RESUMO
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.
Assuntos
Antiulcerosos , Etanol , Inibidor de NF-kappaB alfa , NF-kappa B , Úlcera Gástrica , Animais , Masculino , Ratos , Antiulcerosos/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Extratos Vegetais/farmacologia , Pós , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismoRESUMO
OBJECTIVE: To evaluate synergistic antiulcer activity of ethanolic extracts of Tephrosia purpurea and Bacopa monnieri in ulcer induced rats. METHODS: Ethanolic leaf extracts of both the plants were administered individually and in combination at a dose of 200mg/kg to ulcer induced male albino rats. Omeprazole 10mg/kg was used as standard. Pylorus ligation method, ethanol and indomethacin induced gastric ulcer models were the different gastric ulcer models selected for the induction of ulcer in rats. Ulcer index, ulcer score, total acidity, pH, percentage protection, volume of gastric juice were the parameters evaluated and compared in different groups in all the models. RESULTS: Decrease in the ulcer score, ulcer index, total acidity was observed and percentage protection was significant(*p<0.05 and p<0.01) with the combination extract compared to group received individual plant extracts. CONCLUSION: Our results suggested that combination of two medicinal plants showed synergistic anti ulcer activity and decreased the formation of ulcer lesions in rats.
Assuntos
Antiulcerosos , Bacopa , Sinergismo Farmacológico , Extratos Vegetais , Folhas de Planta , Úlcera Gástrica , Tephrosia , Animais , Ratos , Masculino , Extratos Vegetais/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Bacopa/química , Folhas de Planta/química , Tephrosia/química , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Etanol , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Gastric ulcer is one of the most common and serious conditions in the gastrointestinal tract. One of the main causes of gastric ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have limited their use in clinical practice. Several studies have revealed that metformin and Vitamin C (Vit C) exhibit protective effects against gastric mucosal damage in different animal models. However, no studies indicate their combination's effect on gastric ulcer models. Therefore, this study aims to investigate the protective effects of metformin and Vit C combination on indomethacin-induced gastric ulcers. MATERIAL AND METHODS: In total, thirty rats were divided into six groups, including the control group, rats received indomethacin (50 mg/kg, i.p.), rats received indomethacin and pretreated with ranitidine (100 mg/kg), metformin (100 mg/kg, i.p.), Vit C (100 mg/kg), or metformin combined with Vit C. Four hours after indomethacin administration, rats were euthanized, and gastric tissues were removed for macroscopic, histopathologic, and biochemical examinations. RESULTS: All therapeutics used in this study were found to alleviate gastric mucosal injury caused by indomethacin, as observed in histopathologic and macroscopic evaluations. Both Vit C and metformin were observed to significantly decrease lipid peroxidation and enhance the activity of anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant effectiveness was observed in catalase and GPx activities when Vit C was co-administered with metformin. CONCLUSIONS: In conclusion, the present study revealed that metformin and Vit C combination therapy could potentially treat gastric ulcers associated with indomethacin.
Assuntos
Anti-Inflamatórios não Esteroides , Ácido Ascórbico , Mucosa Gástrica , Indometacina , Metformina , Úlcera Gástrica , Animais , Metformina/farmacologia , Indometacina/toxicidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Ratos , Masculino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Antioxidantes/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Ratos Wistar , Antiulcerosos/farmacologiaRESUMO
E. tournefortii has wound healing properties in folk medicine and 5% infusions are used for stomach ulcers. It is also used in colds, abdominal pain, digestive problems, as an appetite enhancer and antispasmodic. For this purpose, in the study biochemical and histopathological evaluation of the ulcer protective effect of the extract obtained from the E. tournefortii in the indomethacin-induced gastric ulcer model in rats was aimed to develop new strategies in the treatment of ulcers. The phytochemical profile of the plant was elucidated for the first time by LC-HRMS in this study. The results indicate that, in terms of TNF-α, IL-1ß, IL-8, IL-6, PGE2, NF-κB, VEGF, NO, COX-1 and COX-2 biochemical parameters, E. tournefortii protects the gastric mucosa to the inflammation, and also modulates the PGE2 pathway, and has a similar effect or even a more positive effect than the reference substance lansoprazole. According to LC-HRMS analysis results, chlorogenic acid, genistein and quinic acid were the main constituents of E. tournefortii extract with 1397.081, 1014.177 and 992.527µg/g extract, respectively. Considering the anti-inflammatory and antioxidant effects of these phenolic components, it is thought that the major components are responsible for the anti-ulcer activity of the E. tournefortii extract.
Assuntos
Antiulcerosos , Indometacina , Compostos Fitoquímicos , Extratos Vegetais , Úlcera Gástrica , Animais , Ratos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Ratos Wistar , Mucosa Gástrica/efeitos dos fármacos , Dinoprostona/metabolismo , Estrutura MolecularRESUMO
Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20 mg/kg, and the remaining two groups received 250 and 500 mg/kg CMEE for 2 weeks. After that, food was taken away for 24 h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1 ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5 g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500 mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.
Assuntos
Etanol , Extratos Vegetais , Úlcera Gástrica , Proteína X Associada a bcl-2 , Animais , Etanol/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Masculino , Proteína X Associada a bcl-2/metabolismo , Ratos Sprague-Dawley , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/metabolismo , Proteínas de Choque Térmico/metabolismo , Antioxidantes/farmacologia , Estômago/patologia , Estômago/efeitos dos fármacos , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismoRESUMO
Peptic ulcer is a sore on the stomach lining that results from the erosion of the gastrointestinal tract mucosa due to various influencing factors. Of these, Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) stand out as the most prominent causes. This condition poses a significant global health concern due to its widespread impact on individuals worldwide. While various treatment strategies have been employed, including proton pump inhibitors and histamine-2 receptor antagonists, these have notable side effects and limitations. Thus, there is a pressing need for new treatments to address this global health issue. Rutin, a natural flavonoid, exhibits a range of biological activities, including anti-inflammatory, anticancer, and antioxidant properties. This review explores the potential anti-ulcer effect of rutin in experimental models and how rutin can be a better alternative for treating peptic ulcers. We used published literature from different online databases such as PubMed, Google Scholar, and Scopus. This work highlights the abundance of rutin in various natural sources and its potential as a promising option for peptic ulcer treatment. Notably, the anti-inflammatory properties of rutin, which involve inhibiting inflammatory mediators and the COX-2 enzyme, are emphasized. While acknowledging the potential of rutin, it is important to underscore the necessity for further research to fully delineate its therapeutic potential and clinical applicability in managing peptic ulcers and ultimately improving patient outcomes. This review on the anti-ulcer potential of rutin opened a new door for further study in the field of alternative medicine in peptic ulcer management.
Assuntos
Anti-Inflamatórios , Antiulcerosos , Úlcera Péptica , Rutina , Rutina/farmacologia , Rutina/uso terapêutico , Humanos , Úlcera Péptica/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêuticoRESUMO
Yucca filamentosa (YF) is widely used in folk medicine for its anti-inflammatory effects. Our study aimed to evaluate the chemical profile of YF extracts. Additionally, the gastroprotective efficacy of its crude leaf extract and nano-cubosomal formulation was assessed in a rat model of ethanol-induced gastric injury by altering the HMGB-1/RAGE/TLR4/NF-κB pathway. The phytochemical composition of YF was investigated using FTIR spectroscopy and LC-MS/MS techniques. Standardization was further accomplished using HPLC. Rats were treated orally with yucca crude extract or its nano-cubosomal formulation at doses of 25, 50, and 100 mg/kg. Famotidine (50 mg/kg, IP) was used as a reference drug. After 1 h, rats were administered ethanol (1 ml, 95 %, orally). One hour later, the rats were sacrificed, and the serum was separated to determine TNF-α and IL-6 levels. Stomachs were excised for the calculation of the ulcer index and histopathological examinations. Stomach tissue homogenate was used to determine MDA and catalase levels. Additionally, the expression levels of HMGB-1/RAGE/TLR4/NF-κB were assessed. Phytochemical analysis confirmed the predominance of steroidal saponins, sucrose, organic and phenolic acids, and kaempferol. The nano-cubosomal formulation demonstrated enhanced gastroprotective, anti-oxidant, and anti-inflammatory efficacy compared to the crude extract at all tested doses. The most prominent effect was observed in rats pretreated with the YF nano-cubosomal formulation at a dose of 100 mg/kg, which was similar to normal control and famotidine-treated rats. Our results highlighted the enhanced gastroprotective impact of the yucca nano-cubosomal formulation in a dose-dependent manner. This suggests its potential use in preventing peptic ulcer recurrence.
Assuntos
Antiulcerosos , Etanol , Proteína HMGB1 , Extratos Vegetais , Folhas de Planta , Úlcera Gástrica , Yucca , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Etanol/química , Folhas de Planta/química , Masculino , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Proteína HMGB1/metabolismo , Ratos , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antiulcerosos/química , Antiulcerosos/administração & dosagem , Yucca/química , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Ratos Wistar , Nanopartículas/química , Interleucina-6/metabolismo , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its gastroprotective effect against indomethacin-induced damage to the gastric mucosa. Additionally, phytochemical investigation of the methanolic extract afforded eight flavonoids' derivatives (1-8). On pharmacology networking study, the isolated compounds identified 123 unique targets where only 45 targets were related to peptic ulcer conditions, these 45 targets include 11 targets specifically correlate to gastric ulcer. The protein-protein interaction defined the PTGS2 gene as one of the highly interacted genes and the complete pharmacology network defined the PTGS2 gene as the most represented gene. The top KEGG signaling pathways according to fold enrichment analysis was the EGFR tyrosine kinase inhibitor resistance pathway. As a result, these findings highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate, which provides a safer option to chemical antisecretory medicines, which are infamous for their negative side effects. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1ß, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.
Assuntos
Indometacina , Sistema de Sinalização das MAP Quinases , Estresse Oxidativo , Extratos Vegetais , Úlcera Gástrica , Tamaricaceae , Animais , Masculino , Ratos , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antiulcerosos/química , Flavonoides/farmacologia , Flavonoides/química , Mucosa Gástrica/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Farmacologia em Rede , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Tamaricaceae/químicaRESUMO
Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1ß, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.
Assuntos
Antiulcerosos , Etanol , Flavonoides , Flores , Mucosa Gástrica , Extratos Vegetais , Úlcera Gástrica , Animais , Etanol/efeitos adversos , Camundongos , Extratos Vegetais/farmacologia , Flores/química , Flavonoides/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Masculino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/lesões , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Modelos Animais de Doenças , Humanos , NF-kappa B/metabolismo , NF-kappa B/genética , Antioxidantes/farmacologia , Citocinas/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
The study aimed to investigate the alleviation of an ethanol-induced gastric ulcer in mice by apolysaccharide (PSP) from purple sweet potato (Ipomoea batatas (L.) Lam) and explore the mechanism. The anti-ulcer activity was determined by histopathological evaluation, total gastric acidity, pepsin activity, gastric ulcer index and gastric ulcer inhibition rate. The expression levels of inflammatory factors were detected using ELISA. A special protein meter was used to detect the content of immunoglobulin lgM, immunoglobulin lgG, and complements C3 and C4 in the serum of mice. The expression of CD4+/CD8+ lymphocyte subsets of mice was detected using flow cytometry. Western blot analysis was used to examine the effect of PSP on the PI3K/Akt/Rheb/mTOR pathway. The results showed that PSP could effectively reduce the total gastric acidity, pepsin activity, and the index and inhibition rate of gastric ulcers. At the same time, PSP could significantly increase the levels of immunoglobulins (lgG and lgM) and complements (C3 and C4). It could also increase the activity of peritoneal macrophages in mice and the expression of CD4+/CD8+ in the spleen. ELISA analysis showed that the contents of TNF-α, IL-1ß and IL-6 were significantly decreased and the content of IL-10 was significantly increased in the PSP group. The western blot analysis showed that PSP could upregulate the relative protein expressions of MUC5AC, PI3K, p-Akt, Rheb and mTOR. These results indicate that PSP can activate the PI3K/Akt/Rheb/mTOR signaling pathway to improve the immunity of mice and maintain the balance of the immune system, thereby protecting the gastric mucosa and improving stress gastric ulcers.
Assuntos
Ipomoea batatas , Polissacarídeos , Transdução de Sinais , Úlcera Gástrica , Animais , Humanos , Masculino , Camundongos , Antiulcerosos/farmacologia , Etanol , Ipomoea batatas/química , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/imunologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVES: This work was carried out with a view to determining the antioxidant, anti-inflammatory and anti-ulcer properties of the aqueous lyophilized extract of Markhamia lutea. METHODS: In vitro proteinases inhibition, albumin denaturation, hemolysis of red blood cells by heat, inhibition of the proton pump H+/K+ATPase, FRAP (Ferric reducing antioxidant power) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays were performed. In vivo, cold water immersion-induced ulceration and methylene blue-induced ulceration was used to determine the anti-ulcer properties of the lyophilizate (100, 200 and 300â¯mg/kg). RESULTS: In vitro, the lyophilizate (400⯵g/mL) significantly inhibited protein denaturation (66.65â¯%), hemolysis of red blood cells (56.54â¯%), proteinase activity (69.22â¯%); then the IC50 was 26.31⯵g/mL on proton pump activity. It has also developed a strong ferric reducing antioxidant power (EC50=52.96â¯mmol FeSO4/g) as well as free radicals scavenging activity (EC50=22.38⯵g/mL). In vivo, the aqueous lyophilizate (200 and 300â¯mg/kg) protected the gastric mucosa (70.68 and 79.00â¯% protection respectively) and reduced (p<0.05) acetylcholine, calcium and corticosterone concentrations. A decrease in malondialdehyde level, an increased glutathione level and an increased in catalase and SOD activities were recorded. In the methylene blue test, it significantly increased gastric fluid pH, while reducing gastric volume and improving hematological parameters in ulcer animals. In addition, the histological sections show that the aqueous lyophilizate of M. lutea protected the gastric mucosa from the deleterious effects of stress. CONCLUSIONS: The aqueous lyophilizate of M. lutea has anti-ulcer properties thanks to its anti-inflammatory, antioxidant and anti-secretory properties.
Assuntos
Anti-Inflamatórios , Antiulcerosos , Antioxidantes , Liofilização , Extratos Vegetais , Úlcera Gástrica , Antioxidantes/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antiulcerosos/farmacologia , Masculino , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Ratos Wistar , Ratos , CamundongosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Zingiberis 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 STUDY: To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. MATERIAL AND METHODS: First, 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. RESULTS: zCR/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. CONCLUSION: zCR 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.
Assuntos
Medicamentos de Ervas Chinesas , Metabolômica , Farmacologia em Rede , Ratos Sprague-Dawley , Úlcera Gástrica , Animais , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Úlcera Gástrica/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Ratos , Evodia/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Coptis chinensis , Modelos Animais de Doenças , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Citocinas/metabolismo , Citocinas/sangueRESUMO
Rebamipide contributes to the improvement of blood supply of the GI mucosa, activates its barrier function, activates alkaline secretion of the stomach, increases proliferation and metabolism of epithelial cells of the GI tract, cleanses the mucosa from hydroxyl radicals and suppresses superoxides, produced by polymorphonuclear leukocytes and neutrophils in the presence of Helicobacter pylori, protects the GI mucosa from bacterial invasion and the damaging effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the mucosa. Rebamipide, originally developed as a treatment for gastric ulcers, has attracted the attention of researchers as a potential drug for the treatment of UC due to its ability to stimulate mucus production, reduce oxidative stress, and decrease inflammation. Due to the presence of these properties, it is hypothesized that rebamipide may have a protective effect on the intestinal mucosa during prolonged inflammation, making it a promising candidate for inclusion in therapeutic strategies for ulcerative colitis. The results of this study suggest that rebamipide holds potential therapeutic benefits for the treatment of ulcerative colitis.
Assuntos
Alanina , Colite Ulcerativa , Quinolonas , Quinolonas/uso terapêutico , Quinolonas/farmacologia , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/farmacologia , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Ratos , Antiulcerosos/uso terapêutico , Antiulcerosos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Masculino , Progressão da Doença , Modelos Animais de Doenças , Ratos WistarRESUMO
Peptic ulcer, affecting 10 % of the global population, results from imbalances in gastric juice pH and diminished mucosal defences. Key underlying factors are non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection, undermining mucosal resistance. Traditional treatments like proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists exhibit drawbacks such as adverse effects, relapses, and drug interactions. This review extensively explores the ethnomedicinal, synthetic and pharmacological facets of various potential peptic ulcer treatments. Rigorous methodologies involving electronic databases, and chemical structure verification via 'PubChem' and 'SciFinder' enhance the review's credibility. The provided information, spanning medicinal insights to intricate pharmacological mechanisms, establishes a robust groundwork for future research and the development of plant-derived or synthetic molecules for peptic ulcers, offering a promising alternative to conventional therapies.
Assuntos
Úlcera Péptica , Fitoterapia , Humanos , Úlcera Péptica/tratamento farmacológico , Química Farmacêutica , Antiulcerosos/química , Antiulcerosos/farmacologia , AnimaisRESUMO
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.
Assuntos
Extratos Vegetais , Folhas de Planta , Úlcera Gástrica , Animais , Extratos Vegetais/farmacologia , Camundongos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Folhas de Planta/química , Masculino , Antiulcerosos/farmacologia , Metanol/química , Justicia/química , Modelos Animais de Doenças , Cimetidina/farmacologia , Acanthaceae/química , Indometacina , Brasil , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologiaRESUMO
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.
Assuntos
Antiulcerosos , Glicemia , Diabetes Mellitus Experimental , Hipoglicemiantes , Extratos Vegetais , Ratos Wistar , Úlcera Gástrica , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Diabetes Mellitus Experimental/tratamento farmacológico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Úlcera Gástrica/induzido quimicamente , Masculino , Ratos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Metanol/química , Teste de Tolerância a Glucose , Solventes/química , FitoterapiaRESUMO
Using duodenocolic fistula in rats, this study attempts to highlight the particular cytoprotection aspects of the healing of fistulas and therapy potential of the stable gastric pentadecapeptide BPC 157, a cytoprotection mediator (i.e. upgrading minor vessels to induce healing at both fistula's sides). Upon duodenocolic fistula creation (two 'perforated' lesions put together) (assessed at 3, 6, 9, 12, and 15 min), BPC 157, given locally at the fistula, or intragastrically (10 µg/kg, 10 ng/kg), rapidly induces vessel 'recruitment', 'running' toward the defect, simultaneously at duodenum and colon, providing numerous collaterals and branching. The mRNA expression studies done at that time provided strongly elevated (nitric oxide synthase 2) and decreased (cyclooxygenase-2, vascular endothelial growth factor A, nitric oxide synthase (NOS)-1, NOS-3, nuclear factor-kappa-B-activating protein) gene expression. As therapy, rats with duodenocolic fistulas, received BPC 157 10 µg/kg, 10 ng/kg, per-orally, in drinking water till sacrifice, or alternatively, intraperitoneally, first application at 30 min after surgery, last at 24 h before sacrifice, at day 1, 3, 7, 14, 21, and 28. Controls exhibited both defects persisting, continuous fistula leakage, diarrhea, continuous weight loss, advanced adhesion formation and intestinal obstruction. Contrary, all BPC 157-treated rats have closed both defects, duodenal and colonic, no fistula leakage (finally, maximal instilled volume corresponds to healthy rats), no cachexia, the same weight as before surgery, no diarrhea, markedly less adhesion formation and intestinal passage obstruction. Thus, BPC 157 regimens resolve the duodenal/colon lesions and duodenocolic fistulas in rats, and rapid vessels recovery appears as the essential point in the implementation of the cytoprotection concept in the fistula therapy.
Assuntos
Antiulcerosos , Fístula , Proteínas , Ratos , Animais , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular , Citoproteção , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Óxido Nítrico Sintase , Antiulcerosos/farmacologiaRESUMO
Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor ß1 (TGF-ß1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.
Assuntos
Apoptose , Inflamação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Estresse Oxidativo , Pantoprazol , Úlcera Gástrica , Animais , Estresse Oxidativo/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Ratos , Apoptose/efeitos dos fármacos , Pantoprazol/farmacologia , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Ratos Wistar , Antiulcerosos/farmacologia , Antiulcerosos/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Terapia CombinadaRESUMO
BACKGROUND: There are patents available related to fermented food and beverages which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids and exhibits antioxidant activity, which could stimulate the digestive system and be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive juices and reducing gastric acidity. OBJECTIVE: This study explored the potential of using waste peel extract from Citrus limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties of fermented and non-fermented extracts and compare them. Further, the study looked at the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and whether fermentation affected the efficacy of the treatment. METHODS: Thirty female Wistar albino rats were equally distributed into five different groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin (mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract of Mosambi peel (400 mg/kg/b.w). RESULTS: Findings explored that, compared to non-fermented citrus fruit juice, biofermented exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA levels (355.23 ± 100.70 µmol/mg protein vs. 454.49 ± 155.88 µmol/mg protein), and low ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14). CONCLUSION: The results suggest that the bio-fermented product of Citrus limetta peel has better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino rats compared to non-fermented.
Assuntos
Antiulcerosos , Citrus , Fermentação , Extratos Vegetais , Ratos Wistar , Úlcera Gástrica , Animais , Citrus/química , Feminino , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antiulcerosos/farmacologia , Antiulcerosos/química , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Patentes como Assunto , Indometacina/metabolismo , Frutas/química , Antioxidantes/farmacologia , Antioxidantes/química , Omeprazol/farmacologiaRESUMO
OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.