Gastric Ulcers In Rats Research Articles

The protective effect of small black soybean (Vigna Mungo L.) polysaccharide on acetic acid-induced gastric ulcer in SD rats and its impact on gut microbiota and metabolites

Small black soybean (Vigna Mungo L.) is a kind of medicinal and edible plant with many potential health benefits for the human body. In this study, we investigated the potential anti-gastric ulcer effect of Vigna Mungo L. polysaccharides (VMP) using an acetic acid-induced gastric ulcer model in SD rats. The impact of VMP on the levels of antioxidant factors and growth factors in gastric tissue homogenate, serum metabolites, short-chain fatty acids (SCFAs) and gut microbiota in SD rats were analyzed. The results revealed that VMP exhibited a beneficial role in facilitating the healing process of gastric ulcers, specifically by reducing the area of gastric ulcers, increasing the levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and improving oxidative stress status. Additionally, VMP modulated 20 potential serum biomarkers associated with gastric ulcers, thereby exerting a significant impact on multiple crucial metabolic pathways. Notably, VMP notably increased the levels of SCFAs, including acetic acid, propionic acid, i-butyric acid, n-butyric acid, i-valeric acid, n-valeric acid, in the colonic contents of rats with gastric ulcers. Furthermore, VMP effectively ameliorated gut microbiota dysbiosis in gastric ulcer rats by reducing the relative abundance of Firmicutes, Lachnospiraceae_NK4A136_group, Quinella and Lactobacillus, while increasing the relative abundance of Bacteroidota, Bacteroides, Oscillospiraceae_UCG-005, Muribaculaceae, Parasutterella and Ruminococcus. Correlation analysis showed that the relative abundance of Parasutterella and Lachnospiraceae_NK4A136_group were closely related to the changes of SCFAs and serum metabolites. These findings provide potential groundwork for the development of health products aimed at preventing and treating gastric ulcers.

Characterization and gastroprotective effects of Rosa brunonii Lindl. fruit on gastric mucosal injury in experimental rats - A preliminary study.

Gastric ulcer is the most prevalent disorder affecting a large population. Rosa brunonii Lindl. fruit (RBF) has traditionally been used to treat stomach pains. Therefore, the current work aimed to isolate, characterize, and investigate the gastro-protective effect of Rosa brunonii Lindl. fruit chloroform extract (RBFCE) against ethanol-induced gastric ulcers in rats. Quercetin 3-O-glucoside (QUE-G) was isolated and characterized by modern spectroscopic techniques. RBFCE was orally administered at 250 mg/kg, 500 mg/kg, and 750 mg/kg doses for ten days. Gastric ulcer was induced by a single dose of absolute ethanol (5 ml/kg) on the last day of the study. Histological changes were calculated, along with ulcer inhibition and the ulcer index (UI). Gastric juice volume, pH, acidity, mucus content, and protein content were evaluated to understand the mechanism underlying its gastroprotective effect. Omeprazole (OMP) was used as the positive control. RBFCE at a dose of 750 mg/kg significantly (p<0.01) reduced the UI (3.54) and increased the protection rate (67.63%) compared to the negative (ulcer) control group. Treatment with RBFCE in a dose-dependent manner increased the gastric pH, mucus content, and total protein while decreasing gastric juice volume and total acidity. Histopathological studies showed severe gastric mucosal injury and edema in ulcer control animals compared to extract-treated groups. This study demonstrated that oral administration of RBFCE possesses a significant gastroprotective effect due to its anti-secretory and cytoprotective mechanisms. Our findings support the traditional use of RBF to treat the gastric ulcer.

Reversible and Non-Competitive Inhibition of Cyclooxygenase by Indobufen for Efficient Antiplatelet Action and Relief of Gastrointestinal Irritation.

Clinically, indobufen is widely used for the treatment of antiplatelet aggregation and anticoagulation. Prior studies have discovered that abnormal platelet function can be promptly restored to normal when the drug is stopped. Herein, through the study of the enzyme reaction kinetics, we demonstrated that the inhibitory effect of indobufen on cyclooxygenase-1 (COX-1) was reversible and non-competitive. Specifically, the cyclooxygenase inhibition experiment showed that the level of 6-keto-PGF1α in the gastric mucosa of the indobufen-treated groups was significantly higher than that of the aspirin group (###p < 0.001), indicating a higher level of PGI2 in and a better physiological state of the gastric mucosa. Moreover, the rat gastric ulcer index and mucosal section experiments further confirmed the relief of gastrointestinal irritation and the adverse reaction rate of the indobufen-treated group compared to those of the aspirin group. Furthermore, indobufen was verified to exert reversible inhibitory activity on the heme group of COX-1 and thus reversibly inhibit COX-1 activity. In general, compared with aspirin, the long-term oral administration of indobufen yields a lower risk of gastrointestinal symptoms, such as ulcers.

An integrated network analysis, RNA-seq and in vivo validation approaches to explore the protective mechanism of Mongolian medicine formulae Ruda-6 against indomethacin-induced gastric ulcer in rats.

Gastric ulcer (GU) is one of the most prevalent digestive diseases that seriously affects people's health. Previous studies have demonstrated the anti-GU effect of Ruda-6 (RD-6), a classic formulae of traditional Mongolian medicine. However, the underlying mechanism of RD-6 against GU remains elusive. Thus, we conducted an integrative approach of network analysis, RNA-seq, and in vivo validation experiment to elucidate the therapeutic mechanisms of RD-6 in preventing GU. A network analysis was performed to predict the potential targets of RD-6. Rats were pretreated with RD-6 at different doses for 21days, followed by GU induction with indomethacin injection. The ulcer index and inhibition rates were calculated, and the levels of inflammatory related factors were determined by ELISA. The gastroprotective mechanism of RD-6 against ulceration was verified by RNA-seq and the key pathway was detected by in vivo validation. As the network analysis predicted, RD-6 exerts anti-GU effects by regulating 75 targets and 160 signaling pathways. Animal experiment results suggested that pretreatment with RD-6 significantly ameliorated the gastric mucosal injury and inflammatory response, as evidenced by a reduced ulcer index, decreased interleukin (IL)-1β, IL-6, and IL-17 levels, and increased prostaglandin E2 (PGE2) levels in the GU model rats induced by indomethacin. RNA-seq data identified four potential hub genes that were primarily involved in the IL-17 signaling pathway. Furthermore, in vivo validation experiment showed that RD-6 inhibited the IL-17 signaling pathway by down-regulating the expression of IL17RA, proto-oncogene C-Fos (FOS), IL1B and prostaglandin-endoperoxide synthase 2 (PTGS2). Taken together, the present study provides evidence that RD-6 could effectively protect against indomethacin-induced GU, which might be attributed to suppressed inflammation. The IL-17 signaling pathway may be one of the crucial mechanisms that mediates the effect of RD-6.

Preclinical gastroprotective activity of an Eugenia brasiliensis Lam. (Myrtaceae) extract

Gastric ulcers are lesions of the mucous coating membrane of the stomach characterized by burning and epigastric pain as symptoms, which are empirically relieved by Eugenia brasiliensis Lam. (Myrtaceae) extracts. However, there are no studies which evaluated sistematically its gastroprotector potential. Thus, this study aimed to assess the gastroprotector effectiveness of an acetonic extract obtained from leaves of Eugenia brasiliensis in reducing gastric ulcers in rats. Animals were divided in groups and submitted to alcohol and indomethacin models of gastric lesion after previous treatment with the extract and to acetic acid-induced ulcer followed by six days exposure to the extract. Ethanol-induced gastric lesion was reduced by 30 and 100 mg/Kg of the extract in 36% and 68%, respectively. Indomethacin-induced gastric lesion area was reduced by 30, 100 and 300 mg/Kg of the extract in 66%, 88% and 73%, respectively. Acetic acid-induced gastric ulcer was reduced in 72% by 100 mg/Kg extract. Data indicate that Eugenia brasiliensis acetonic extract was effective in reducing gastric lesion in all models tested, which can be attributed to modulation of the inflammatory response and antioxidant activity enhancement by polyphenols, resulting in direct contribution to decrease cell damage which brings consequent gastric ulcer reduction.

Investigating the Protective Effect of Leaves of Calotropis procera (Aiton) for In-vivo Anti-oxidant and Antiulcer Activity using Pylorus Ligation Method

Background: Calotropis procera (Aiton) (Apocynaceae) is a traditional Indian medicinal plant and used in folk medicine for the past decade for the treatment of gastrointestinal disorders. Therefore the current investigation was undertaken to explore the gastroprotective effect of C. procera (Aiton) leaves extract using pylorus ligation-induced gastric ulcer in rats. Methods: The crude powder material was successively extracted with different solvents and concentrated at reduced pressure in a rotary evaporator. The current investigation was carried out by a pylorus ligation-induced gastric ulcer model in rats. Omeprazole, 20 mg/kg and 100, 250, and 500 mg/kg ethanol extract of C. procera (Aiton) leaves were administered orally for 15 consecutive days, on the last day six hours after pylorus ligation animals were sacrificed and the amount of gastric juice, pH, total and free acidity, ulcer index, and pro-inflammatory cytokines along with antioxidant parameters and total protein were also studied. Results: Pretreatment of C. procera (Aiton) leaf extract at the doses 250 and 500 mg/kg, significantly (p &lt; 0.001) decrease the volume of gastric juice, free and total acidity as well as gastric lesions, and secretion of pro-inflammatory cytokine. On the other hand, the pH of gastric juice, mucin content, and total protein was also significantly decreased. Moreover, pretreatment of C. procera (Aiton) significantly (p &lt; 0.001) boost the enzymatic activity and level of different antioxidant markers and attenuated the pylorus ligation-induced level of MDA (p &lt; 0.05) in experimental animals. Conclusion: From this study, it is concluded that the ethanol leaf extract of C. procera (Aiton) extract possess considerable antiulcer and antioxidant potential. For further research findings, it is necessary to explore the mechanism of action for anti-ulcer activity.

Betalain-Enriched Beetroots Exhibit Antiulcer and Anti-inflammatory Potentials

Introduction. Recently, plant natural food colorants have received a growing interest due to their therapeutic and preventive activities against various diseases. This study is aimed at evaluating the phytochemical composition by high-performance liquid chromatography with diode array detection (HPLC-DAD) and at evaluating the antiulcer effect of red beetroot betalains (BRB). Materials and Methods. Ethanol was used for gastric mucosa damage, ulcer, and inflammation induction in rat. Results. HPLC-DAD data revealed the existence of numerous compounds, including betanidin 5-glucoside (43.22%), isobetanidin 5-glucoside (18.47%), 2,17-bidecarboxy-neobetanin (7.07%), 2-O-glucosyl-betanin (4.03%), 17-decarboxy-betanidin (3.61%), neobetanin (3.24%), and eight other compounds whose yields were too low. In vitro as in gastric tissues in rats, BRB potentially inhibited key enzymes—relation to gastric ulceration and damage as pepsin, lipoxygenase, and hyaluronidase activities. In ethanol-induced gastric ulcer and inflammation, BRB administration at doses 200, 400, and 800 mg/kg significantly ( p ≤ 0.05 ) decreases the ulcer areas (UA) and index (UI); increases the curative index (CI) by 78.1, 78.4, and 78%, respectively; and ameliorates the pathological damage induced by ethanol. In addition, BRB administration to rat gastric ulcer rats prevented significantly ( p ≤ 0.05 ) the decrease of gastric mucus (GM) content (by 116%) and reduced the stress oxidant, evidenced by a significant ( p ≤ 0.05 ) decrease of gastric mucosa thiobarbituric acid reactive species (TBARS) (by 28%) and mucus juice pepsin by 56%. Conclusion. Taken together, BRB exerted potential therapeutic efficacy for gastric ulceration.

Xiangshao Decoction alleviates gastric mucosal injury through NRF2 signaling pathway and reduces neuroinflammation in gastric ulcer rats

BackgroundA type of gastric mucosal injury disease known as gastric ulcer (GU) is clearly connected to the aberrant release of gastric acid. Traditional botanicals have the potential for anti-inflammation, anti-oxidation, and other multitarget therapies, as well as being safe. PurposeThe purpose of this study was to investigate the potential effects of Xiangshao Decoction (XST) on gastric mucosal injury in GU rats and to explore the possible molecular mechanisms. MethodsAfter identifying XST and its components, we established GU rats and cell models by acetic acid and H2O2 induction, respectively. SOD and MDA indexes in gastric tissues and GES-1 cells, and the serum levels of BDNF, ALT, and AST were detected with relevant kits, changes of the gastric mucosa were observed and recorded, and gastric tissue pathology was observed by H&E staining. The production of ROS in GES-1 cells was detected by fluorescent probes. Cell transfection techniques were used to silence or overexpress NRF2. The mRNA or protein expressions of NRF2, KEAP1, NQO1, HO-1, SOD2, IL-1β, IL-6, TNF-α, IBA1, GFAP, or γ-H2AX in the gastric tissue, hippocampus, or GES-1 cells were measured via qPCR, Western blot, immunofluorescence staining, or immunohistochemical staining. ResultsThe pH of gastric acid, ulcer score, and pathological damage score in GU rats could be reversed by XST administration. Expressions of IL-1β, IL-6, and TNF-α in the gastric mucosal tissues and the hippocampus of GU rats after administration of XST were down. Expressions of NRF2, NQO1, HO-1, SOD2, etc. in the gastric mucosal tissues and BDNF in the hippocampus were up-regulated. The production of ROS and MDA and the expressions of IL-1β, IL-6, TNF-α, and KEAP1 in H2O2-induced GES-1 cells were significantly reduced after XST intervention, while the activities of SOD and the expression of NRF2, NQO1, HO-1, and SOD2 were significantly increased, and these could be blocked by silencing NRF2 expression. ConclusionsXST can improve oxidative stress injury and inflammatory response in GU rats and cell models, and its mechanism is mediated by the NRF2 signaling pathway.

Silver nanoparticles synthesized from Quercus brantii ameliorated ethanol-induced gastric ulcers in rats by decreasing oxidative stress and improving antioxidant systems.

Gastric ulcers are caused by an imbalance between aggressive and defensive factors. The green synthesis of silver nanoparticles is becoming a new and promising method in the treatment of gastrointestinal ulcers. This study was conducted to investigate the protective and antioxidant effects of silver nanoparticles synthesized from Quercus brantii extract (NSQBE) on gastric damage induced by alcohol in rats. In this study, silver nanoparticles were produced by the green synthesis method using oak extract. The structure and morphology of nanoparticles were confirmed by various techniques such as UV-Vis spectroscopy, fourier transforms infrared spectrometer (FTIR), scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-rayanalysis(EDX), and dynamic light scattering )DLS(. For the animal studies, 30 male Wistar rats weighing 200 ± 20g were randomly selected and divided into five groups (the normal, ethanolic, NSQBE treatment (received doses of 20 and 5mg/kg), and standard (received a dose of 50mg/kg of ranitidine) groups. After the rats were euthanized, their stomach was removed. A part of the stomach tissue of rats was used for histopathological studies, and the other part was used to study biochemical parameters such as the level of reactive oxygen species (ROS), protein carbonyl oxidation (PCO), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) as well as nitric oxide (NO). Our results showed that in the ethanol group, the levels of ROS, MDA, PCO, and serum NO were higher than in the normal group. In addition, reduced GSH, CAT, SOD, tissue NO, gastric mucus, and antioxidant potential were decreased. In rats pretreated with NSQBE and ranitidine, the levels of ROS, MDA, PCO, and serum NO decreased, and the levels of GSH, CAT, SOD, tissue NO, gastric mucus, and antioxidant potential were increased in comparison to the ethanol group. The results of this study showed that silver nanoparticles synthesized using Quercus brantii are a promising approach for the treatment of gastric ulcers.

Protective Effects of Aqueous Extracts of the Herb of Paederia scandens (Lour.) Merr. against HCl/EtOH-Induced Gastric Ulcer in Rats: Involvement and Inhibitors’ Identification of NF-κB Signaling

Paederia scandens (Lour.) Merr. (P. scandens), as an edible and medicinal herb, is commonly used for treating gastric ulcer in China; however, its mechanistic and effective substances’ studies remain limited. This study aimed to investigate the antigastric ulcer effects of aqueous extracts of P. scandens (PS-AE) and explore the involvement of NF-κB signaling in this effect. In addition, the study aimed to identify the effective substances by exploring NF-κB inhibitors. The main components of PS-AE were identified using an UPLC-MS method. HCl/EtOH-induced acute gastric ulcer in rats, and LPS-stimulated RAW264.7 cells were used to determine the antigastric ulcer effects of PS-AE in vivo and in vitro, respectively. Histopathological changes of the ulcer tissues were observed using staining methods of HE and PAS; secretions of inflammatory cytokines and oxidative stress indexes were measured using biochemical test kits; protein levels of NF-κB signaling pathway-related molecules were measured using Western Blot. NF-κB inhibitors’ identification in P. scandens was performed by developing HipHop pharmacophore model, and the results were further validated by molecular docking. In vivo, PS-AE significantly attenuated gastric ulcer in rats; reduced inflammation by adjusting the inflammatory cytokines TNF-α, IL-1β, and IL-6 levels; and induced oxidative stress can be alleviated via adjusting the levels of SOD, MDA, and GSH-Px. In addition, PS-AE may play an anti-inflammatory role mainly through NF-κB signaling pathway. Following pharmacophore modeling and molecular docking, 13 potential inhibitors targeting NF-κB were identified. In addition, in vitro, PS-AE and paederoside could significantly inhibit the activation of NF-κB p65 and the productions of downstream cytokines including NO, TNF-α, and IL-6. PS-AE protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway. 13 potential NF-κB-targeting inhibitors are probably effective substances contributing to the herb’s pharmacological effect. In practical application, Paederia scandens, a traditional food and medicinal plant, possessed diversified chemical components and multiple pharmacological activities (anti-inflammatory, bacteriostasis, and antioxidative.). In China, P. scandens has been used as a traditional medicine to treat gastritis for hundreds of years, and it may be a potentially effective dietary product to improve gastric ulcer. This study shows that P. scandens exerts protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway, which provides pharmacological justifications for the functional food use of P. scandens for treating gastric disease.

Gastroprotective Effect of Bidens pilosa L. Leaves against Indomethacin-Induced Gastric Ulceration in Rats

Gastroprotective Effect of Bidens pilosa L. Leaves against Indomethacin-Induced Gastric Ulceration in Rats

Evaluation of anti-ulcer activity of methanolic extract Combretum paniculatum Vent. in rats and mice using pylorus –ligation induced model

Combretum paniculatum (CP) vent is popularly used in traditional medicine to treat peptic ulcer disease. The anti-ulcer activities of 80% methanol leaf extract of CP was evaluated in rats and mice. The effects of CP extract on gastric ulcer in rats and mice in pylorus ligation –induced model was studied using varying concentrations (200, 400 and 800 mg/kg body weight). Omeprazole (20mg/kg body weight) was used as the reference drug. Parameters such as volume, PH of gastric fluid, ulcer sore, percentage ulceration, percent inhibition of the ulcer sore, ulcer index and percent inhibition of ulcer index were determined. Histopathological study was also conducted. Data were analyzed using One-way analysis of variance followed by Tuckey’s post hoc test and P&lt; 0.05 was considered as statistically significant as well as P&lt; 0.01 as statistically highly significant. The oral median Lethal dose (LD50) was found to be greater than 2000mg/kg, phytochemicals such as flavonoids, tannins, phenols, alkaloids, terpenoids, glycosides and steroids were found to be present while saponins were found to be absent. CP highly significantly (P&lt;0.01) reduced gastric ulcer index by 49.6%, 62.4% and 87.6% , CP posseses both dose-dependent and time dependent anti-ulcer activities. This study validates the anti-ulcer pharmacological activities of this plant, further investigation should be carried out to isolate specific phytochemicals as well as authenticate the mechanisms of action responsible for these activities.

Gastroprotective effect of sumatriptan against indomethacin-, stress- and ethanol-induced gastric damage in male rats: Possible modulatory role of 5-hydroxytryptamine 1B/1D receptors and pro-inflammatory cytokines.

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT1B/1D ) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-α, IL-1β and microscopic features. Sumatriptan (0.1mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors.

Liuwei Anxiao San protects gastric mucosa from gastric ulcer in rats by regulating the JAK2/STAT3 pathway

Mongolian medicine prescriptions are recognized as promising gastroprotective agents. This study is to explore the effects and mechanisms of Liuwei Anxiao San (LAS) in gastric ulcer (GU). GU rat models were established using acetic acid, followed by treatment with LAS at different doses and/or the JAK2 agonist Coumermycin A1 (CA1). The ulcerous area and inhibition rates were calculated. The mucosal damage and cell apoptosis in gastric tissues were assessed by H&E and TUNEL staining. The activities of SOD, GSH-Px, and CAT, and MDA levels were measured. The levels of pro-inflammatory and anti-inflammatory factors were determined by ELISA. The activation of the JAK2/STAT3 pathway was determined by Western blot. As the results suggested, LAS dose-dependently ameliorated gastric mucosal damage and inhibited oxidative stress and inflammatory response, evidenced by increased activities of SOD, GSH-Px, and CAT, decreased MDA level, increment of anti-inflammatory factors and decrement of pro-inflammatory factors, and inhibited the activation of the JAK2/STAT3 pathway in GU rats. CA1 partly abolished the function of LAS on gastric mucosal injury, oxidative stress, and inflammation in GU rats. In conclusion, LAS protects against gastric mucosal injury in GU rats through inhibition of oxidative stress and inflammation by suppressing the JAK2/STAT3 pathway.

Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies.

Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. However, the gastric mucosa protection of FCPP has not been reported yet, and its effective mechanism is unclear. In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP.

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway.

Clinical manifestation of gastric ulcers is frequent, in addition to their costly drug regimens, warranting the development of novel drugs at lower costs. Although Bassia indica is well characterized for its anti-inflammatory and antioxidant potential, capacity of its ethanol extract (BIEE) to prevent stomach ulcers' progression has not been reported. A nuclear protein termed high-mobility group box 1 (HMGB1) plays a key role in the formation of stomach ulcers by triggering a number of inflammatory responses. The main purpose of the current investigation was to evaluate the in vivo anti-inflammatory and anti-ulcerogenic capabilities of BIEE against ethanol-induced gastric ulcers in rats via the HMGB1/TLR-4/NF-B signaling pathway. HMGB1 and Nuclear factor kappa (NF-B) expression, IL-1β and Nrf2 contents showed an increase along with ulcer development, concurrent with an increase in immunohistochemical TLR-4 level. In contrast, pre-treatment with BIEE significantly reduced HMGB1 and Nuclear factor kappa (NF-B) expression levels, IL-1β and Nrf2 contents and ulcer index value. Such protective action was further confirmed based on histological and immunohistochemical TLR-4 assays. Untargeted analysis via UPLC-ESI-Qtof-MS has allowed for the comprehensive characterization of 40 metabolites in BIEE mostly belonged to two main chemical classes, viz., flavonoids and lipids. These key metabolites, particularly flavonoids, suggesting a mediation for the anti-inflammatory and anti-ulcerogenic properties of BIEE, pose it as a promising natural drug regimen for treatment of stomach ulcers.

Andrographis paniculata as Promising Novel Protective Therapy of Oxidative Stress in Indomethacin-Induced Gastric Ulcer in Rats

This research investigated the effect of Andrographis paniculata (AP) on oxidative stress following indomethacin-induced gastric ulcer in rats. A total of 20 male albino Wistar rats (150-180g) used for this study were grouped into four (n=5): 1, Negative Control; 2, Positive Control and 3, test group treated with normal chow, 20mg/kg indomethacin, 20 mg/kg indomethacin plus omeprazole at 20mg/kg and 20mg/kg indomethacin plus AP at 16.7 mg/kg respectively. After treatment period, estimation of oxidative stress parameters was carried out on the animals. The LD50 of aqueous extract of AP was 50mg/kg bw. Body weight change was significantly reduced in omeprazole treated group compared to all other groups while extract treated group had significantly increased body weight change. There was a significant increase in malondialdehyde (MDA) level of ulcer untreated group compared to other groups. The two treated groups had significantly reduced MDA compared to ulcer untreated group. There was a significant decrease in the levels of GPx and SOD of ulcer untreated group compared to control. Meanwhile, these were significantly increased in extract and omeprazole treated groups compared to ulcer untreated group. Catalase was significantly increased in all three groups when compared to control but its level was significantly increased in extract treated group compared to ulcer untreated and omeprazole treated groups. From this study, AP has proved to protect against oxidative stress implicated in the pathogenesis of ulcer. If this result is applicable to humans, further research and use of AP in ameliorating debilitating consequences of peptic ulcer should be encouraged.

Genistein ameliorated experimentally induced gastric ulcer in rats via inhibiting gastric tissues fibrosis by modulating Wnt/β-catenin/TGF-β/PKB pathway

ABSTRACTObjectivesGastric ulcer (GU) is a prevalent chronic digestive disease affecting about 10% of the world's population leading to gastrointestinal perforation and bleeding. Genistein is a legume flavonoid with antioxidants, anti-inflammatory and antibacterial activities. Therefore, we aimed to investigate the ability of genistein to reduce experimentally induced GU in rats by affecting gastric tissue fibrosis Wnt/β-catenin/TGF-β/SMAD4 pathway.MethodsThirty rats were used. Ten rats served as control, and GU was induced in twenty rats using a single dose of indomethacin (80 mg/kg) orally. Following induction of GU, ten were treated with genistein 25 mg/kg orally. The gastric tissues were isolated to investigate markers of gastric fibrosis, Wnt, β-catenin, transforming growth factor (TGF)-β, SMAD4, and Protein kinase B (PKB). In addition, gastric sections were stained with PAS and anti-TGF-β antibodies.ResultsInvestigation GU micro-images revealed degeneration in both surface cells and glandular epithelial cells, which was improved by genistein. In addition, treatment with genistein significantly reduced the expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB.ConclusionBesides antioxidant activity, genistein improves experimentally induced GU in rats, at least in part, via reduction of gastric tissue fibrosis as indicated by reduction in expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB.

Anti-ulcer and gastro protective effects of dexlansoprazole in experimentally induced gastric ulcer in rats

Anti-ulcer and gastro protective effects of dexlansoprazole in experimentally induced gastric ulcer in rats

The apelin-apela receptor APJ is necessary for formation and healing of ischemia reperfusion-induced gastric ulcer in rats

The apelinergic system widely expressed and regulates hormone-enzyme secretion, motility, and protective mechanisms of the stomach. This system consists of the apelin receptor (APJ) and two peptides known as apela and apelin. The IR-induced experimental gastric ulcer model is a well-known and commonly used one that induces hypoxia and causes the release of proinflammatory cytokines. Expressions of apelin and its receptor APJ are induced by hypoxia and inflammation in the gastrointestinal tract. Apelin has been shown to affect angiogenesis positively, considered the most critical component of the healing process. Although it is known that apelin and AJP expressions are induced by inflammatory stimuli and hypoxia, stimulate endothelial cell proliferation and have a role in regenerative angiogenesis, no information or has been found in the literature regarding the role of APJ in the formation and healing of gastric mucosal lesions induced by I/R. So, we conducted a study to clarify the role of APJ in formation and healing mechanisms of IR-induced gastric lesions. Male Wistar rats were divided into five groups; control, sham-operated, IR, APJ antagonist treated-IR group (F13A+IR), and the healing groups. F13A was intravenously given to the animals. Gastric lesion index, mucosal blood flow, PGE2, NOx, 4-HNE-MDA, HO activity, and protein expressions of VEGF and HO-1 were measured. F13A application before the IR increased the mucosal injury, F13A application following the ischemia delayed the mucosal healing during the reperfusion period. Consequently, blocking apelin receptors may worsen gastric injury due to the IR and delay mucosal healing.