RESUMEN
We studied the effect of enteral administration of GABA on the gastric mucosa in male Wistar rats (n=47) with modeled metabolic stress (food deprivation for 9 days with free access to water). The relative weights of the adrenal glands and thymus were determined, and histological examination of the stomach was performed. In control rats, modeling the metabolic stress was accompanied by the development of erosive damage to the gastric mucosa related to blood supply disturbances. Administration of GABA prevented erosions and exhibited a pronounced gastroprotective effect. Thus, administration of GABA can be a promising method for the prevention and treatment of erosive gastric lesions associated with metabolic stress.
Asunto(s)
Mucosa Gástrica , Ratas Wistar , Estrés Fisiológico , Ácido gamma-Aminobutírico , Animales , Masculino , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacología , Ratas , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Estrés Fisiológico/efectos de los fármacos , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Timo/efectos de los fármacos , Timo/patología , Timo/metabolismo , Privación de Alimentos , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Úlcera Gástrica/prevención & control , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Peucedanum praeruptorum Dunn (PPD) was used to treat gastrointestinal disease in China before the Tang Dynasty, and it was considered a "Top-grade" herb in Shennong Bencaojing, known for its ability to relieve the stomach Qi and indigestion. AIM OF THE STUDY: Alcohol consumption can induce severe gastric mucosal injury that lacks effective and safe interventions. We aimed to investigate the gastroprotective effects of Peucedanum praeruptorum Dunn leaf (PPL) after bolting in alcohol-induced gastric damage in mice. MATERIALS AND METHODS: Mice were orally administered PPL aqueous extract at doses of 2.5, 5, and 10 g/kg for 5 consecutive days prior to the induction of gastric damage model with ethanol. Gastric tissue was stained by hematoxylin and eosin (H&E), and the levels of pro-inflammatory cytokines and oxidative stress indicators were determined using ELISA and RT-qPCR. RNA-seq was used to detect differentially expressed genes (DEGs) in the gastric tissue, while Western blotting was employed to measure the expressions of IL-17, TNF-a, and AKT pathways. RESULTS: Treatment with PPL alleviated alcohol-induced gastric damage in mice, whereas dried root (PPD) and stem (PPS) of Peucedanum praeruptorum Dunn had no gastroprotective function. The content of peucedanocoumarin I was higher in the dried PPL compared to PPD and PPS, with an increase in peucedanocoumarin I content in PPL after boiling. Additionally, PPL administration (5, 10 g/kg) decreased pro-inflammatory factors, such as interleukin-6 (IL-6), IL-8, IL-4, IL-1ß, IL-18, and tumor necrosis factor (TNF-a) in alcohol-induced gastric injury mice (p < 0.05), and improved oxidative stress markers, including superoxide dismutase enzymes (SOD), catalase (CAT), and malondialdehyde (MDA) (p < 0.05). RNA-seq data revealed that PPL treatment inhibited alcohol-induced inflammation-related signals, including IL-17 and TNF pathways, and restored alcohol-inhibited gastric digestive and metabolic functions, such as xenobiotics metabolism of cytochrome P450, and protein digestion and absorption pathways. Notably, treatment with PPL downregulated the expressions of IL-17 A, TNF-a, monocyte chemoattractant protein-1 (MCP-1), and AKT-phosphorylation induced by ethanol exposure (p < 0.05). Thus, the aqueous extract of PPL provided protection against alcohol-induced gastric injury by mitigating inflammation and oxidative stress in mice, suggesting a potential novel therapeutic approach for alcohol-induced gastric damage.
Asunto(s)
Apiaceae , Etanol , Estrés Oxidativo , Extractos Vegetales , Hojas de la Planta , Animales , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Etanol/química , Masculino , Apiaceae/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & controlRESUMEN
Anisomeles indica (L.) Kuntze is a traditional herb with multiple medicinal properties and with potential for preventing or treating various diseases. Acteoside, one of the active ingredients in A. indica, is prepared into commercially available products of A. indica HP813 powder. In this study, the gastroprotective effects of A. indica HP813 powder were evaluated. Wistar rats were treated with A. indica HP813 powder at doses of 0, 207.5, 415, and 830 mg/kg body weight for 28 days. Then, gastric ulcers were induced by the oral administration of 70% ethanol (10 mL/kg body weight) on day 28. The rats were sacrificed at the end of the trial, and stomach tissues were collected. These stomach tissues were then used for macroscopic, microscopic, and immunohistochemical analyses. The results indicated that the area of gastric ulcer was 48.61%, 35.30%, and 27.16% in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. In addition, the lesion scores were 2.9, 2.4, and 2.3 in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. The immunochemical staining of the gastric tissue revealed that A. indica HP813 powder reduced the expressions of TNF-α and NF-κB proteins in the gastric tissue, which had been induced by ethanol. Finally, A. indica HP813 powder protected the gastric ulcer from ethanol damage through IκB-α induction. The present results demonstrated that A. indica HP813 powder has protective effects against ethanol-induced gastric ulcer.
Asunto(s)
Antiulcerosos , Etanol , Inhibidor NF-kappaB alfa , FN-kappa B , Úlcera Gástrica , Animales , Masculino , Ratas , Antiulcerosos/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Extractos Vegetales/farmacología , Polvos , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismoRESUMEN
Gastric ulcer is a highly prevalent digestive tract disease across the world, which is recurrent and hard to cure, sometimes transforming into gastric cancer if left untreated, posing great threat to human health. To develop new medicines for gastric ulcer, we ran a series of screens with ethanol stress model in GES-1 cells, and we uncovered that lamivudine rescued cells from ethanol toxicity. Then, we confirmed this discovery using the well-established ethanol-induced gastric ulcer model in mice and our findings suggest that lamivudine can directly activate phosphoglycerate kinase 1 (PGK1, EC 2.7.2.3), which binds and stimulates superoxide dismutase 1 (SOD1, EC 1.15.1.1) to inhibit ferroptosis and ultimately improve gastric ulcer. Moreover, AAV-PGK1 exhibited comparable gastroprotective effects to lamivudine. The findings are expected to offer novel therapeutic strategies for gastric ulcer, encompassing both lamivudine and AAV-PGK1.
Asunto(s)
Ferroptosis , Lamivudine , Ratones Endogámicos C57BL , Fosfoglicerato Quinasa , Úlcera Gástrica , Animales , Úlcera Gástrica/prevención & control , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Ratones , Fosfoglicerato Quinasa/metabolismo , Fosfoglicerato Quinasa/genética , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Humanos , Lamivudine/farmacología , Masculino , Etanol , Línea Celular , Superóxido Dismutasa-1/metabolismo , Superóxido Dismutasa-1/genéticaRESUMEN
Acid-related diseases (ARD) are the most common among digestive diseases. The main goals of therapy of ARD are to reduce the influence of aggression factors (production of HCl, pepsin) and increase the protective properties of the mucous membrane of the upper digestive tract. Also currently in medicine, one of the therapeutic and preventive methods is the use of chloride-hydrocarbonate sodium boron mineral waters. In this study, we compared the efficacy of table mineral waters in the therapy of induced gastropathy in Wistar rats. The study of the effect of mineral waters on the gastric mucosa of Wistar rats has provided valuable information that can be applied in medical practice for the treatment and prevention of various diseases of the gastrointestinal tract in humans. Careful analysis of the data obtained has shown that certain types of mineral waters can significantly reduce inflammatory processes and promote regeneration of the gastric mucosa, which makes them a useful addition to traditional treatment methods such as pharmacotherapy.
Asunto(s)
Mucosa Gástrica , Aguas Minerales , Ratas Wistar , Animales , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Ratas , Masculino , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & controlRESUMEN
This study aims to explore the protective effect of Albizia chinensis saponin on ethanol-induced acute gastric ulcer in rats and elucidate its mechanisms. SD rats were deprived of water for 24 hours before the experiment. The control group and model group were administered water by gavage, and the positive drug group received rabeprazole sodium solution(40 mg·kg~(-1)) by gavage. The experimental groups were given different doses of Albizia chinensis saponin solution(3, 10, and 30 mg·kg~(-1)). After 30 minutes, the control group received 1.5 mL of water by gavage, while the other groups were administered an equal volume of 95% ethanol for modeling. After six hours, the rats were killed by cervical dislocation, and the stomachs were collected. The ulcer area was measured, and the ulcer index was calculated. Hematoxylin-eosin(HE) staining was performed to assess histopathological changes in gastric tissue. Periodic acid-Schiff(PAS) staining was used to evaluate the distribution of gastric mucosal surface mucus. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of phospholipids and aminohexose in the gastric mucosa. Western blot was performed to determine the expression levels of the bicarbonate transporter, matrix metalloproteinase, and tight junction-associated proteins in gastric tissue. Immunohistochemistry(IHC) staining was conducted to quantify the number of positive cells for secreted mucin and tight junction-associated proteins. The results showed that the gastric tissue surface of rats in the control group was smooth without ulceration, and the gastric ulcer index of rats in the model group was 35±11. Albizia chinensis saponin at doses of 3, 10, and 30 mg·kg~(-1) resulted in inhibition rates of gastric ulcer of 46%(P<0.01), 85%(P<0.001), and 100%(P<0.001), respectively. Severe disruption of gastric mucosal structure and absence of the mucus layer were observed in the model group. Compared with the model group, the Albizia chinensis saponin group showed intact gastric mucosal surface mucus layer, significantly increased levels of phospholipids and aminohexose in the mucus, increased number of MUC5AC positive cells, and upregulated expression levels of the bicarbonate transporter SLC26A3 and CFTR. It also showed decreased phosphorylation of JNK and c-Jun, reduced expression levels of MMP-8, elevated expression of TIMP-1, and increased expression levels of Occludin and ZO-1. In conclusion, Albizia chinensis saponin enhances the function of the mucus-bicarbonate barrier by upregulating the content of MUC5AC, phospholipids, and aminohexose and increasing the expression levels of the bicarbonate transporter SLC26A3 and CFTR. Moreover, Albizia chinensis saponin exerts its protective effects on gastric ulcers by inhibiting the JNK signaling pathway to prevent excessive activation of MMP-8, thereby reducing the degradation of Occludin and ZO-1 and enhancing the mucosal barrier function. In summary, Albizia chinensis saponin exerts its anti-gastric ulcer effects by simultaneously enhancing the mucus barrier and the mucosal barrier.
Asunto(s)
Albizzia , Medicamentos Herbarios Chinos , Etanol , Mucosa Gástrica , Moco , Ratas Sprague-Dawley , Saponinas , Úlcera Gástrica , Animales , Saponinas/farmacología , Ratas , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Etanol/efectos adversos , Masculino , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/prevención & control , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Albizzia/química , Moco/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/administración & dosificación , HumanosRESUMEN
INTRODUCTION: Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others. AIMS: To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers. MATERIALS AND METHODS: The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.). RESULTS: MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity. CONCLUSIONS: This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.
Asunto(s)
Extractos Vegetales , Hojas de la Planta , Úlcera Gástrica , Animales , Extractos Vegetales/farmacología , Ratones , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Hojas de la Planta/química , Masculino , Antiulcerosos/farmacología , Metanol/química , Género Justicia/química , Modelos Animales de Enfermedad , Cimetidina/farmacología , Acanthaceae/química , Indometacina , Brasil , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patologíaRESUMEN
BACKGROUND: Indomethacin is an anti-inflammatory drug that causes ulcers on the gastric mucosa due to its use. Probiotic bacteria are live microorganisms, and it has been stated by various studies that these bacteria have antioxidant and anti-inflammatory effects. In this study, we investigated the possible protective effect of various types of probiotic bacteria (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against acute gastric mucosal damage caused by indomethacin. METHODS: Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5 mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100 mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1 ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100 mg/kg dose of indomethacin was given. After the application, the rats were anesthetized with ketamine xylazine, killed under appropriate conditions, the abdominal cavity was opened and the stomach tissues were removed. The obtained gastric tissues were used in the biochemical and histopathological analyses discussed below. All data were statistically evaluated by one-way ANOVA using SPSS 20.00, followed by Duncan Post hoc test. The data were expressed as mean ± SD. P < 0.05 was considered statistically significant. RESULTS: As a result, the administration of indomethacin caused gastric damage, stimulating oxidative stress, inflammation, and apoptosis. We found that the use of probiotic bacteria reduces oxidative stress (TOC), increases the activity of antioxidant enzymes (TAC), suppresses inflammation (IL-6 and Tnf-α), and inhibits apoptosis (Bax and Bcl-2) (P < 0.05). CONCLUSION: Probiotic treatment can mitigate gastric damage and apoptosis caused by indomethacin-induced gastric damage in rats. Probiotic also enhances the restoration of biochemical oxidative enzymes as it has anti-inflammatory, antioxidant, and antiapoptotic properties.
Asunto(s)
Apoptosis , Mucosa Gástrica , Indometacina , Inflamación , Estrés Oxidativo , Probióticos , Úlcera Gástrica , Indometacina/efectos adversos , Probióticos/farmacología , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , Úlcera Gástrica/metabolismo , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratas , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Inflamación/metabolismo , Masculino , Ratas Wistar , Antioxidantes/metabolismo , Antioxidantes/farmacologíaRESUMEN
BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: SpragueâDawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
Asunto(s)
Aspirina , Mucosa Gástrica , Gastrinas , Omeprazol , Inhibidores de la Bomba de Protones , Ratas Sprague-Dawley , Animales , Aspirina/efectos adversos , Aspirina/administración & dosificación , Omeprazol/farmacología , Omeprazol/administración & dosificación , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/administración & dosificación , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Gastrinas/sangre , Masculino , Ratas , Esquema de Medicación , Humanos , Úlcera Péptica/prevención & control , Úlcera Péptica/inducido químicamente , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Úlcera Gástrica/prevención & control , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.
Asunto(s)
Quimiocina CCL5 , Clorhidrato de Duloxetina , Mucosa Gástrica , Indometacina , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Serotonina , Transducción de Señal , Úlcera Gástrica , Factor A de Crecimiento Endotelial Vascular , Animales , Clorhidrato de Duloxetina/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Masculino , Indometacina/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quimiocina CCL5/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , Úlcera Gástrica/metabolismo , Serotonina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
The present study was designed to assess Tradescantia spathacea's antidiabetic ability, as well as the antiulcer activity of the entire plant extract. The diabetic condition was evaluated using Streptozotocin's oral glucose tolerance test, diabetes-alloxan and diabetes-models. Antiulcer activities were observed in rats where gastric ulcers were either caused by oral administration of ethanol, or pyloric ligation. Standards include ranitidine, glibenclamide and sucralfate. In all models, the blood glucose levels of animals treated with the test extract were found to be significantly lower compared to diabetic care. Similarly, in all models, the ulcer index in the animals treated with the test extract was found to be significantly lower relative to the animals under vehicle supervision. Our findings say T. Spathacea extract has essential anti-diabetic properties, as well as antiulcer properties.
Asunto(s)
Antiulcerosos , Glucemia , Diabetes Mellitus Experimental , Hipoglucemiantes , Extractos Vegetales , Ratas Wistar , Úlcera Gástrica , Animales , Hipoglucemiantes/farmacología , Hipoglucemiantes/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Antiulcerosos/farmacología , Antiulcerosos/aislamiento & purificación , Diabetes Mellitus Experimental/tratamiento farmacológico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , Úlcera Gástrica/inducido químicamente , Masculino , Ratas , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Metanol/química , Prueba de Tolerancia a la Glucosa , Solventes/química , FitoterapiaRESUMEN
Gastric ulcer is a disturbing disease that impacts many people worldwide. Pioglitazone (Piog), a thiazolidinedione, and ligustrazine (Ligu), a natural component of Ligusticum chuanxiong possess gastroprotective properties. However, the underlying mechanism is not well elucidated. The present study aimed to investigate the gastroprotective effects of Piog (15 mg/kg, p.o.), Ligu (15 mg/kg, p.o.), and their combination against ethanol-induced gastric ulcer in rats. Omeprazole (10 mg/kg) was used as a standard. Pre-treatment for 7 days with Piog, Ligu, and (Piog+Ligu) effectively alleviated ethanol-predisposed oxidative stress and inflammation through restoring HO-1, GSH, and SOD tissue levels and decreasing elevated MDA, TNF-α, ICAM, I-NOS, and IL-1ß contents. Moreover, Piog, Ligu, and (Piog+Ligu) markedly inhibited the ethanol-induced increase of gastric NF-KB and BAX. In contrast, this pre-treatment regimen significantly accelerated protein expression of SIRT1, Nrf2, and Bcl-2, along with autophagic proteins, ATG5 and Beclin. Interestingly, macroscopic, histopathological examination and mucin content were in harmony with previous results, where pre-treatment with Piog, Ligu, and (Piog+Ligu) showed a declined mucosal injury as evidenced by the remarkable decrease of the ulcer area percentage by 62.3%, 38.7%, and 91.2%, respectively, compared to the ethanol-ulcerated group. In conclusion, Piog and Ligu exhibited remarkable gastroprotective properties. Our study was the first to show that Piog, Ligu, and (Piog+Ligu) ameliorated oxidative stress, inflammation, and apoptosis and accelerated the autophagic process via the upregulation of the upstream SIRT1 protein. It is worth mentioning that future studies are needed to pave the way for the clinical use of Piog and Ligu as gastro-protective agents.
Asunto(s)
Etanol , Estrés Oxidativo , Pioglitazona , Pirazinas , Sirtuina 1 , Úlcera Gástrica , Regulación hacia Arriba , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , Úlcera Gástrica/metabolismo , Etanol/toxicidad , Sirtuina 1/metabolismo , Masculino , Pirazinas/farmacología , Pirazinas/uso terapéutico , Pioglitazona/farmacología , Pioglitazona/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Ratas , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Ratas Sprague-Dawley , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismoRESUMEN
Recently, Enterococcus has been shown to have gastric protective functions, and the mechanisms by which Enterococcus modulates gastric function are still being investigated. Herein, we investigated how Enterococcus faecium (Efm) and E. faecium-derived extracellular vesicles (EVs) (EfmEVs) exert protective effect against ethanol-induced gastric injury by investigating the effect of EfmEVs on gastric mucosal ulcer scoring, histological lesion, mucosal glycoprotein production, acidity, anti-oxidative function, and inflammatory responses in rat. Pretreatment with Efm showed significant reduction of ethanol-induced gastric injury, as evidenced by the lowering of ulcer index, histological lesion, gastric pH, and inflammatory responses and the enhancement of mucosal glycoprotein production and anti-oxidative function. Further functional studies on three bioactive components [inactivated Efm, EfmEVs (EVs), and EV-free supernatants] of the bacterial culture showed that EVs are mostly responsible for the gastroprotective effect. Moreover, EV secretion is beneficial for the gastroprotective effect of Efm. Hence, EVs mediated the protective effect of Efm against ethanol-induced gastric injury by lowering inflammatory responses and enhancing anti-oxidative function and may be a potent anti-inflammatory and anti-oxidative strategy to alleviate hyperinflammatory gastrointestinal tract conditions.IMPORTANCEThis study indicated that Enterococcus faecium provided a protective effect against rat gastric injury, which involved improvement of the mucosal glycoprotein production, anti-oxidative function, and inflammatory responses. Furthermore, we confirmed that three bioactive components (inactivated Efm, extracellular vesicles, and EV-free supernatants) of E. faecium culture also contributed to the gastroprotective effect. Importantly, E. faecium-derived EVs showed an effective impact for the gastroprotective effect.
Asunto(s)
Enterococcus faecium , Úlcera Gástrica , Ratas , Animales , Estrés Oxidativo , Úlcera , Etanol/toxicidad , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/patología , GlicoproteínasRESUMEN
The primary goal of the investigation was to analyse the anti-inflammatory and antioxidant properties of Gamma-linolenic acid (GLA) on rats with indomethacin (IND)-induced gastric ulcers. Thirty rats were divided into five groups: Control, IND (50 mg/kg, p.o.), IND pretreated with GLA 100 mg/kg (p.o. for 14 d), IND pretreated with GLA 150 mg/kg (p.o. for 14 d) and IND pretreated with omeprazole (20 mg/kg, p.o. for 14 d). The stomach tissues were examined to calculate the ulcer index and pH and analyse biochemical markers (prostaglandin E2 (PGE2), cyclooxygenase 1 (COX1), TNF-1, IL-6 and intercellular adhesion molecule-1 (ICAM1)) and oxidative stress parameters (malondialdehyde: (MDA), superoxide dismutase (SOD), glutathione (GSH) and CAT (catalase)) as well as undergo histopathological assessment. GLA 100 and 150 mg/kg showed a protective effect against IND-induced gastric damage. It reduced levels of COX1, TNF-1, IL-6 and ICAM and increased PGE2 levels. GLA also normalised antioxidant function by modulating MDA, SOD, GSH and CAT. GLA intervention protects against IND-induced gastric ulcers by restoring oxidant/antioxidant balance and reducing inflammation.
Asunto(s)
Antioxidantes , Dinoprostona , Indometacina , Estrés Oxidativo , Ratas Wistar , Úlcera Gástrica , Ácido gammalinolénico , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/tratamiento farmacológico , Indometacina/efectos adversos , Antioxidantes/farmacología , Ratas , Estrés Oxidativo/efectos de los fármacos , Ácido gammalinolénico/farmacología , Masculino , Dinoprostona/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Interleucina-6/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Superóxido Dismutasa/metabolismo , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Glutatión/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Antiinflamatorios/farmacología , Ciclooxigenasa 1/metabolismo , Malondialdehído/metabolismo , Omeprazol/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Kaempferia galanga L., a medicinal and edible Plant, was widely distributed in many Asian and African counties. It has been traditionally used to treat gastroenteritis, hypertension, rheumatism and asthma. However, there is a lack of modern pharmacology studies regarding its anti-gastric ulcer activity. AIM OF THE STUDY: The objective of this study is to investigate the protective effects of an extract from K. galanga L. rhizome (Kge) and its active components kaempferol and luteolin on ethanol-induced gastric ulcer. MATERIALS AND METHODS: The kge was prepared by ultrasonic-assisted extraction, and the contents of kaempferol and luteolin were determined by HPLC. The mice were randomly divided into seven groups: blank control (0.5 % CMC-Na; 0.1 mL/10 g), untreatment (0.5 % CMC-Na; 0.1 mL/10 g), Kge (100, 200 and 400 mg/kg), kaempferol (100 mg/kg) and luteolin (100 mg/kg) groups. The mice were treated intragastrically once daily for 7 days. At 1 h post the last administration, the mice in all groups except the blank control group were intragastrically administrated with anhydrous alcohol (0.1 mL/10 g) once to induce gastric ulcer. Then, fasting was continued for 1 h, followed by sample collection for evaluation by enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction assay. RESULTS: The contents of kaempferol and luteolin in Kge were determined as 3713 µg/g and 2510 µg/g, respectively. Alcohol induced severely damages with edema, inflammatory cell infiltration and bleeding, and the ulcer index was 17.63 %. After pre-treatment with Kge (100, 200 and 400 mg/kg), kaempferol and luteolin, the pathological lesions were obviously alleviated and ulcer indices were reduced to 13.42 %, 11.65 %, 6.54 %, 3.58 % and 3.85 %, respectively. In untreated group, the contents of Ca2+, myeloperoxidase, malondialdehyde, NO, cyclic adenosine monophosphate and histamine were significantly increased, while the contents of hexosamine, superoxide dismutase, glutathione peroxidase, and prostaglandin E2 were significantly decreased; the transcriptional levels of IL-1α, IL-1ß, IL-6, calcitonin gene related peptide, substance P, M3 muscarinic acetylcholine receptor, histamine H2 receptor, cholecystokinin 2 receptor and H+/K+ ATPase were significantly increased when compared with the blank control group. After pre-treatment, all of these changes were alleviated, even returned to normal levels. Kge exhibited anti-gastric ulcer activity and the high dose of Kge (400 mg/kg) exhibited comparable activity to that of kaempferol and luteolin. CONCLUSION: The study showed that K. galanga L., kaempferol, and luteolin have protective effects against ethanol-induced gastric ulcers. This is achieved by regulating the mucosal barrier, oxidative stress, and gastric regulatory mediators, as well as inhibiting the TRPV1 signaling pathway and gastric acid secretion, ultimately reducing the gastric ulcer index.
Asunto(s)
Alpinia , Antiulcerosos , Úlcera Gástrica , Ratones , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Etanol/toxicidad , Quempferoles/farmacología , Quempferoles/uso terapéutico , Rizoma/metabolismo , Úlcera/tratamiento farmacológico , Luteolina/farmacología , Histamina/metabolismo , Mucosa Gástrica , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/metabolismoRESUMEN
The aim of this study was to evaluate the effect of Citrus sinensis essential oil (EO) on the proximate composition of yogurt over a 28-day shelf life and to investigate the therapeutic and prophylactic effects of functional yogurt on ibuprofen-induced gastric ulcers in a rat model. It was observed that the yogurt group containing C. sinensis EO had higher acidity, total solids, and ash values. Histologic evaluation of the stomachs of rats with gastric ulcers revealed that rats fed with functional yogurt had fewer lesions compared to the control group. The treatment group had fewer lesions than the positive control (p > 0.05). Lesions in the glandular mucosa of the prophylactic group were significantly lower than those in the positive control group (p < 0.05). Yogurt with C. sinensis EO may be beneficial in reducing the severity of ulcers and improving overall health.
Asunto(s)
Citrus sinensis , Aceites Volátiles , Úlcera Gástrica , Humanos , Ratas , Animales , Anciano , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Ibuprofeno/efectos adversos , Yogur , Aceites Volátiles/farmacología , Mucosa GástricaRESUMEN
The aim of this study was to investigate the potential of Ipomoea carnea flower methanolic extract (ICME) as a natural gastroprotective therapy against ethanol-induced gastric ulcers, particularly in individuals exposed to ionizing radiation (IR). The study focused on the Nrf2/HO-1 signaling pathway, which plays a crucial role in protecting the gastrointestinal mucosa from oxidative stress and inflammation. Male Wistar rats were divided into nine groups, the control group received distilled water orally for one week, while other groups were treated with ethanol to induce stomach ulcers, IR exposure, omeprazole, and different doses of ICME in combination with ethanol and/or IR. The study conducted comprehensive analyses, including LC-HRESI-MS/MS, to characterize the phenolic contents of ICME. Additionally, the Nrf2/HO-1 pathway, oxidative stress parameters, gastric pH, and histopathological changes were examined. The results showed that rats treated with IR and/or ethanol exhibited histopathological alterations, increased lipid peroxidation, decreased antioxidant enzyme activity, and reduced expression levels of Nrf2 and HO-1. However, pretreatment with ICME significantly improved these parameters. Phytochemical analysis identified 39 compounds in ICME, with flavonoids, hydroxybenzoic acids, and fatty acids as the predominant compounds. Virtual screening and molecular dynamics simulations suggested that ICME may protect against gastric ulceration by inhibiting oxidative stress and inflammatory mediators. In conclusion, this study demonstrates the potential of ICME as a natural gastroprotective therapy for preventing gastric ulcers. These findings contribute to the development of novel interventions for gastrointestinal disorders using natural plant extracts particularly in individuals with a history of radiation exposure.
Asunto(s)
Extractos Vegetales , Úlcera Gástrica , Animales , Ratas , Antioxidantes/farmacología , Etanol/química , Mucosa Gástrica/metabolismo , Metanol/química , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Ratas Wistar , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Úlcera Gástrica/prevención & control , Espectrometría de Masas en Tándem , Úlcera/patologíaRESUMEN
The objectives of the present study were to evaluate the acute toxicity, gastroprotective, therapeutic, anti-inflammatory and anti H. pylori activities of T. vulgaris total plant extract against ethanol-induced gastric ulcers in Sprague Dawley rats. Animals were divided into five groups i.e G-1 (Normal Control), Group 2 (ulcer control) were administered orally with 0.5% Carboxymethylcellulose (CMC), Group 3 (omeprazole treated) was administered orally with 20 mg/kg of omeprazole and Groups 4 and 5 (Low dose and High dose of the extract) were administered orally with 250, and 500 mg/ kg of Thymus vulgaris extract, respectively. After 1 hour, the normal group was orally administered with 0.5% CMC (5 ml/kg), whereas absolute alcohol (5ml/ kg) was orally administered to the ulcer control group, omeprazole group, and experimental groups. Stomachs were examined macroscopically and microscopically. Grossly, rats pre-treated with T. vulgaris demonstrated significantly decreased ulcer area and an increase in mucus secretion and pH of gastric content compared with the ulcer control group. Microscopy of gastric mucosa in the ulcer control group showed severe damage to gastric mucosa with edema and leukocytes infiltration of the submucosal layer. However, rats pretreated with omeprazole or Thyme vulgaris exhibited a mild to moderate disruption of the surface epithelium and lower level of edema and leukocyte infiltration of the submucosal layer. The T. vulgaris extract caused up-regulation of Hsp70 protein, down-regulation of Bax protein, and intense periodic acid Schiff uptake of the glandular portion of the stomach. Gastric mucosal homogenate of rats pre-treated with T. vulgaris exhibited significantly increased superoxide dismutase (SOD) and catalase (CAT) activities while malondialdehyde (MDA) level was significantly decreased. Based on the results showed in this study, Thymus vulgaris extract can be proposed as the safe medicinal plants for use and it has considerable gastroprotective potential via stomach epithelium protection against gastric ulcers and stomach lesions.
Asunto(s)
Antiulcerosos , Úlcera Gástrica , Thymus (Planta) , Ratas , Animales , Ratas Sprague-Dawley , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Úlcera/tratamiento farmacológico , Etanol/toxicidad , Etanol/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Mucosa Gástrica/metabolismo , Omeprazol/efectos adversos , Antioxidantes/metabolismo , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Edema/tratamiento farmacológicoRESUMEN
Gastric hyperacidity and ulceration are chronic diseases characterized by repeated healing followed by re-exacerbation. The study aims to protect against gastric hyperacidity without interfering with gastric acid secretion. Pylorus ligation-induced hyperacidity is commonly utilized in the induction of gastric ulcers.Forty-two rats were distributed into seven groups (n = 6). Group I comprised sham-operated group. Group II served as pylorus-ligation group. Groups III-VII were given oral Linagliptin (LN; 3 and 6 mg/kg), L-arginine (LA; 150 and 300 mg/kg) and their combination (LN 3 + LA 150 mg/kg), respectively for 7 days. On the 8th day, groups II-VII were subjected to pylorus-ligation.Treatment of pylorus-ligated rats with LN, LA and their combination improved the gastric hyperacidity as exhibited by a marked reduction in the gastric juice volume, total and free acidities and pepsin contents with a noticeable increase in pH. Pre-treatment with LN, LA and their combination showed a marked alleviation in the gastric inflammatory indicators evidenced by reduction in the gastric levels of MCP-1and Il-1ß as well as elevation of eNOS levels versus the sham-operated group. A marked up-regulation in the gastric gene expression of PGE, EP4 and VEGF accompanied by an improvement of the histopathologic pictures/scores, and TNF-α and caspase-3 immuno-staining were also recorded.By estimating the combination-index, it can be concluded that combining LN with LA exhibited prophylactic synergistic effects in ameliorating pylorus ligated-induced hyperacidity, mainly via up-regulation of EP4 receptor and improvement of vascular endothelial damage through VEGF expression in gastric mucosa.
Asunto(s)
Píloro , Úlcera Gástrica , Ratas , Animales , Píloro/cirugía , Linagliptina/farmacología , Linagliptina/uso terapéutico , Linagliptina/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ligadura , Mucosa Gástrica , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Úlcera Gástrica/prevención & control , Arginina/farmacologíaRESUMEN
Oxidative stress and inflammation have pivotal roles in gastric ulcer development caused by alcohol consumption. Trace element boric acid taken into the human and animal body from dietary sources displays strong antioxidant and anti-inflammatory functions. However, the mechanisms underlying these actions of boric acid remain unclear, and its effectiveness in preventing gastric lesions is unknown. Therefore, the present study was undertaken to evaluate the protective effects of boric acid in alcohol-induced gastric ulcer and elucidate its potential mechanisms. Gastric ulcer was induced by 75% oral ethanol administration in rats, and the effectiveness of prophylactic boric acid treatment at 100 mg/kg concentration was assessed by histopathological examination, ELISA assay and qRT-PCR. Gross macroscopic and histopathological evaluations revealed that boric acid alleviated gastric mucosal lesions. Boric acid decreased reactive oxygen species (ROS) and malondialdehyde (MDA) concentration and the overall oxidation state of the body while improving antioxidant status. It reduced the concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mRNA expression of JAK2 and STAT3 was decreased while the expression of AMPK was increased with boric acid pretreatment. Moreover, Sema3A and PlexinA1 levels were elevated upon boric acid pretreatment, and homocysteine levels were reduced. Our results demonstrated that boric acid protects gastric mucosa from ethanol-induced damage by regulating oxidative and inflammatory responses. In addition, our findings suggested that the gastroprotective activity of boric acid could be attributed to its regulatory function in the IL-6/JAK2/STAT3 signaling modulated by AMPK and that Sema3A/PlxnA1 axis and homocysteine are potentially involved in this process.