Acetic Acid-induced Chronic Gastric Ulcers Research Articles

Mesenchymal Stem Cells Accelerate Recovery of Acetic Acid-Induced Chronic Gastric Ulcer by Regulating Ekt/Akt/TRIM29 Axis.

Chronic gastric ulcer (CGU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Mesenchymal stem cells (MSCs) have been proven to have beneficial therapeutic effects in many human diseases. Here, a CGU model induced by acetic acid in mice was used to evaluate the repair effects and potential mechanism of human umbilical cord-derived MSCs (hUC-MSCs) and hUC-MSCs derived conditioned medium (hUC-MSC-CM). We found that hUC-MSCs and hUC-MSC-CM treatment significantly repaired morphological characteristics of CGU, improved proliferation and decreased apoptosis of gastric cells, and promoted the generation of new blood vessels in granulation tissues. In addition, we could detect the homing of MSCs in gastric tissue, and MSCs may differentiate into Lgr5-positive cells. As well as this, in vitro experiments showed that hUC-MSC-CM could promote cell proliferation, stimulate cell cycle progression, and reduce the incidence of apoptosis. The transcriptome of cells and the iTRAQ proteome of gastric tissues suggest that MSCs may play a therapeutic role by increasing the expression of TRIM29. Additionally, it was found that knocking down TRIM29 significantly decreased the ameliorative effects of hUC-MSC-CM on cell apoptosis. As a result of further molecular experiments, it was found that TRIM29 is capable of phosphorylating Erk/Akt in specific cell type. As a whole, it appears that hUC-MSCs can be an effective therapeutic approach for promoting gastric ulcer healing and may exert therapeutic effects in the form of paracrine and differentiation into gastric cells.

Evaluation of Acetic Acid-Induced Chronic Gastric Ulcer Healing by Propionyl-L-Carnitine Administration.

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-β1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-β1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.

PH-Responsive Hydrogel as a Potential Oral Delivery System of Baicalin for Prolonging Gastroprotective Activity

Gastric ulcer is one of the most common gastrointestinal diseases, and natural products have obvious advantages in the treatment of gastrointestinal diseases. Baicalin (Bai) extracted from scutellaria baicalensis exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities. Herein, a pH-responsive sodium alginate/polyaspartate/CaCO3 (SA/PASP@CaCO3) in situ hydrogel was established for the oral delivery of Bai. In this study, we detected the gelling properties, mechanical strength, in vitro erosion, and in vitro release behavior of the hydrogels. Meanwhile, the efficiency of Bai/SA/PASP@CaCO3 hydrogel on ethanol-induced acute gastric ulcers, acetic acid-induced chronic gastric ulcers, and H2O2-stimulated human gastric epithelial GES-1 cells was explored. The pathological examination revealed that Bai-loaded hydrogel alleviated acute and chronic gastric ulcers. In vivo and in vitro results further confirmed that Bai/SA/PASP@CaCO3 in situ hydrogels significantly relieved oxidative stress injury. Moreover, through Western blot assay, Bai/SA/PASP@CaCO3 hydrogel was also found to dramatically increase the proteins levels of NRF2, HO-1, and Bcl2, and reduce levels of p-JNK, cleaved-caspase-3 and Bax; through flow cytometry, it was observed to significantly inhibit the H2O2-induced apoptosis of GES-1 cells. Importantly, the Bai/SA/PASP@CaCO3 in situ hydrogel system showed better anti-gastric ulcer efficiency than free drug, and could serve as a potential drug delivery system for the clinical treatment of gastric ulcers.

Gastric protective effect of Alpinia officinarum flavonoids: mediating TLR4/NF-κB and TRPV1 signalling pathways and gastric mucosal healing

Context Our previous studies have found that total flavonoid of Alpinia officinarum Hance (Zingiberaceae) (F.AOH) had protective effects on gastric ulcer (GU). Objective To investigate the protective mechanism of F.AOH on acetic acid-induced chronic GUs in rats and ethanol-induced GES-1 cells damage. Materials and methods In vivo: Gastric damage was induced in SD rats by administering acetic acid after oral treatment with F-AOH at 54, 27 and 13.5 mg/kg (2 weeks of continuous gavage). After a comprehensive evaluation of rats’ serum and gastric tissue-related indicators, gene transcriptome sequencing, qPCR and Western blotting were used to investigate the mechanism further. In vivo: GES-1 cells were incubated with F-AOH (8, 4 and 2 μg/mL) for 16 h and treated with 7% ethanol for 4 h. Transwell and flow cytometry were employed to detect migration and apoptosis of cells. Results F.AOH effectively reduced the area of GUs in rats (from 11.2 ± 1.89 to 2.19 ± 0.95), reversing ethanol-induced cells apoptosis (from 23 ± 1.3 to 8.11 ± 0.93%). It also inhibited the expression of endothelin-1 (ET-1) and iNOS proteins, decreasing the levels of TNF-α IL-6 in serum, improving oxidative stress levels and increasing the expression of Bcl-2/Bax dimer genes. In addition, 4005 differentially expressed genes between the acetic acid model and the drug groups. Through experimental verification, F.AOH can inhibit the activation of TLR4/NF-κB signalling pathway and TRPV1 receptor. Conclusions F.AOH, as an effective gastric protective plant component, had potential therapeutic value in anti-inflammatory pain and antioxidative stress gastrointestinal diseases.

Therapeutic potential of Ferula foetida(Bunge) Regel on gastric ulcer model in rats.

The plant Ferula foetida(Bunge) Regel (FFBR) has a long history in Asian traditional medicine. This study aimed to evaluate the ulcer healing potential of FFBR umbel ethanolic extract on acetic acid-induced chronic gastric ulcer in rats. First, the gastric ulcer model was imitated by serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed by ethanolic extract of FFBR umbel (100 mg/kg, 200 mg/kg, and 300 mg/kg), omeprazole (40 mg/kg), or saline for 12 days. Eventually, on the 13th day, animals were sacrificed, and their stomachs were taken out. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. In addition, the expression of NF-κB p65 was investigated by immunohistochemistry. Compared to the untreated rats with gastric ulcer, FFBR extract significantly decreased ulcer area even superior to omeprazole in a dose-dependent manner. Moreover, histological examination revealed that the extract (300 mg/kg) accelerated the epithelialization and differentiation of proliferative cells to mucosal tissue. The FFBR extract (300 mg/kg) increased tissue levels of VEGF and PGE2, but it did not affect MDA levels in rats with gastric ulcers. FFBR treatment (all doses) could significantly inhibit the expression of NF-κB p65 in gastric tissue. Taken together, experimental findings suggested that FFBR could accelerate the healing process of gastric ulcers in rats through mediating NF-κB and VEGF/PGE2 pathways.

Role of Daucus carota in Enhancing Antiulcer Profile of Pantoprazole in Experimental Animals.

The carrot plant (Daucus carota) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).

Antichronic Gastric Ulcer Effect of Zinc-Baicalin Complex on the Acetic Acid-Induced Chronic Gastric Ulcer Rat Model.

Background Baicalin (BA) has been shown to have anti-inflammatory and antioxidant activity. Zinc is a nutrient element. Objective This study is aimed at investigating the antichronic gastric ulcer activity of Zn-Baicalin complex (BA-Zn) and its related mechanisms in an acetic acid-induced gastric ulcer rat model. Results The severely ulcerated gastric mucosa of model rats had lower GSH-Px (52.21 ± 7.13) and SOD (7.03 ± 0.10) activity, and higher MDA (2.39 ± 0.03) content compared to sham rats. BA-Zn reduced the gastric ulcer index in a dose-dependent manner, significantly increased SOD activity and GSH-Px level, and reduced the MDA content and IL-8 and TNF-α levels in the gastric mucosa. BA-Zn (6.5 and 13 mg/kg) exerted a greater antiulcerogenic effect than both BA and zinc-gluconate, leading to a reduced ulcer index (18.43 ± 1.11, 15.00 ± 1.44), decreased MDA content (1.33 ± 0.07, 0.63 ± 0.01), and increased SOD activity (17.62 ± 0.11, 20.12 ± 0.32) and GSH-Px levels (102.12 ± 9.11, 120.25 ± 9.07). In addition, our results from Western blot suggested that BA-Zn (6.5 and 13 mg/kg) has a greater antiulcerogenic effect than both BA and zinc-gluconate. Conclusion The BA-Zn complex possesses greater antichronic gastric ulcer properties compared to BA and zinc-gluconate due to its ability of oxidation resistance and anti-inflammatory effects.

Manuka Honey Exerts Antioxidant and Anti-Inflammatory Activities That Promote Healing of Acetic Acid-Induced Gastric Ulcer in Rats

Gastric ulcers are a major problem worldwide with no effective treatment. The objective of this study was to evaluate the use of manuka honey in the treatment of acetic acid-induced chronic gastric ulcers in rats. Different groups of rats were treated with three different concentrations of honey. Stomachs were checked macroscopically for ulcerative lesions in the glandular mucosa and microscopically for histopathological alterations. Treatment with manuka honey significantly reduced the ulcer index and maintained the glycoprotein content. It also reduced the mucosal myeloperoxidase activity, lipid peroxidation (MDA), and the inflammatory cytokines (TNF-α, IL-1β, and IL-6) as compared to untreated control group. In addition, honey-treated groups showed significant increase in enzymatic (GPx and SOD) and nonenzymatic (GSH) antioxidants besides levels of the anti-inflammatory cytokine IL-10. Flow cytometry studies showed that treatment of animals with manuka honey has normalized cell cycle distribution and significantly lowered apoptosis in gastric mucosa. In conclusion, the results indicated that manuka honey is effective in the treatment of chronic ulcer and preservation of mucosal glycoproteins. Its effects are due to its antioxidant and anti-inflammatory properties that resulted in a significant reduction of the gastric mucosal MDA, TNF-α, IL-1β, and IL-6 and caused an elevation in IL-10 levels.

Development and evaluation of gastroretentive raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions for gastric ulcer treatment

Novel raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions were developed to prolong the gastric residence time and provide for a controlled release therapy of curcumin to treat gastric ulcers. The solid dispersions of curcumin with Eudragit® EPO were prepared by the solvent evaporation method at various ratios to improve the solubility and the dissolution of curcumin. The optimum weight ratio of 1:5 for curcumin to Eudragit® EPO was used to incorporate into the raft forming systems. The raft forming formulations were composed of curcumin-Eudragit® EPO solid dispersions, sodium alginate as a gelling polymer and calcium carbonate for generating divalent Ca2+ ions and carbon dioxide to form a floating raft. All formulations formed a gelled raft in 1min and sustained buoyancy on the 0.1N hydrochloric acid (pH 1.2) surface with a 60–85% release of curcumin within 8h. The curative effect on the acetic acid-induced chronic gastric ulcer in rats was determined. The curcumin raft forming formulations at 40mg/kg once daily showed a superior curative effect on the gastric ulcer in terms of the ulcer index and healing index than the standard antisecretory agent: lansoprazole (1mg/kg, twice daily) and a curcumin suspension (40mg/kg, twice daily). These studies demonstrated that the new raft forming systems containing curcumin solid dispersions are promising carriers for a stomach-specific delivery of poorly soluble lipophilic compounds.

Proulcerogenic effect of water extract of Boswellia sacra oleo gum resin in rats

Context: The water extract of Boswellia sacra Flueck. (Burseraceae) is used in the treatment of gastric and hepatic disorders in the Arab countries.Objective: The effect of Boswellia sacra water extract on gastric secretion and experimentally induced gastric ulcers in rats was studied.Materials and methods: Acetic acid-induced chronic gastric ulcers, pylorus ligation, aspirin-induced, ethanol-induced, and restraint plus cold stress-induced gastric ulcer models were employed. The effect on normal rats was also studied. The water extract of B. sacra was administered orally at doses of 2 and 5 ml/kg once daily ranging from single dose to 30 d treatment depending on the model. The extract was subjected to GC-MS analysis to determine the presence of various phytoconstituents.Results: Boswellia sacra water extract (5 ml/kg, p.o (per os)) aggravated acetic acid-induced chronic ulcers, wherein an increase in ulcer index (p < 0.01) and ulcer score (p < 0.05) was observed. In pylorus-ligated rats, the extract increased gastric content volume (p < 0.01), free acidity (p < 0.01), total acidity (p < 0.01), ulcer index (p < 0.01), and pepsin activity (p < 0.05). There was no significant effect on the development of ethanol-induced and aspirin-induced ulcers while an increase in the development of stress-induced ulcers was observed (p < 0.01). The extract did not produce any ulcers when administered to normal rats. The dose of 2 ml/kg was less proulcerogenic compared with 5 ml/kg. The GC-MS analysis revealed the presence of several phytoconstituents that included menthol, 3-cyclohexen-1-ol, and octanoic acid.Conclusion: Boswellia sacra water extract has proulcerogenic activity due to its gastric hypersecretory effect.

Aqueous Extract of Enantia chlorantha (Annonaceae) Prevents the Delay in Chronic Gastric Ulcer Healing Caused by Indomethacin in Rats

Aims: To investigate the ability of Enantia chlorantha aqueous extract to heal acetic acid-induced chronic gastric ulcers and to prevent the delay in chronic ulcer healing induced by indomethacin. Study Design: Random allocation of male rats to groups of five rats each. Place and Duration of Study: Department of Animal Biology and Physiology, Animal Physiology Laboratory (Gastroenterology Research Unit) University of Yaounde 1 and Department of Biomedical Sciences (Pathology Unit), University of Buea between January and April 2015. Methodology: Gastric ulcers were produced 5 days after submucosal injection of 30% acetic acid (0.05 ml) at the lesser curvature of rat stomachs corpus. The extract (250 and 500 mg/kg) was administered p.o. during 10 days. Ulcer healing was delayed by indomethacin administered s.c. at 1 mg/kg once daily for 2 weeks from 5 days after the acid injection. Extract or sucralfate were administered concomitantly. Mucus secretion and oxidative stress parameters (superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT)) were measured, and macroscopic and histological assessment of ulcer healing was done. Results: Ulcer healing rates were 82.7% and 88.6% for the 250 and 500 mg/kg doses of extract following 10 day treatment of acetic acid-induced ulcers vs 55.7% and 85.2% for spontaneous healing and Ranititine, respectively. Spontaneous healing (60.9%) was significantly (P<0.01) delayed by indomethacin (22.5% healing rate). Co-administration of extract (250-500 mg/kg) or sucralfate (100 mg/ kg) significantly (P<.001) inhibited the adverse effect of indomethacin, raising healing rates to 76.7%, 82.2% and 85.8%, respectively. Indomethacin significantly depressed gastric mucus production (39.79 mg) but extract and sucralfate restored values to 40.08-55.75 mg and 70.06 mg, respectively. Indomethacin raised MDA levels and decreased antioxidant enzyme levels. These effects were counteracted by E. chlorantha extract. Microscopy showed advanced re-epithelialisation with recovery of ulcer craters due to extract. Conclusion: E. chlorantha accelerates the spontaneous healing of acetic acid-induced chronic gastric ulcers, and prevents the delay in chronic gastric ulcer healing caused by indomethacin. The healing-promoting effect of the extract could be due not only to stimulation of gastric mucus secretion but also to enhanced re-epithelialisation and inhibition of enhanced lipid peroxidation in the ulcerated gastric tissue.

Zinc(II)–curcumin accelerates the healing of acetic acid-induced chronic gastric ulcers in rats by decreasing oxidative stress and downregulation of matrix metalloproteinase-9

Gastric ulcers form as a result of a multifaceted process which includes acid secretion, reactive oxygen species generation and extracellular matrix (ECM) degradation. The aim of this study was to investigate the possible mechanisms underlying the anti-ulcerogenic effects of the Zn(II)-curcumin complex, a curcumin derivative, on the healing of acetic acid-induced gastric ulcers in rats. The severely ulcerated gastric mucosa of control animals had a lower glutathione level (GSH) and superoxide dismutase activity (SOD), and increased malondialdehyde (MDA) content compared to sham operated rats (P<0.001). Zn(II)-curcumin solid dispersions (equivalent to 12, 24 and 48 mg/kg) dose-dependently reduced the gastric ulcer index, significantly increased SOD activity and GSH levels, and reduced the MDA content and matrix metalloproteinase-9 (MMP-9) mRNA expression in the gastric mucosa (P<0.05, compared to control animals). Zn(II)-curcumin exerted a greater anti-ulcerogenic effect than curcumin at the same dose (24 mg/kg), leading to a reduced severity of gastric ulcers, lower MDA content, and increased SOD activity and GSH levels (P<0.05). In conclusion, these results confirm that the Zn(II)-curcumin complex possesses an enhanced mucosal barrier defense activity compared to curcumin alone, due to its synergistic ability to decrease oxidative stress and attenuate MMP-9-mediated inflammation.

Gastroprotective Effects of Ascaridole on Gastric Ulcer in Rats

ObjectiveTo evaluate the gastroprotective activity of ascaridole. MethodsThe gastroprotective effect of ascaridole was evaluated on ulcer healing in rats with acetic acid-induced chronic gastric ulcer, pylorus ligation- and Aspirin-induced gastric ulcer. Ascaridole was ig administered with the dosages of 10 and 20 mg/kg once daily for 7 d. ResultsAscaridole showed the significant anti-ulcer effects. In acetic acid-induced gastric ulcer rats, the ulcer areas after 10 and 20 mg/kg of ascaridole treatment were (65.1 ± 20.0) and (50.6 ± 11.0) mm2, respectively, which were significant lower (P < 0.01) than that of the control group [(116.7 ± 35.8) mm2]. For pylorus ligation model, ascaridole showed a gastric ulcer healing effect in a dose-dependent manner. Ascaridole at the dose of 20 mg/kg showed 50% ulcer protection and had a significant (P < 0.05) gastroprotective activity since it decreased the total acidity and pepsin activity. Compared to the control group, the two dosages of ascaridole showed the significant reduction (P < 0.05) in the ulcer index on Aspirin-induced ulcer. ConclusionThis study provides evidence that ascaridole shows potential efficacy on the healing of gastric ulcers induced by acetic acid, Aspirin, and pylorus ligation.

Gastric antisecretory and cytoprotective effects of leaf extracts of Amaranthus tricolor Linn. in rats

The present study was aimed to evaluate the antiulcer activity of leaf extracts of Amaranthus tricolor Linn. (Amaranthaceae) in rats. The effects of A. tricolor leaves on gastric secretion and the effect of gastric cytoprotection were evaluated using five different models of gastric ulcers: acetic acid-induced, pylorus ligation-induced, ethanol-induced, indomethacin-induced and ischemia-reperfusion-induced gastric ulcers. The different extracts, namely, ethanolic extract (EAT), petroleum ether extract (PEAT), chloroform extract (CAT) and ethyl acetate extract (EAAT) of A. tricolor leaves were administered at a dose of 200 mg/kg per oral (p.o.). The acute oral toxicity study revealed that all the extracts were safe up to 2 000 mg/kg, p.o; hence one-tenth of this dose was selected for evaluation of antiulcer activity. The EAT and EAAT (200 mg/kg, p.o.) showed gastric ulcer-healing effect in acetic acid-induced chronic gastric ulcers. The EAT and EAAT inhibited gastric secretion in pylorus-ligated rats and showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced gastric ulcers, while PEAT and CAT showed no significant antiulcer effect. The leaf extracts of A. tricolor are found to possess very good antiulcer property in the experimental animal models of gastric ulcers which is consistent with the literature report in folk medicine.

Effects of Morinda citrifolia aqueous fruit extract and its biomarker scopoletin on reflux esophagitis and gastric ulcer in rats

The present study was carried out to evaluate the effect of dried mature unripe Morinda citrifolia L. (Rubiaceae) fruit, commonly known as "Noni", in an aqueous extract preparation (AFE) as used in Thai traditional medicine and its biomarker scopoletin on gastro-esophageal inflammatory models that are related to the claimed pharmacological properties of AFE and/or resembled the human esophagitis or gastric ulcer. The powder of dried mature unripe Noni fruit was boiled in water until it became a sticky paste and was then dried into a powder by lyophilization. The pharmacological activity of AFE and pure scopoletin at the same equivalent dose present in AFE was investigated in rat on gastro-esophageal inflammatory models (acid reflux esophagitis, acute gastritis induced by ethanol and serotonin, and chronic gastric ulcer induced by acetic acid); gastric biochemical parameters and gastrointestinal motility. AFE (0.63-2.50 g/kg) significantly prevented the formation of acid reflux esophagitis, reduced the formation of ethanol-induced acute gastric lesions, suppressed the development of gastric lesions in response to serotonin, and accelerated the healing of acetic acid-induced chronic gastric ulcer in rats with equal potency to those obtained by standard antisecretory agents (ranitidine and lansoprazole). AFE also significantly inhibited gastric acid secretion and pepsin activity in pylorus ligated rats. Additionally, AFE strongly increased the gastrointestinal transit of charcoal meal with a higher potency than cisapride. Pure scopoletin, when compared at the same equivalent dose containing in AFE, possessed similar antiulcer and antisecretory properties to that of AFE although it exerted a less prokinetic activity than AFE. The findings indicated that AFE as well as its biomarker: scopoletin may be beneficial as a potential preventive and therapeutic agent for gastro-esophageal inflammatory diseases, mainly through its antisecretory and prokinetic activities including an inhibitory activity on serotonin, free radicals, and cytokine-mediated inflammation. Additionally, scopoletin might be one of the biomarker constituents to use for the quality assessment of Noni fruit products used for treating gastro-esophageal inflammatory diseases.

Yogurt ContainingLactobacillus gasseriOLL 2716 (LG21 yogurt) Accelerated the Healing of Acetic Acid-Induced Gastric Ulcer in Rats

We have reported that LG21 yogurt containing Lactobacillus gasseri OLL 2716 (LG21 yogurt) inhibits the formation of HCl-induced acute gastric lesions through the generation of prostaglandin E₂. This study aimed to determine the role of viable Lactobacillus in the healing of acetic acid-induced chronic gastric ulcer. LG21 yogurt or γ-ray radiated LG21 yogurt was administered orally twice a day for 10 d at a dose of 5 ml/kg. LG21 yogurt significantly accelerated the healing of the ulcer, but γ-ray radiated LG21 yogurt did not. However, both yogurts significantly inhibited HCl-induced gastric erosive lesions and enhanced the generation of gastric mucosal prostaglandin E₂. From the above results, it was found that viable bacteria are needed to accelerate the healing of chronic gastric ulcer, but not to inhibit gastric lesions.

Effect of hyperprolactinaemia as induced by pituitary homografts under kidney capsule on gastric and duodenal ulcers in rats.

The effect of hyperprolactinaemia, induced by two or four pituitary homografts under the kidney capsule, on gastric and duodenal ulcers has been studied. The acute gastric ulcer models used were pylorus ligation, indometacin-induced and ethanol-induced gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by mercaptamine hydrochloride. After pylorus ligation, there was an approximate 30-40% increase in gastric secretion, a significant increase in total acidity (P < 0.01) and in the ulcer index (P < 0.01) in rats bearing pituitary homografts under the kidney capsule when compared with the sham-operated control. Hyperprolactinaemia did not affect the formation of ethanol-induced gastric ulcers but showed a 40% reduction in the development of indometacin-induced gastric ulcers. It also produced a 20% increase in the ulcer index in acetic acid-induced chronic gastric ulcers and a 30% increase in ulcer area in mercaptamine-induced duodenal ulcers. Our results showed that hyperprolactinaemia induced gastric acid secretion and thereby aggravated gastric and duodenal ulcers in rats. Hyperprolactinaemia did not affect gastric cytoprotection.

Effect of Centrally Administered Losartan on Gastric and Duodenal Ulcers in Rats

The effect of centrally administered losartan, an AT₁ receptor antagonist, on gastric acid secretion and gastric cytoprotection was studied using different models of gastric ulcers, such as acetic acid-induced chronic gastric ulcers, pylorus ligation, ethanol-induced and stress-induced acute gastric ulcers and cysteamine hydrochloride-induced duodenal ulcer. Losartan was administered intracerebroventrically (i.c.v.) at 2 different doses (125 and 250 μg/kg). Both doses of losartan increased the healing of acetic acid-induced chronic gastric ulcers. In pylorus-ligated rats, a significant reduction in free acidity, total acidity and ulcer index was observed with high dose (250 μg/kg, i.c.v.), while low dose (125 μg/kg, i.c.v.) produced reduction only in free acidity and ulcer index. Both doses also produced a significant antiulcer effect in ethanol-induced and stress-induced gastric ulcers. Losartan also reduced ulcer area in cysteamine-induced duodenal ulcer. We conclude that AT₁ receptor antagonism in the brain increases healing of gastric ulcers and reduces gastric acid secretion and increases gastric mucin content.

Comparative antiulcer effect of Bisdemethoxycurcumin and Curcumin in a gastric ulcer model system

The antiulcer effect of bisdemethoxycurcumin, a yellow pigment found mainly in rhizomes of Curcuma longa, was compared with curcumin in gastric ulcer model systems to validate its clinical application as a remedy for peptic ulcer. Western blot analysis of mouse macrophage cell line RAW 264.7 activated with lipopolysaccharide showed that bisdemethoxycurcumin inhibited inducible nitric oxide synthase (iNOS) production significantly but had no effect on tumor necrosis factor-alpha (TNF-alpha) production, whereas curcumin showed stronger suppression of iNOS protein production and inhibited TNF-alpha protein production significantly. However, bisdemethoxycurcumin and curcumin possessed similar potency in scavenging nitric oxide generated from mouse macrophage cell line RAW 264.7. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that both curcuminoids inhibited the induction of iNOS dose-dependently at the transcriptional level and curcumin also appeared to inhibit the induction of TNF-alpha at post-transcriptional level. In an animal model, intraduodenal administration of bisdemethoxycurcumin (5-80 mg/kg body wt.) showed a strong inhibitory effect on gastric acid secretion in pylorus-ligated rats whereas curcumin (5-20 mg/kg body wt.) showed a less inhibitory effect, with maximum potency at a dose of 20mg/kg body wt. Moreover, oral administration of bisdemethoxycurcumin at doses of 20-80 mg/kg body wt. twice daily for 10 days showed a significant curative efficacy in accelerating the healing of acetic acid-induced chronic gastric ulcer and promotion of mucosal regeneration in the ulcerated portion in a dose-related manner with potency equal to curcumin. In contrast, the curative potency of curcumin tended to decrease at doses over 160 mg/kg body wt./day. Western blot analysis in ulcerated gastric mucosa showed that bisdemethoxycurcumin dose-dependently reduced the increased protein expression level of iNOS but not TNF-alpha. These results indicated that bisdemethoxycurcumin directly accelerates gastric ulcer healing with potency equal to curcumin. Its antiulcer effect might be due to its properties of decreasing gastric acid secretion and enhancing the mucosal defensive mechanism through suppression of iNOS-mediated inflammation.

Effect of peroxisome proliferator‐activated receptor‐α agonist (bezafibrate) on gastric secretion and gastric cytoprotection in rats

The effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) on gastric secretion and gastric cytoprotection was evaluated using five different models of gastric ulcers: acetic acid-induced chronic gastric ulcers, pylorus ligation, ethanol-induced, indomethacin-induced and ischemia-reperfusion-induced gastric ulcers. Bezafibrate, a PPAR-alpha agonist was administered at two different doses of 10 and 100 mg/kg body weight intraperitoneanally. Both doses of bezafibrate showed significant antiulcer effect in ethanol-induced, indomethacin-induced and pylorus ligation-induced gastric ulcers. Bezafibrate increased healing of ulcer in acetic acid-induced chronic gastric ulcer model. Both doses were also effective in preventing gastric lesions induced by ischemia-reperfusion. It was concluded that PPAR-alpha activation increases healing of gastric ulcers and also prevents development of gastric ulcers in rats.