a basis for their health product development.

Antinociceptive and gastroprotective activities of Bocconia arborea S. Watson and its bioactive metabolite dihydrosanguinarine in murine models

Ethnopharmacological relevanceBocconia arborea S. Watson (Papaveraceae) is known as “palo llora sangre” and is used in Mexican traditional medicine for the treatment of infections, it is also used as anxiolytic, analgesic, and antidiabetic, among others. Aim of the studyto evaluate the antinociceptive and gastroprotective activities of extracts from B. arborea and dihydrosanguinarine (DHS) in murine models. Materials and methodsOrganic extracts [hexane (HEX), dichloromethane (DCM) and methanol (MeOH)] were obtained by maceration. DHS was isolated and purified from HEX and DCM by precipitation and chromatographic column, respectively. Organic extracts and DHS were evaluated to determine their antinociceptive effect using formalin test in murine model. Also, the ambulatory effect of the HEX and DHS was determined in Open field test. The possible mechanism of action of DHS was explored in the presence of naltrexone (NTX, 1 mg/kg, i.p.), and picrotoxin (PTX, 1 mg/kg, i.p.). Gastric damage as possible adverse effect or gastroprotection were also investigated. Whereas DHS acute toxicological study was done, and 100 mg/kg of DHS was examined by electroencephalographic (EEG) analysis to discard neurotoxic effects. ResultsThe B. arborea extracts significantly showed effects in both neurogenic and inflammatory phases of the formalin test, where the HEX extract reached the major antinociceptive effect. A significant and dose-response (10, 30, and 100 mg/kg) antinociceptive activity was observed with the HEX (ED50 = 69 mg/kg) and DHS (ED50 = 85 mg/kg) resembling the effect of the reference analgesic drug tramadol (30 mg/kg). The significant effect of DHS was inhibited in the presence of NTX and PTX. Neither the extracts or DHS produced sedative effects or gastric damage per se at antinociceptive doses. The EEG analysis demonstrated central depressant activity but not sedative or neurotoxic effects at the highest antinociceptive dosage tested, and LD50 is higher than 2000 mg/kg. ConclusionsHEX, DCM, and MeOH extracts showed significant antinociceptive activity, and DHS was identified as one of bioactive compounds without producing sedative, neurotoxic or gastric damage effects, as possible adverse effects reported for analgesic drugs. A role of opioid and GABAA neurotransmission appears to be involved as mechanisms of action of DHS, suggesting its potential for pain therapy and reinforcing the traditional use of B. arborea.

The effects of dragon fruit (Hylocereus polyrhizus) extract on indomethacin-induced stomach ulcer in rats.

The aim of this study was to investigate the effects of red dragon fruit (Hylocereus polyrhizus) extract (DFE) on the stomach in ulcer model induced by indomethacin in rats. Effects of DFE were evaluated in indomethacin-induced gastric damage model on Sprague-Dawley rats. Experimental model: all rats were fasted for 24 h. At the end of this period, DFE was administered to the ulcer-induced groups. One hour after this application, a dose of 25 mg/kg of indomethacin was applied by oral gavage to all groups except the HEALTHY and DFE1000 groups. Six hours after indomethacin administration, the rats were euthanized with high-dose anesthesia and the experiment was terminated. Macroscopic and microscopic analyses for investigating ulcerative area, molecular and biochemical analyses for oxidative damages investigation and molecular analyses for the effect mechanism of indomethacin and DFE were conducted on stomach tissues in the study. While oxidative stress-associated markers such as MDA, BAX, and Caspase 3 increased dramatically in the indomethacin group, GSH antioxidant levels decreased. It was observed that these parameters were significantly improved in DFE 500 mg/kg and DFE 1000 mg/kg groups compared to ulcer group, and the results of especially DFE 1000 mg/kg group were similar to famotidine group. We observed that our histopathological findings also supported all our other findings. Dragon fruit extract was protected against indomethacin-induced ulcer damage by decreased MDA levels, increased GSH levels, and inhibition of Caspase 3, BAX, and Cox-2, and activation of Cox-1. PRACTICAL APPLICATIONS: People of all ages around the world suffer from gastric ulcer which is one of the most common gastrointestinal ailments. The etiological factors of the disease are using of cigarette and alcohol, nutritional deficiencies, infections, and using non-steroidal anti-inflammatory drugs which use frequent and indiscriminate. Indomethacin is one of the NSAIDs and is commonly preferred to induce ulcer modeling in rats due to its gastric toxicity potential. Current anti-ulcer drugs have many serious side effects. Patients who suffered from gastric ulcer tend to discontinue the drug because of side effects. Therefore, patients need new agents that are non-toxic, have few side effects, and are easily accessible anti-ulcer drugs. Dragon fruit, as a medicinal herb, is highly valuable and widely used in traditional medicine, and may provide gastroprotective activity. Studies have shown that H. polyrhizus has antioxidant activities. We consider the effects of dragon fruit extract (DFE) to be a therapeutic drug for an indomethacin-induced ulcer model.

Rivastigmine ameliorates indomethacin experimentally induced gastric mucosal injury via activating α7nAChR with inhibiting oxidative stressand apoptosis.

The current study aimed to investigate the potential ameliorative role of Rivastigmine (RIVA), the anti-Alzheimer drug, against the gastric mucosal injury caused by indomethacin (IND). The rats were divided into four groups: group I was given a vehicle as a control, group II was given RIVA (0.3 mg/kg) once daily intraperitoneal (ip) for 2 weeks, group III was given a single IP dose of 30 mg/kg IND, and group IV was given RIVA ip 2 weeks before the administration of IND. The gastric mucosal injury was detected by the estimation of ulcer index, gastric acidity, pepsin, and mucin concentrations. Malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), total nitrite/nitrate (NOx), and the expression of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor kappa B (NF-κB), Hemoxygenase 1 (HO-1), and caspase-3 were all measured in gastric tissue. In addition, histological assessment and proliferating cell nuclear antigen (PCNA) immuno-expression were studied. Gastric mucosal injury induced by IND was indicated by both biochemical and histopathological assessments. RIVA Pretreatment reduced ulcer index, MDA, TNF-α, IL-6, NF-κB, and caspase-3 and increased SOD, GSH, NOx, and HO-1. RIVA improved the suppressed nuclear immunoreaction for PCNA observed with IND. The current findings provide novel evidence that RIVA possesses a prophylactic action against IND-induced gastric mucosal damage in rats. Despite being a cholinergic drug that is associated with increased pepsin and stomach acidity, RIVA protected against IND-induced gastric mucosal injury via activating α7nAChR and inhibiting oxidative stress and apoptosis.

Gastroprotective effect of vitamin U in D-galactosamine-induced hepatotoxicity.

Galactosamine (GalN) is a well-known agent for inducing viral hepatitis models in rodents, but it can cause toxicity on different organs. Vitamin U (Vit U) has been proved as a powerful antioxidant on many toxicity models. The present study was designed to investigate the protective effects of Vit U on GalN-induced stomach injury. Rats were divided into four groups as follows: control (group I), Vit U given animals (50 mg/kg per day; group II), GalN administered animals (500 mg/kg at a single dose; group III), GalN + Vit U given animals (at the same dose and time, group IV). At the end of the 3rd day, animals were killed, and stomach tissues were taken. They were homogenized and centrifuged. In comparison to the control group, glutathione, total antioxidant capacity levels, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and Na+ /K+ -ATPase activities of GalN group were found to be decreased. On the contrary, lipid peroxidation, advanced oxidized protein products, hexose-hexosamine, fucose, sialic acid, reactive oxygen species levels, as well as the activities of myeloperoxidase, xanthine oxidase, and lactate dehydrogenase were elevated. Administration of Vit U reversed these abnormalities in the GalN group. It can be concluded that Vit U exerts its unique antioxidant effect and prevents GalN-induced gastric damage.

Gastroprotective effect of Alhagi maurorum (camel thorn) in ethanol-induced gastric damage in mice

Background: Alhagi maurorum is a medicinal plant found in different regions of the world including the eastern part of Libya.
 Aim: It is widely used in liver diseases with its hepatoprotective activity but its effect as an anti-ulcerogenic is not known locally. This study was undertaken to investigate the anti-ulcer effect the Alhagi maurorum has.
 Methods: A camel thorn extract (CTE) was prepared and administered to a group of mice for five days before they received ethanol to induce gastric ulcers. Comparable groups were a negative control group of mice that received normal saline and a positive control group of mice that received ethanol. The histopathological study of all stomachs was performed and graded according to the lesion scoring system.
 Result: Statistically, the mice that received CTE showed a significant improvement in the lesion score as compared to the animals that received ethanol.
 Conclusion: We conclude the Alhagi maurorum has gastroprotective activity against ethanol-induced gastric ulcers.

Protective effect of valerian extract capsule (VEC) on ethanol- and indomethacin-induced gastric mucosa injury and ameliorative effect of VEC on gastrointestinal motility disorder

Context Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases. Objective To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases. Materials and methods Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01–1 mg/mL) on ACh/BaCl2-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248–992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice. Results Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p < 0.01; PGI2 p < 0.05;), along with the alleviation of the levels of MPO (ethanol: 15.56 ± 0.82 vs. 12.15 ± 2.60, p < 0.01; indomethacin: 9.65 ± 3.06 vs. 6.36 ± 2.43, p < 0.05), MDA (ethanol: 1.66 ± 0.44 vs. 0.81 ± 0.58, p < 0.01; indomethacin: 1.71 ± 0.87 vs. 1.09 ± 0.43, p < 0.05), and inflammatory mediators. VEC decreased the high tone induced by ACh/BaCl2 and promoted intestinal transit in normal and neostigmine/adrenaline-induced mice. Discussion and conclusions VEC showed a potential gastroprotective effect, suggesting that VEC is a promising phytomedicine for the treatment of GI diseases.

Capsaicin Inhibits Inflammation and Gastric Damage during H pylori Infection by Targeting NF-kB-miRNA Axis.

Helicobacter pylori (H. pylori) infection is considered as one of the strongest risk factors for gastric disorders. Infection triggers several host pathways to elicit inflammation, which further proceeds towards gastric complications. The NF-kB pathway plays a central role in the upregulation of the pro-inflammatory cytokines during infection. It also regulates the transcriptional network of several inflammatory cytokine genes. Hence, targeting NF-kB could be an important strategy to reduce pathogenesis. Moreover, treatment of H. pylori needs attention as current therapeutics lack efficacy due to antibiotic resistance, highlighting the need for alternative therapeutic approaches. In this study, we investigated the effects of capsaicin, a known NF-kB inhibitor in reducing inflammation and gastric complications during H. pylori infection. We observed that capsaicin reduced NF-kB activation and upregulation of cytokine genes in an in vivo mice model. Moreover, it affected NF-kB–miRNA interplay to repress inflammation and gastric damages. Capsaicin reduced the expression level of mir21 and mir223 along with the pro-inflammatory cytokines. The repression of miRNA further affected downstream targets such as e-cadherin and Akt. Our data represent the first evidence that treatment with capsaicin inhibits inflammation and induces antimicrobial activity during H. pylori infection. This alternative approach might open a new avenue in treating H. pylori infection, thus reducing gastric problems.

Effects of Ganoderic Acid A on Gastrointestinal Motility and Brain-Gut Peptide in Rats with Functional Dyspepsia.

Objective The therapeutic effect of drugs for functional dyspepsia (FD) is still limited. Ganoderic acid A (GAA) has anti-inflammatory and cellular protective activities. The aim of this study is to explore the therapeutic effect of GAA on FD. Methods The FD rat model was established via tail damping and forced exercise fatigue. The gastric emptying rate and intestinal propulsion rate of the rats in each group were then detected, and the pathological damage of gastric antrum and duodenum tissues was observed by hematoxylin-eosin (HE) staining. An enzyme-linked immunosorbent assay (ELISA) was conducted to determine the levels of motilin (MTL), vasoactive intestinal peptide (VIP), leptin, gastrin (GAS), calcitonin gene-related peptide (CGRP), and somatostatin (SS) in plasma, and Western blot was used to detect the protein expression levels of occludin, zonula occluden-1 (ZO-1), and junctional adhesion molecule-1 (JAM-1) in the duodenal tissue. Results Treatment with GAA significantly raised the gastric emptying rate and intestinal propulsion rate of FD rats and histologically alleviated the gastric and duodenal damage. Meanwhile, GAA positively regulated the secretion of brain-gut proteins, such as upregulation of MTL, GAS, and SS and downregulation of VIP, leptin, and CGRP. In addition, GAA treatment increased the protein expression levels of occludin, ZO-1, and JAM-1 in the duodenal tissue of the FD rats. Conclusion GAA may exhibit protective effects on FD by regulating the secretion of brain-gut peptide, protecting the intestinal barrier and improving gastrointestinal motility.

Opioid Use in Murine Model Results in Severe Gastric Pathology that May Be Attenuated by Proton Pump Inhibition

Opioids are the gold standard for chronic and acute pain management; however, their consequence on gastric function is relatively understudied. Opioid users have a higher incidence of gastric dysfunction, worse quality of life, increased hospitalizations, and increased use of antiemetic and pain modulator medications. The current study shows that morphine treatment in the murine model results in greater disruption of gastric epithelial cell morphology, increased gastric cell apoptosis, elevated inflammatory cytokines, and matrix metallopeptidase-9 secretion. Morphine treatment also increases gastric acid secretion and causes delays in gastric emptying. Moreover, morphine treatment causes an increase in systemic IL-6 level, which plays an important role in morphine-induced delayed gastric emptying and gastric damage. IL-6 knockout mice show a significant level of reduction in morphine-induced gastric delaying, acid retention, and gastric damage. Thus, morphine-mediated gastric damage is a consequence of the accumulation of acid in the stomach due to increased gastric acid secretion and delayed gastric emptying. Treatment with a proton pump inhibitor resulted in a significant reduction in morphine-induced gastric inflammation, gastric delaying, and improved morphine tolerance. Hence, these studies attribute morphine-mediated induction in gastric acidity and inflammatory cytokines as drivers for morphine-associated gastric pathology and show the therapeutic use of proton pump inhibitors as an inexpensive approach for clinical management of morphine-associated pathophysiology and analgesic tolerance.