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The composition of an ethanol extract from the roots of Rumex tianschanicus Losinsk of the Trans-Ili Alatau wild flora was studied in order to determine its antiulcer activity. The phytochemical composition of the anthraquinone-flavonoid complex from (AFC) R. tianschanicus revealed the presence of numerous polyphenolic compounds, the most abundant of which are anthraquinones (1.77%), flavonoids (6.95%), and tannins (13.39%). The use of column chromatography (CC) and thin-layer chromatography (TLC) in conjunction with UV, IR, NMR spectroscopy, and mass spectrometry data allowed the researchers to isolate and identify the major components of the anthraquinone-flavonoid complex's polyphenol fraction: physcion, chrysophanol, emodin, isorhamnetin, quercetin, and myricetin. The gastroprotective effect of the polyphenolic fraction of the anthraquinone-flavonoid complex (AFC) of R. tianschanicus roots was examined in an experimental model of rat gastric ulcer induced by indomethacin. The preventive and therapeutic effect of the anthraquinone-flavonoid complex at a dose of 100 mg/kg was analyzed using intragastric administration per day for 1 to 10 days, followed by a histological examination of stomach tissues. It has been demonstrated that prophylactic and prolonged use of the AFC R. tianschanicus in laboratory animals resulted in significantly less pronounced hemodynamic and desquamative changes in the epithelium of gastric tissues. The acquired results thus offer fresh insight into the anthraquinone and flavonoid metabolite component composition of R. tianschanicus roots, and they imply that the examined extract can be used to develop herbal medicines with antiulcer activity.

Context Gastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption. Materials and Methods Chemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analysed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis. Results UPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signalling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect. Conclusion Present results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.

Gastric injury is mainly described by inflammation of the gastric epithelium. Recently, our group of work demonstrated that Prosthechea karwinskii leaves extract induces both an in vitro antioxidative action and an in vivo gastroprotective effect in a rat. However, the molecules involved in the gastroprotective action by Prosthechea karwinskii are not known. Thus, the aim of this study is to determine whether Prosthechea karwinskii extract modifies anti-inflammatory and antioxidative biomarkers in an in vivo rat model of indomethacin-induced gastric injury. Rats were orally administered with indomethacin and Prosthechea karwinskii leaf extract. Our results suggest that the gastroprotective effect of Prosthechea karwinskii leaf extract is related to the reduction in leukocyte infiltration and antioxidative action in a model of indomethacin-induced gastric injury. Further studies are warranted to investigate the role of the compounds identified in the gastroprotective action of Prosthechea karwinskii leaves extract.

Soft corals and their secondary metabolites represent an exceptional source of potential drugs. In this regard, Sarcophyton glaucum-derived secondary metabolites were examined for their preventive activities against indomethacin-induced gastric ulcer. Extraction and chromatographic processing of a specimen of S. glaucum collected from the Red Sea waters of Jeddah city resulted in the isolation of eight metabolites including two furanone-based cembranoids (1 and 2), two known pyran-based cembranoids (3 and 4), a known aromadendrene derivative (5), a δ-lactone fatty acid derivative (6), and two known gorgostane-type sterols (7 and 8). Compounds 1 and 6 are new chemical structures, named Δ 12(20) -sarcophine and sarcoglaucanoate, respectively. In an initial pilot experiment, compounds 1 and 2 showed significant protective activities against indomethacin-induced peptic ulcer in rats. These data were evidenced by their ability to ameliorate the elevated ulcer indices and prevent histopathological alterations observed in the untreated animals. Their effects were mediated by enhanced mucin as shown by Alcian blue and periodic acid-Schiff (PAS) staining of stomach sections. Compounds 1 and 2 exerted significant antioxidant properties as they prevent reduced glutathione (GSH) depletion, malondialdehyde (MDA) accumulation, and superoxide dismutase (SOD) exhaustion. Furthermore, immunohistochemical analyses indicated that both compounds inhibited the expression of interleukin-6 (IL-6) and tumor necrosis-α (TNF-α) as compared to indomethacin alone-treated animals. These actions were accompanied by significant enhancement of tumor growth factor-β (TGF-β) expression. In conclusion, two cembranoids exhibited protective activities against indomethacin-induced peptic ulcer. This is, at least partly, mediated by their pro-mucin, antioxidant, anti-inflammatory, and TGF-β stimulating properties., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Gastric ulcer develops from imbalance of gastro-aggressive and protective factors. As existing drugs have adverse effects, use of natural products is in continuous expansion. In this study, we prepared nanoformulation with catechin and polylactide-co-glycolide to provide a sustained, controlled and targeted delivery. Materials & methods: Detailed characterization and toxicity study of nanoparticles were done on cells and Wistar rats. The comparative actions of free compound and nanocapsule were investigated in vitro and in vivo during treatment of gastric injury. Results: Nanocatechin improved bioavailability, reduced gastric damage at a significantly lower dose (2.5 mg/kg) by safeguarding from reactive oxygen species, restored mitochondrial integrity and downregulated MMP-9 and other inflammatory mediators. Conclusion: Nanocatechin is a better alternative for preventing and healing gastric ulcers.

Background: Gastric mucosal injury caused by ethanol is a common gastrointestinal disease. Quinoa (Chenopodium quinoa Willd.), as a nutrient-rich grain, plays a significant role in preventing and treating gastric mucosal damage. The present study aimed to explore the protective effect of quinoa on alcohol-induced gastric mucosal damage and its possible mechanism., Results: The ethanol-induced gastric mucosal injury rat model was used for in vivo experiments and H 2 O 2 -induced GES-1 cells for in vitro experiments to elucidate the protective effect of quinoa. The results show that quinoa water extract can increase the superoxide dismutase level and decrease the malondialdehyde level in vitro and in vivo. Furthermore, quinoa also reduced the bleeding point and bleeding area in rats with ethanol-induced gastric mucosal injury and improved gastric histopathological changes. H 2 O 2 significantly increased the levels of inflammatory factors in GES-1 cells, which were markedly ameliorated by quinoa water extract. Likewise, quinoa water extract regulated the protein expression levels of Nrf2, Keap1, HO-1, p-IKK, and p-NF-κB through Nrf2 and nuclear factor-κB signaling pathways, reducing the production of oxidative stress and inflammation, thereby repairing the damaged gastric mucosa., Conclusion: The findings of this study demonstrated that quinoa shows protective effect against ethanol-induced gastric mucosal injury through its anti-inflammatory and anti-oxidant effects. We propose that our research will provide a reference for quinoa as a functional food. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Acute gastric mucosal injury is a common gastrointestinal disorder, which influences patients' life quality. It was found that ovotransferrin (OVT) reduces the abundance of Helicobacter pylori associated with gastric disease in the intestine of immunosuppressed mice. To clarify its gastric protective function, the present study investigated the effect of OVT on BALB/c mice with ethanol-induced gastric mucosal injury. Results showed that OVT attenuated the ethanol-induced gastric mucosal injury. Furthermore, OVT effectively downregulated the expression of inflammatory markers (tumor necrosis factor-α, interleukin (IL)-1β and IL-6) but enhanced the secretion of IL-4, IL-10 and prostaglandin E2. And OVT pretreatment significantly inhibited the activation of the MAPK/NF-κB pathway. Additionally, OVT improved gastric antioxidant ability by increasing superoxide dismutase and glutathione levels and decreasing malondialdehyde and myeloperoxidase content. Pretreatment with OVT modulated the equilibrium between B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X. The above results indicated that OVT alleviated inflammatory responses, oxidative stress and apoptosis in gastric mucosal injury mice caused by ethanol.

Objectives: Elaeocarpus ganitrus , a member of the Eleocarpaceae family, is valued in Hinduism and Ayurveda, and is frequently used as a remedy for a variety of illnesses. The plant is reputed to treat a number of stomach issues. The purpose of the study was to produce high-quality scientific data regarding gastroprotective behavior, docking experiments with cholinergic receptors, and HPTLC (with lupeol and ursolic acid). To develop the mechanism of herbal extracts, in vitro anticholinergic and antihistaminic activities were evaluated. Different leaf extracts were treated with various reagents to determine the presence of various metabolites. An examination of the histopathology was conducted to determine the full impact of the extract., Methods: Methanolic extract was chosen for HPTLC investigations after extraction with various solvents. A mobile phase of toluene, ethylacetate, and formic acid (8:2:0.1) was chosen. Molecular docking was utilized to examine how ursolic acid and lupeol are bound to cholinergic receptors (M 3 ). Different extracts (aqueous and ethanolic) were tested for their ability to provide gastroprotection in Wistar rats at different doses (200 and 400 mg/kg)., Results: Phytochemical analysis of different extracts showed the presence of different primary and secondary metabolites. HPTLC data showed the presence of both standards. Docking studies exhibited very good interactions with the M 3 receptor. Pharmacological studies revealed that extract-treated groups significantly reduced the ulcer index in all of the models mentioned above. The histopathological analysis clearly supports the biochemical studies, which were conducted utilizing various doses and found to be effective in a dose-dependent manner. The in vitro analysis proved that the abovementioned extracts may act as antagonists of acetylcholine and histamine., Conclusion: The data obtained would be valuable for the production of the monograph of the plant and conducting concept-related clinical studies in the future. More investigation is required since the gathered scientific data may lead to new research opportunities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.

Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.

Context: Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years., Objective: To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP., Materials and Methods: An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis., Results: Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold)., Discussion and Conclusions: This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.

Aims: This study aimed to evaluate the gastroduodenal protective action of crude fraction extracted from P. caribaeorum mucus in Wistar rats., Main Method: Initially, phytochemical screening was performed to measure secondary metabolites present in the extract. Subsequently, studies of gastroprotective action in Wistar rats were developed. The animals were randomly divided into six experimental groups: SF0.9% group, misoprostol group, and test groups (200, 100, 10, and 1 mg/kg) that received different doses of the crude fraction of zoanthid mucus (CFZM) diluted in SF0.9%. After 14 days of treatment, acute gastric ulcers were induced by gavage by administering aspirin (200 mg/kg). The stomach and duodenum were removed for histopathological and gene analysis of the mucosa., Key Findings: The present study found that all investigated metabolites showed negative results. The crude fraction showed a gastric and duodenal protective effect evidenced by an increase in the amount and production of mucins (MUC1 and MUC5AC) and mucus production area in the stomach. Histopathological analysis evidenced a decrease in epithelial damage in the duodenum, with a more significant extension of intestinal villi and a greater amount of goblet cells., Significance: The crude fraction, extracted from P. caribaeorum, showed gastric and duodenal protective action and is not inert in murine gastroduodenal tissues., Competing Interests: Conflict of interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Found in humid regions and waterways and popularly used to treat gastrointestinal problems among other applications, the present study evaluated the M. aquatica essential oil (OEMa) as a therapeutic alternative to treat gastrointestinal disorders. Produced by steam distillation, chemical composition of OEMa was determined by GC-MS analysis. The ethanol-induced ulcer and the dose-repeated acetylsalicylic acid (ASA)-induced gastrointestinal lesions models in rats evaluated, respectively, the prophylactic and curative effects of EOMa on peptic ulcers. The EOMa's effect on gastric secretion, gastric mucus and gastrointestinal motility were evaluated in in vivo models. The curative effect of EOMa on acute colitis was evaluated using the DSS-induced colitis model in mice. Obtained in 0.17% yield (w/w), with carvone (54.82 ± 1.39 g/100 g oil) as the main constituent, EOMa (at 75 mg/kg) showed potent gastroprotective effect (> 90%) mediated by non-protein sulfhydryl compounds (NPSH) and nitric oxide (NO) modulation alongside reduction in gastric secretion volume and total acidity. EOMa did not affect gastric mucus production and gastrointestinal motility. In dose-repeated ASA-induced gastrointestinal lesions model, EOMa (at 25 mg/kg) promoted the inflammatory process resolution both in gastric and duodenal walls by modulating NPSH, NO and myeloperoxidase levels. Despite delaying in 2 days the clinical symptoms worsening, EOMa (at 25 mg/kg) was not able to protect colon tissues from DSS-induced acute colitis as evidenced by macroscopic, biochemical, and histopathological parameters. This is the first report of Mentha aquatica essential oil as a promising herbal medicine for peptic ulcers treatment together with an adjuvant effect in IBD., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Fruits of Ammi majus , commonly called bishop's weed, contain a significant amount of furanocoumarins. Alloimperatorin (Allo, 6 ) was isolated from the free coumarin fraction of fruits, beside 8-hydroxypsoralen ( 1 ), methoxsalen ( 2 ), heraclin ( 3 ), isoimperatorin ( 4 ), imperatorin ( 5 ), isoheraclenin ( 7 ) and heraclenin hydrate ( 8 ). Piroxicam (Px) is a widely used pain-relieving drug that demonstrated side effects, including gastric ulceration and hepatorenal toxicity., Objective: This study aimed to investigate the protective potential of Alloimperatorin against Px-induced gastric ulceration and hepatorenal toxicity., Material & Methods: Rats were divided into four groups: Negative control, Px-induced rats, Allo + Px co-treated group, and Pc + Px co-treated group. Allo (25 mg/kg body weight) and Pc (25 mg/kg body weight) treatments were received 5 days before and 4 days after Px intoxication for 4 days (50 mg/kg body weight). Serum prostaglandin E2 (PG-E2) and liver and kidney functions were measured. Oxidative stress markers were evaluated in the three tissues. Histopathological features and caspase-3 immunoexpression were monitored., Results & Discussion: Px triggered gastric ulceration, increased indices of liver and kidney functions, decreased PG-E2 levels, provoked oxidative stress, and activated caspase-3 immunoexpression. Co-treatment with Allo demonstrated protective activities., Conclusion: Alloimperatorin exhibited anti-oxidative, anti-inflammatory, and anti-apoptotic activities.

Background: Caragana ambigua has been the part of the dietary routines of the regional people in south-west Pakistan and has traditionally been used for the treatment of diabetes there. There is an increased production of reactive oxygen species in diabetics, leading to gastrointestinal disorders. Natural antioxidants exhibit gastroprotective effects owing to their free-radical scavenging action. C. ambigua possesses appreciable phenolic and flavonoid content; thus, it has the potential to protect against gastrointestinal disorders (e.g. gastric ulcer)., Results: This study reports the anti-ulcer potential of C. ambigua. Four different fractions (chloroform, ethyl acetate, butanol, and aqueous) of plant were compared against omeprazole. Ulcer index, ulcer inhibition percentage, gastric pH and volume, total acidity, gastric protein, gastric wall mucus, and histopathology of gastric walls of rats were assessed. All fractions exhibited a reduction in ulcer index and promotion of percentage of ulcer inhibition compared with the ulcer control group. Furthermore, the fractions revealed a significant (P < 0.001) diminution in gastric volume and total acidity with an increase in pH. Among the fractions investigated, the chloroform fraction unveiled the most promising anti-ulcer activity, which is comparable to omeprazole. Liquid chromatography-tandem mass spectrometry screening of fractions revealed the presence of formononetin and biochanin A (isoflavones reported to have anti-ulcer properties) in the chloroform fraction., Conclusion: This study establishes that C. ambigua possesses significant potential in reducing gastric ulcer progression. Formononetin and biochanin A are chiefly responsible for the stated bioactivity due to the fact that these compounds were solely present in the chloroform fraction. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Preparations of Helicteres sacarolha (Malvaceae) leaves and roots are used in the form of decoction, infusion or maceration, to treat gastrointestinal disturbances, among others. Studies supporting some of its ethnomedicinal uses are still incipient. The present study aimed to investigate it potential effect on chronic ulcer, ulcerative colitis and possible prokinetic activities as part of its mechanism of action. The powdered leaves of Helicteres sacarolha (HEHs) was prepared by maceration in 70 % hydroethanolic solution. Its qualitative phytochemical constituents were investigated by direct flow injection analysis coupled to atmospheric pressure chemical ionization ion trap tandem mass spectrometry (FIA-APCI-IT-MS n ). The gastric ulcer healing effect was evaluated in acetic acid induced chronic ulcer in mice and the lesions were evaluated, including analysis of blood plasma cytokine levels. The prokinetic properties (gastric emptying and intestinal transit) were carried out in mice. Potential anti-ulcerative colitis activity was evaluated in rats using 2,4,6-trinitrobenzenesulfonic acid (5 % TNBS) -induced colitis. All animal experiments were carried out at the doses of 20, 50 and 250 mg/kg (p.o.). Eight compounds were putatively identified, specifically lariciresinol, and its derivatives, kaempferol derivatives and Tricin-O-Glc. The extract promoted increased gastric ulcer healing at all doses tested. Modulation of the cytokines involved inhibition of some key pro-inflammatory cytokines with maximum effect on IL-1β (70 %, 50 mg/kg, p<0.05), TNF-α (79 %, 20 mg/kg, p<0.01), and in the anti-inflammatory cytokines, namely IL-10 (57 %, 50 mg/kg, p<0.05) and IL-17 (79 %, only at 50 mg/kg, p<0.05). Histological findings demonstrated a mitigated inflammatory activity, and tissues undergoing regeneration. HEHs treatment caused delayed gastric emptying, and increased intestinal transit, but had no effect in the experimentally induced ulcerative colitis. We report for the first time putatively the presence of Lariciresinol and tricin derivatives from the hydroethanolic leaves extract of H. sacarolha. Its possible mechanism of actions of gastric ulcer healing involves cytokines modulation, mitigation of inflammatory response and tissue regeneration and provoked opposing effect in the gastrointestinal system. The present study demonstrates the therapeutic potential of H. sacarolha leaves used in Brazilian ethnomedicine in the treatment of chronic gastric ulcer., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Geraniol (GE) is dietary acyclic monoterpene alcohol found in essential oils from aromatic plants with therapeutic value against gastric ulcers already described., Hypothesis/purpose: To assess whether oral GE accelerates gastric healing or prevents ulcer recurrence, and to evaluate the hypothesis that GE promotes antiulcer effects by the inhaled route and that promotes changes in the behavior of ulcerated rodents., Methods: Gastric healing effects, underlining mechanisms, and behavioral changes were measured in80% acetic acid-induced gastric ulcer model in rats receiving GE by oral (30 mg/kg) or inhaled route (1 mg/L of air/min); whereas the effects of GE to avoid ulcer recurrence was evaluated in mice submitted to 10% acetic acid plus IL-1β ulcer., Results: GE administered by both routes accelerates gastric healing, increasing mucin and GSH levels, CAT, and GST activities, and reducing MPO activity. Moreover, oral, and inhaled GE minimized ulcer recurrence reducing gastric TNF and IL-6 levels and preserving mucin levels. Interestingly, the inhalation or oral intake of GE promotes anxiolytic-like effects in ulcerated rats., Conclusion: Data altogether suggest that the GE accelerates gastric healing through the strengthening of protective factors of the gastric mucosa, promoting a quality healing that reduces the recurrence of the lesion. Besides, the anxiolytic-like effect of GE may also contribute to its gastric healing action since anxiety is recognized as one of the etiologic agents of ulcers., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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/BaCl 2 -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/BaCl 2 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.

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 α 2 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., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

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 PGE 2 , 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 PGE 2 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.

Ethnopharmacological Importance: Casearia sylvestris Sw. (Salicaceae) is a native plant from the Americas, where it is also known as "guaçatonga" or "erva-de-bugre." Although its leaves have been commonly used to treat inflammation and gastrointestinal disorders in South America, the antiulcer effects of an aqueous extract from this medicinal plant, similar to popular use, have not to be investigated yet., Aim of the Study: This study evaluated the hypothesis that the aqueous extract a of C. sylvestris (AEC) prevents the gastric ulcers and accelerates the healing of ulcers already installed, by assessing ultrasound imaging, histological and biochemical analyses., Materials and Methods: Rats (females) were treated with AEC (3, 30 or 300 mg/kg) prior to the ethanol or piroxicam-induced gastric ulcers. The healing effect of AEC (300 mg/kg) was examined in 80% acetic acid-induced ulcer in rats, whereas the quality of healing was evaluated in recurrent 10% acetic acid-induced ulcer in mice with recurrence induced by interleukin 1β. To assess the responses of the lesions, in addition to the classical methods used to analyze gastroprotection (ex vivo), we also measured the gastric wall thickness (in vivo) using ultrasonography. After euthanasia, the extent of ulcer was determined and the levels of reduced glutathione (GSH), lipid hydroperoxides (LOOH), nitrate, and the activities of myeloperoxidase (MPO), N-acetyl-β-D-glycosaminidase (NAG), superoxide dismutase (SOD), and glutathione S-transferase (GST) were measured. The antisecretory activity of AEC was also examined based on pylorus ligated rats. Furthermore, gastric tissue samples were analyzed histologically, and phytochemical analyses of the C. sylvestris extract were parallelly performed., Results: The AEC (30 or 300 mg/kg) prevented ulcers in the ethanol- and piroxicam-induced acute. Moreover, the AEC at a dose of 300 mg/kg also accelerated the gastric healing of acetic acid-induced ulcer in rats by 48% and the ultrasonography records shown a decrease in the wall thickness and the extent of edema of ulcerous lesions promoted by the extract. The gastric healing effect of AEC was also accompanied by reduced MPO and NAG activities at acetic acid-induced ulcer in rats; as well as was by the reduction in the nitrate and LOOH levels, the increase in mucin and SOD activity, and by a partial recovery of GSH levels. The AEC (300 mg/kg) minimized the ulcer recurrence in mice exposed to IL-1β, but the extract administration did not change pH or peptic activity of gastric juice in pylorus ligated rats., Conclusion: The results of this study provide convincing evidence for the therapeutic efficacy of C. sylvestris with respect to gastroprotection and indicate that ultrasound examination would be a potentially promising approach for evaluating gastroprotective effects in vivo. Collectively, our findings indicate that the gastric the gastroprotective and healing effects of aqueous extract C. sylvestris involve a reduction in acid secretion, promotion of the antioxidant system, reductions in the migration of neutrophils and mast cells, with a consequent lower inflammatory response, and the preservation of mucin., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

Aegle marmelos is cost-effective valuable South Asian tree. The folklore data reported its wide range pharmacological effects. In spite of vast reported work on various parts, the dry ripe fruit extract has not yet been studied for gastric ulcers. Present study is planned to investigate its potential protective effects against ethanol-induced gastric injury in rats. In current study the gastro protective effect of ethanolic crude extract of A. marmelos dried ripe fruit at 200, 400 and 800mg/kg body weight were studied in albino rats. Ranitidine used as standard drug (50mg/kg body weight). Absolute ethanol increase the degree of ulceration (UI) in rats while a significant improvement in the level of inhibition against ulceration was observed in test and standard groups as compare to control. Pre-fed test drug exhibited a significant reduction in the sore area (UI), accelerate % age protection and increased of gastric content in dose dependence manner. Test drug at 800mg/kg dose showed marked deduction in mean UI 3.0, significant increase in protection 83% with pH 7.3 (p<0.01). Standard drug exhibited 3.25 UI, 81% protection with pH 7.1. In conclusion, it was found that dry ripe fruit of A. marmelos possesses a significant anti-ulcer effect in rats.

Background: Pronounced anti-inflammatory and anti-apoptotic features have been characterized for the angiotensin receptor blocker irbesartan. Yet, its effect on ethanol-induced gastropathy has not been studied. The present work explored the potential modulation of inflammatory, apoptotic, and autophagic events by irbesartan for the attenuation of ethanol-evoked gastric mucosal injury., Methodology: Wistar rats were divided into control, control + irbesartan, ethanol, ethanol + irbesartan, and ethanol + omeprazole groups. Macroscopic examination, histopathology, immunohistochemistry, and biochemical assays were applied to examine the gastric tissues., Key Findings: Irbesartan administration (50 mg/kg; by gavage) in ethanol-evoked gastropathy improved the gastric pathological manifestations (area of gastric lesion and ulcer index scores), histopathological changes, and microscopic damage scores. These beneficial effects were interceded by suppression of the HMGB1-associated inflammatory events and the linked downregulation of the nuclear NF-κBp65 protein expression. In the meantime, curtailing of the NLRP3 inflammasome by irbesartan was observed with consequent decline of the pro-inflammatory cytokine IL-1β. In tandem, upregulation of the antioxidant Nrf2 and the cytoprotective PPAR-γ were seen. Together, suppression of the pro-inflammatory cues and pro-oxidant signals attenuated the pro-apoptotic events as evidenced by Bcl-2 upregulation, Bax downregulation, and caspase 3 dampened activity. Regarding gastric autophagy signals, irbesartan diminished SQSTM-1/p62 accumulation and upregulated Beclin 1. This was associated with gastric AMPK/mTOR pathway activation evidenced by increased AMPK (Ser487) phosphorylation and lowered mTOR (Ser2448) phosphorylation., Conclusion: Suppression of the inflammatory and apoptotic signals and upregulation of the pro-autophagy events may advocate the promising gastroprotective actions of irbesartan against ethanol-induced gastric injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Sweet potato (Ipomoea batatas) is accredited as a functional food because of its nutraceutical compounds. These dietary components may help heal lesions and ulcer scars in the stomach. This research was designed to examine the antioxidant and antiulcerative potential of sweet potato (red skin, white flesh) against aspirin-induced gastric ulcers in a rabbit model., Methods: Sweet potato samples were analyzed for in vitro analysis, such as 2,2-diphenyl-1-picrylhydrazyl assay, total phenolic content, and total flavonoid content. In a bioefficacy study, rabbits were divided into five groups (n = 6) in which G 0 received the standard diet only, G 1 150 mg/kg aspirin, G 2 20 mg/kg omeprazole, G 3 1000 mg/kg aqueous extract of sweet potato, and G 4 1000 mg/kg ethanolic extract of sweet potato. After completion of the trial, the animals were decapitated and examined for antiulcer parameters, serum analysis, and hematologic parameters., Results: The mean values for 2,2-diphenyl-1-picrylhydrazyl, total phenolic content, and total flavonoid content were 57%, 927 mg gallic acid equivalent/100 g, and 1901 µg quercetin equivalent/g, respectively. The values for gastric volume, acid output, ulcer scores and index, total oxidant status, white blood cell count, and lymphocyte count were increased significantly (P < 0.05) for the positive control group compared with G 2 , G 3 , and G 4 . Gastric pH and body weight at the end of the experiment were significantly reduced for the positive control group (P < 0.05) compared with G 2 , G 3 , and G 4 . Histology test results of gastric tissues in G 1 depicted severe epithelial damage compared with G 2 , G 3 , and G 4 ., Conclusions: The results for the antiulcer parameters ascertained the antiulcer activity of sweet potato in aspirin-induced gastric ulcer models., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle .

The goal of this study was to determine the effect of hirsutidin on ethanol-induced stomach ulcers in rats. Rats ( n = 24 rats/group) were separated at random into the following groups: normal saline-treated (normal control), ethanol-treated (ethanol control), 10 mg/kg hirsutidin + ethanol-treated (hirsutidin 10), and 20 mg/kg hirsutidin + ethanol-treated (hirsutidin 20). All the groups received the respective treatment orally for 7 days. On day 7, i . e., after 24 h of fasting, except for the normal control group, all the groups orally received 5 mL/kg of ethanol. Four hours later, rats were anaesthetized, serum was isolated from the blood, and biochemical tests were performed. The stomach tissue was utilized for ulcer grading, histology, and biochemical analysis. The rats developed stomach acidity and ulcers after being given ethanol based on increased ulcer score, disturbed cellular architecture, increased oxidative stress, myeloperoxidase and decreased endogenous antioxidants, and nitric oxide and prostaglandin E2 concentration. Ethanol-treated rats also displayed increased tumor necrosis factor-α, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and inflammatory cytokines. The treatment with hirsutidin protected and significantly restored all serum parameters in ethanol-induced stomach ulcers and may have antiulcer activity.

In this research antidiabetic, analgesic and antiulcer potential of traditional ethnomedicinal plant: Emex spinosa (L.) Campd. (Family Polygonaceae) was evaluated by extracting its phytoconstituents using methanol (MeOH) solvent through maceration protocol. The quantitative phytochemical analysis of the extract revealed flavonoids were highest in leaf extract (15.63±0.93 mg/mL) and with (11.5±0.57 mg/mL) in stem. Alkaloids and tanins were also present in the samples in various conc. while saponins were absent. To confirm pharmaceutical potential of plant against ulcer, diabetes and analgesic infirmities, a model experimental animal wistar albino rats (Rattus norvegicus) were used. In antiulcer study, using hot plate method the maximum results were observed with 250 mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41, and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. For analysis of antiulcer potential of the plants parts doses of 250 and 500 mg/kg was applied to check the reclamation of ethanol-induced acute ulcer and of Aspirin-induced chronic ulcer of stomach. In order to confirm efficacy of the drug potential of plant following parameters like microscopic evaluation, gastric volume, total acidity, mucosa weight, ulcer index, pH and histopathology of stomach were analyzed. In antidiabetic analysis, in an acute study after a single dose of 500 mg/kg extract after 2hrs the blood glucose levels were 367±51.09958NS, 416±59.79548NS, 437.5±61.96437NS mg/dL for leaf, stem and fruit, respectively. After4hrs 351.75±88.27644NS mg/dl, 448.25±25.64948NS mg/dl, 445.25±27.07205NS mg/dl and after 6hrs 354.5±92.70428NS, 442±24.60691NS, a440±33.16625NS mg/dl, respectively. The analgesic activity was explored by applying hot plate, tail flick and formalin paw licking method. In hot plate method the maximum results were observed with 250mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41 and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. The respective plant extracts at 250mg/kg showed a gradual rise in latency time when compared to the control. It was concluded that all three components of E. spinosa perform proved to be significant as potential source of herbal medicines to cure different prevalently occurring diseases. Furthermore, it was confirmed through results analysis that plant t can be used to discover novel drug using dedicated high throughput techniques and ethnopharmacological approaches., Competing Interests: The authors have declared that no competing interests exist.

Gastric ulcer (GU) is a peptic disease with high morbidity and mortality rates affecting approximately 4% of the population throughout the world. Current therapies for GU are limited by the high relapse incidence and side effects. Therefore, novel effective antiulcer drugs are urgently needed. Ginsenosides have shown good anti-GU effects, and the major intestinal bacterial metabolite of ginsenosides, protopanaxatriol (PPT), is believed to be the active component. In this study, we evaluated the anti-GU effect of PPT in rats in an acetic acid-induced GU model. High (H-PPT) and medium (M-PPT) doses of PPT (20.0 and 10.0 mg/mg/day) significantly reduced the ulcer area and the ET-1, IL-6, EGF, SOD, MDA and TNF-α levels in serum were regulated by PPT in a dose-dependent manner. We also investigated the mechanisms of anti-GU activity of PPT based on metabolomics coupled with network pharmacology strategy. The result was that 16 biomarkers, 3 targets and 3 metabolomic pathways were identified as playing a vital role in the treatment of GU with PPT and were further validated by molecular docking. In this study, we have demonstrated that the integrated analysis of metabolomics and network pharmacology is an effective strategy for deciphering the complicated mechanisms of natural compounds.

We investigated the potential gastroprotective effects of chrysin on indomethacin induced gastric ulcers in rats. We used six groups of animals: control; indomethacin (Indo); reference (Ulcuran®); indomethacin + 25 mg/kg chrysin (Indo + CHR25); indomethacin + 50 mg/kg chrysin (Indo + CHR50); indomethacin + 100 mg/kg chrysin (Indo + CHR100). All doses of chrysin were given orally to rats before indomethacin. Gastric lesions were examined macroscopically and microscopically. The effects of treatment with chrysin were assessed versus a single dose of 30 mg/kg Ulcuran® (generic ranitidine) as reference standard. We also investigated gastric mucosal superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), malonaldehyde (MDA) and arginase activities, and COX-2, PGE 2 , iNOS, TNF-α, IL-1β, NFκB, MPO, Bax, caspase-3 and 8-OHdG levels. We assessed caspase-3 and Bax levels using immunohistochemistry. Compared to the control and reference groups, SOD, CAT, GPx and arginase activities and GSH levels decreased, and MDA levels increased in the indomethacin induced gastric ulcer group. iNOS, TNF-α, IL-1β, NFκB, MAPK-14, MPO, Bax and 8-OHdG levels were increased in the indomethacin treated gastric group, while COX-2 activity and PGE 2 levels were decreased. The three doses of chrysin co-administered with indomethacin increased COX-2 activity and PGE 2 levels in rats with ulcers. Chrysin exhibited gastroprotective effects on indomethacin induced gastric ulcer due to its antioxidant, anti-inflammatory and anti-apoptotic activities.

Background: The analgesic drugs are the main cause of gastric ulcer. The objective of this study was to determine the gastroprotective ability of flavonoid, 6-aminoflavone in a rat pyloric ligation model of aspirin associated gastro-ulcerogenesis., Methods: A laboratory based experimental study was conducted in the animal house and research laboratory at Khyber Medical College, Peshawar from July to November 2019. A total of 42 adult male Spargue-Dawely rats were divided into seven groups. Flavonoid, 6-aminoflavone was administered orally in doses of 10, 25 and 100 mg/kg with misoprostol, as standard at 50 µg/kg orally for 4 days. On the last day aspirin was given orally at 200 mg/kg and the pyloric ligation surgery was performed. After 4 hours all animals were killed by cervical dislocation. The gastric tissues were collected for histomorphological study. The obtained data were expressed as mean±SEM. Analysis was carried out by using ANOVA. p value ˂0.05 was considered significant., Results: The animals treated with the different doses of 6-aminoflavone showed a marked protective effect in the histological observations. The 10 mg/kg dose had a mild protective effect as occasional ulcerative changes were observed. However, doses of 25 and 100 mg/kg significantly caused the reduction in the ulcer score. These effects produced were equipotent to the gastroprotective effectiveness inherent in the misoprostol. ., Conclusion: These findings conclude that 6-aminoflavone as like other flavonoids has a significant gastroprotective propensity with significant effect produced at doses of 25 and 100 mg/kg and can be used as a part of therapy management for the treatment of gastrointestinal disease particularly ulcerative condition.

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., (© 2022 Wiley Periodicals LLC.)

Silver nanoparticles (Ag NPs) have unique properties and display an important role in bioactivities such as antimicrobial, antiviral, antifungal, and anticancer. Stable Ag NPs were prepared by reaction of silver nitrate solution with extract of Melissa and characterized by UV-Vis spectroscopy, AFM, SEM, XRD, and Zeta potential. The resulted Ag NPs have a size range between 20 and 35 nm. The current study aims to evaluate the gastroprotective effect of Ag NPs against ethanol-induced gastric ulcers in rats. Thirty rats were randomly divided into five groups. The experimental groups were fed 175 and 350 ppm/p.o of Ag NPs orally. Ag NPs improved the adversative influence of ethanol-induced stomach damage as confirmed by declining ulcer index and raised the percentage of ulcer prevention. Significantly reduced ethanol-induced gastric lesions were evidenced by increased mucus secretion and pH of stomach content, decreased ulcer area, nonappearance of edema, and leucocyte penetration of the subcutaneous layer. In gastric homogenate, Ag NPs displayed a substantial upsurge in superoxide dismutase (SOD), catalase (CAT) activities, and significantly reduced malondialdehyde (MDA) levels., Ag NPs increased the intensity of periodic acid Schiff stained (PAS) and produced over-regulation of HSP-70 and down-regulation of Bax proteins. Ag NPs confirmed gastro-protection which might be attributed to its antioxidant effect, increased mucus secretion, increased SOD, and CAT, reduced MDA level, over-regulation of HSP-70 protein, and down-regulation of Bax protein., Competing Interests: Declaration of Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Use of non-steroidal anti-inflammatory drugs (NSAIDs) is one of the leading causes of gastric ulcers. Excellent therapeutic properties have made the use of NSAIDs widespread. Nano-drug delivery to reduce systemic toxicity through modulating drug pharmacokinetics may be a better choice. Presently, we investigated if naproxen nanoformulation (PVA capped NPRS-MgO NPs) is less toxic to be used as an alternative drug. Groups of mice were assigned to control, NPRS-treated, CNF-treated, UNF-treated, and MgO NPs-treated groups. Analyses included gross examination of gastric mucosa, calculation of ulcer and inhibition indices, determination of tissue levels of reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and reduced glutathione (GSH), histological and immunohistochemical assessment of i-NOS, COX-2, and caspase-3 of stomach mucosa, q-PCR for the detection of mRNA expression of IL-1β, IL-6, and TNF-α. Results were compared statistically at P < 0.05. Compared to NPRS-treated mice which developed multiple ulcers, had elevated MDA and ROS levels, and deceased CAT, POD, SOD, and GSH levels, significantly increased expression of IL-1β, IL-6, and TNF-α mRNA, damaged surface epithelium with disrupted glandular architecture and leucocyte infiltration of lamina propria with a marked increase in mucosal COX-2, i-NOS, and caspase-3 expression, oral administration of coated and uncoated naproxen nanoformulations prevented the gross mucosal damage by a restoration of all biochemical, histological, and immunohistochemical alterations to near control levels. The present study demonstrates that naproxen sodium nanoformulation has a gastroprotective action and in the clinical setting can be a better alternative to conventional naproxen., Competing Interests: Declaration of Competing Interest No potential conflicts of interest relevant to this article are reported., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Paspalidium flavidum (watercrown grass), a medicinal plant, is traditionally used in liver ailments and stomach problems. The hepatoprotective and gastroprotective activities of the aqueous methanol extract of Paspalidium flavidum (AMEPF) were studied in experimental animal models. Paracetamol and aspirin were used to induce hepatotoxicity and gastric ulcer in rats, respectively. Biochemical hepatic parameters, gastric pH, total acidity, ulcer index, percentage protection, nitric oxide and TNF-α were measured in AMEPF-treated groups. Moreover, GC-MS analysis of AMEPF was performed. Pretreatment with AMEPF improved the blood lipid profile and restored liver function tests in paracetamol-induced hepatotoxicity. While in aspirin-induced gastric ulcer, oral administration of AMEPF significantly reduced (P<0.05) the gastric lesions, total acidity and ulcer scoring index, TNF-α with upregulation of nitric oxide when compared with the Diseased group. AMEPF exhibited anti-lipid peroxidation activity. Histopathological studies were in good agreement with the biochemical findings. GC-MS analysis revealed the presence of anti-oxidant phyto-constituents, including oleic acid and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) in AMEPF. This study suggested that aqueous methanol extract from the leaves of P. flavidum has beneficial hepatoprotective and gastroprotective activities related to its anti-oxidant phytochemicals.

This study aimed to apply transcriptomics to determine how Molor-Dabos-4 (MD-4) protects healthy rats against indomethacin (IND)-induced gastric ulcers and to identify the mechanism behind this protective effect. Rats were pretreated with MD-4 (0.3, 1.5, or 3 g/kg per day) for 21 days before inducing gastric ulcers by oral administration with indomethacin (30 mg/kg). Unulcerated and untreated healthy rats were used as controls. Effects of the treatment were assessed based on the ulcer index, histological and pathological examinations, and indicators of inflammation, which were determined by enzyme-linked immunosorbent assay. Transcriptomic analysis was performed for identifying potential pharmacological mechanisms. Eventually, after identifying potential target genes, the latter were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). After pretreatment with MD-4, gastric ulcers, along with other histopathological features, were reduced. MD-4 significantly (p < 0.05) increased the superoxide dismutase (SOD) levels in ulcers and reduced pepsin, TNF-α, and IL-6 levels. RNA-seq analysis identified a number of target genes on which MD-4 could potentially act. Many of these genes were involved in pathways that were linked to anti-inflammatory and antioxidant responses, and other protective mechanisms for the gastric mucosa. qRT-PCR showed that altered expression of the selected genes, such as Srm, Ryr-1, Eno3, Prkag3, and Eef1a2, was consistent with the transcriptome results. MD-4 exerts protective effects against IND-induced gastric ulcers by reducing inflammatory cytokines and pepsin and increasing the expression of SOD levels. Downregulation of Srm, Ryr-1, Eno3, Prkag3, and Eef1a2 genes involved in regulating arginine and proline metabolism, calcium signaling pathway, HIF-1 signaling pathway, oxytocin signaling pathway, and legionellosis are possibly involved in MD-4-mediated protection against gastric ulcers.

Background: Previous studies found metformin as an effective agent to suppress oxidative stress, inflammation, and apoptosis in various inflammatory diseases. The present study investigated the effect of metformin against 2 experimental gastric injury models in rats, using macroscopical, histopathological, biochemical, and immunostaining studies., Methods: After 24 hours of fasting, male Sprague-Dawley rats (280-400 g) (n = 8 per group) received indomethacin (80 mg/kg; indo ulcer group) or absolute ethanol (5 mL/kg; ethanol ulcer group) or vehicle orally by gavage. Metformin (500 mg/kg) was given orally for 3 days prior to indomethacin or ethanol challenge. Ranitidine (50 mg/kg) was given orally for 3 days before indomethacin or ethanol administration as a positive control. On day 3, the animals were euthanized 6 hours after indo or 1 hour after ethanol challenge. Gastric samples were used for macroscopic scoring, histopathological examinations, and biochemical assays. Trunk blood was collected for the assessment of interleukin-1β level., Results: In both ethanol ulcer and indo ulcer groups, metformin decreased the extent of gastric lesions macroscopically and microscopically, improved the high chemiluminescence levels, and the percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with untreated ulcer groups. Gastric blood flow analysis revealed significant increases in both metformin-treated ulcer groups compared to untreated ulcer groups., Conclusion: The findings of the present work demonstrated the gastroprotective effect of metformin against the development of gastric mucosal lesions induced by ethanol and indomethacin in non-diabetic, normoglycemic rats via its antioxidant and anti-apoptotic properties and partly from its ability to restore blood flow.

This study evaluated the protective potentials of Moringa oleifera leaf alcoholic extract (MOLE) against bisphenol A (BPA)-induced stomach ulceration and inflammation in rats. Control rats received olive oil. Second group administered MOLE (200 mg/kg bwt) by oral gavage. Third group was given BPA (50 mg/ kg bwt) for 4 weeks. Fourth group administrated BPA and MOLE simultaneously. Fifth group was given MOLE for 4 weeks then administered BPA and MOLE for another 4 weeks. Bisphenol A induced gastric ulceration and decreased the volume of gastric juice, prostaglandin E2 (PGE2), reduced glutathione (GSH) and interleukin 10 (IL-10) contents, superoxide dismutase (SOD) activity, and proliferating cell nuclear antigen (PCNA) protein in stomach tissues, while increased the titratable acidity, malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) contents, and caspase-3 and NF‑κB proteins in stomach tissue. However, MOLE ameliorated BPA-induced gastric ulceration and significantly increased the volume of gastric juice, PGE2, GSH and IL-10 contents, SOD activity, and PCNA protein while significantly decreased titratable acidity, MDA, TNF-α and IL-6 contents, and of NF‑κB and caspase-3 proteins in gastric tissue. This study indicated that MOLE protected stomach against BPA-induced gastric injury via its anti-oxidant, anti-apoptotic, and anti-inflammatory activities., (© 2022. The Author(s).)

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., (© 2022 Wiley Periodicals LLC.)

The main bioactive constituents in the standardized Ginkgo biloba leaf extract (EGb 761) are the terpene lactones and flavonoid glycosides. EGb 761's antioxidant and anti-inflammatory properties have previously been demonstrated. Indomethacin-induced gastric ulcers have a multifactorial etiology and represent a major restriction to its therapeutic utility. The underlying ulcerogenic process involves oxidative and inflammatory biomolecular insults. This study was performed to explore the curative and preventative benefits of EGb 761 in experimentally-induced ulcers. To develop gastric ulcers in mice, indomethacin (40 mg/kg) was administered orally. EGb 761 (200 mg/kg) was given by gavage for 7 days before (preventative) and after (therapeutic) indomethacin administration. The histological alterations and macroscopic mucosal lesions were assessed. In gastric tissue homogenates, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and inflammatory cytokines were measured. The expressions of cyclooxygenase-2 (COX-2), cytokines, and proliferating cell nuclear antigen (PCNA) in the stomach mucosa were also investigated. The ulcer index, histological alterations, gastric oxidants, and inflammatory biomarkers were all significantly increased by indomethacin. In stomach specimens, it increased COX-2 and PCNA expression. EGb 761 treatments, both prophylactic and therapeutic, resulted in significant reductions in ulcer lesions, nitrosative and oxidative damage, and inflammatory markers, along with the lowering of COX-2 and PCNA expressions. Furthermore, in the fight against stomach ulcers, EGb 761 treatment was found to be more efficient than prevention.

Peptic ulcer is an acid-induced lesion that is usually found in the stomach and duodenum. It is usually a case of imbalance between the acid (and other injurious factors) and the mucosal defense mechanisms. Indomethacin is one of the most ulcerogenic drugs that is prescribed over-the-counter for the management of musculoskeletal problems. Capparis spinosa is one of the most important species in the Capparidaceae family, which has a wide range of diversity. Caper ( Capparis spinosa L.) is a common member of the genus Capparis (Capparidaceae family). The present study was designed to compare the effect of C. spinosa extract as a gastroprotective agent with indomethacin as an induction agent and ranitidine as a standard drug. To this aim, 40 adult male Wistar rats were randomly divided into 4 groups (n=10 each), including Control +: indomethacin-treated group, Control -: receiving physiological saline solution, C.S: C. spinosa -treated group; and ranitidine-treated group (50 mg/kg) as a standard agent for the treatment of the gastric ulcer. After the experimental period, all the animals were sacrificed by anesthesia overdose and their stomachs were removed. The gastroprotective effect of C. spinosa was investigated by studying prostaglandin E2 (PGE2), Gastrin, anti-tumor necrosis factor alpha (TNF-α), and Interleukin 1 beta (IL1-β), along with histopathological examination. The results showed a significant increase in PGE2 levels in the ranitidine-treated group with a significant reduction in Gastrin, TNF-α, and IL1-β. The recorded data obtained from the histopathological study showed a significant improvement in the treated group with the extract of C. spinosa . The study concluded that C. spinosa had gastroprotective properties possibly through enhancing PGE2 which was acting as anti-inflammatory inhibiting neutrophil infiltration., Competing Interests: The authors declare that they have no conflict of interest.

Isoxazole derivatives are significant enough due to their wide range of pharmacological and therapeutic activities. The purpose of the current study is to use computational, in vitro, in vivo, and extensive molecular approaches to examine the possible anti-ulcer activity of 4-benzylidene-3 methyl-1,2-isoxazol-5(4H)-one (MBO). Biovia Discovery Studio visualizer (DSV) was utilized for virtual screening. A tissue antioxidant investigation, H + /K + -ATPase test, and anti-H. pylori activities were carried out. ELISA, immunohistochemistry, and PCR methods were employed for the proteome analysis. An ethanol-induced stomach ulcer model was used to examine the anti-ulcer potential in rats. The binding affinities for MBO ranged from -5.4 to -8.2 Kcal/mol. In vitro findings revealed inhibitory activity against H. pylori and the H + /K + -ATPase pump. It also enhanced levels of glutathione, catalase, and glutathione-S-transferase and reduced lipid peroxidation levels in gastric tissues of rats. In vivo results showed the gastro-protective effect of MBO (30 mg/kg) in ulcerative rat stomachs. The proteomic study revealed decreased expression of inflammatory markers (cyclooxygenase-2, p-NFkB, and TNF-α). In RT-PCR analysis, the expression levels of H + /K + -ATPase were reduced. Furthermore, ADMET (absorption, distribution, metabolism, excretion and toxicity) studies revealed that MBO has high GIT solubility and has a safer profile for cardiac toxicity. This study suggests that MBO displayed anti-ulcer potential, which may have been mediated through the inhibition of the H + /K + -ATPase pump, as well as antioxidant and anti-inflammatory pathways. It has the potential to be a lead molecule in the treatment of peptic ulcers with fewer adverse effects.

The aim of this study was to screen out the active ingredients of Yuanhu Zhitong prescription (YZP) before and after vinegar processing to play an anti-alcoholic gastric ulcer role through spectrum-effect relationship. First, the fingerprint of 16 batches of YZP was studied using the ultra-high-performance liquid chromatography-quadrupole mass spectrometry detector analysis (UPLC-QDA) method. Second, gastric lesion was induced by anhydrous ethanol. The degree of gastric mucosa injury was evaluated by hematoxylin and eosin staining, and the contents of malondialdehyde and tumor necrosis factor α and superoxide dismutase were detected using the enzyme-linked immunosorbent assay kit. Sixteen batches of YZP were analyzed using the spectrum-effect relationship method. Finally, absorption, distribution, metabolism, and excretion (ADME) was used to evaluate the bioavailability of potential compounds. The results showed that the UPLC-QDA method could successfully establish the fingerprint of YZP. Hematoxylin and eosin staining and biochemical indicators showed that YZP had obvious anti-alcoholic gastric ulcer action. Coptisine chloride, corydaline, berberine chloride, palmatine, imperatorin, and phellopterin were screened out using the spectrum-effect method, and all of them possessed good bioavailability. The results of this study suggest that YZP plays an anti-ulcer role by exerting antioxidant and anti-inflammatory effects through six main active components., (© 2022 John Wiley & Sons Ltd.)

Ischaemia and reperfusion (I/R)-induced gastrointestinal disorders are caused by free radicals, resulting in organ damage and functional disarrangement. This study aimed to investigate the healing effects of hydroalcoholic extracts from the leaves of Eugenia punicifolia (Kunth) DC. (HEEP) in male and female Wistar rats with I/R-induced peptic injuries, and the role of antioxidants in improving this response. After I/R-induced gastric and duodenal injuries, male and female [intact (INT) and ovariectomized (OVZ)] rats were orally treated with HEEP for 6 days. Biochemical analysis was used to determine the catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities, as well as malondialdehyde and reduced glutathione levels, to measure the gastric and duodenal healing process. Six days of HEEP treatment significantly decreased the I/R-induced gastric [male (73.68%), INT (52.83%), and OVZ (43.13%)] and duodenal damage [male (57.03%), INT (56.04%), and OVZ (54.83%)] in all groups. In OVZ rats, the healing effect of HEEP occurred because of the increased activity of SOD (2x) and CAT (1.16x) in the gastric mucosa. In the duodenal mucosa of INT rats, the extract reduced MPO (20.83%) activity. The 6-day HEEP treatment improved the healing of I/R-induced peptic ulcer injury, with the system acting differently in males and females. The antioxidant system is an important component of the HEEP activity during post-I/R mucosal recovery. This result revealed the importance of antioxidant compounds in minimizing the severity of I/R-related events., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The present study aims to investigate the newly synthesized organotin (IV) complex (2E, 2'E) dibutylstannanediyl bis (4-(4-nitrophenyl) amino)-4-oxobut-2-enoate (DTN) for its anti-ulcer potential. Characterization performed by carbon nuclear magnetic resonance spectroscopy proved that all values are in the expected ranges of the new compound. Gastroprotective activity of DTN was evaluated through in-silico, anti-H. pylori, in-vitro, in-vivo, and ex-vivo proteomic analysis. In-silico analysis shows that DTN possess stable binding with protein targets involved in gastric ulcer pathophysiology. DTN exhibited an inhibitory effect against 2,2-diphenyl-1-picrylhydrazyl, H. pylori and hydrogen potassium ATPase (H + /K + -ATPase). The antiulcer activity was performed using an ethanol-induced gastric ulcer model in rats. Anti-oxidant profile of DTN showed a significant increase in glutathione-S-transferase, glutathione and catalase levels whereas lipid peroxidation levels were reduced. Histopathological findings confirmed that DTN protected the gastric mucosa of rats. Inflammatory markers tumor necrosis factor-alpha, nuclear factor kappa B, cyclooxygenase-2, interleukin 6 and interleukin-1β were reduced and prostaglandin-E 2 restored expression of these cytokines in DTN pretreated animals when analyzed by using immunohistochemistry, enzyme-linked immunosorbent assay and western blot techniques. In real-time polymerase chain reaction technique, the expression of H + /K + -ATPase was downregulated in DTN pretreated group. DTN did not cause any mortality up to 400 mg/Kg. This study indicates that the newly synthesized compound DTN, possess stable binding against selected targets. DTN exhibits a gastro-protective effect, mediated via anti-H. pylori, H + /K + -ATPase inhibition, anti-oxidant and anti-inflammatory pathways, exploring its therapeutic potential in gastric ulcer management., (© 2022. The Author(s).)

Ethnopharmacological Relevance: Tagetes erecta L. (Asteraceae), popularly known as Aztec Marigold, is used in South America to treat several ailments. Despite reports that T. erecta flowers are used in folk medicine to treat gastrointestinal diseases, there is no study regarding its gastric healing effects., Aim of the Study: The effect of dry extract of T. erecta L. (DETe) in gastric healing and gastric ulcer recurrence was evaluated, contributing to the validation of the antiulcer potential of this medicinal plant., Methods: Rats were treated orally with vehicle (1 ml/kg), omeprazole (20 mg/kg), or DETe (3, 30 or 300 mg/kg) for 7 days, twice a day. The lesion area was evaluated, and the levels of reduced glutathione (GSH) and lipoperoxides (LOOH) and the activity of the superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and myeloperoxidase (MPO) were measured. The ulcer recurrence was evaluated in mice and induced by interleukin (IL)-1β (1 μg/kg, i.p). The recurred area, gastric wall thickness, GSH and cytokines levels, MPO and N-acetylglucosaminidase (NAG) activities were measured., Results: DETe accelerated the healing of gastric ulcers only at 300 mg/kg, reducing the ulcerated area by 66%. In parallel, DETe reduced LOOH levels, SOD, CAT and MPO activities, while increasing GST activity and mucin amount. In the recurrence model, DETe reduced the lesion area by 94%, and in parallel decreased the gastric wall thickness and TNF levels, while increasing IL-10 amount., Conclusions: Corroborating the popular use of T. erecta, DETe favors the antioxidant system and reduce gastric inflammation, accelerating the gastric healing process and reducing the ulcer recurrence., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The prescription of Wei-Tong-Xin (WTX) is improved based on the prescription "Wanyingyuan", a famous decoction documented in the book of Huatuozhongzangjing in the Han dynasty. Many years of clinical verification have demonstrated that WTX can be used to treat gastrointestinal diseases, especially gastric ulcer (GU). However, the potential pharmacological mechanism is undefined., Aim of the Study: This research was conducted to explore the pharmacological mechanisms under the consideration of the therapeutical effect of WTX against GU by combining the network pharmacology strategy and in-vivo verified experiments., Materials and Methods: A prediction network describing the relationship between WTX and GU was established based on information collected from multiple databases. Then, the intersecting protein-protein interaction (PPI) network of the drug-disease overlapping gene targets was constructed, and several key targets related to both WTX and GU were obtained. Besides, the Gene Ontology (GO) biological enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the key target genes and pathways of WTX against GU. Then, the candidate targets and signaling pathways of network pharmacology were validated in a rat model of GU induced by indomethacin following the results and available proof., Results: There are 243 targets obtained from the 65 active ingredients in WTX, and 1362 disease targets related to GU were identified. Then, 6 key targets were determined with the PPI interaction network, which was structured from 126 overlapping gene targets. GO and KEGG analyses revealed that the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway might play a crucial role in the therapeutic mechanism of GU. In vivo verified experiments, WTX significantly reduced the ulcer area and improved the histopathological appearance of gastric tissues. Moreover, down-regulated the protein levels of IL6, TNF-α, and Caspase 3 in the gastric tissues while up-regulating the expression of p-PI3K, p-AKT, p-P53, and VEGFA compared to the model group., Conclusion: WTX, an ancient traditional Chinese medicine (TCM) compound prescription, may affect the inflammatory response and apoptosis process by regulating PI3K/AKT signaling pathway and related gene targets. Therefore, it is an effective drug candidate for the modern treatment of GU., (Copyright © 2022 Elsevier B.V. All rights reserved.)