Ulcers In Rats Research Articles

Inhibition of cytokine-like protein 1 transcription hinders wound-healing process in diabetic rats.

This study explored the function and mechanism of cytokine-like protein 1 (CYTL1) in regulating the wound-healing process of rats with diabetes mellitus (DM). A wound was made in diabetic rats, in which CYTL1 overexpression or HDAC1 expression-interfering adenovirus was injected. The wound area on day 0, 7, 14 and 21 was observed and photographed to calculate the wound-healing rate. The wound tissues were collected for H&E, Masson staining and CD31 immunohistochemistry. The HDAC1 and CYTL1 mRNA and protein expressions in wound tissues were detected by RT-qPCR and western blot. The regulation of HDAC1 on CYTL1 was predicted by hTFtarget and AnimalTFDB database. The H3K27Ac level in the CYTL1 promoter was detected by chromatin immunoprecipitation (ChIP). Diabetic rats with CYTL1 overexpression or interfered HDAC1 expression had accelerated the wound-healing rate, in which massive fibroblasts, attenuated inflammatory infiltration and increased collagen and microvessel density were observed. Further experiments found that HDAC1 can inhibit CYTL1 transcription and expression by inhibiting H3K27Ac expression in CYTL1 promoter. Collected evidence showed HDAC1 can inhibit CYTL1 transcription by down-regulating the H3K27Ac level in CYTL1 promoter to slow down the wound-healing process in diabetic ulcer rats.

Comparative Effect of Curcuma longa and Piper nigrum Extract and their Mixture on some Haematological Indices of Indomethacin-Induced Gastric Ulceration in Albino Rats

Peptic ulcer disease (PUD) which includes gastric and duodenal ulcer is one of the unresolved medical problems facing numerous patients in a wide range of age of both sexes worldwide. Many medicinal plants are known to exhibit antiulcer activity and some have been confirmed scientifically to possess gastro protective and antiulcer property and also found to be useful in its treatment. Among these medicinal plants turmeric (Curcuma longa) and black pepper (Piper nigrum) have been reported to possess gastroprotective potentials. However, the effect of the combination of turmeric and black pepper on the haematological indices of ulcerated rats hasn’t been considered. As a result, this study was designed to evaluate the effect of aqueous extract of Curcuma longa and Piper nigrum on some haematological parameters of indomethacin-induced gastric ulceration in albino rats. Total of sixty (60) albino rats was used for this study. After acclimatization for 14 days, the animals were randomly allocated into six groups (n=10).Group A (normal control): rats was fed on pellet and allowed free access to water, rats in Group B (Ulcerated control) were given only indomethacin at a dose of 50mg/Kg body weight. Animals in group C (Standard control) was given indomethacin after pre-treatment with omperazole (20mg/kg) body weight. Group D,E, and F comprised ulcerated rats pre-treated with turmeric (200mg/kg body weight), black pepper (100mg/kg body weight), turmeric and black pepper (200mg/Kg + 100mg/kg respectively) body weight. Treatments with the reference drug and extracts lasted for 21 days prior to ulcer induction on the twenty-third day.4 h post ulcer induction, the animals were humanely sacrificed under chloroform anaesthesia and blood samples were collected for further haematological studies. The result obtained from this study showed that there were no significant (p > 0.05) differences in PCV, HbC, TWBC, NEUT, MON, EOS, BAS, RBC and PLT levels across all groups, with LYM being significantly (p < 0.05) different in group E compared with Group F. The study found that Curcuma longa and Piper nigrum extracts, either alone or in combination, do not significantly alter haematological indices in albino rats with gastric ulcers caused by indomethacin, suggesting they may be beneficial without negative systemic impact. However, lymphocyte levels significantly decreased in the group treated with a mixture of Curcuma longa and Piper nigrum, suggesting a potential mild immunomodulatory effect. Keywords: Haematological Indices, Indomethacin, Ulcer, Curcuma longa and Piper nigrum

Comparative Effect of Curcuma longa and Piper nigrum Extract and their Mixture on some Gastric Secretory Parameters of Indomethacin-induced Gastric Ulceration in Albino Rats

Peptic ulcer disease (PUD) which includes gastric and duodenal ulcer is one of the unresolved medical problems facing numerous patients in a wide range of age of both sexes worldwide. Many medicinal plants are known to exhibit antiulcer activity and some have been confirmed scientifically to possess gastro protective and antiulcer property and also found to be useful in its treatment. Among these medicinal plants turmeric (Curcuma longa) and black pepper (Piper nigrum) have been reported to possess gastroprotective potentials. However, the effect of the combination of turmeric and black pepper on some gastric secretory parameters of ulcerated rats hasn’t been considered. As a result, this study was designed to evaluate the effect of ethanol extract of Curcuma longa and Piper nigrum on some gastric secretory parameters of indomethacin induced gastric ulceration in albino rats. Total of sixty (60) albino rats was used for this study. After acclimatization for 14 days, the animals were randomly allocated into six groups (n=10).Group A (normal control): rats was fed on pellet and allowed free access to water, rats in Group B (Ulcerated control) were given only indomethacin at a dose of 50mg/Kg body weight. Animals in group C (Standard control) was given indomethacin after pre treatment with esomperazole (20mg/kg) body weight. Group D, E, and F comprised ulcerated rats pre treated with turmeric (200mg/kg body weight), black pepper (100mg/kg body weight), turmeric and black pepper (200mg/Kg + 100mg/kg respectively) body weight. Treatments with the reference drug and extracts lasted for 21 days prior to ulcer induction on the twenty-third day.4 h post ulcer induction, the animals were humanely sacrificed under chloroform anaesthesia and gastric content drained into a centrifuge tube for further studies on some gastric secretory parameters. The study showed that TA levels were significantly (p < 0.05) higher in group B compared to the control group and all other groups. Conversely, TA levels were significantly (p < 0.05) lower in groups C, D, E, and F compared to the control, with group F showing the lowest levels among these, particularly lower than groups C and E. GpH levels were significantly (p < 0.05) lower in group B when compared to groups C, D, E, and F. However, GpH levels were significantly (p < 0.05) higher in groups D and E compared to the control, with group E having higher GpH levels than group C. Additionally, pepsin levels were significantly (p < 0.05) elevated in group B relative to the control and other groups. Pepsin levels were also significantly (p < 0.05) higher in groups C, D, E, and F compared to the control, with group C having lower levels than groups D and E. It can therefore concluded based on the findings of this study that the combination of turmeric and black pepper extract had more gastroprotective effect than the individual extracts alone suggestive of the synergistic effect of these plants in the management of peptic ulcer disease. Keywords: Curcuma longa, Piper nigrum, Indomethacin and Gastric Ulceration

Effect of Trichosanthes cucumerina Methanol Extract on CRP and Fibrinogen Levels in Diabetic Ulcer Rat Models

Diabetic ulcers can be fatal for people with long-term diabetes. This is caused by the spread of diabetic ulcers and inadequate care for the wound, which can induce an infection and even death. This study aims to determine inflammatory markers, specifically fibrinogen and C-Reactive Protein (CRP), as indicators of healing, particularly in a rat model of diabetic ulcers treated with Trichosanthes cucumerina methanol extract. The methods used were making extracts, measuring blood glucose levels, measuring CRP, and measuring fibrinogen levels in 25 male Wistar rats. Based on the results of glucose and fibrinogen examinations in all groups before treatment and after treatment, it showed a decrease in glucose and fibrinogen levels. Meanwhile, the results of CRP examinations, before and after treatment did not show any differences. The results of statistical analysis showed that there was a significant difference of p<0.05 in pre and post glucose, as well as pre and post fibrinogen.The extract that reduced fibrinogen levels the most was group 3 with 500 mg/KgBW. Meanwhile, CRP levels before and after treatment did not show a decrease.

Magnesium metal-organic framework microneedles loaded with curcumin for accelerating oral ulcer healing.

Oral ulcers are a common oral mucosal disease that seriously affect the quality of life. Traditional drug treatments have shown unsatisfactory efficacy and potential adverse reactions. In this study, curcumin-loaded multifunctional magnesium metal-organic framework-embedded hyaluronic acid-soluble microneedles patches were developed to optimize treatment strategies for oral ulcers. This microneedles patch achieves efficient release of curcumin and Mg2+ in the ulcer through precisely targeted delivery and controllable release mechanism, significantly regulates inflammation, promotes cell migration and angiogenesis, and accelerates the ulcer healing process. At the same time, the synergistic effect of curcumin and gallic acid effectively alleviated oxidative stress, while the backplate ε-poly-L-lysine and needle tip Mg2+ jointly constructed an antibacterial barrier to effectively inhibit pathogens. Verification using an oral ulcer rat model showed that the microneedles patch exhibited excellent therapeutic effects. This not only opens up a new avenue for clinical oral treatment but also marks a breakthrough in nanobiomaterials science and drug delivery technology and heralds a broad prospect in the field of oral ulcer treatment in the future.

Gastroprotective role of a flavonoid-rich subfraction from Fridericia chica (Bonpl.) L. G. Lohmann: a medicinal plant used in the Amazon region.

Fridericia chica is an Amazonian plant used to treat stomach disorders. However, the pharmacological activity of flavonoids in the extract has yet to be investigated. Therefore, we considered that a flavonoid-rich F. chica subfraction (FRS) has gastroprotective functions. For this, before the induction of gastric ulcers with ethanol or piroxicam, the rats received vehicle (water), omeprazole (30mg/kg), or FRS (30mg/kg), and the ulcer area was measured macro and microscopically, and the antisecretory action was investigated in pylorus-ligated rats. In addition, the roles of nitric oxide (NO) and nonprotein sulfhydryl compounds (NP-SH) in the gastroprotective effects of FRS were studied. FRS reduced ethanol- and piroxicam-induced ulcerations by 81% and 77%, respectively, as confirmed histologically. Antioxidant effects were observed for FRS through the maintenance of GSH and LPO levels, and the SOD and CAT activity similar to those found in the nonulcerated group. Moreover, FRS avoided the increase in MPO activity and TNF, IL-6, IL-4 and IL-10 levels. Moreover, mucin staining increased in ulcerated rats receiving FRS, and the pharmacological mechanism gastroprotective seems to involve the NO and NP-SH in addition to antisecretory actions. The chemical study by mass spectrometry confirmed the presence of flavonoids in FRS, and molecular docking studies have shown that these compounds interact with cyclooxygenase-1 and NO synthase. Furthermore, there was no indication that FRS had cytotoxic effects. Our results support the popular use of F. chica, and we conclude that the gastroprotection effect promoted by FRS can be attributed to the combined effect of the flavonoids.

Dampened inflammatory response in oral ulcer after topical therapy of adipose mesenchymal stem cell secretome

ObjectivesResearch has demonstrated that modulating inflammation can significantly accelerate the healing of oral ulcers. Our study focused on the adipose mesenchymal stem cell secretome (AdMSCS), which is rich in immunoregulatory molecules capable of dampening the immune response and interfering with inflammatory pathways. We assessed both inflammatory pathway expression and macrophage phenotypes at the sites of oral ulcers. MethodsWe induced oral ulcers in the inferior fornix mucosa of 20 healthy male Wistar rats (Rattus norvegicus). These subjects were treated topically with adipose MSC metabolite (AdMSCM) oral gel three times daily, for durations of 3 and 7 days. We performed immunohistochemical analyses to evaluate the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 at the ulcer sites. Additionally, we assessed macrophage polarization by examining the ratio of M2/M1 macrophages, identified through CD68+Φ (M1) and CD163+Φ (M2) cells. Data were analyzed using one-way analysis of variance, followed by post-hoc Tukey's Honestly Significantly Difference test. ResultsApplication of AdMSCM oral gel significantly reduced the expression of TLR4 and NF-κB p65. This treatment also enhanced macrophage polarization towards the anti-inflammatory M2 phenotype at the ulcer sites (p < 0.05). ConclusionThe topical application of AdMSCM oral gel effectively modulates the inflammatory response, enhancing healing processes in the oral ulcer rat model. This suggests its potential utility as a therapeutic agent in managing oral ulcers.

Gastroprotective effect of SKM-Gelcocid suspension on indomethacin induced gastric ulcer in female Wistar rats

Background: Peptic ulcer causes painful ulcers or lesions in the stomach or duodenum. It is also known as a gastric ulcer, which is damage to the gastric wall or lower portion of the esophagus. In the allopathic system, many medications such as H2 receptor antagonists, and anti-H. pylori, proton pump inhibitors, and others with rapid therapeutic activities were utilized to treat peptic ulcers.Purpose: The main aim of this work is to report an in-vivo gastro protective investigation of Saminathapuram Karuppana Gounder Maeilanandhan- Gelcocid suspension (SKM-GS), an Ayurveda formulation, using indomethacin-induced gastric ulcer rats.Study Design and Methods: In the present study we have reported the gastroprotective effect of SKM-GS, an Ayurveda formulation. Indicators such as gastric ulcer area, ulcer index, gastric wall mucus, non-protein sulfhydryl groups (NP-SH), and anti-oxidant enzymes secreted by treatment with SKM-GS on Indomethacin-induced ulcers in female Wistar rats.Result: The results showed a significant (p>0.001) reduction in gastric ulcer area, ulcer index, and an increase in ulcer preventive index. It further revealed an increase in gastric wall mucus and NP-SH secretion. Treatment with SKM-GS showed decreased levels of malondialdehyde (MDA) levels and increased levels of glutathione (GSH) and glutathione peroxidase (GPx) enzymes in the indomethacin-induced gastric ulcer rats. Female Wistar rats when treated with 200 mg/kg and 400 mg/kg of SKM-GS identical to Lansoprazole (Lanso) showed an increase in gastroprotective activity in a dose-dependent manner.Conclusion: The SKM-GS's gastro-protective properties were similar to the well-known anti-ulcer, Lansoprazole. These effects may be due to antioxidant activity.

Untargeted serum and gastric metabolomics and network pharmacology analysis reveal the superior efficacy of zingiberis rhizoma recens-/euodiae fructus-processed Coptidis Rhizoma on gastric ulcer rats

Ethnopharmacological relevanceZingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear. Aim of the studyTo further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. Material and methodsFirst, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence. ResultszCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways. ConclusionzCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU.

(-)-Fenchone Prevents Cysteamine-Induced Duodenal Ulcers and Accelerates Healing Promoting Re-Epithelialization of Gastric Ulcers in Rats via Antioxidant and Immunomodulatory Mechanisms.

(-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. In the cysteamine-induced duodenal ulcer model, fenchone (37.5-300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-β). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.

Biological effects of dates powder or with biscuit on injured gastric ulcer rats

Biological effects of dates powder or with biscuit on injured gastric ulcer rats

Pharmacological mechanism of antiulcer activity of chromatographic Fraction B obtained from &lt;i&gt;Acacia nilotica&lt;/i&gt; seedpods in experimental rats

Acacia nilotica (Lam) is an important multipurpose tree with many indigenous uses. It is most widely found in Northern Nigeria, tropical and sub-tropical countries. It is used therapeutically to alleviate and manage many illnesses. Acacia nilotica seedpod is used in local traditional medicine to treat gastric-related disorders. The present study was aimed at evaluating the possible mechanism of gastroprotection of chromatographic fraction B derived from Acacia nilotica n-butanol partitioned extract using ethanol for ulcer induction. Chromatographic fractionation of the n-butanol solvent partitioned extract yielded three different fractions (FA, FB, and FC). The possible mechanism of action of FB was assessed by investigating the involvement of endogenous nitric oxide, non-protein sulfhydryl group, and prostaglandin. The ulcer index of ulcerated rats pre-treated with NG-nitro-L-arginine methyl ester (L-NAME) which is a nitric oxide synthase inhibitor and subsequently administered with Fraction B was not significantly higher (p&gt;0.05) from rats in the ulcerated group. Similarly, Pre-treatment with N-ethylmaleimide (NEM), a blocker of endogenous sulfhydryl to ethanol-induced ulcerated rats that were treated with chromatographic FB gave an ulcer index that was not significantly different (p&gt;0.05) from the ulcerated control group. However, prostaglandin synthesis inhibition by pretreatment with indomethacin did not affect the gastroprotective activity of FB. The study concludes that the observed anti-ulcerogenic activity exhibited by chromatographic Fraction B of Acacia nilotica n-butanol partitioned extract is possibly due to the increase in nitric oxide (NO) synthesis and endogenous sulfhydryl group.

Albizzia chinensis (Osbeck) Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway.

Around the world, there is a high incidence of gastric ulcers. YS, an extract from the Chinese herb Albizzia chinensis (Osbeck) Merr, has potential therapeutic applications for gastrointestinal diseases. Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol. The ethanol-induced gastric ulcer rat model was used to assess the protective effect of YS. A pathological examination of gastric tissue was performed by H&E staining. GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells. Endogenous NRF2 was knocked down using small interfering RNA. Immunoprecipitation was used to detect ubiquitination of NRF2. Co-immunoprecipitation was used to detect the NRF2-Keap1 interaction. YS (10 and 30 mg/kg, i.g.) significantly reduced the ulcer index, decreased MDA level, and increased SOD and GSH levels in gastric tissues damaged by ethanol. YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue. In addition, YS regulated NQO1 and HO-1 via NRF2 in H2O2-induced oxidative injured GES-1 cells. Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2, thereby increasing its stability and expression of downstream factors. NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H2O2. YS reduced the NRF2-Keap1 interaction, promoting NRF2 translocation into the nucleus, which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

Phenolic profile and chronic gastric ulcer healing effects of Cameroonian propolis

BackgroundGastric ulcers continue to affect millions of people worldwide, with reported cases of fatalities and the diagnosis, prevention and treatment constitute a burden on the patients especially in case of chronic ulcers which are difficult to treat. Natural medicines such as propolis provide suitable therapeutic alternatives in the treatment and curation of ulcers. ObjectiveThis work focused on the evaluation of the phenolic profile and healing effect of Cameroonian propolis on gastric ulcers in rats. MethodsIdentification and quantification of phenolic compounds in the propolis extract was done using HPLC-DAD. Chronic gastric ulcers were induced using ethanol (70%; 1 mL/200 g p.o.)/indomethacin (1 mg/kg p.o.), and “unhealed” gastric ulcerations were induced using acetic acid (30%)/indomethacin (1 mg/kg p.o.). The animals were administered with the vehicle (Tween 20, 1 mL/100 g p.o.), propolis extract (200 mg/kg, 400 mg/kg and 600 mg/kg p.o.) or sucralfate (50 mg/kg p.o.), once daily for ten to fourteen days. At the end of each treatment period, the animals were sacrificed and ulcer indices, gastric mucus weight, histological and oxidative stress parameters were assessed. ResultsEight phenolic compounds were identified and quantified and most abundant were Caffeic acid (45.31 ± 0.25 µg/g), Chrysin (37.65 ± 0.17 µg/g) and p-Hydroxy benzoic acid (34.14 ± 0.21 µg/g). The treatment of ulcerated rats (chronic and unhealed gastric ulcer models) with propolis extract at 200 mg/kg, 400 mg/kg and 600 mg/kg resulted in reduction of ulcer index compared to negative controls in both models. Histological observation of stomach tissues showed that treatment with propolis extract led to a dose-dependent normalization of the mucosa. There was a significant increase (P < 0.05; P < 0.01 and P < 0.001) in mucus weight that accompanied the healing of the ulcers. Furthermore, doses of 200 mg/kg, 400 mg/kg and 600 mg/kg of the propolis extract induced an increase in the amounts of SOD, catalase, nitrite and GSH while MDA concentrations decreased in both models. ConclusionThe healing effect of propolis extract is due to the stimulation of mucus production followed by an improvement of in vivo antioxidant status. These results support the use of propolis in the development of new pharmacological strategies for the management of peptic ulcers disease.

Overexpression of HSP27 accelerates stress-induced gastric ulcer healing via the CXCL12/CXCR4 axis.

Chronic stress often triggers gastrointestinal complications, including gastric injury and ulcers. Understanding the role of heat shock protein 27 (HSP27) in stress-induced gastric ulcers could unveil novel therapeutic targets. Here, we established a stress-induced gastric ulcer rat model using water immersion restraint stress and administered adenovirus-packaged HSP27 overexpression vector. Gastric ulcer severity was scored, and mucosal changes were assessed. Gastric epithelial and endothelial cells were treated with lipopolysaccharide and transfected with HSP27 overexpression vectors to evaluate cell viability, migration and angiogenesis. Expression levels of HSP27, C-X-C motif chemokine ligand 12 (CXCL12) and C-X-C motif chemokine receptor 4 (CXCR4) were measured in tissues and cells. HSP27 expression was initially low during stress-induced gastric ulceration but increased during ulcer healing. HSP27 overexpression accelerated ulcer healing in rats, promoting gastric epithelial cell proliferation and migration and gastric endothelial cell angiogenesis through the CXCL12/CXCR4 axis. Inhibitor IT1t reversed the effects of HSP27 overexpression on cell proliferation, migration and angiogenesis. In summary, HSP27 overexpression facilitated ulcer healing, which was partially mediated by the CXCL12/CXCR4 axis.

Topical Adipose Mesenchymal Stem cell metabolites regulate the expression of MMP-1, MMP-9, EGF, TGF-β in oral mucosa ulcer rat model

ObjectiveMatrix metalloproteinase (MMP-1 and −9), Epidermal Growth Factor (EGF), and Transforming Growth factor (TGF)-β are expressed in the oral ulcer wound-healing process. The Adipose mesenchymal stem cell metabolites (AdMSCMs) may accelerate wound-healing. This study aimed to investigate the expression of MMP-1, MMP-9, EGF, and TGF-β in the oral mucosa ulcer rat model treated with topical AdMSCMs. Materials and MethodsOral ulcer models were created in twenty healthy male Wistar rats (Rattus novergicus) divided into AdMSCMs and control groups. The oral ulcer model was treated topically using AdMSCMs oral gel three times daily for 3 and 7 days. The expression of MMP-1, MMP-9, EGF, TGF-β was evaluated through histological examination using the immunohistochemistry method. Independent t-test was used to compare the mean of expression of MMP-1, MMP-9, EGF, TGF-β between control and treatment groups (AdMSCMs), and paired t-test was used to analyze the mean between day 3 and day 7 of each group. ResultsA lower expression of MMP-1, MMP-9 in AdMSCMs group and higher expression EGF and TGF-β in AdMSCMs group compared to the control group in day 3 and day 7. Independent t-test results showed a significant difference in the expression of MMP-1, MMP-9, EGF between the control and AdMSCMs group in day 3 and day 7. Only TGF-β expression mean difference between day 3 and day 7 showed a significant difference compared to the control groups (p < 0.05) ConclusionsAdMSCMs oral gel may accelerate oral ulcer healing models by reducing the expression MMP-1, MMP-9, and increasing EGF and TGF-β expressions during the wound-healing process.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway

BackgroundGastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved.MethodsAn ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done.ResultsThe ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group.ConclusionsAloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Long noncoding RNA XIST promotes cell proliferation and migration in diabetic foot ulcers through the miR-126-3p/EGFR axis

BackgroundThe prevalence of diabetic foot ulcers (DFUs) has caused serious harm to human health. To date, a highly effective treatment is lacking. Long noncoding RNA X-inactive specific transcript (lncRNA XIST) has been the subject of mounting research studies, all of which have found that it serves as a protective factor against certain diseases; however, its function in DFUs is not entirely understood. This study was performed to determine the importance of the lncRNA XIST in the pathogenesis and biological function of DFUs.MethodsDiabetic ulcer skin from rats was analysed using haematoxylin-eosin (HE), Masson’s trichrome, and immunohistochemistry (IHC) staining. The differences in the expression of genes and proteins were examined with real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Next, the interaction was verified with a dual luciferase gene reporter assay. In addition, CCK-8, Transwell, and wound healing assays were used to assess the proliferation and migration of HaCaT cells.ResultsThe lncRNA XIST and epidermal growth factor receptor (EGFR) were downregulated, while microRNA-126-3p (miR-126-3p) was increased in diabetic ulcer rat skin tissues and high glucose-induced HaCaT cells. In addition, we found that the lncRNA XIST binds to miR-126-3p and that EGFR is directly targeted by miR‑126‑3p. Silencing XIST contributed to upregulated miR-126-3p expression, thus lowering EGFR levels and inhibiting the proliferative and migratory abilities of high glucose-treated HaCaT cells; however, the miR-126-3p inhibitor and overexpression of EGFR reversed this effect.ConclusionDecreased lncRNA XIST expression inhibits the proliferative and migratory abilities of high glucose-induced HaCaT cells by modulating the miR-126-3p/EGFR axis, causing delayed wound healing.

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.