Ethanol-induced Gastric Ulcer Research Articles

Untargeted serum and liver metabolomics analyses reveal the gastroprotective effect of polysaccharide from Evodiae fructus on ethanol-induced gastric ulcer in mice

This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.

Isoalantolactone protects against ethanol-induced gastric ulcer via alleviating inflammation through regulation of PI3K-Akt signaling pathway and Th17 cell differentiation

Gastric ulcer (GU) is one of the most prevalent digestive system diseases in humans, and it has been linked to inflammation. Previous studies have demonstrated the anti-inflammatory potential of isoalantolactone (IAL), a sesquiterpene lactone isolated from Radix Inulae. However, the pharmacological effects of IAL on GU and its mechanism of action are still unclear. Hence, the present study is aimed to investigate the anti-inflammatory potential of IAL on GU. Firstly, we assessed the effect of IAL on ethanol-induced injury of human gastric epithelial cells and the levels of inflammatory cytokines in cell culture supernatants. Then, the anti-inflammatory effects of IAL were confirmed in vivo using zebrafish inflammation models. Furthermore, the mechanism of IAL against GU was preliminarily discussed through network pharmacology and molecular docking studies. Quantitative real-time PCR assays were also used to confirm the mechanism of IAL action. ALB, EGFR, SRC, HSP90AA1, and CASP3 were found for the first time as the key targets of the IAL anti-GU. PI3K-Akt signaling pathway and Th17 cell differentiation were identified to play a crucial role in the anti-GU effects of IAL. In conclusion, we found that IAL has anti-inflammatory effects both in vitro and in vivo, and showed potential protective effects against ethanol-induced GU.

PH-Responsive Hydrogel as a Potential Oral Delivery System of Baicalin for Prolonging Gastroprotective Activity

Gastric ulcer is one of the most common gastrointestinal diseases, and natural products have obvious advantages in the treatment of gastrointestinal diseases. Baicalin (Bai) extracted from scutellaria baicalensis exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities. Herein, a pH-responsive sodium alginate/polyaspartate/CaCO3 (SA/PASP@CaCO3) in situ hydrogel was established for the oral delivery of Bai. In this study, we detected the gelling properties, mechanical strength, in vitro erosion, and in vitro release behavior of the hydrogels. Meanwhile, the efficiency of Bai/SA/PASP@CaCO3 hydrogel on ethanol-induced acute gastric ulcers, acetic acid-induced chronic gastric ulcers, and H2O2-stimulated human gastric epithelial GES-1 cells was explored. The pathological examination revealed that Bai-loaded hydrogel alleviated acute and chronic gastric ulcers. In vivo and in vitro results further confirmed that Bai/SA/PASP@CaCO3 in situ hydrogels significantly relieved oxidative stress injury. Moreover, through Western blot assay, Bai/SA/PASP@CaCO3 hydrogel was also found to dramatically increase the proteins levels of NRF2, HO-1, and Bcl2, and reduce levels of p-JNK, cleaved-caspase-3 and Bax; through flow cytometry, it was observed to significantly inhibit the H2O2-induced apoptosis of GES-1 cells. Importantly, the Bai/SA/PASP@CaCO3 in situ hydrogel system showed better anti-gastric ulcer efficiency than free drug, and could serve as a potential drug delivery system for the clinical treatment of gastric ulcers.

Gastroprotective effects of ginsenoside Rh4 against ethanol-induced gastric mucosal injury by inhibiting the MAPK/NF-κB signaling pathway.

Ginsenoside Rh4, a bioactive component extracted from Panax ginseng, exhibits various pharmacological activities, such as anti-inflammatory, anti-oxidation, anti-diabetes, anti-obesity, antitumor and immunity enhancement. However, the gastroprotective effect of ginsenoside Rh4 remains unknown. The present study evaluated the gastroprotective effect and potential mechanism of ginsenoside Rh4 in an ethanol-induced gastric ulcer model. Ginsenoside Rh4 (15, 30, and 60 mg kg-1) and omeprazole (30 mg kg-1) were administered orally for 7 days. The results showed that pretreatment with ginsenoside Rh4 reduced the gastric injury area and percentage of mucosal lesions in gastric tissue. Besides, treatment with ginsenoside Rh4 increased superoxide dismutase (SOD) activity, glutathione (GSH) and nitric oxide (NO) levels, reduced the content of malonaldehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), mediated the prostaglandin E-2-cyclooxygenase-2 (PGE2-Cox-2) pathway, and mitigated inflammation and oxidative stress via blockade of proinflammatory mitogen-activated protein kinase-nuclear factor κB (MAPK/NF-κB) signaling pathways. Furthermore, ginsenoside Rh4 significantly enhanced the protein expression of B-cell lymphoma gene 2 (Bcl-2), decreased the protein expression of Bcl-2-associated X protein (Bax) and tumor necrosis factor receptor superfamily member 6 (Fas), and inhibited the number of apoptotic cells in gastric tissues. The present work demonstrated that ginsenoside Rh4 exerted a considerable gastroprotective effect against ethanol-induced gastric ulcers in rats.

Gastroprotective Activities of Aqueous and 80% Methanol Leaf Extracts of Stephania abyssinica (Quart.-Dill. and A. Rich.) Walp. (Menispermaceae) in Rats.

An ethnobotanical study showed that the leaf of Stephania abyssinica (S. abyssinica) is used for the treatment of gastritis, but there is no scientific investigation. The aim of this study was to evaluate the gastroprotective activities of both aqueous and 80% methanol leaf extracts of S. abyssinica in experimental rats. Decoction and maceration techniques were used to prepare aqueous and 80% methanol leaf extracts, respectively. The extracts were evaluated against pyloric ligation, indomethacin, and ethanol-induced gastric ulcer models at doses of 100, 200, and 400 mg/kg. Negative control received 2% tween 80, while positive controls received 20 mg/kg of omeprazole and 100 µg/kg of misoprostol. Parameters, such as ulcer index, gastric mucin content, gastric juice volume, pH, and free and total acidity were measured. In the pyloric ligation induced gastric ulcer model, all doses of both extracts significantly reduced the ulcer index and gastric juice volume, while doses of 200 and 400 mg/kg exhibited a significant increment in mucus content and gastric juice pH as well as decrease in free and total acidity as compared to negative control. In indomethacin and ethanol induced gastric ulcer models, pretreatment with both extracts significantly reduced the ulcer index and enhanced gastric mucin content in a dose-dependent manner. Phytochemical screening of both extracts showed the existence of flavonoids, phenols, tannins, saponins, alkaloids, and coumarins with high contents of phenols, flavonoids, and alkaloids in 80% methanol extract. This study revealed that aqueous and 80% methanol leaf extracts of S. abyssinica possessed remarkable gastroprotective activities against experimentally induced gastric ulcer models, and this possibly justify the traditional use of S. abyssinica leaves to treat gastritis.

Gastroprotective effects of Triticum aestivum Linn., extract on ethanol-induced gastric ulcer in Wistar rats

Introduction and Aim: Triticum aestivum (wheatgrass) is high in nutrient availability and antioxidant enzymes. It also functions as a detoxifier and aids in the rejuvenation of healthy cells. The current study sought to determine the gastroprotective impact of aqueous ethanolic extract of wheatgrass on the ethanol-induced gastric ulcer.
 
 Materials and Methods: Wistar rats were given an oral dosage of 100% ethanol (1 ml/200g) to cause gastric ulcers. A reference medicine called omeprazole was given orally at dosages of 20 mg/kg body weight and 200 and 400 mg/kg of wheatgrass extract, respectively. Blood samples were taken an hour after ethanol administration, and the stomachs of deceased rats were then examined biochemically, macroscopically, and microscopically.
 
 Results: The gastric ulcer index considerably decreased after taking wheatgrass extract orally, which showed a considerable attenuation of gastric ulcer. The serum level of TNF-? and the activity of the gastric MPO were both significantly enhanced by pre-treatment with wheatgrass extract. Furthermore, compared to the ethanol-induced group, wheatgrass pre-treatment dramatically boosted gastric levels of enzymatic and non-enzymatic antioxidants, including CAT, TAC, and GSH with concurrent reductions in MDA levels. Further evidence for these conclusions came from histopathology research, which showed that wheatgrass had a healing impact on the hemorrhagic shock brought on by ethanol poisoning.
 
 Conclusion: Due to its propensity to decrease oxidative stress and gastric inflammation, wheatgrass extract may have gastroprotective effects on ethanol-induced stomach ulcers.

Evaluation of gastroprotective and phytochemical properties of Terminalia superba engl. & diels (combretaceae) stem bark methanol extract

ABSTRACT Peptic ulcer is a disease that is affecting a large part of the population world-wide irrespective of the race and tribe. Advances made in the search for an ideal or perfect antiulcer drug has been eroded by cost, side effects and treatment failure. Search for cheap, safe, and effective drugs continues. It is the aim of the research to identify the secondary metabolites present in Terminalia superba Engl. & Diels (Combretaceae) stem bark methanol extract and investigate its gastroprotective properties. Methanol extract of T. superba was prepared by cold maceration extraction method using methanol. The extract was concentrated and subjected to acute toxicity test using Lorke’s method, and phytochemical investigation using standard methods. Gastro-protective activity was investigated by three models: aspirin- induced gastric ulcer, hypothermic restraint stress-induced ulcers and ethanol-induced gastric ulcer. The extract was safe in mice at doses below 2154 mg per Kg body weight and the extract contained the major secondary metabolites-alkaloids, flavonoids tannins, saponins, terpenoids, steroids. Pre-treatment with the extract reduced gastric ulceration in rats. There was a 77.3% reduction in the aspirin model, 75.2 % in the ethanol model and an 84 % in the Hypothermic restraint stress-induced ulcers model. There was a statistically significant difference at p= .05 between the treated groups and the un-treated group The methanol extract of Terminalia superba bark is rich in the major secondary metabolites and has gastro-protective a property.

Anti-ulcer Activity of Polyherbal Formulation from Indian Medicinal Plants Cumin Cyminum, Trigonella Foenum Graecum, Piper Nigrum, Curcuma Longa

Aim: The objective of this study was to assess the Anti-ulcer Activity of the Polyherbal Formulation made from the seeds of Cumin Cyminum, Trigonella Foenum Graecum, Piper Nigrum L. and rhizomes of Curcuma Longa in Wistar albino rats. Methods: Male Albino Rat of Wistar strain were used to evaluate the Polyherbal Formulation’s anti-ulcer properties utilising an ethanol-induced gastric ulcer model. The effectiveness of PHF was assessed by determining, gastric pH and gastric mucus, GSH, malondialdehyde (MDA), and nitric oxide (NO) levels in stomach tissues. Results: The administration of the 400 mg/kg dosage of polyherbal formulation significantly exhibits the gastroprotective effects, when compared to the ethanol group. Conclusion: PHF, containing seeds extracts of Cumin Cyminum, Trigonella Foenum Graecum, Piper Nigrum L. and rhizomes of Curcuma Longa was found to possess antiulcer properties in ethanol induced experimental animal models of gastric ulcers, and these findings suggest that the significant gastroprotective activity could be mediated by its antioxidant activity.

Therapeutic Potency of Ovothiol A on Ethanol-Induced Gastric Ulcers in Wistar Rats.

Peptic ulcer is a widespread disease, with a lifetime frequency of 5−10% among the general population and an annual incidence of 0.1−0.3%. Ovothiol A is naturally produced from sea urchin eggs with special antioxidant activity. Gastric ulcers were induced in rats by a single ethanol dose (5 mL/kg). The rats were divided into control, ulcer, and ulcer with 250 and 500 mg/kg ovothiol A doses. Molecular docking studies were used to examine the interactions between ovothiol A and the H+/K+ ATPase active site residues. Ovothiol A led to a significant decline (p < 0.05) in gastric juice volume, ulcer index, MDA, IL-6, and cytochrome c, while levels of gastric juice pH, GSH, CAT, GST, SOD, and NO increased. Histopathological investigation of stomach sections revealed architecture preservation of the gastric mucosa after ovothiol A administration. The anti-ulcerogenic activity of ovothiol A includes scavenging free radicals, inhibition of inflammation, regulation of apoptosis, and stabilization of fibroblast growth factors to promote gastric ulcers healing.

Gastroprotective and anti-Helicobacter pylori potentials of essential oils from the oleoresins of Araucaria bidwillii and Araucaria heterophylla

Plant resins or oleoresins comprise a chemically complex mixture of different classes of compounds. Oleoresin of the genus Araucaria combines essential oil (EO) and resin. It possesses gastroprotective, cytotoxic, and timicrobial, antipyretic, and anti-inflammatory activities. The study aimed to investigate the EOs from the oleoresins of two Araucaria species, A. bidwillii and A. heterophylla, chemically and biologically for their gastroprotective, anti-inflammatory, antioxidant, and anti-Helicobacter pylori potentials. The chemical composition of both species cultivated in Egypt was analyzed with GC-MS and compared with those cultivated abroad using principal component analysis (PCA). There were 37 and 17 secondary metabolites identified in A. heterophylla and A. bidwillii, respectively. The EOs of both species showed a pronounced inhibitory effect on Helicobacter pylori activity in vitro. The gastroprotective effect was assessed in vivo using ethanol-induced gastric ulcer model in rats. Inflammatory cytokines, oxidative stress, and the nuclear factor-kappa B (NF-κB) biomarkers were assessed in the stomach tissues. The ulcer index and percentage of ulcer protection were determined. Stomach sections were examined histopathologically by staining with (H/E) and periodic acid Schiff (PAS). Moreover, the proliferative index was determined using the Ki-67 immunostaining. The treatment of rats with EOs (50, 100, and 200 mg/kg, orally) 1 hour prior to ethanol administration showed promising gastroprotective, anti-inflammatory, and antioxidant potentials. These findings declared the gastroprotective role played by both EOs with the superiority of A. bidwillii over A. heterophylla via modulation of oxidative stress/NF-κB/inflammatory cytokines. Their use can be recommended to protect against the recurrence of peptic ulcers.

Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice.

Foxtail millet has been traditionally considered to possess gastroprotective effects, but studies evaluating its use as a treatment for gastric ulcers are lacking. Here, we assessed the antiulcer effects of foxtail millet protein hydrolysate (FPH) and explored its mechanism by using blocking agents. In a mouse model of ethanol-induced gastric ulcers, pretreatment with FPH reduced the ulcerative lesion index, downregulated the expression of inflammatory cytokines in the gastric tissue, increased the activity of antioxidant enzymes, and improved the oxidative status. FPH increased constitutive the activity of nitric oxide synthase (cNOS), NO levels, and mucin expression in gastric mucosa, and inhibited the activation of the ET-1/PI3K/Akt pathway. In a mouse model of pyloric ligation-induced gastric ulcers, FPH inhibited gastric acid secretion and decreased the activity of gastric protease. Pretreatment of mice with the sulfhydryl blocker NEM and the NO synthesis inhibitor L-NAME abolished the gastroprotective effect of FPH, but not the KATP channel blocker glibenclamide and the PGE2 synthesis blocker indomethacin. Among the peptides identified in FPH, 10 peptides were predicted to have regulatory effects on the gastric mucosa, and the key sequences were GP and PG. The results confirmed the gastroprotective effect of FPH and revealed that its mechanism was through the regulation of gastric mucosal mucus and NO synthesis. This study supports the health effects of a millet-enriched diet and provides a basis for millet protein as a functional food to improve gastric ulcers and its related oxidative stress.

Gastroprotective effects of Combretum paniculatum (Combretaceae) leaf extract and fractions on absolute ethanol-induced gastric ulcer in rats

BackgroundCombretum paniculatum (Combretaceae) Vent. is commonly used in traditional medicine to treat ulcers and gastrointestinal disorders, including distended spleens and the liver. This study investigated the gastroprotective effects of C. paniculatum leaf extract and its fractions on absolute ethanol-induced gastric ulcers in rats and explored their effects on endogenous antioxidant (SOD, MDA, GSH, and Catalase) levels. Butanol, n-hexane, and ethyl acetate extracts (100 and 200 mg/kg), omeprazole (20 mg/kg), and control (3% Tween 80) were administered orally.ResultsThe methanolic extract and fractions of C. paniculatum exhibited varying degrees of ulcer protection. MECP exhibited significant (P < 0.05) ulcer protection (55.56%) at 200 mg/kg; at 100 and 200 mg/kg, HFCP induced considerable (P < 0.01 & 0.001) ulcer reduction (64.44% and 80.00%), respectively; EAFCP offered substantial (P < 0.05) ulcer reduction (57.78%) at 200 mg/kg, whereas BFCP produced significant (P < 0.01) ulcer protection (73.33% and 68.89%) at 100 and 200 mg/kg against absolute ethanol-induced ulcer. MDA levels were substantially reduced after pretreatment with the extract and fractions, whereas SOD, GSH, and catalase levels were significantly enhanced.ConclusionThese findings suggest that C. paniculatum leaf extract and fractions possess gastroprotective actions against ethanol-induced ulcers and exert these effects through antioxidant mechanisms. Therefore, the traditional use of C. paniculatum leaves in the treatment of ulcers is justified.

Melanin from Sepia pharaonis ink alleviates mucosal damage and reduces inflammation to prevent alcohol-induced gastric ulcers

Melanin (MSI) is the primary component of Sepia pharaonis ink. Studies have demonstrated melanin's anti-inflammatory and antioxidant activities in colitis. In the present study, the protective effect of ink melanin against ethanol-induced gastric mucosal damage in mice was investigated. After oral administration of MSI for 12 days, the mice were treated with anhydrous ethanol (0.2 mL) to establish the gastric ulcer model. Histopathological analysis showed that MSI reduced the ulcer area and bleeding symptoms of gastric tissue. MSI exhibited significant antioxidant properties by upregulating superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) activities and decreasing malondialdehyde (MDA) content. The expression levels of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), and prostaglandin E−2 (PGE2) significantly decreased during gastric mucosal injury, while MSI significantly reversed the effects. Furthermore, MSI reduced the expression of inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and the protein expression of toll-like receptor 4 (TLR4), p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). In addition, MSI repressed gastric cell apoptosis by decreasing the expression of Caspase-3. In conclusion, MSI alleviated ethanol-induced gastric ulcer injury by modulating oxidation stress and inflammatory cytokines and maintaining the mucosal barrier, which can be used as therapeutic functional food or nutritional supplement to prevent gastric ulcers. Meanwhile, the mechanism of MSI targeted gastric TLR4/MAPKs pathway deserves further verification.

Evaluation of the antioxidant and anti-ulcer activities of the ethanolic extract of Fumaria officinalis

Fumaria officinalis which belong to the Papaveraceae family is used to treat stomach-related ailments in Iraqi folk medicine. The aim of this study was to determine the anti-ulcer and antioxidant activities of a 70% ethanol extract of F. officinalis . Extracts of the aerial parts F. officinalis at doses of 200 and 400 mg/kg body weight and the standard drug, esomeprazole at a dose of 20 mg/kg body weight were orally administered daily for 21 days after ulcer induction. The rats were sacrificed, and their stomachs were subjected to macroscopic and microscopic studies. The ethanolic extract showed a significant curative effect on ethanol-induced ulcer compared to the effects observed in the control and esomeprazole groups, especially at 400 mg/kg. Haematoxylin-eosin staining revealed remarkable improvement in gastric mucosal alteration, especially in rats treated with 400 mg/kg F. officinalis compared to the control. F. officinalis had high DPPH free radical scavenging activity (IC 50 : 189.2 ± 0.31 µg/mL) compared to ascorbic acid (215.5 ± 2.41 µg/mL). Further, HPLC analysis of the ethanolic extract revealed the presence of rutin, quercetin, ferulic, and p-coumaric acid in various quantities. In silico , rutin and quercetin were found to have the highest affinities of -9.4 and -7.6 kcal/mol, respectively with human H+/K+-ATPase α chain active sites, and the highest binding site energy values with Na+/K+-ATPase and pig gastric H+/K+- ATPase, respectively. Altogether, F. officinalis may be a potential candidate for the treatment of gastric ulcers. • Fumaria officinalis ethanolic extract treated ethanol-induced gastric ulcer. • Gastric ulcer healing mode of action of Fumaria officinalis involves inhibition H+/K+-ATPase, which is mediated mainly by rutin and quercetin. • In vitro antioxidant was assessed by DPPH, TPC and TFC assay. • HPLC analysis of ethanolic extract demonstrated the existence of flavonoids and phenolic acid in different quantities.

Lactoferrin mitigates ethanol-induced gastric ulcer via modulation of ROS/ICAM-1/Nrf2 signaling pathway in Wistar rats.

We aimed to investigate the gastroprotective effect of lactoferrin (LF; 100 & 300 mg/kg) in male Wistar rats versus gastric ulcers induced by 96% ethanol. Rats were randomly allocated into 4 groups: control, ethanol, ethanol+LF100, and ethanol+LF300. LF100 & 300 were given 15 days before ulcer induction. At the end of the experiment, the gastric mucosa was examined macroscopically and microscopically. The ethanol group showed damage and degeneration of the stomach mucosa in addition to elevation of oxidative and inflammatory biomarkers. LF showed explicit healing of the gastric mucosal damage. LF reduced gastric malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), and intracellular adhesion molecule-1 (ICAM-1). On the other hand, LF elevated the depleted reduced glutathione (GSH) and Nuclear factor-erythroid factor 2 (Nrf2). Our current study is the first to study the antiulcer effect of LF via its potential modulatory effects on the ROS/ICAM-1/Nrf2 signaling pathway. Moreover, we concluded that pretreatment with LF100 & 300 mitigated the ethanol-induced gastric ulcer via modulation of both oxidative stress and inflammatory responses.

Achillea millefolium Essential Oil Mitigates Peptic Ulcer in Rats through Nrf2/HO-1 Pathway.

Extreme ethanol ingestion is associated with developing gastric ulcers. Achillea millefolium (yarrow) is one of the most commonly used herbs with numerous proven pharmacological actions. The goal of the hereby investigation is to explore the gastroprotective action of yarrow essential oil against ethanol-induced gastric ulcers and to reveal the unexplored mechanisms. Rats were distributed into five groups (n = 6); the control group administered 10% Tween 20, orally, for two weeks; the ethanol group administered absolute ethanol (5 mL/kg) to prompt gastric ulcer on the last day of the experiment. Yarrow essential oil 100 or 200 mg/kg + ethanol groups pretreated with yarrow oil (100 or 200 mg/kg, respectively), orally, for two weeks prior to gastric ulcer induction by absolute ethanol. Lanso + ethanol group administered 20 mg/kg lansoprazole, orally, for two weeks prior to gastric ulcer induction by ethanol. Results of the current study showed that ethanol caused several macroscopic and microscopic alterations, amplified lipid peroxidation, pro-inflammatory cytokines, and apoptotic markers, as well as diminished PGE2, NO, and antioxidant enzyme activities. On the other hand, animals pretreated with yarrow essential oil exhibited fewer macroscopic and microscopic modifications, reduced ulcer surface, and increased Alcian blue binding capacity, pH, and pepsin activity. In addition, yarrow essential oil groups exhibited reduced pro-inflammatory cytokines, apoptotic markers, and MDA, restored the PGE2 and NO levels, and recovered the antioxidant enzyme activities. Ethanol escalated Nrf2 and HO-1 expressions, whereas pretreatment of yarrow essential oil caused further intensification in Nrf2 and HO-1. To conclude, the current study suggested yarrow essential oil as a gastroprotective agent against ethanol-induced gastric lesions. This gastroprotective effect could be related to the antioxidant, anti-inflammatory, and anti-apoptotic actions of the essential oil through the instigation of the Nrf2/HO-1 pathway.

Protective Effects of Piperine on Ethanol-Induced Gastric Mucosa Injury by Oxidative Stress Inhibition.

Piper nigrum Linnaeus is often used as a treatment for chills, stomach diseases, and other ailments. Piperine has many biological functions; however, its mechanism for preventing gastric mucosal damage is still unclear. The objective of this study was to investigate the preventive effects of piperine on ethanol-induced gastric mucosal injury by using GES-1 cells and rats. SOD, CAT, GSH-Px and MDA were effectively regulated in GES-1 cells pre-treated with piperine. Piperine significantly increased SOD, CAT and GSH-Px activities, but decreased the ulcer area, MDA, ROS and MPO levels in the gastric tissues of rats. RT-PCR analysis showed that piperine downregulated the mRNA expression levels of keap1, JNK, ERK and p38, and upregulated the mRNA transcription levels of Nrf2 and HO-1. Western blotting results indicated that piperine could activate the protein expression levels of Nrf2 and HO-1 and inhibit the protein expression levels of keap1, p-JNK, p-ERK and p-p38. In conclusion, piperine suppressed ethanol-induced gastric ulcers in vitro and in vivo via oxidation inhibition and improving gastric-protecting activity by regulating the Nrf2/HO-1 and MAPK signalling pathways.

Dimethyl Cardamonin from Fruits of Campomanesia reitziana D. Legrand Promotes Gastroprotection and Gastric Healing Effects in Rodents.

Campomanesia reitziana D. Legrand (Myrtaceae) displays antiulcer properties when given to rodents. The major active chemical components of C. reitziana are chalcones, including 4',6'-dihydroxy-2'-methoxy-3',5'-dimethylchalcone or dimethyl cardamonin (DMC); therefore, we hypothesized that this compound could have antiulcer effects and the present study aimed to evaluate its gastroprotective and gastric healing properties. DMC was isolated from the fruits of C. reitziana, and its gastroprotective effect was evaluated by ethanol and indomethacin-induced gastric ulcer models in mice (0.1 mg/kg, i.p. and 1 and 3 mg/kg, p.o.). Oxidative stress and inflammatory parameters were analyzed in the gastric tissue. Moreover, its gastric healing effect was evaluated in rats. In addition, the compound's mode of action was evaluated in vivo and in vitro by measuring H+ -K+ -ATPase activity. Finally, the cytotoxic potential of DMC was tested in fibroblasts and human gastric adenocarcinoma cells. The DMC reduced the ethanol-induced gastric ulcer in mice by 77 %, increased the adhered mucus, and reduced lipoperoxides levels. The block of nonprotein sulfhydryls (NP-SH) compounds by pretreatment with N-ethylmaleimide (NEM), the inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), or the antagonism of α2 receptor using yohimbine reversed the gastroprotective effects of DMC. Furthermore, DMC reduced the acidity of gastric content in pylorus-ligated rats but did not change H+ , K+ -ATPase (isolated from rabbit) activity in vitro. DMC reduced the lesion area in acetic acid-induced ulcers and decreased myeloperoxidase activity. DMC did not change the viability of fibroblast cells (L929) but reduced the viability of human gastric adenocarcinoma cells (AGS). The results confirmed that DMC could significantly enhance the gastric healing process and prevent ulcers due to improving protective factors on the gastric mucosa and reducing gastric acid secretion.

Pomegranate peel boosts the potential of Manuka honey to protect against ethanol-induced gastric ulcers in rats by enhancing its anti-inflammatory and antioxidant mechanisms

Pomegranate peel boosts the potential of Manuka honey to protect against ethanol-induced gastric ulcers in rats by enhancing its anti-inflammatory and antioxidant mechanisms

Amelioration of ethanol-induced gastric ulcer in rats by quercetin: implication of Nrf2/HO1 and HMGB1/TLR4/NF-κB pathways

Gastric ulcer is a serious medical condition that can be developed due to an imbalance in the protective and destructive factors of the gastric system. Available therapies do not provide definite cure, thus, there is an urge to seek for alternative treatments. Quercetin is a natural flavonoid that possesses antioxidant and anti-inflammatory properties. In the current study, the antiulcerogenic effect of quercetin in ethanol-induced gastric ulcer (EI-GU) rat model was compared to Antodine® (a reference drug), to elucidate the potential underlying mechanisms. Quercetin (50 mg/kg) and Antodine® (20 mg/kg) were given orally for one week post ulcer induction by ethanol. EI-GU was associated with downregulation of SOD, CAT, Nrf2 and HO1, and accompanied by upregulation of inflammatory markers (i.e., HMGB1, NF-κB and TNFα) and an increase in Bax/Bcl2 ratio. Administration of quercetin resulted in a significant reduction in gastric volume in the stomach of ulcerative rats by 86% and a significant decrease in gastric lesion count by 3.5- folds, as compared with the ulcerative rats. Moreover, rats treated with quercetin showed upregulation of Nrf2 by 3.3-fold change and in HO1 by 3.5-fold change when compared to ulcerated rats, and decreased HMGB1, TLR4, NF-κB p65 and TNF-α by 50%, 53%, 52.9% and 54.9%, respectively. Treatment of rats with quercetin reduced Bax and Bax/Bcl2 ratio and increased Bcl2 relative to ulcerated rats. Thus, it can be concluded that the ulcerogenic curative properties of quercetin were mediated by antioxidant, anti-inflammatory and antiapoptotic activities.