RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ferula sinkiangensis K.M.Shen (F. sinkiangensis) is a local medicinal material unique to Xinjiang, China, and has been used in traditional Chinese medicine, Xinjiang Uyghur medicine, and Kazakh medicine. According to the Pharmacopoeia of the People's Republic of China, it has the functions of eliminating accumulation, resolving symptoms, dispersing lumps and killing insects, and is often used in the treatment of gastrointestinal diseases. AIM OF THE STUDY: To investigate the protective effect of the aerial parts of F. sinkiangensis on acute gastric ulcer by UHPLC-Q-Orbitrap-MS/MS technology, pharmacodynamic evaluation, network pharmacology and molecular biology experiments, and to explore its pharmacodynamic material basis and potential molecular mechanism against gastric ulcers. MATERIALS AND METHODS: UHPLC/MS technology was used to identify the common compounds in F. sinkiangensis resin (EEFR) and its aerial parts (DEAF) in order to detect the similarity of their components. After 7 days of pre-administration, the mouse model of acute gastric ulcer was established. The effects of DEAF on anti gastric ulcer activity were systematically evaluated by injury index analysis, histopathological examination, and changes in cytokine levels and enzyme activities. At the same time, network pharmacology research was carried out for the identified compounds, and the core targets and pathways of DEAF anti-gastric ulcer were screened, and the combination of compounds and targets was simulated by molecular docking. Finally, Western blot was used to verify the core pathway. RESULTS: 20 identical chemical constituents, including Ferulic acid, Coumarin, Isoferulic acid and Farnesiferol A, etc. were identified in EEFR and DEAF by UHPLC/MS, and the potential active ingredients of the anti-gastric ulcer activity of DEAF was preliminarily identified. The pharmacodynamic results showed that DEAF significantly reduced the content of MDA, inhibited MPO activity, and increased SOD activity, while reducing the content of GAS, IL-6 and TNF-α and increasing the content of IL-10. This indicates that DEAF has excellent anti-gastric ulcer activity, and the anti-gastric ulcer effect of DEAF was comparable to that of EEFR. The network pharmacology analysis showed that PI3K-Akt and MAPK signaling pathway played an important role in the treatment of gastric ulcer by DEAF. Further molecular biological experiments confirmed that DEAF could inhibit the expression of p-Akt/Akt, p-JNK/JNK and Keap-1, and promote the expression of Bcl-2/Bax, Nrf2 and HO-1, revealing the potential anti gastric ulcer mechanism of DEAF. CONCLUSION: This study systematically evaluated the pharmacological effect of DEAF against gastric ulcers, preliminarily identified the potential active ingredients of DEAF against gastric ulcers, and revealed that it can exert an anti-gastric ulcer effect by regulating the PI3K-Akt/JNK/Nrf2 signaling pathway. The research results provide a theoretical basis for the anti-gastric ulcer activity of the aerial parts of F. sinkiangensis, which is conducive to the subsequent research on the aerial parts.
Assuntos
Antiulcerosos , Ferula , Extratos Vegetais , Úlcera Gástrica , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Úlcera Gástrica/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/isolamento & purificação , Camundongos , Componentes Aéreos da Planta/química , Etanol/toxicidade , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ferula/química , Fator 2 Relacionado a NF-E2/metabolismo , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Antiulcerosos/uso terapêutico , Cloreto de Metileno/química , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Modelos Animais de Doenças , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Farmacologia em RedeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hibiscus syriacus L. flower (HSF) is a well-established medicinal and dietary resource in traditional practices across China, Japan, and Korea. In Traditional Chinese Medicine, it is characterized by a sweet-bitter taste and cool nature, and is traditionally used to clear heat, promote diuresis, cool the blood and detoxify. Documented use dates back to the Ming Dynasty in China for treating gastric ailments. The custom of consuming HSF tea for gastrointestinal benefits remains common, particularly in southern China. However, the active components and mechanism of action underlying its efficacy against gastritis are not fully elucidated. AIM OF THE STUDY: This study aims to investigate the material basis and potential mechanism of gastric mucosal protective activity of HSF. MATERIALS AND METHODS: The chemical profile of HSF can be characterized using UPLC-Q Exactive-Orbitrap HRMS and phytochemical isolation techniques. The efficacy of HSF was evaluated in vivo using an ethanol-induced gastric ulcer model in rats and in vitro using ethanol-stimulated GES-1 cells. The ELISA, Hoechst 33342 staining, ROS staining, network pharmacology and molecular docking were employed for mechanistic analysis. Immunohistochemistry, qRT-PCR and western blotting analysis was used to validate the underlying mechanism of anti-gastric ulcer. RESULTS: A total of 158 compounds, primarily flavonoids, phenolic acid, benzoic acids, and cinnamic acids, were identified from HSF extracts, suggesting flavonoid glycosides as the characteristic components. Both in vivo and in vitro experiments demonstrated that HSF significantly alleviated ethanol-induced gastric mucosal damage by mitigating inflammatory responses, ameliorating oxidative stress and enhancing cell vitality. Further mechanistic studies revealed that the protective effects of HSF were mediated through the modulation of the Nrf2/HO-1, AKT, and JNK signaling pathways. CONCLUSION: This study demonstrates that Hibiscus syriacus L. flower protects against ethanol-induced gastric mucosal injury by regulating the Nrf2/HO-1, AKT, and JNK pathways. These findings provide a scientific basis for the traditional use of HSF and underscore its dual value as a dietary ingredient and a health-promoting agent.
Assuntos
Antiulcerosos , Hibiscus , Extratos Vegetais , Úlcera Gástrica , Hibiscus/química , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Etanol/toxicidade , Flores/química , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Masculino , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Antiulcerosos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/isolamento & purificação , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Linhagem Celular , Heme Oxigenase-1/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Simulação de Acoplamento Molecular , Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)RESUMO
Propyl gallate (PG) is an edible food-grade antioxidant, but its gastroprotective potential has not been extensively evaluated. This study evaluated the protective effects of PG on indomethacin-induced gastric mucosal injury in Wistar rats. Male rats were assigned to control (C), vehicle (Vehicle), PG-treated (20, 40, and 100 mg/kg; LPG, MPG, and HPG), and positive control (omeprazole, 30 mg/kg; OM). Following 7 days of pretreatment, indomethacin (100 mg/kg) was administered to all groups except group C, and the gastric tissues were collected for further analysis. PG pretreatment significantly reduced ulcer area in a dose-dependent manner (p < 0.05). PG also suppressed gastric inflammatory protein expression (NF-κB, COX-2, TNF-α, IL-6, and iNOS), restoring prostaglandin E2 (PGE2) levels, and enhanced antioxidant defenses, as evidenced by increased glutathione (GSH) levels and superoxide dismutase (SOD) activity. These findings demonstrate that PG exerts marked gastroprotective effects through combined anti-inflammatory and antioxidant mechanisms.
Assuntos
Mucosa Gástrica , Indometacina , Galato de Propila , Úlcera Gástrica , Animais , Ratos Wistar , Indometacina/efeitos adversos , Masculino , Ratos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo , Úlcera Gástrica/prevenção & controle , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Mucosa Gástrica/metabolismo , Galato de Propila/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Glutationa/metabolismo , Dinoprostona/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Antioxidantes/administração & dosagemRESUMO
BACKGROUND: Innovative treatment strategies are required for stomach ulcers because of their multifactorial nature. Nanotechnology has emerged as a promising and transformative platform for the formulation and targeted delivery of therapeutic agents. METHODS AND FINDINGS: The gastroprotective potential of both in its free form and encapsulated in calcium alginate beads was evaluated against ethanol-induced gastric ulceration in rats. Phytol-loaded nanoemulsions were incorporated into alginate beads to achieve controlled release. Alginate beads showed a pH-dependent release pattern. The release behavior showed a higher release rate at pH 6.8 than at pH 1.2. Phytol release kinetics followed the Korsmeyer-Peppas model, indicating a release mechanism governed by diffusion and polymer relaxation. Rats were pretreated with Phytol and/or nano-Phytol at 10 or 20 mg/kg doses administered one hour before ethanol exposure. Gastric ulcer was induced by administration of EtOH (1 mL/kg, p.o.) 0.5 h after NG-nitro-L-Arginine Methyl Ester (L-NAME) or Aminoguanidine (AMG) injection. Phytol treatment led to a reduction in ulcer index and severity and improved stomach gross morphology. Also, interleukin-6 (IL-6) gastric contents were reduced, whereas transforming growth factor ß (TGF-ß1) was elevated, and histopathological features were ameliorated. Western blot analysis revealed that nano-Phytol exerted greater inhibitory effects on caspase-3 and Nuclear Factor kappa B (NF-κB) than unformulated Phytol. Interestingly, Phytol's pharmacological effects on ulcers were enhanced by its nanoformulation in a dose-dependent way without exhibiting any toxicity symptoms. Confocal laser scanning microscopy (CLSM) confirmed significantly improved tissue penetration of nano-Phytol within the stomach layers compared to the Phytol. The Phytol or nano-Phytol gastroprotective effects were modified via the co-administration of L-NAME and AMG. CONCLUSIONS: The nano-Phytol formulation significantly enhanced the gastroprotective effect of Phytol against ethanol-induced gastric ulcers, primarily through modulation of the nitric oxide (NO) synthase pathway, suppression of inflammation, and upregulation of the growth factor TGF-ß1.
Assuntos
Alginatos , Hidrogéis , Óxido Nítrico Sintase , Úlcera Gástrica , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , NF-kappa B/metabolismo , Alginatos/química , Etanol/efeitos adversos , Ratos , Masculino , Interleucina-6/metabolismo , Emulsões/química , Fator de Crescimento Transformador beta/metabolismo , Óxido Nítrico Sintase/metabolismo , Hidrogéis/química , Nanopartículas/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gastric ulcer (GU) is a prevalent gastrointestinal disease. Codonopsis Radix (CR), including three species of Codonopsis pilosula (Franch.) Nannf. (CP), C. pilosula Nannf. var. modesta (Nannf.) L. T. Shen (CPM) and C. tangshen Oliv. (CT), is a traditional Chinese herb widely used to enhance the function of the spleen and regulate the gastrointestinal tract, which is effective in treating GU. Nevertheless, the pharmacodynamic material basis and underline mechanism of CR for the gastroprotection remains unknown. AIM OF THE STUDY: This study aims to explore the gastroprotective efficacy and potential mechanistic of different species and fractions from CR on ethanol-induced rat GU model, and to clarify the active substances that expressed pharmacological effects based on spectrum-effect relationship study. MATERIALS AND METHODS: Ethanol extracts from three different species of CR and different fractions from extract of CPM were administered orally to rats once daily with dosage of 3, 9, 18 g/kg for 7 days prior to the ethanol-induced GU model being established. After modeling, samples were taken for histopathological and biochemical analysis to elucidate the mechanism. In addition, grey relational analysis (GRA) was utilized to establish the relationship between pharmacodynamic indices and chromatographic patterns. And then, the anti-GU effects of underline active ingredients tangshenoside I (TSI) and lobetyolin (LBT) were further validated. RESULT: Pretreatment with the different species and fractions of CR could effectively improve gastric damage and reduce ulcer index in rats, with CPM showing the best efficacy. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced while the malondialdehyde (MDA) level was decreased, suggesting antioxidant effects. Additionally, they demonstrated anti-inflammatory properties by regulating the concentrations of inflammatory markers such as interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and nitric oxide (NO). Furthermore, the results of the spectrum-effect relationship and pharmacodynamic validation showed that TSI and LBT could be considered as the main components of CR for treating GU. CONCLUSION: CR has a good effect on preventing GU. TSI and LBT are potentially active compounds in the gastroprotective effects of CR. Altogether, they exert the anti-GU effect through anti-inflammatory and antioxidant pathways.
Assuntos
Antiulcerosos , Codonopsis , Medicamentos de Ervas Chinesas , Úlcera Gástrica , Animais , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Codonopsis/química , Masculino , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Antiulcerosos/uso terapêutico , Ratos , Ratos Sprague-Dawley , Etanol , Medicamentos de Ervas Chinesas/farmacologia , Extratos Vegetais/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Modelos Animais de DoençasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gastric ulcer (GU) is a significant public health challenge that impacts millions globally. Palm tree species (family Arecaceae) have been traditionally adopted for inflammatory and gastrointestinal conditions, among which Aiphanes eggersii Burret remains under exploration. AIM OF THE STUDY: For the first time, the phenolic profile of defatted aqueous ethanol extract (DAEE) of the palm tree Aiphanes eggersii Burret was carried out, in addition to the anti-ulcer potential of DAEE in an ethanol-induced gastric ulcer (GU) model in rats was assessed. MATERIALS AND METHODS: The chemical composition was determined using HPLC/MS, chromatographic, and spectroscopic techniques. Rats were pretreated with DAEE (200, 400, and 800 mg/kg) or sucralfate (100 mg/kg) for 14 days before the induction of GU with a single dose of ethanol (5 mL/kg). Gastric tissues were evaluated macroscopically, biochemically, and histologically. RESULTS: Seven phenolics were isolated, viz, vicenin II (1), rutin (2), quercitrin (3), kaempferin (4), cirsimaritin (5), quercetin (6), and caffeic acid (7). In addition, fifty-one metabolites belonging to various classes were tentatively identified using HPLC/MS. The DAEE significantly declined the ulcer index and improved the gastric protection dose independently. It enhanced the antioxidant effect via decreasing MDA and increasing GSH, SOD, and CAT. It suppressed pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, as well as the NF-κB/p65 pathway. Moreover, it upregulated HO-1/Nrf2 signaling, restored PGE2 levels, and decreased the levels of COX-1 and COX-2. Histological findings confirmed mucosal protection and healing. CONCLUSION: The phenolic-rich extract of A. eggersii Burret exhibits potent gastroprotective activity, supporting its potential as a natural therapeutic for GU management, while clinical investigation is needed.
Assuntos
Antiulcerosos , Extratos Vegetais , Úlcera Gástrica , Animais , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Antiulcerosos/uso terapêutico , Antiulcerosos/química , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Úlcera Gástrica/metabolismo , Úlcera Gástrica/prevenção & controle , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/isolamento & purificação , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Componentes Aéreos da Planta/química , Masculino , Etanol , Heme Oxigenase (Desciclizante)/metabolismo , Ratos Wistar , Fenóis/farmacologia , Proteínas de Membrana/metabolismo , Ratos Sprague-Dawley , Modelos Animais de DoençasRESUMO
BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal disease linked to the consumption of non-steroidal anti-inflammatory drugs (NSAIDs), with traditional therapies often causing several adverse effects and drug interactions. AIM: The primary aim of this study was to assess the protective effects of nifuroxazide at three different doses against indomethacin-induced GU. METHODS: Rats were pretreated orally once daily for 14 days with either nifuroxazide (10, 20, or 40 mg/kg) or famotidine (25 mg/kg), the standard reference drug. After 24 h of fasting, a single oral dose of 50 mg/kg indomethacin was used to induce GU. Six hours later, rats were anesthetized using ketamine. RESULTS: Nifuroxazide dose-dependently mitigated the rise in ulcer index, retained gastric mucin content, and alleviated histopathological changes. These gastroprotective effects were due to the attenuation of oxidative stress, evidenced by reduced malondialdehyde (MDA) levels and increased levels of reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Furthermore, nifuroxazide lessened gastric mucosal inflammation by lowering gastric high mobility group box 1 protein (HMGB1), nuclear factor kappa B p65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), and signal transducer and activator of transcription 3 (STAT3) levels, toll-like receptor 4 (TLR4) and interleukin-1 beta (IL-1ß) expressions, as well as serum levels of C-reactive protein (CRP). In addition, nifuroxazide mitigated apoptosis by inhibiting immunohistochemical expression of caspase-3. CONCLUSIONS: Nifuroxazide has the potential to be repurposed as a novel gastroprotective therapy that restores gastric mucosal barrier integrity via the mitigation of gastric oxidative stress, inflammation, and apoptosis.
Assuntos
Hidroxibenzoatos , Nitrofuranos , Úlcera Gástrica , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/prevenção & controle , Ratos , Fator 2 Relacionado a NF-E2/metabolismo , Indometacina/farmacologia , Masculino , Proteína HMGB1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Nitrofuranos/farmacologia , Nitrofuranos/administração & dosagem , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/administração & dosagem , Caspase 3/metabolismo , Fator de Transcrição RelA/metabolismo , Anti-Inflamatórios não Esteroides , Ratos Sprague-Dawley , Relação Dose-Resposta a Droga , Heme Oxigenase (Desciclizante)/metabolismo , Antiulcerosos/farmacologia , Heme Oxigenase-1/metabolismoRESUMO
BACKGROUND: Peptic ulcers, particularly gastric ulcers (GUs), are multifactorial disorders with unclear mechanisms. Black garlic (BG) has shown gastroprotective effects. This study evaluated the effects of BG and epigallocatechin gallate-impregnated BG (EG) in acidic ethanol (AE)-induced GU model mice. Mice were pretreated with BG or EG (50-200 mg/kg) for 7 days before ulcer induction. Oral acute toxicity evaluations for BG and EG were also conducted. RESULTS: Oral acute toxicity evaluations showed elevated serum renal function indices at 5 g/kg of BG and 10 g/kg of EG but without histopathological liver or kidney damage. Both BG and EG pretreatments reduced ulcer indices, with EG offering stronger and significant protection. EG pretreatments also showed higher gastric mucosal accumulations. They significantly decreased AE-induced malondialdehyde levels and restored glutathione, superoxide dismutase, and catalase. AE-induced serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), as well as gastric transcript levels of TNF-α, IL-6, IL-1ß, cyclooxygenase-2, inducible nitric oxide synthase, and myeloperoxidase, were suppressed. EG further reduced AE-induced phosphorylations of extracellular signal-regulated kinase, c-jun-N-terminal kinase, p38, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inhibitor of κB. CONCLUSION: EG2 showed stronger gastroprotective activity than BG by modulating oxidative stress, inflammatory response, and mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways. This study supports the application of EG as a value-added functional food ingredient for GU prevention. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assuntos
Antiulcerosos , Catequina , Alho , Extratos Vegetais , Úlcera Gástrica , Animais , Catequina/análogos & derivados , Catequina/administração & dosagem , Catequina/química , Alho/química , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Camundongos , Etanol/efeitos adversos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Modelos Animais de Doenças , NF-kappa B/genética , NF-kappa B/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Antiulcerosos/administração & dosagem , Interleucina-6/genética , Interleucina-6/metabolismo , Glutationa/metabolismo , Catalase/metabolismo , Catalase/genética , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Estresse Oxidativo/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
Wenweishu (WWS), a traditional gastritis formula, was studied to elucidate its mechanisms in preventing water immersion restraint stress-induced gastric ulcers (GU) in rats. The degree of gastric tissue damage was assessed in experimental rats based on the gastric mucosal ulcer index and pathological observation. The antioxidant properties of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were detected in gastric tissues, along with expression levels of inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6. The core components, primary targets, and putative mechanisms of WWS were predicted using network pharmacology and molecular docking and validated via immunohistochemistry and immunoblotting analyses. WWS reduced the ulcer index, increased SOD and GSH-px, and decreased IL-1ß, IL-6, TNF-α, and MDA levels. A total of 126 WWS components were identified and associated with 4920 GU-associated targets via network pharmacological analysis. Data from Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed associations of the core targets with multiple pathways, in particular, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Molecular docking analysis confirmed significant docking activity of the main bioactive components with the core targets tumor protein (TP53) and protein kinase Bα (AKT1). Immunohistochemistry and Western blot analyses showed that WWS markedly suppressed phosphorylation levels of Akt and PI3K proteins in gastric tissues. WWS exerts a protective effect on the gastric mucosa by inhibiting the PI3K/Akt pathway, attenuating inflammatory factors and oxidative damage. The collective findings provide a scientific basis for the application of WWS in the management of GU.
Assuntos
Antiulcerosos , Medicamentos de Ervas Chinesas , Proteínas Proto-Oncogênicas c-akt , Úlcera Gástrica , Estresse Psicológico , Animais , Úlcera Gástrica/etiologia , Úlcera Gástrica/metabolismo , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos Sprague-Dawley , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ratos , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Estresse Psicológico/complicações , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antioxidantes/farmacologiaRESUMO
PURPOSE: To evaluate proteins from Plumeria pudica latex (LPPp) for their protective effect against ethanol-induced gastric injury in mice. METHODS: The LPPp fraction was obtained by collecting P. pudica latex in tubes containing distilled water, followed by centrifugation and dialysis. The female Swiss mice (Mus musculus) received saline or LPPp (40 mg/kg) intraperitoneally 1 hour before oral administration of 500 µL of 50% ethanol. One hour later, the animals were euthanized, and their stomachs were removed for evaluation of tissue lesion area, histopathological analysis, and measurements of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and nitrate/nitrite (NO3/NO2). An independent experiment assessed the effect of LPPp on gastric mucus production. RESULTS: The LPPp-treated animals showed a significant reduction in the mean injured areas of gastric tissue (0.73 ± 1.01 mm2) compared to the ethanol group (37.99 ± 3.11 mm2). Histopathological analysis revealed significant preservation of tissue architecture in the LPPp group compared to ethanol group. Additionally, LPPp maintained tissue levels of MDA, GSH, SOD, and NO3/NO2 comparable to the saline group and influenced gastric mucus production favorably (p < 0.05). CONCLUSION: These results suggested that LPPp has a protective effect against ethanol-induced gastric lesions, likely involving antioxidant activity and increased gastric mucus production.
Assuntos
Apocynaceae , Etanol , Látex , Extratos Vegetais , Proteínas de Plantas , Úlcera Gástrica , Animais , Etanol/toxicidade , Camundongos , Feminino , Látex/farmacologia , Látex/química , Malondialdeído/análise , Glutationa/análise , Superóxido Dismutase/análise , Apocynaceae/química , Extratos Vegetais/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Proteínas de Plantas/farmacologia , Proteínas de Plantas/uso terapêutico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Modelos Animais de Doenças , Antioxidantes/farmacologiaRESUMO
The pectic polysaccharide WGPP-1a (46.8 kDa) has been obtained from wax gourd peel (WGP) which is a popular soup ingredient and Chinese herbal medicines in China. Monosaccharide composition, methylation analysis, FT-IR and NMR demonstrate that WGPP-1a is composed of rhamnogalacturonan I (RG-I) and homogalacturonan (HG) domains with mass ratios of 4:1. The RG-I domains contain a highly branched structure that is substituted primarily with ß-D-1,4-galactan, α-L-1,5-arabinan and ß-D-1,4-glucan. In ethanol-induced gastric ulcer mice, WGPP-1a reduced ulcer area, restored mucosal glycoproteins. In vitro, WGPP-1a enhanced GES-1 cell viability and reduced apoptosis. Untargeted LC-MS metabolomics of murine gastric tissues revealed 322 differential metabolites (163 upregulated, 159 downregulated) between Model and control groups, with WGPP-1a treatment restoring 120 metabolites (53 upregulated, 67 downregulated). PCA and OPLS-DA demonstrated WGPP-1a's reversal of ethanol-induced perturbations. KEGG pathway enrichment identified eight core pathways modulated by WGPP-1a, including PI3K/AKT signaling, Linoleic acid metabolism, and mTOR/FoxO pathways. Notably, Mechanistically, WGPP-1a activated the PI3K/AKT pathway, elevating Bcl-2/Bax ratios and suppressing the expression levels of pro-apoptotic proteins Bax and Caspase3. These results suggest that WGPP-1a may be an effective agent for protecting against alcoholic gastric ulcers and provides a new perspective for the resource utilization of WGP.
Assuntos
Cucurbitaceae , Pectinas , Extratos Vegetais , Úlcera Gástrica , Animais , Masculino , Camundongos , Cucurbitaceae/química , Etanol , Pectinas/química , Pectinas/isolamento & purificação , Pectinas/farmacologia , Pectinas/uso terapêutico , Pectinas/ultraestrutura , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/prevenção & controle , Humanos , Linhagem Celular , Animais não EndogâmicosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, Cordia africana Lam. roots, have been used in the treatment of gastro-intestinal complaints and the management of peptic ulcer diseases. AIM OF THE STUDY: Quantitative determination of Cordia africana Lam. roots constituents was performed to investigate their phytochemical composition and their anti-ulcer mechanism. MATERIALS AND METHODS: Cordia africana Lam. roots were subjected to extraction and fractionation. Antimicrobial activities of the extract and its factions were tested against Helicobacter pylori, and minimum inhibitory concentration (MIC) was measured. Then, an in vivo ethanol-induced model in rats was performed (at two tested doses: 200 mg/kg, 400 mg/kg, and pantoprazol 10 mg/kg against ethanol 5 mL/kg by oral gavage) with subsequent histopathological analysis. Oxidative and gastric inflammatory markers were measured. The phytochemical profile was confirmed using quantitative High-performance liquid chromatography (HPLC). Finally, molecular docking was performed to investigate the binding mode among the most abundant quantified compounds, viz., kaempferol, myricetin, naringenin, quercetin, and rosmarinic acid and three chosen proteins. RESULTS: Among the tested fractions, Cordia africana ethyl acetate fraction (CAEt) gave the least MIC (7.82 µg/mL). Besides, at its high dose (400 mg/kg; orally), CAEt significantly reduced the ulcer number and severity by 26 % each, lowered malondialdehyde by 39 %, and increased glutathione and prostaglandin E2 levels by 92 % and 27 %, respectively, compared to pantoprazol. It exhibited similar potency to pantoprazol in decreasing tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant-1, while it significantly decreased nuclear factor-kappa B more than pantoprazol by 7 %. Nineteen compounds were quantified using HPLC, showing that phenolic compounds and flavonoids were the most abundant phytoconstituents. In-silico molecular docking screening revealed the interaction between the five most quantified compounds and nuclear factor kappa B, prostaglandin E2, and tumor necrosis factor alpha proteins. CONCLUSION: CAEt possesses potent gastroprotective properties via the reduction of gastric ulcer severity, decreasing oxidative stress, and inflammatory markers in ethanol-induced stomach damage. CAEt could be a promising candidate for gastric ulcer treatment and further studies on gastric-related diseases.
Assuntos
Antiulcerosos , Infecções por Helicobacter , Helicobacter pylori , Extratos Vegetais , Úlcera Gástrica , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/química , Etanol/toxicidade , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antiulcerosos/isolamento & purificação , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/microbiologia , Helicobacter pylori/efeitos dos fármacos , Raízes de Plantas/química , Masculino , Acetatos/química , Ratos , Simulação de Acoplamento Molecular , Ratos Wistar , Infecções por Helicobacter/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismoRESUMO
We investigated the safety of Parkia pendula exudate polysaccharide (PePp) for acute toxicity and its gastroprotective effect on ethanol-induced gastric ulcers. In the acute toxicity test, animals were treated with a single dose of PePp (2000 mg/kg body weight) and evaluated for behavioral parameters, morbidity and mortality; also biochemical, hematological, and histopathological analysis. The mice were pretreated with a single dose of PePp (10, 25, 50 mg/kg) or ranitidine (80 mg/kg) before gastric ulcer induction with ethanol (99.9 %, orally). Subsequently, the stomachs were analyzed for macroscopic and histopathological parameters and the activity of catalase (CAT), superoxide dismutase (SOD), lipid peroxidation, and cytokines IL-6, TNF-α and IL-10. PePp did not cause any changes in acute toxicity parameters. Pretreatment with PePp inhibited the formation of gastric ulcers by 52 %, 71 %, and 83 % at doses of 10, 25 and 50 mg/kg, respectively. Macroscopic improvements and treating gastric tissue exudative inflammatory infiltrate reduction were dose-dependent on PePp. In gastric tissue, PePp presented antioxidative effects, evidenced by increasing CAT and SOD activities and reducing lipid peroxidation; it also showed anti-inflammatory effects, evidenced by reduced IL-6 and TNF-α levels and elevated IL-10 levels. PePp is toxicologically safe and has a gastroprotective effect on ethanol-induced gastric ulcers.
Assuntos
Etanol , Polissacarídeos , Úlcera Gástrica , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Úlcera Gástrica/tratamento farmacológico , Etanol/efeitos adversos , Interleucina-6/metabolismo , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Camundongos , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Masculino , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gastric ulcer (GU) is a common multifactorial gastrointestinal disorder, affecting millions of people worldwide. Mu Jin Powder (MJP), a renowned herbal pair, was recorded in Yizong Jinjian by Wu Qian during the Qing dynasty. This combination has been integrated into traditional Chinese medicine (TCM) prescriptions for gastrointestinal diseases, particularly GU, and has demonstrated significant results in modern medicine studies. However, the specific advantages of MJP for GU and its underlying mechanisms remain insufficiently understood, requiring further investigation. AIM OF THE STUDY: To assess the preventive effects of MJP on ethanol-induced gastric mucosal injury and elucidate its underlying mechanisms. MATERIALS AND METHODS: This study was based on ethanol induced SD rat model to elucidate the pharmacological effects of MJP. The chemical components of MJP and the absorbed components in the serum of treated rats were identified by UPLC-Q-TOF-MS. Serum metabolomics and Network pharmacology were applied to investigate the potential mechanisms of MJP against GU, and the mechanistic pathways were verified through PCR and Western blot analyses. RESULTS: In vivo pharmacological experiments demonstrated that MJP significantly reduced ulcer area and improved the histopathological features of gastric tissues. Fifty-three chemical components were determined in MJP, and 18 absorbed components were detected in the serum of treated rats for the first time. Non-targeted serum metabolomics revealed 28 significantly altered differential metabolites, most of which were modulated and normalized by MJP. Comprehensive network pharmacology and metabolomics analyses indicated that MJP exerted anti-GU effects by intervening in 5 key target proteins (PTG2, CHRNA7, CA1, PTG1, CASP3, and AKT1) and regulating differential metabolites. PCR and Western blot analyses suggested that MJP may inhibit the PI3K/Akt/NF-κB pathway to prevent ethanol-induced gastric ulcers. CONCLUSIONS: Mu Jin Powder effectively ameliorates ethanol-induced gastric ulcers in rats, potentially by inhibiting the PI3K/Akt/NF-κB pathway.
Assuntos
Curcuma , Medicamentos de Ervas Chinesas , Saussurea , Úlcera Gástrica , Masculino , Animais , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/sangue , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle , Farmacologia em Rede , Etanol/efeitos adversos , Depressores do Sistema Nervoso Central/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Avaliação Pré-Clínica de Medicamentos , Curcuma/química , Saussurea/química , Fitoterapia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Estresse Oxidativo/efeitos dos fármacos , Inflamação/prevenção & controle , Estômago/metabolismo , Proteína X Associada a bcl-2/metabolismo , Caspase 3/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismoRESUMO
Rhamnetin is a naturally occurring flavonoid compound found in many wild plant species and indigenous fruits. Despite its numerous biological potentials, such as anti-inflammatory, antioxidant and antimicrobial effects, there is a lack of literature elucidating its gastroprotective action and anticipating molecular mechanism. Natural products can be a good alternative to overcome the side effects and relapses associated with anti-ulcer drugs. This study aims to elucidate rhamnetin's acute toxicity and gastroprotective effects using the indomethacin ulceration model. Animals were arbitrarily divided into five groups: a negative control group (A) and a positive control group (B), both treated with 1% carboxymethyl cellulose; a reference group (C) receiving 20 mg/kg omeprazole; and low-dose (D) and high-dose (E) rhamnetin groups receiving 30 and 60 mg/kg, respectively. After 1 h, rats in Groups B-E were subjected to indomethacin-induced ulceration. Toxicity evaluations indicated the safety of rhamnetin at doses of up to 400 mg/kg in rats, without any noticeable physiological alterations. Rhamnetin (30 and 60 mg/kg) administered orally 1 h before indomethacin-induced gastric ulcer ameliorated the stomach lesions and lowered the ulcer index area by 73.81% and 77.87%, respectively. Rhamnetin supplementation ameliorated histopathological alterations and restored gastric barriers, including gastric pH and mucin secretion. Moreover, rhamnetin-treated rats exhibited increased anti-apoptotic heat shock protein 70 and decreased Bax protein in stomach tissues. These findings were in line with lowered accumulated MDA, increased superoxide dismutase, catalase and prostaglandin E2 levels, reduced serum inflammatory mediators (TNF-α and interleukin-6) and elevated interleukin-10 cytokines. The outcomes indicate rhamnetin's cicatrising and gastroprotective effects against indomethacin-mediated ulceration, possibly due to its modulatory actions on oxidative stress, inflammation and apoptotic pathways.
Assuntos
Proteínas de Choque Térmico HSP70 , Indometacina , Quercetina , Úlcera Gástrica , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Indometacina/efeitos adversos , Ratos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Masculino , Proteína X Associada a bcl-2/metabolismo , Quercetina/farmacologia , Quercetina/análogos & derivados , Quercetina/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Malondialdeído/metabolismo , Interleucina-10/metabolismo , Ratos WistarRESUMO
In order to evaluate anti-inflammatory role of eucalyptol (100, 200, and 400 mg/kg orally), inflammation was induced in rats using 0.1 ml of histamine and 0.1 ml of formaldehyde. Furthermore, in vivo gastroprotective potential of eucalyptol (100, 200 and 400 mg/kg) was determined via the intraperitoneal injection of 25 mg/kg indomethacin as an ulcerative agent and omeprazole (30 mg/kg) orally as a standard. Estimation of biochemical (PGE2, ICAM-1, COX-I, COX-II, eNOS and 5-LOX) and oxidative stress (SOD, CAT, GSH, and MDA) markers were carried out in gastric tissues using ELISA. The morphological and histopathological features of the gastric tissues were studied. In vitro, eucalyptol stabilized red blood cell membranes and inhibited protein denaturation, with the maximum effect observed at a concentration of 6400 µg/mL. Eucalyptol significantly reduced rat paw edema in histamine- and formaldehyde-induced inflammation models. It increased gastric PGE2, COX-I and eNOS levels, and decreased COX-II, 5-LOX and ICAM-1. Eucalyptol reduced ulcer indices and improved histopathological changes. Eucalyptol also increased antioxidants levels with decreased MDA levels in isolated rat stomach tissues. Therefore, eucalyptol shows gastroprotective effects against histamine- and formaldehyde induced inflammation and indomethacin-induced gastric ulcers through the modulation of the COX/LOX, ICAM-1, eNOS pathways and oxidative stress biomarkers.
Assuntos
Eucaliptol , Indometacina , Molécula 1 de Adesão Intercelular , Óxido Nítrico Sintase Tipo III , Úlcera Gástrica , Animais , Indometacina/toxicidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/tratamento farmacológico , Eucaliptol/farmacologia , Ratos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Ratos Wistar , Estresse Oxidativo/efeitos dos fármacos , Lipoxigenase/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Dinoprostona/metabolismoRESUMO
Filipendula palmata (Pall) Maxim, is a wild edible herb in Northeast China. However, little is known about its constituents and bioactivities. In this study, the gastroprotective effect of the n-butanol fraction of F. palmata in mice induced by ethanol was investigated. The chemical research was performed using multiple chromatographic approaches. In addition, the active component and mechanism of action were researched. The results showed that F. palmata significantly alleviated ulcer damage in mice, prevented gastric mucosa from the lesion induced by absolute ethanol, increased superoxide dismutase and catalase levels, and decreased malondialdehyde content. Further study revealed that F. palmata downregulated the production of TNF-α and IL-6 in serum and the expression in LPS-induced RAW 264.7 cells. The chemical study led to the isolation of thirteen compounds, one of which exhibited significant anti-inflammatory activities by facilitating the polarization of macrophages. Our work revealed that F. palmata possessed gastroprotective efficacy, and anti-inflammation and antioxidation were involved in the mechanisms. The main components in the n-butanol fraction of F. palmata, flavonoids, having an anti-inflammatory effect in RAW 264.7 cells, might be related to the antiulcer activity.
Assuntos
Antiulcerosos , Filipendula , Extratos Vegetais , Úlcera Gástrica , Animais , Camundongos , Células RAW 264.7 , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Antiulcerosos/farmacologia , Antiulcerosos/química , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Filipendula/química , Masculino , Interleucina-6/sangue , Interleucina-6/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Etanol , Antioxidantes/farmacologia , Superóxido Dismutase/metabolismo , Flavonoides/farmacologia , Flavonoides/análise , Macrófagos/efeitos dos fármacos , Malondialdeído/metabolismo , Catalase/metabolismoRESUMO
The present study aimed to unveil the gastroprotective potential of Vaccinium macrocarpon (VM) extract and its mechanism of action against indomethacin (INDO)-induced gastric ulcers in rats. To achieve this goal, rats were pretreated with either omeprazole (20 mg/kg) or VM (100 mg/kg) orally for 14 consecutive days. Gastric tissue samples were collected and various parameters were evaluated to understand the mechanism of VM's action, including the levels of superoxide dismutase, malondialdehyde, glutathione, CAT and transforming growth factor beta (TGF-ß), as well as the mRNA expression levels of tumour necrosis factor alpha, interleukin 1 beta, nuclear factor kappa B (NF-κB) and inhibitor kappa B (IκB). Additionally, the immunopositivity of cyclooxygenase (COX)-1, COX-2, PGE2, proliferating cell nuclear antigen (PCNA) and caspase-3 was assessed. The total amount of phenolic compounds present in the VM extract was high (58.08 µg/mL gallic acid equivalent/mg extract). The healing effect of VM was demonstrated by an increase in the expression of PCNA. Furthermore, the level of TGF-ß was found to increase upon treatment with VM. Analyses of COX-1, COX-2 and PGE2 expression in gastric tissue confirmed the gastroprotective effect of VM. Notably, the expression of NF-κB was markedly reduced, whereas that of IκB was substantially increased. Overall, the findings of this study demonstrate that VM extract has gastroprotective and curative effects against INDO-induced ulcers through its antioxidant, anti-inflammatory, mucosal regenerative and anti-apoptotic activities. Therefore, VM may serve as a useful adjuvant treatment for nonsteroidal anti-inflammatory drugs-induced gastric ulcer disease.
Assuntos
Anti-Inflamatórios , Antioxidantes , Apoptose , Indometacina , Extratos Vegetais , Úlcera Gástrica , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/veterinária , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Ratos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Masculino , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Antiulcerosos/farmacologia , Antiulcerosos/administração & dosagem , Ratos Sprague-Dawley , Ratos WistarRESUMO
Gastric ulcers (GUs) are superficial diffuse lesions of the gastric mucosa that are characterised by being vulnerable to infection, difficult to cure and liable to recur. Bletilla ochracea Schltr. (BO) has the effects of astringent hemostasis, muscle growth and pain relief. We examined the effects of BO on acute GUs and their potential mechanisms from the perspectives of inflammation, oxidative stress and gut microbiota. Results indicated that BO alleviated pathological injury to the gastric mucosa and markedly alleviated oxidative stress and inflammation. In addition, BO significantly upregulated the levels of Nrf2, HO-1, NQO1 protein, and downregulated the levels of NF-κB p65, TLR4 protein. Moreover, BO significantly increased promoting the nuclear transfer of Nrf2 and markedly reduced the nuclear translocation of NF-κB p65. Furthermore, BO effectively modulated gut microbiota by increasing the diversity of species and relative abundance. Our study provided evidence that BO alleviated ethanol-induced acute GUs by activating the Nrf2/HO-1 and inhibiting the NF-κB p65/TLR4 signalling pathway, regulating dysbiosis of gut microbiota.
Assuntos
Microbioma Gastrointestinal , Estresse Oxidativo , Úlcera Gástrica , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Etanol/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Masculino , Receptor 4 Toll-Like/metabolismo , Camundongos , Inflamação/tratamento farmacológico , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Heme Oxigenase-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismoRESUMO
The ethanol-induced BALB/c mice and human gastric epithelial cell (Ges-1 cell) models were used to investigate the Sargassum siliquastrum fucoidan (SFuc) gastroprotective capability. The injury score and histopathological sections of the stomach were used to evaluate the gastroprotective capability. The western blotting and RT-PCR methods determined the signaling mechanism of mice's gastric injury. SFuc is fucoidan with a molecular weight of 300.7 and 25.1 kDa. The injury score and ulcer index of the SFuc-200 group decreased by 3.85 and 2.06 folds in contrast with the Model group, respectively. The findings indicated that SFuc reduced oxidative stress and inflammatory factor expression in the gastric mucosa by downregulating the levels of associated genes within the TLR-4, MyD88, and MAPK/NF-κB signaling pathways. Meanwhile, the SFuc-200 group promoted the expressions of EGF and PGE 2 by 1.53 and 1.52 folds, respectively. Together with the expression inhibition of p38, ERK, JNK, and NF-κB proteins in gastric tissue to help for differentiation of gastric cells. In addition, SFuc significantly reduced apoptosis occurrence in mice and Ges-1 cells. Our study provides potential mechanism clues of the SFuc's resistance to ethanol-induced gastric mucosal damage, suggesting its potential functional food for gastric protection.