Ulcer Model Research Articles

Rapid-release and user-friendly costunolide/dehydrocostuslactone hydrophilic nanofibers: Therapeutic effects on acute gastric ulcers.

Gastric ulcers often cause postprandial epigastric pain, especially in acute cases. Abnormal motility, with about 50 % of patients having delayed gastric emptying, contributes to ulcer development. Costunolide (COS) and dehydrocostuslactone (DEH), derived from "Mu xiang" herbs, show potential in treating ulcers and regulating gastrointestinal motility. However, their poor solubility and bioavailability limit in vivo use. This study uses electrospinning to develop hydrophilic nanofibers loaded with COS and DEH in a polyvinylpyrrolidone (PVP) matrix for treating acute gastric ulcers. The production process for costunolide / dehydrocostuslactone nanofibers (COS/DEH/NFs) was optimized, characterized, and tested in pharmacodynamic studies. The results showed that COS and DEH remained in a non-crystalline state within COS/DEH/NFs, enhancing their in vitro release. With 21 % drug incorporation, COS/DEH/NFs released over 70 % of COS and more than 50 % of DEH within 20 min in body fluids. In treatment, COS/DEH/NFs suppressed pro-inflammatory cytokines, resisted oxidative stress, promoted gastric mucosal repair, and enhanced gastrointestinal motility. In a mouse model of acute gastric ulcer, high-dose COS/DEH/NFs achieved a 77.09 % ulcer inhibition rate, and low-dose COS/DEH/NFs resulted in gastric residual and intestinal propulsion rates of 73.55 % and 69.89 %, respectively. The drug loading of COS/DEH/NFs is 14.76 ± 0.26 %, with an encapsulation efficiency of 68.77 ± 1.14 %. COS/DEH/NFs is a new choice for treating acute gastric ulcers with gastrointestinal bloating due to its convenience and swallow-free use, providing rapid symptom relief.

Evaluation of the antiulcer activity of ethanolic extract and solvent fractions of Calendula tripterocarpa Rupr. in experimental rats and their DART-ToF-MS profiling

In this study, antiulcer activity of ethanolic extract and solvent fractions of the aerial part of Calendula tripterocarpa was investigated using ethanol-induced model of gastric ulceration in rats. The results showed that ethyl acetate, non-polar components and diethyl ether fractions have a remarkable antiulcerogenic activity; because they exhibited control-ulcer protection by 85.2%, 77.7% and 62.9%, respectively. The acute toxicity study showed that the extract is highly safe; the median lethal dose (LD50) was more than 5000 mg/kg. Moreover, the obtained results were confirmed by the sub-chronic toxicity and showed no alteration in the liver and kidney functions. Our data suggests that C. tripterocarpa possesses significant antiulcer activity and it can be used as a source for an antiulcer drug. Around 100 compounds are elucidated from this plant using direct analysis in real-time of flight-mass spectrometry for the first time, of which four well-known compounds were not isolated or reported previously.

Human artificial chromosome carrying R-spondin1 and IL-22 expression cassettes in rejuvenated MSCs enhances therapeutic efficacy in ulcerative colitis model mice.

Ulcerative colitis (UC) is an incurable intestinal disease, with current treatments mainly focused on inflammation control and, in severe cases, surgical resection. Recent studies have highlighted the need for new therapies that promote tissue regeneration. R-spondin-1 (RSPO1) and interleukin-22 (IL-22) have shown anti-inflammatory and regenerative effects in UC models, but have short half-lives and poor targeting abilities. Another therapeutic tool, mesenchymal stem cells (MSCs), offer promising migratory and homing capabilities; however, the preparation of homogeneous therapeutic MSCs at sufficient levels in vitro is challenging. Therefore, we developed a novel line of MSCs (HAC-MSC) with significant therapeutic effects in dextran sodium sulfate (DSS)-induced colitis mice. Construction of HAC-MSC involved a two-part strategy: 1) establishment of a non-integrating human artificial chromosome (HAC) vector carrying therapeutic genes encoding IL22 and RSPO1; and 2) transfer of the HAC to previously characterized rejuvenated MSCs (rej-MSCs) prepared using Sendai virus technology for prolonged proliferation capacity in vitro. HAC-MSC stably and efficiently produced therapeutic factors in vitro and, following intraperitoneal administration to DSS-induced colitis mice, showed continuous expression of the therapeutic factors over 5 days. Additionally, HAC-MSC-treated mice showed alleviation of the disease activity index score, reduced depth of injury, and promotion of intestinal growth compared with MSC-treated mice. Furthermore, effective treatment with HAC-MSC required only a fraction (1 %-10 %) of the number of cells needed for conventional MSC therapy. These findings highlight the outstanding potential of rej-MSCs carrying therapeutic factor-loaded HACs as a cell therapy tool with prospective applications in the treatment of UC and other diseases.

Suppression of TRIM72-mediated endoplasmic reticulum stress facilitates FOXM1 promotion of diabetic ulcer healing.

Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif-containing protein 72 (TRIM72)-mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5'-monophosphate-activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1-overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72-mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers.

Indomethacin-Induced Gastric Ulcer in Rats: Gastroprotectivity of Muscari neglectum in Water

Background and Objectives: The plant Muscari Mill. is employed in both raw and cooked forms for the treatment of gastric diseases, as an expectorant, and for the treatment of warts and the enhancement of urine. A review of the scientific literature revealed no studies investigating the effect of Muscari neglectum (MN) water extract on gastric diseases. The objective of this study was to determine the effect of a water extract of the MN plant on indomethacin-induced gastric ulcer in rats, using a series of biochemical (SOD, CAT, GSH and MDA levels) and histopathological parameters. Methods: 60 male Sprague Dawley rats were utilized for the purposes of evaluating the acute toxicity and gastric ulcer models, with a total of 36 rats employed for these experiments (n = 6). The rats were divided into six groups: intact; indomethacin; famotidine; indomethacin and MN (100, 200, 400 mg/kg). Results: The Gastric tissue examinations at biochemical, macroscopic and pathological levels showed that MN extracts effectively prevented indo-methacin-induced gastric mucosal damage. The 400 mg/kg dose exhibited the most effective antiulcer effect, with a 69% protective efficacy. This dose caused an increase in the SOD, CAT and GSH levels and a decrease in the MDA levels compared to the IND group. Furthermore, an LC-MS/MS analysis was conducted on the water extract of MN, resulting in the identification of 14 phenolic compounds. Conclusions: Biochemical analyses and histopathological examinations demonstrated that the water extract of MN exhibited a beneficial protective effect against gastric ulceration due to its high antioxidant content.

Simulation in podiatry teaching and learning: A scoping review.

In podiatry, there are a variety of clinical tasks that require precision and skill and it is expected that clinicians will obtain these skills during their training. Simulation is a dynamic teaching tool used in healthcare to enhance skill and knowledge acquisition. Currently, the extent and nature of the research on the use of simulation in podiatry teaching and learning are not clear. A scoping review was conducted to identify the extent and nature of research activity on the use of simulation in podiatry teaching and learning and identify gaps in the existing literature. Any research relating to simulation use in podiatry teaching including various designs and focusing on simulations aimed at improving podiatry teaching or learning were eligible for inclusion. A systematic search was conducted on February 14, 2024 of the following databases: Embase (via Embase.com), MEDLINE (via PubMed), CINAHL, and the Web of Science. Additional papers were identified via bibliographies of included studies. Content analysis of content relating to podiatry teaching and learning was performed and grouped into broad themes, then further narrowing to six themes. A total of 21 research studies were deemed eligible for inclusion focusing on diverse aspects of podiatry simulation utilized in high-income countries exclusively. Conducted between 1997 and 2023, these studies were categorized into six key themes: skill improvement, communication and professionalism, clinical competencies and patient safety, educational enhancement, and anatomy and histology education. The simulations, carried out by or assessed for podiatry professionals, staff, or students, ranged from high-fidelity medical mannequins to low-fidelity simulations such as a grapefruit model of a diabetes-related foot ulcer. Overall, the findings suggest that simulation teaching in podiatry, whether through direct skill enhancement or through educational impact assessments, holds potential in improving competency, confidence, and educational outcomes in podiatry practice. This scoping review identified a small yet diverse evidence base for simulation modalities in podiatry education, demonstrating gaps in long-term effects and comparative effectiveness studies. It highlights the urgent need for research focused on longitudinal impacts, evaluating various simulation technologies and standardizing best practices to improve podiatry education and align with clinical and patient care needs.

Anti-inflammatory activity of Ziziphus jujuba hydroalcoholic extract in acetic acid-induced ulcerative colitis model.

Ulcerative colitis (UC) is a common gastrointestinal (GI) disorder characterized by chronic inflammation. Current treatments primarily focus on symptom management, but they have inherent limitations. Global attention is increasingly directed towards exploring herbal remedies as complementary approaches. This study aims to investigate the effects of the hydroalcoholic extract of jujuba on an experimental model of ulcerative colitis. In this study, 15 male BALB/c mice were divided into three experimental groups. The first group served as the untreated UC model, acting as the positive control (PC). The second group received treatment with the hydroalcoholic extract of Ziziphus jujuba, while the third group was treated with mesalamine. UC was induced by injecting 100 μL of 4 % acetic acid (AA) intra-rectally several times. Treatment commenced after the onset of symptoms such as diarrhea and bloody stools. The mice were eventually euthanized ethically, and their spleen and intestinal tissues were collected for analysis. Evaluations included the Disease Activity Index (DAI), myeloperoxidase activity (MPO), nitric oxide (NO) levels, cytokine levels (IL-1β, IL-6, TNF-α), and gene expression (iNOS, COX-2, and cytokines). The hydroalcoholic extract of the jujuba plant significantly reduced MPO, NO, the DAI, and the production and expression of inflammatory cytokines, as well as the genes iNOS and COX-2, in the group receiving this extract compared to the positive control group (p<0.05). The study demonstrates that the hydroalcoholic extract of Ziziphus jujuba significantly reduces inflammation markers such as TNF-α, NO, MPO, IL-1β, and IL-6 in a mouse model of ulcerative colitis. Additionally, itdownregulates the expression of pro-inflammatory genes, including iNOS and COX-2. These findings suggest that Z.jujuba extract has potential as an effective anti-inflammatory treatment for managing ulcerative colitis symptoms.

Phytochemical Investigation and Antiulcer Potential of Strychnos Nux vomica Seed Extract in Adult Wistar Rats

The current work sought to assess the possible anti-ulcer efficacy of Strychnos nux-vomica methanolic seed extracts in rats by conducting a thorough phytochemical analysis. This study aims to indicate and discover beneficial molecules present in the seeds with the potential for its medicinal use. This work aimed to determine the primary phytochemicals that have antiulcer properties while maintaining safe profiles at dosages that work. Strychnine is the main phytoconstituent, and it is present in 0.65 % of Nux vomica seeds and is responsible for gastric ulcer activity. When given in 0.05%, it shows therapeutic action. The methanolic seed extract's phytochemical screening identified alkaloids, flavonoids, tannins, and glycosides. Wistar rat models of ulceration produced by methanol were used to evaluate the anti-ulcer efficacy. Four groups of rats were used: control, ulcer-induced (indomethacin induced ulcer), conventional therapy (20 mg/kg omeprazole), and test treatment (50 mg/kg and 100 mg/kg of S. nux-vomica methanolic extract). The outcomes showed that rats treated with S. nux-vomica extract had a significantly lower ulcer index than the control group (p &lt; 0.01). In particular, the ulcer index dropped by 63% in the 100 mg/kg group, which was similar to the omeprazole therapy as a whole (p&gt; 0.05). Reduced stomach mucosal injury was further confirmed by histopathological investigation in the groups who received extract treatment. The originality of this work consists in the safe therapeutic application of S. nux-vomica seeds, usually recognized for their poisonous qualities, in the treatment of stomach ulcers. The findings imply that the S. nux-vomica seed methanolic extract has strong antiulcer properties, providing a unique therapeutic option for ulcer treatment.

Anti-ulcer activity of &lt;i&gt;Trianthema portulacastrum&lt;/i&gt; leaves in rats using an experimental ulcer model

Anti-ulcer activity of &lt;i&gt;Trianthema portulacastrum&lt;/i&gt; leaves in rats using an experimental ulcer model

Inhibition of the Wnt/β‑catenin signaling pathway and SOX9 by XAV939 did not alleviate inflammation in a dextran sulfate sodium‑induced ulcerative colitis model.

The Wnt/β-catenin signaling pathway has been reported to be hyperactivated during the pathogenesis of ulcerative colitis (UC). The present study aimed to explore the therapeutic efficacy of the Wnt/β-catenin signaling inhibitor XAV939 in mitigating UC symptoms. Utilizing a dextran sulfate sodium (DSS)-induced UC mouse model, the present study aimed to evaluate the impact of XAV939 on intestinal morphology through hematoxylin and eosin staining and to measure the expression levels of critical proteins in the Wnt/β-catenin signaling cascade. XAV939 did not exert a significant influence on the morphological features and inflammatory status of the intestinal epithelium. However, XAV939 was found to effectively suppress the Wnt/β-catenin signaling pathway and its downstream target SOX9. This suppression implied a reduction in the differentiation of intestinal stem cells into secretory cell progenitor cells. Additionally, XAV939 was ineffective at reversing the DSS-induced decrease in expression levels of Villin and peroxisome proliferator-activated receptor γ, which suggested that it did not facilitate the differentiation of intestinal absorptive cells. The present findings indicated that the Wnt/β-catenin signaling pathway may not be the predominant mechanism in the pathogenesis of DSS-induced UC.

A gelatin/acrylamide-based hydrogel for smart drug release monitoring and radiation-induced wound repair in breast cancer

Radiotherapy is a common local treatment for breast cancer, and while it is effective in targeting tumor cells, it inevitably causes significant side effects. These include excessive production of reactive oxygen species (ROS), repeated inflammatory, and severe skin ulceration, all of which can hinder the wound healing process. As a result, there is a pressing need for multifunctional medical dressings that can support wound repair following radiotherapy. In this study, we introduced a novel double-network interpenetrating hydrogel (GEMC), which combined gelatin grafted dopamine (GEDA), acrylamide, nano-clay (NC), and curcumin loaded nanoparticles (CCNPs). Unlike traditional single-function hydrogels, the GEMC hydrogel offered a combination of antioxidant properties, tissue adhesion, and real time drug tracking, effectively addressing the multifaceted challenges of wound healing after radiotherapy. The GEMC hydrogel exhibited impressive antioxidant activity and superior mechanical properties, which collectively improve the support and protection of wounded surfaces. Furthermore, GEMC promoted skin regeneration, angiogenesis and reduced inflammatory in a mouse model of radiotherapy-induced skin ulceration. These results highlight the hydrogel's potential to accelerate would healing and enhance the effectiveness of post-radiotherapy wound care, providing a promising new approach to improving the quality of skin recovery following radiotherapy.

Co-Administration of Vitamin U and Antacids in Diets Relieves Gastric Ulcers in Finishing Pigs.

One hundred and forty [(Landrace × Yorkshire) × Duroc] barrows and gilts (86.5 ± 1.5 kg) were used in a 28-day experiment in a randomised complete block design. A model of gastric ulcer was established by adding aspirin to the diet or by fasting. The five dietary treatments were TRT1 (basal diet), TRT2 (basal diet + fasting), TRT3 (basal diet + 0.05% vitamin U and antacids (VA)), TRT4 (basal diet + aspirin + fasting) and TRT5 (basal diet + aspirin + fasting + 0.1% VA). The active ingredients of VA are vitamin U 50 mg/g, magnesium oxide MgO 60 mg/g, sodium carbonate Na2CO3 70 mg/g. The result showed a significant increase in final body weight (p = 0.047) and average daily gain (p = 0.033) in TRT5 compared with TRT1 and TRT2 (p < 0.05). There was no significant difference in carcass scores among treatment groups (p > 0.05). The stomach keratinisation score was significantly higher in TRT2 and TRT4 than that in TRT3 (p = 0.032). Stomach keratinisation score decreased from 1.9 to 1.4 in TRT5 compared with TRT4 (p > 0.05). In conclusion, the addition of VA to the diet can improve the degree of gastric ulcer to a certain extent and effectively improve growth performance.

Changes in the lipid balance in the gastric mucosa in rats under acute stress

BACKGROUND: Stress gastric ulcers are a type of peptic ulcer that develops in response to severe physiological or psychological stress. The causes of stress ulcers in the gaster have not yet been fully studied. AIM: To evaluate the composition of lipids in the gastric mucosa in rats under acute stress. MATERIALS AND METHODS: All rats included in the study (n=30) were divided into two groups. Group 1 (main group, n=20) included animals with a model of stress gastric ulcer created by stimulation with electrical impulses for 12 h. Group 2 (control group, n=10) included animals with no manipulations. At the end of the experiment, the effective and total concentration in blood serum of all animals was measured, followed by the calculation of the albumin binding reserve, and the plasma toxicity index. We also visually assessed the degree of damage to the gastric mucosa and determined the lipid composition. RESULTS: Our study showed that a stressful situation led to endogenous intoxication in group 1. A decrease in the level of phosphatidylcholine by 16.3% and phosphatidylserine by 18.6% in stressed rats demonstrates the destruction of the cell membrane associated with apoptosis, which macroscopically manifested as spot hemorrhages, erosions, and ulcers in the gastric mucosa. An increase in monoacylglycerol by 34.4% and diacylglycerol by 53.4% in group 1 indicates an increase in membrane permeability and induction of regenerative processes. CONCLUSION: In a stressful situation, a decrease in both total and effective albumin concentrations contributes to endogenous intoxication, leading to lipid imbalance, cell membrane damage, and the development of acute gastric mucosal injury.

The therapeutic efficacy of adipose mesenchymal stem cell-derived microvesicles versus infliximab in a dextran sodium sulfate induced ulcerative colitis rat model

ABSTRACT Ulcerative colitis (UC) is a chronic relapsing intestinal inflammation that is becoming of increasing incidence worldwide and has insufficient treatment. Therefore, finding effective therapies remains a priority. A dextran sodium sulfate colitis model was established to elucidate colonic layers alterations and compare adipose mesenchymal stem cell-derived microvesicles (MSC-MVs) versus infliximab (IFX) efficacy through biochemical, light, and electron microscope studies. Fifty-four rats were allocated to 4 groups: Control (Con), UC, UC+IFX, and UC+MSC-MVs groups. End body weights (BW) and serum malondialdehyde (MDA) levels were recorded. Colitis severity was estimated by disease activity index (DAI). Colonic specimens were processed to evaluate the histological structure, collagen content, surface mucous and goblet cells, CD44, TNF-α, and GFAP immune expression. Morphometric and statistical analyses were performed. The UC group revealed congested, stenosed colons, a significant decline in end BW, and a significant increase in serum MDA and DAI. Furthermore, disturbed histoarchitecture, inflammatory infiltration, depletion of surface mucous and goblet cells, increased collagen, and TNF-α expression and decreased GFAP expression were observed. Alterations were partially attenuated by IFX therapy, whereas MSC-MVs significantly improved all parameters. In conclusion, MSC-MVs were a superior therapeutic option, via attenuating oxidative stress and inflammatory infiltration, in addition to restoring intestinal epithelial integrity and mucosal barrier.

Acceptable daily intake of aspartame aggravates enteritis pathology and systemic inflammation in colitis mouse model.

In this study, a dextran sodium sulfate-induced ulcerative colitis model in C57BL/6 mice was used to explore the effect of acceptable daily intake (ADI) of aspartame on inflammation in colonic tissues. The effects of aspartame on the inflammatory state of the colon in mice were comprehensively evaluated by comparing the body weight, colon length/colon length index, splenic index, disease activity index (DAI) score, histological activity index (HAI) score, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, claudin-3, and occludin, the infiltration characteristics of macrophage and neutrophil and the composition of the gut microbiota in the control group, aspartame group, ulcerative colitis model group, and aspartame + ulcerative colitis group. We demonstrated that, in a mouse model of dextran sulfate-induced ulcerative colitis, ADI of aspartame caused a significant decrease in body weight, colon length/colon length index, DAI scores, and expression levels of the proteins claudin-3 and occludin. Moreover, ADI of aspartame caused an increase in the splenic index, HAI scores, the levels of proinflammatory factors TNF-α, IL-1β, and IL-6 both in intestinal tissue and serum and infiltration of macrophages and neutrophils in colon tissues. These results showed that ADI of aspartame promoted intestinal pathology and systemic inflammation in a mouse model of colitis.

Promotion of Epithelial Healing in Oral Mucositis by hESC-Derived Mesenchymal Stem Cells via the PI3K/AKT Pathway

Introduction: Oral mucositis (OM) is a common and debilitating side effect of cancer therapies such as radiotherapy, chemotherapy, hematopoietic cell transplant, or their combinations. Method: This study focused on the reparative effects of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) in OM and possible mechanisms. An ulcer model was created in the rat buccal mucosa to mimic an in vivo animal model of OM mucosal injury, and hESC-MSCs were injected 48h later to assess their reparative effects. In vitro, the efficacy of hESC-MSCs in regulating apoptosis and proliferation in LPS- or 5-fluorouracil (5-FU)-injured HaCaT cells was studied using a transwell coculture system. Subsequently, the PI3K inhibitor LY24002 was used to assess whether hESC-MSCs regulated injured HaCaT cells through the PI3K/AKT pathway. In vivo, we found that hESC-MSCs injection promoted OM healing in rats through the acceleration of re-epithelialization and a decrease in apoptosis. Results: In vitro, our findings revealed that the hESC-MSCs treatment led to a reduction in the quantity of HaCaT cells undergoing apoptosis. Western blot analysis revealed that hESC-MSCs activated AKT, resulting in increased protein levels of PCNA and BCL-2 and decreased protein levels of Bax and Caspase-3 whereas LY294002 reversed these changes. Conclusion: These findings suggest that hESC-MSCs promoted OM wound healing by stimulating the proliferation of epithelial cells and inhibiting their apoptosis in rat models. Furthermore, hESC-MSCs might mediate the PI3K/AKT pathway to modulate apoptosis/proliferation injured by LPS or 5-FU in HaCaT cells.

A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study.

Critical knowledge gaps have impeded progress towards reducing the global burden of disease due to Mycobacterium ulcerans, the cause of the neglected tropical disease Buruli ulcer (BU). Development of a controlled human infection model of BU has been proposed as an experimental platform to explore host-pathogen interactions and evaluate tools for prevention, diagnosis, and treatment. We have previously introduced the use case for a new human model and identified M. ulcerans JKD8049 as a suitable challenge strain. Here, we present a provisional protocol for an initial study, for transparent peer review during the earliest stages of protocol development. Following simultaneous scientific peer review and community/stakeholder consultation of this provisional protocol, we aim to present a refined protocol for institutional review board (IRB) evaluation.

STUDY OF ANTI-ULCER, ANTI-INFLAMMATORY AND IMMUNOMODULATORY ACTIVITIES OF FRUITS POLYEXTRACT OF ZIZIPHUS JUJUBA MIL L.

Introduction. Plant-based drugs and medicines are used in medical practice for the treatment of a wide range of diseases, including gastrointestinal diseases: chronic gastritis and/or gastroduodenitis, gastric and duodenal ulcers. The purpose of the work is to study and evaluate of anti-ulcer, anti-inflammatory and immunomodulatory activities of jujuba fruits (Ziziphus Jujuba Mill.) polyextract. Material and methods. Experimental samples of CO2 extract, alcoholic extract, thick extract, dry extract and polyextract of Ziziphus Jujuba Mill fruits were studied. Biological activity of the samples was evaluated using a specific enzyme biotest system based on inducible NO synthase in vitro. The acute toxicity affecting the exudative phase of the acute reaction was studied in a model of formaldehyde edema of the paw of mice, as a result of screening the polyextract of jujube fruits which has the most pronounced pharmacological activity, and also studied its antiulcer effect on an ethanol model of damage to the gastric mucosa in rats. Results. As a result of screening studies using a specific enzyme biotest system based on inducible NO synthase, immunomodulatory properties were discovered in all experimental jujube fruit extracts. Polyextract of jujube fruits demonstrated the most pronounced immunomodulatory therefore it was chosen for further pharmacological studies. In accordance with the classification of toxicity of chemical substances according to the standards of the Russian Federation, polyextract of jujube fruits is a low-toxic substance. The polyextract has an anti-inflammatory effect, it suppresses the development of the exudative phase of inflammation in a model of formaldehyde edema of mouse paws. A significant gastroprotective effect of the polyextract of the fruits of Ziziphus Jujuba Mill was revealed in an experimental model of rat gastric ulcer caused by the administration of ethanol. Conclusions. Polyextract of jujube fruits has a wide range of biological activity: immunomodulatory, anti-inflammatory, antiulcer, and is also a low-toxic substance. This extract is promising for further in-depth study and the creation of a new effective herbal medicine based on it.

Agmatine attenuates the severity of immunometabolic disorders by suppressing macrophage polarization: an in vivo study using an ulcerative colitis mouse model

Agmatine, an endogenous polyamine generated by the gut microbiota, positively affects host lifespan by regulating mononuclear cell or macrophage function. Although the regulatory pathways governing monocyte/macrophage differentiation have been well studied, the influence of the microbiome and its metabolites on monocyte/macrophage function have not been fully elucidated. To address this, we aimed to investigate the mechanisms whereby agmatine inhibits immunometabolic disorders using the colon of ulcerative colitis (UC) model mice. Agmatine (10 mM) attenuated pathological damage to colonic tissue and significantly improved the survival rate of UC model mice. In particular, treatment of UC model mice with 0.4, 2, and 10 mM agmatine resulted in mortality rates of 70 %, 20 %, 10 %, and 0 %, respectively. In a macrophage-depletion model, agmatine regulated the inflammatory microenvironment by affecting macrophages: it reduced the proportion of M1 macrophages and increased that of M2 macrophages in UC model mice. In cultured macrophages, agmatine inhibited lipopolysaccharide-induced inflammatory cytokine and NO secretion, as detected by enzyme-linked immunosorbent assay and the Griess assay, respectively. Agmatine partially reduced inflammatory factor production by inhibiting histone deacetylase, as detected by fluorometric assay. These findings provide evidence that agmatine efficiently suppresses macrophage polarization in UC mice, highlighting its potential as an anti-inflammatory agent against UC.

Comparison of Dietary Supplementation with Krill Oil, Fish Oil, and Astaxanthin on an Experimental Ethanol-Induced Gastric Ulcer Model: A Biochemical and Histological Study

Background/Objectives: Despite advances in ulcer treatment research, the search for new, safe, and effective strategies for preventing and treating ulcer diseases persists. Methods: In this study, the protective effects of dietary supplementation with krill oil (KO), fish oil (FO), and astaxanthin (ASX) on an ethanol-induced gastric ulcer model were compared during biochemical and histological observations. Sprague–Dawley (n = 64) rats randomly divided into four groups—normal control (vehicle), KO, FO, and ASX groups—received the supplements via the orogastric route at a rate of 2.5% (v/w) of their daily feed consumption for 4 weeks. Then, ulcer induction was performed with ethanol. Results: The ulcer group showed increased levels of malondialdehyde (MDA), chemiluminescence (CL), and myeloperoxidase (MPO) activity and decreased levels of glutathione in the gastric tissues. While KO, FO, and ASX supplementation decreased chemiluminescence levels in the ulcer group, only ASX supplementation decreased MDA levels and MPO activity. Conclusions: In conclusion, supplementation with KO or FO has a similar protective effect against ethanol-induced ulcer damage, as it inhibits ROS formation and reduces lipid peroxidation. However, ASX supplementation has a higher protective effect than KO or FO supplementations against experimental ethanol-induced gastric lesions in rats, as it inhibits ROS formation and reduces neutrophil infiltration and lipid peroxidation.