Gastric Ulcers In Rats Research Articles

Gastroprotective effect of Vien Khoi Tim capsules on indomethacin-induced gastric ulcers in rats

Available anti-ulcer drugs unveil partial effectiveness and numerous adverse reactions. Plants offer an alternative strategy in the search for new drugs in the therapy and prevention of peptic ulceration. The present study investigated the possible protective effect of the herbal formulation Vien Khoi Tim (VKT) on indomethacin-induced gastric mucosal damage in rats. VKT was tested at two doses (1.44 & 0.48 capsules/kg/d po) ten days before the indomethacin single-dose challenge (40 mg/kg po). Animals were sacrificed six hours after indomethacin administration, and gastric tissues were collected for gross observation and histopathological analyses. The results revealed that the administration of indomethacin caused evident gastric mucosal damage with morphological and histological manifestations. VKT pretreatment tended to avert the rise in lesion numbers, reduce the ulcer index, and improve the severity of bleeding streaks and epithelial sloughing in gastric mucosa on the macroscopic examination compared to the model group. It is worth noting that no ulcerative lesions were observed in the gastric tissues of rats receiving VKT upon microscopic examination. Our results indicated that Vien Khoi Tim capsules might possess a protective role against indomethacin-induced gastric ulcers. Additional research is needed to better understand the mechanism by which Vien Khoi Tim capsules exert their gastroprotective effect.

The protective effects of betanin against experimental gastric ulcer by reduction of ROS and suppression of inflammatory genes via NF-κB, iNOS, COX-2 and TNF-α pathways

Betanin, a prominent compound found in beetroot, however, the potential protective effects of this compound against gastric damage and ulceration have yet to be explored. This study aims to investigate the impact of purified beetroot betanin (Bet) on the activities of inflammatory enzymes and gene expressions associated with inflammation in gastric tissues. Gastric ulcer rats were induced by ethanol at dose 5ml/kg body weight. Ulcerated rats were treated by purified betanin or omeprazole; from which some inflammation-related genes and gastric-inflammation enzymes were investigated using RT-PCR and biochemical analysis, respectively. Bet effectively suppressed the activities of key enzymes involved in gastric mucosal inflammation, including 5-Lipoxygenase (5-LO), Hyaluronidase (HAase), and myeloperoxidase (MPO), by 58%, 50%, and 45%, respectively. Docking studies showed Bet binding to catalytic sites or key regions for enzymes’ activities, thus explaining the inhibitory capacity. Bet ingestion decreased the expression levels of inflammation-related genes, factor-kappa B (NF-ϰB) by 57%. This down-regulation subsequently led to a reduction in the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor-α (TNF-α). Bet ingestion supressed thiobarbituric acid reactive substance (TBARS) rates by 59%, augmented nitric oxide (NO) level by 107% and protected gastric tissues from damage and ulceration. Bet revealed gastro-protective effects as confirmed by a reduction in the ulceration surface area and the acidity by 75.9% and 40%, respectively, and a significant increase in the weight of mucus and the curative index by 117% and 74.5%, respectively. In conclusion, these outcomes of physiological and molecular-based investigations are indicative of potential use of Bet as a functional food additive for the prevention of gastric ulcer.

Exploring the Effect of Deep-Sea Water on the Therapeutic Potential of the Anti-Inflammatory Response in an Indomethacin-Induced Gastric Ulcer Rat Model.

Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.

Protective effect of barbigerone against ethanol-induced ulcers via the interleukins/ICAM-1/Bcl-2 pathway.

The objective of the study was to assess the protective effects of barbigerone in ethanol-induced gastric ulcers in rats. Male Wistar rats (180±20 g) were used in the study (n=06). The rats were randomly divided into different groups, i.e., the normal group, ethanol control, and barbigerone 10 and 20 mg/kg group. Various biochemical parameters were assessed - total acidity and pH values, oxidative stress biomarkers such as superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and catalase (CAT) along with markers, i.e., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, intercellular adhesion molecule-1 (ICAM-1) and expression of B-Cell Leukemia/Lymphoma 2 (Bcl-2). Also, histopathology was performed. Treatment with barbigerone in the ethanol-induced-ulcer rats restored the levels of biochemical parameters such as SOD, GSH, MDA, CAT, and markers expression, including TNF-α, IL-6, IL-1β, ICAM-1, and Bcl-2 with protected against cellular necrosis. Barbigerone protective effects can be attributed to its ability to reduce oxidative stress and inflammation, as well as promote gastroprotection against ethanol-induced ulcers in rats.

Apple extract protects against indomethacin-induced gastric ulcers in rats by suppressing oxidative stress – The implication of Nrf-2/HO-1 signaling pathway: In silico and in vivo studies

Gastric ulcers represent a worldwide health problem, characterized by erosions with different degrees in the gastrointestinal mucosa. In the current study, we explore the protective effects of the extract of apple seeds (Malus domestica, family: Rosaceae), regarded as environmental wastes, against indomethacin-induced gastric ulcers in rats. The chemical composition of the seeds extract was investigated through liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS). The metabolomics profiling resulted in identification of 17 compounds (1–17) of different chemical classes. The gene ontology analysis demonstrated that the total extract of M. domestica seeds possess an antiulcer activity through PI3K-Akt signaling pathway as the top identified signaling pathway. The present research work evidenced the reuse of apple seeds waste as an effective therapy to treat NSAIDs-induced gastric ulcer, attributed to its anti-inflammatory and antioxidant properties. It is important to note that the extract does not cause the undesirable effects of traditional antisecretory drugs.

Anti-ulcerogenic activity of the powder fraction of leaves of Aspillia africana against ethanol-induced gastric ulcer in rats: Possible role of mucus and antioxidant effect

Massive alcohol drinking can lead to gastric ulcer. In the present study we investigated the gastroprotective effect of powder fraction of the leaves of Apillia africana (AA) in ethanol (EtOH) induced oxidative stress and peptic ulcer in rats. The rats were divided into six treatment groups, which were the normal control group, negative control group (ethanol-induced) and tree treatment groups: AA at the doses of 100 mg/kg body weight (BW), 200 mg/kg BW and 400 mg/kg BW, and the positive control group treated with famotidin at the dose of 100 mg/kg BW. Gastroprotective effect was measured by the ulcerative lesion index, ulcer surface area, percentage of lesion area. Antioxidant and histopathological analyses were also conducted to gain additional data regarding the gastroprotective effect of AA in the rats’ stomachs. AA showed protected the gastric mucosa from ethanol ulceration, as revealed by the improved macroscopic and histological appearance. AA significantly increased the gastric homogenate content of GSH and inhibited the lipid peroxidation as revealed by the reduced gastric content of malondialdehyde (MDA). AA possesses gastro-protective activity, which could be attributed to a mucus production, antioxidant, and regeneration activities.

Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats

BACKGROUND Atractylodes japonica Koidz. ex Kitam. (A. japonica , Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it’s often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. AIM To investigate the protective effects of A. japonica on acetic acid-induced GU rats. METHODS The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. RESULTS 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1β, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. CONCLUSION These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.

Cytoprotective Effects of Hydro-extracts of the Inner Bark of the Oak Tree Fruit (Jaft) on the Healing Process of Aspirin-Induced Gastric Ulcers in Rats

Introduction: A gastric ulcer is a mucosal lesion of the stomach that may occur after taking non-steroidal anti-inflammatory drugs such as aspirin, especially in cardiovascular diseases. The aim of this study was to evaluate the cytoprotective effects of the aqueous extract of oak (Jaft) against the mucosal damage effects of aspirin. Methods: Seventy-two female Wistar rats weighing 200‒240 g were prepared and divided into 6 groups. Groups I, II, and III received the Jaft extract at doses of 250 mg/kg/d, 500 mg/kg/d, and 750 mg/kg/d, respectively, and Group IV received omeprazole at a dose of 200 mg/kg/d. Groups V (patient’s control) and VI (healthy control) both received saline (0.9%) at 1 mL/kg/d . Mice were given aspirin (200 mg/kg/d) for inducing the gastric ulcer. After 14 days, they were anesthetized with ether, their stomachs were removed, and the blocks of tissue were prepared. The tissues were stained using the hematoxylin-eosin (H&E) dye and analyzed by the Olympus light microscope and OLYSIA software. Finally, IBM SPSS 26.0 software was used for statistical analysis of the data. Results: The means±standard deviation (SD) of the mucosal thickness in groups taking the Jaft extracts (250, 500, and 700 mg) decreased compared to the aspirin group (P<0.05). In addition, the mean±SD of the mucosal gland thickness and mucosal folds in group V (with aspirin) decreased compared to the 250, 500, and 700 extract groups (P>0.05). The epithelial cell destruction, edema, venous congestion, and destruction of the capillaries of the mucosal and sub-mucosal areas in the extract groups decreased compared to the V group. Likewise, the number of mucosal cells in the gastric gland and the size of gastric parietal cells in the extract groups decreased compared to the V group. Conclusion: This study generally elucidated the cytoprotective effect of the Jaft extract in the mouse model of gastric ulcer.

Retraction: In Vivo Antioxidant and Antiulcer Activity of Parkia speciosa Ethanolic Leaf Extract against Ethanol-Induced Gastric Ulcer in Rats.

Retraction: In Vivo Antioxidant and Antiulcer Activity of Parkia speciosa Ethanolic Leaf Extract against Ethanol-Induced Gastric Ulcer in Rats.

Assessing the hypolipidemic and gastro-liver protective activity of herbal combination with emphasis on PPI amid selected multiple antihypertensive drug combination in experimental animal models.

Peptic ulcer (PU) and hypertension are chronic diseases affecting up to 10% and 30% of the adult population worldwide. Most of these patients will require treatment with a combination of antihypertensive medicines, which have adverse effects on the body's different organs. This study specifically focused on antihypertensive multi-drug induced PU disease and disturbance of liver function. During a 14-day oral administration of antihypertensive drugs, Cilnidipine (1 mg/kg), Rosuvastatin (1 mg/kg), Bisoprolol (0.52 mg/kg), and Clopidogrel (7.81 mg/kg) were observed for their effects on the stomach lining and liver function in Wister albino rats. This study aimed to assess the potential of an herbal combination of (BO) + (BA) + (ZO) 0.26 mg/kg body weight (b.w.) Powder and water mixture on the ulcer, lipid profile, and liver function for 14 days in the treatment of the indomethacin-induced gastric ulcers in rats at doses of 30 mg/kg b.w. for three days. Esomeprazole (20 mg/kg b.w.) is used as a standard reference to evaluate antiulcer activity in rat models. The experiment suggests that the gastroprotective effect of the herbal combination can be attributed to its reducing effect on the peptic and the Serum Glutamic Pyruvic Transaminase (SGPT) levels and within the normal range of 34.67 ± 0.88 IU/L. The results for Total Cholesterol (TC), Triglyceride (TG), High-density lipoprotein (HDL) and Low-density lipoprotein (LDL) of the herbal combination were 52 ± 9.81495 (mg/dl), 70 ± 12.12435 (mg/dl), 23.33 ± 6.06446 (mg/dl), 14.5 ± 1.32790 (mg/dl), respectively, where the standard group (atorvastatin) 5 mg/kg TC, TG, HDL and LDL were 69.77 ± 9.92 (mg/dl), 47.7 ± 10.35 (mg/dl), 33.43 ± 5.70 (mg/dl), 26.8 ± 3.70 (mg/dl), and control group total cholesterol, triglyceride, HDL and LDL were 68.67 ± 2.20 (mg/dl), 124.07 ± 2.94 (mg/dl), 49.14 ± 1.05 (mg/dl), 54.11 ± 1.15 (mg/dl). CThis investigation reported that antihypertensive drugs did not produce gastrointestinal (GI) toxicity, and the morphological structure of the organ was not changed. So, it could be concluded that the herbal combination used in this experiment has a promising role in controlling lipid profile, liver function, and antiulcer effects. Moreover, multiple drug therapy for hypertension does not cause any harm to the stomach. Further investigations might be carried out on a larger scale to make these statements more valid.

Mechanisms of anti-ulcer actions of Prangos pabularia (L.) in ethanol-induced gastric ulcer in rats

Peptic ulcer disease is the greatest digestive disorder that has increased incidence and recurrence rates across all nations. Prangos pabularia (L.) has been well documented as a folkloric medicinal herb utilized for multiple disease conditions including gastric ulcers. Hence, the target study was investigation the gastro-protection effects of root extracts of Prangos pabularia (REPP) on ethanol-mediated stomach injury in rats. Sprague Dawley rats were clustered in 5 cages: A and B, normal and ulcer control rats pre-ingested with 1 % carboxymethyl cellulose (CMC)); C, reference rats had 20 mg/kg omeprazole; D and E, rats pre-supplemented with 250 and 500 mg/kg of REPP, respectively. After one hour, group A was given orally 1 % CMC, and groups B-E were given 100 % ethanol. The ulcer area, gastric acidity, and gastric wall mucus of all stomachs were determined. The gastric tissue homogenates were examined for antioxidant and MDA contents. Moreover, the gastric tissues were analyzed by histopathological and immunohistochemically assays. Acute toxicity results showed lack of any toxic effects or histological changes in rats exposed to 2 and 5 g/kg of REPP ingestion. The ulcer controls had extensive gastric mucosal damage with lower gastric juice and a reduced gastric pH. REPP treatment caused a significant reduction of the ethanol-induced gastric lacerations represented by an upsurge in gastric mucus and gastric wall glycoproteins (increased PAS), a decrease in the gastric acidity, leukocyte infiltration, positively modulated Bax and HSP 70 proteins, consequently lowered ulcer areas. REPP supplementation positively modulated oxidative stress (increased SOD, CAT, PGE2, and reduced MDA) and inflammatory cytokines (decreased serum TNF-α, IL-6, and increased IL-10) levels. The outcomes could be scientific evidence to back-up the folkloric use of A. Judaica as a medicinal remedy for oxidative stress-related disorders (gastric ulcer).

Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo.

Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.

A preparation technology of volatile components in Linggui Zhugan decoction based on the transfer of cinnamaldehyde and its anti-gastric ulcer effect

PurposeThis study aims to preserve the volatile components of Linggui Zhugan (LGZG) decoction, offering an experimental foundation for subsequent preparations efforts. MethodsTwo modern sample preparation processes were compared with the traditional method approach using HPLC fingerprints. After identifying the main volatile components in LGZG aqueous decoction, the inclusion method of inclusion compounds (IC-LGZG) was established and optimized at laboratory, pilot and production scales. Characterization, stability testing of IC-LGZG, and experiments on gastric ulcer rats were conducted to validate the transferability of chemical composition and pharmaceutical efficacy. ResultsThe study focused on preserving the volatile components in LGZG modern preparations. HPLC analysis revealed cinnamaldehyde (CA) as the main volatile component in LGZG decoction. The optimized IC-LGZG preparation involved heating aromatic water to 40 °C, adding 20 g/L of β-Cyclodextrin (β-CD), keeping warm and stirring at 300 r for 30 min. This process exhibited good repeatability across different verification tests at varying scales. IC-LGZG obtained effectively transferred CA molecules into the β-CD molecules via encapsulation, remaining stable when stored in sealed and dark conditions. Finally, CA, IC-LGZG and M−LGZG (a mixture of IC-LGZG and water-soluble extract powder) effectively prevented the formation of gastric ulcer by mitigating reductions in IL-10, SOD and the increase of TNF-α, NO, MDA in serum. ConclusionThe IC-LGZG prepared using this process successfully transfers volatile components, both chemically and pharmacologically, making it suitable for modern preparations of LGZG.

Protective Effects of Ethanol Extract from Hippophae rhamnoides L. Leaves against Indomethacin-Induced Gastric Ulcer in Rats

We aimed to determine the effects of ethanol extract of Hippophae rhamnoides L. leaves on indomethacin-induced gastric ulcer in rats. 35 male Sprague Dawley rats were divided into 7 groups (n=5) at random: healthy; Hippophae rhamnoides L. leaves ethanol extract (HR) III; indomethacin; indomethacin+famotidine; indomethacin+HRI (100 mg/kg); indomethacin +HRII (250 mg/kg) and indomethacin +HRIII (500 mg/kg). All rats except the healthy group fasted for 24 hours. At the end of this period, HR and famotidine (20 mg/kg) were administered by oral gavage to the corresponding rat groups. Five minutes after the HR treatments, 25 mg/kg of indomethacin was applied by oral gavage to all groups except the Healthy and HR III groups. Six hours after indomethacin administration, stomach tissues were removed for investigation macroscopic and biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels). HR administration improved ulcerative injury in stomach tissues caused by the indomethacin-induced gastric ulcer. HR administration reduced indomethacin-induced ulcer areas. Moreover, HR treatment significantly decreased malondialdehyde levels, increased glutathione levels, and elevated superoxide dismutase activity. HR significantly improved gastric ulcer by alleviating oxidative stress that could be important in ulcer. HR may be a new potential treatment option for ulcer treatment with an antioxidant effect. These findings may provide a mechanistic basis for using HR leaves to treat gastric ulcer.

Integration of gut microbiome and serum metabolome revealed the effect of Qing-Wei-Zhi-Tong Micro-pills on gastric ulcer in rats

Ethnopharmacological relevanceQing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined. Aim of the studyThe present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism. Materials and methodsThe Wistar male rats (7 weeks old; weight 180–200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease. ResultsQWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats. ConclusionQWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.

Huang-Qi-Jian-Zhong-Tang accelerates healing of indomethacin-induced gastric ulceration in rats via anti-inflammatory and antioxidant mechanisms

Ethnopharmacological relevanceHuang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China. Aim of the studyIn the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved. Materials and methodsObservations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflammatory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-κB and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-IκBβ, and p–NF–κB were evaluated through immunofluorescence analysis. ResultsThe administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-κB and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of IκΒβ, NF-κB, JAK, and STAT. ConclusionsThe therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-κB and STAT signaling pathways.

Comparison of the Effect of Keeping Rats in the Mountains and on the Plain on the Development of Streptozotocin-Induced Diabetes and Gastric Ulceration

Hypoxia can correct the development of diabetes and its complications in animals and humans, and diabetes exacerbates the gastric ulceration. However, the effect of hypoxia on the gastric ulceration in diabetes remains unknown. The task of the work was to compare the effect of keeping rats in the mountains under moderate natural hypoxia and on the plains on the development of type 1 diabetes and the gastric ulceration. Two weeks after the rats acclimatized to hypoxia (Elbrus region, 2125 m above sea level), they were injected with streptozotocin (STR, 50 or 70 mg/kg) or its vehicle. Simultaneously, rats on the plains were injected with STR (or its vehicle) at the same doses. Indomethacin (IM, 35 mg/kg) was administered two weeks after STR or its vehicle injection in rats after 24 h of fasting, both in the mountains and on the plains, which led to the gastric erosion formation 4 h later. The injection of STR (50 and 70 mg/kg) caused a dose-dependent increase in blood glucose levels in rats both in the mountains and on the plains, which indicates the development of diabetes of varying severity. In rats on the plains the administration of STR (50 and 70 mg/kg) led to a dose-dependent increase in the area of erosions induced by IM compared with those in control animals (STR vehicle). In rats in the mountains, an aggravation of gastric mucosal injury caused by IM was observed, both in control rats (STR vehicle) and in animals with STR-induced diabetes, compared with the gastric injury in rats of the corresponding groups on the plains. The greatest increase in the proulcerogenic effect of STR in the mountains was observed when it was administered at a dose of 70 mg/kg. Thus, persistent moderate hypoxia may lead to an increase in IM-induced gastric ulceration in rats with type 1 diabetes, and, in addition, by itself exacerbate the ulcerogenic effect of IM.

Retraction Note: Protective and therapeutic effects of the flavonoid "pinocembrin" in indomethacin-induced acute gastric ulcer in rats: impact of anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Retraction Note: Protective and therapeutic effects of the flavonoid "pinocembrin" in indomethacin-induced acute gastric ulcer in rats: impact of anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Therapeutic impact of Aloe Vera Gel on Ethanol Induced Gastric Ulcer in Rat Through Modulation of MYD88 Gene Expression

Therapeutic impact of Aloe Vera Gel on Ethanol Induced Gastric Ulcer in Rat Through Modulation of MYD88 Gene Expression

Caffeic acid phenethyl ester attenuates indomethacin-induced gastric ulcer in rats.

Gastric ulcer is one of the most frequent gastrointestinal ailments worldwide. Indomethacin, one of the most potent NSAIDs, suffers undesirable ulcerogenic activity. Caffeic acid phenethyl ester (CAPE) has known health benefits. The current study examined the potential of CAPE to combat indomethacin-induced gastric ulcers in rats. Animals were randomized into 5 groups: control, Indomethacin (50 mg/kg) mg/kg), Indomethacin + CAPE (5 mg/kg/day), Indomethacin + CAPE (10 mg/kg), and Indomethacin + Omeprazole (30 mg/kg). CAPE prevented the rise in ulcer index, attenuated histopathological changes and preserved gastric mucin concentration. CAPE efficiently significantly prevented accumulation of malondialdehude (MDA) and prevented exhaustion of the enzymatic activities of catalase (CAT) and superoxide dismutase (SOD). Further, CAPE prevented the rise in the expression of tumor necrosis factor-α (TNF-α), cyclo-oxygenase-2 (COX-2) and nuclear factor kapp-B (NFκB). This was associated with down-regulation of Bax and up-regulation of Bcl-2 mRNA. Finally, CAPE prevented induced indomethacin-induced decrease in heat shock protein 70 (HSP70) in gastric tissues. In conclusion, CAPE possesses the ability to prevent indomethacin-induced gastric ulcer in rats. This involves, at least partially, antioxidation, anti-inflammation, anti-apoptosis and enhancement of HSP70 expression.