RESUMEN
The present study aimed to investigate the protective effects and molecular mechanisms of Dendrobium officinale polysaccharides on gastric mucosal injuries. Following one week of continuous intragastric administration, a gastric mucosal injury model was established using intragastric administration of anhydrous ethanol. The area of gastric ulcer was measured, the contents of interleukin- 6 (IL-6), epidermal growth factor receptor (EGFR), and thyroid transcription factor 1 (TFF-1) in serum were detected by enzyme linked immunosorbent assay (ELISA), and the expressions of EGFR, TFF-1, IL-6, Raf-2, MAP kinase kinase 1 (MEK1), MEK2, and ERK1 in the gastric tissue were determined utilizing qPCR, Western blotting and immunohistochemistry. Simultaneously, Dendrobium officinale polysaccharides and anhydrous ethanol were added to the gastric mucosal cells (GES1) cultured in vitro, and the protective effects of Dendrobium officinale polysaccharides on cell viability was detected using Cell Counting Kit (CCK)-8. The addition of Dendrobium officinale polysaccharides markedly improved the gastric epithelial defect, inflammatory cell infiltration, and redness and swelling stemmed from gastric mucosal injuries and greatly reduced the area of gastric ulcer. The inhibition rates of gastric ulcer were 48.12 ± 2.98, 42.95 ± 1.52, and 27.96 ± 2.05% in the high, medium, and low concentration Dendrobium officinale polysaccharide groups, respectively. Dendrobium officinale polysaccharides could increase the expressions of EGFR and TFF-1 and decrease the expressions of IL-6, Raf-2, MEK1, MEK2, and ERK1. Dendrobium officinale polysaccharides could reduce the level of inflammatory factors and protect gastric mucosa by inhibiting the expression of MAPK pathway genes and proteins.
Asunto(s)
Antiinflamatorios/administración & dosificación , Dendrobium/química , Etanol/efectos adversos , Mucosa Gástrica/citología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Polisacáridos/administración & dosificación , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Línea Celular , Supervivencia Celular , Modelos Animales de Enfermedad , Mucosa Gástrica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Genes erbB-1/efectos de los fármacos , Humanos , Interleucina-6/metabolismo , Masculino , Extractos Vegetales , Polisacáridos/farmacología , Ratas , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Factor Trefoil-1/efectos de los fármacos , Factor Trefoil-1/metabolismoRESUMEN
In Cameroon, local plants are traditionally used as remedies for a variety of ailments. In this regard, several papers report health benefits of Cameroonian spices, which include antioxidant and anti-microbial properties, whereas gastric anti-inflammatory activities have never been previously considered. The present study investigates the antioxidant and anti-inflammatory activities of hydro-alcoholic extracts of eleven Cameroonian spices in gastric epithelial cells (AGS and GES-1 cells). The extracts showed antioxidant properties in a cell-free system and reduced H2O2-induced ROS generation in gastric epithelial cells. After preliminary screening on TNFα-induced NF-κB driven transcription, six extracts from Xylopia parviflora, Xylopia aethiopica, Tetrapleura tetraptera, Dichrostachys glomerata, Aframomum melegueta, and Aframomum citratum were selected for further studies focusing on the anti-inflammatory activity. The extracts reduced the expression of some NF-κB-dependent pro-inflammatory mediators strictly involved in the gastric inflammatory process, such as IL-8, IL-6, and enzymes such as PTGS2 (COX-2), without affecting PTGS1 (COX-1). In conclusion, the selected extracts decreased pro-inflammatory markers by inhibiting the NF-κB signaling in gastric cells, justifying, in part, the traditional use of these spices. Other molecular mechanisms cannot be excluded, and further studies are needed to better clarify their biological activities at the gastric level.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Células Epiteliales/efectos de los fármacos , Extractos Vegetales/farmacología , Especias/análisis , Camerún , Mucosa Gástrica/citología , Humanos , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Estragole is an aromatic organic compound belonging to the class of phenylpropanoids derived from cinnamic aldehydes and present in essential oils of plant species, such asRavensara anisata (madeira), Ocimum basilicum (manjericão/alfavaca) and Croton zehntneri (canelinha). Pharmacological studies report its anti-inflammatory, antioxidant and vasorelaxant activity. HYPOTHESIS/PURPOSE: This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity and the related mechanisms of action. METHODS: Acute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, piroxicam and pylorus ligation-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were using the ethanol-gastric lesions protocol. RESULTS: In the acute oral toxicity assay, doses of 300 or 2000 mg/kg of estragole administered orally in Swiss mice did not induce any behavioral changes. However, the dose of 2000 mg/kg showed a decrease in water and feed intake. Lethal dose 50 % (LD50) was set to be equal to or greater than 2500 mg/kg, according to OECD. In all evaluated protocols, estragole (31.25, 62.5, 125 and 250 mg/kg) significantly reduced the area of ââulcerative lesion when compared to control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotectant, antioxidant and immunoregulatory effects were evaluated. Results showed that treatment with estragole (250 mg/kg) reduced (p < 0.05) the volume of the gastric juice. Besides, sulfhydryl groups, nitric oxide, mucus and prostaglandins seems to be involved in the gastroprotective property. Treatment also increased (p < 0.001) levels of reduced glutathione (GSH), interleukin-10 (IL-10) and positive cells marked for glutathione peroxidase (GPx) and cyclooxygenase 2 (COX-2). It also reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) (p < 0.05) levels. CONCLUSION: Thus, it is possible to infer that estragole presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms.
Asunto(s)
Anisoles/uso terapéutico , Antiulcerosos/uso terapéutico , Antioxidantes/uso terapéutico , Factores Inmunológicos/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Derivados de Alilbenceno , Animales , Anisoles/farmacología , Antiinflamatorios no Esteroideos , Antiulcerosos/farmacología , Antioxidantes/farmacología , Citocinas/inmunología , Citoprotección , Etanol , Mucosa Gástrica/citología , Factores Inmunológicos/farmacología , Masculino , Ratones , Piroxicam , Ratas Wistar , Estómago/efectos de los fármacos , Estómago/patología , Úlcera Gástrica/etiología , Úlcera Gástrica/inmunología , Úlcera Gástrica/patología , Estrés PsicológicoRESUMEN
The intake of dietary lipids is known to affect the composition of phospholipids in gastrointestinal cells, thereby influencing passive lipid absorption. However, dietary lipids rich in polyunsaturated fatty acids, such as vegetable oils, are prone to oxidation. Studies investigating the phospholipid-regulating effect of oxidized lipids are lacking. We aimed at identifying the effects of oxidized lipids from moderately (18.8 ± 0.39 meq O2/kg oil) and highly (28.2 ± 0.39 meq O2/kg oil) oxidized and in vitro digested cold-pressed grape seed oils on phospholipids in human gastric tumor cells (HGT-1). The oils were analyzed for their antioxidant constituents as well as their oxidized triacylglycerol profile by LC-MS/MS before and after a simulated digestion. The HGT-1 cells were treated with polar oil fractions containing epoxidized and hydroperoxidized triacylglycerols for up to six hours. Oxidized triacylglycerols from grape seed oil were shown to decrease during the in vitro digestion up to 40% in moderately and highly oxidized oil. The incubation of HGT-1 cells with oxidized lipids from non-digested oils induced the formation of cellular phospholipids consisting of unsaturated fatty acids, such as phosphocholines PC (18:1/22:6), PC (18:2/0:0), phosphoserine PS (42:8) and phosphoinositol PI (20:4/0:0), by about 40%-60%, whereas the incubation with the in vitro digested oils did not affect the phospholipid metabolism. Hence, the gastric conditions inhibited the phospholipid-regulating effect of oxidized triacylglycerols (oxTAGs), with potential implications in lipid absorption.
Asunto(s)
Antioxidantes/metabolismo , Digestión , Jugo Gástrico/metabolismo , Fosfolípidos/metabolismo , Aceites de Plantas/metabolismo , Línea Celular Tumoral , Ácidos Grasos Omega-3/metabolismo , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Humanos , Oxidación-Reducción , Triglicéridos/metabolismo , Vitis/químicaRESUMEN
BACKGROUND & AIMS: Gastric chief cells, a mature cell type that secretes digestive enzymes, have been proposed to be the origin of metaplasia and cancer through dedifferentiation or transdifferentiation. However, studies supporting this claim have had technical limitations, including issues with the specificity of chief cell markers and the toxicity of drugs used. We therefore sought to identify genes expressed specifically in chief cells and establish a model to trace these cells. METHODS: We performed transcriptome analysis of Mist1-CreERT-traced cells, with or without chief cell depletion. Gpr30-rtTA mice were generated and crossed to TetO-Cre mice, and lineage tracing was performed after crosses to R26-TdTomato mice. Additional lineage tracing experiments were performed using Mist1-CreERT, Kitl-CreERT, Tff1-Cre, and Tff2-Cre mice crossed to reporter mice. Mice were given high-dose tamoxifen or DMP-777 or were infected with Helicobacter pylori to induce gastric metaplasia. We studied mice that expressed mutant forms of Ras in gastric cells, using TetO-KrasG12D, LSL-KrasG12D, and LSL-HrasG12V mice. We analyzed stomach tissues from GPR30-knockout mice. Mice were given dichloroacetate to inhibit pyruvate dehydrogenase kinase (PDK)-dependent cell competition. RESULTS: We identified GPR30, the G-protein-coupled form of the estrogen receptor, as a cell-specific marker of chief cells in gastric epithelium of mice. Gpr30-rtTA mice crossed to TetO-Cre;R26-TdTomato mice had specific expression of GPR30 in chief cells, with no expression noted in isthmus stem cells or lineage tracing of glands. Expression of mutant Kras in GPR30+ chief cells did not lead to the development of metaplasia or dysplasia but, instead, led to a reduction in labeled numbers of chief cells and a compensatory expansion of neck lineage, which was derived from upper Kitl+ clones. Administration of high-dose tamoxifen, DMP-777, or H pylori decreased the number of labeled chief cells. Chief cells were eliminated from epithelia via GPR30- and PDK-dependent cell competition after metaplastic stimuli, whereas loss of GRP30 or inhibition of PDK activity preserved chief cell numbers and attenuated neck lineage cell expansion. CONCLUSIONS: In tracing studies of mice, we found that most chief cells are lost during metaplasia and therefore are unlikely to contribute to gastric carcinogenesis. Expansion of cells that coexpress neck and chief lineage markers, known as spasmolytic polypeptide-expressing metaplasia, does not occur via dedifferentiation from chief cells but, rather, through a compensatory response from neck progenitors to replace the eliminated chief cells.
Asunto(s)
Células Principales Gástricas/fisiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Receptores de Estrógenos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Azetidinas/toxicidad , Comunicación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Linaje de la Célula/efectos de los fármacos , Linaje de la Célula/fisiología , Ácido Dicloroacético/administración & dosificación , Modelos Animales de Enfermedad , Mucosa Gástrica/citología , Mucosa Gástrica/efectos de los fármacos , Infecciones por Helicobacter/microbiología , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Metaplasia/inducido químicamente , Metaplasia/microbiología , Metaplasia/patología , Ratones , Ratones Noqueados , Piperazinas/toxicidad , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/antagonistas & inhibidores , Receptores de Estrógenos/genética , Receptores Acoplados a Proteínas G/genética , Células Madre/fisiología , Tamoxifeno/toxicidadRESUMEN
Aim: The objective of this study was to investigate the possible synergy between doxycycline and photodynamic therapy against Helicobacter pylori and to evaluate the possible side effects on adenocarcinoma gastric cells with and without protoporphyrin IX. Materials & methods: Three H. pylori strains (ATCC 700392, 43504 and 49503) were grown on solid medium either with, or without, doxycycline at subinhibitory concentrations, and irradiated for 10, 20 and 30 minutes with a 400 nm-peaked light source. The phototoxicity tests on AGS cells were evaluated by MTT assay. Results: The photodynamic therapy and doxycycline combination showed an antibacterial synergistic effect with no significant toxicities. Conclusion: The synergistic treatment could be considered as an interesting therapeutic option.
Asunto(s)
Antibacterianos/farmacología , Doxiciclina/farmacología , Helicobacter pylori/efectos de los fármacos , Fotoquimioterapia/métodos , Protoporfirinas/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Dermatitis Fototóxica , Sinergismo Farmacológico , Mucosa Gástrica/citología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/efectos de la radiación , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/radioterapia , Humanos , Pruebas de Sensibilidad Microbiana , Fotoquimioterapia/efectos adversosRESUMEN
BACKGROUND: The extract of Celastrus orbiculatus (COE) have been studied for anti-Helicobacter pylori (H. pylori) activity and anti-cancer effects in vitro and in vivo. However, the molecular mechanism by which COE inhibits H. pylori-induced inflammatory response has not been fully elucidated so far. METHODS: The effects of COE on viability, morphological changes, inflammatory cytokine secretion, protein and mRNA expression were analyzed by MTT assay, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, western blot and real-time PCR (RT-PCR), respectively. The methylation level of programmed cell death 4 (PDCD4) promoter was investigated by methylation-specific PCR. (MSP) . RESULTS: COE effectively inhibited the H.pylori-induced inflammatory response by regulating epithelial-mesenchymal transition (EMT). The methylation level of PDCD4 promoter was suppressed by COE, which increased the expression ofPDCD4. Moreover, COE could inhibit microRNA-21 (miR-21) expression, as shown by an enhancement of its target gene PDCD4. Furthermore, both miR-21 over-expression and PDCD4 silencing attenuated the anti-inflammatory effect. of COE. CONCLUSIONS: COE inhibits H. pylori induced inflammatory response through regulating EMT, correlating with inhibition of miR-21/PDCD4 signal pathways in gastric epithelial cells.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Celastrus/química , Transición Epitelial-Mesenquimal/efectos de los fármacos , Helicobacter pylori , MicroARNs/metabolismo , Extractos Vegetales/farmacología , Proteínas de Unión al ARN/metabolismo , Antiinflamatorios/farmacología , Proteínas Reguladoras de la Apoptosis/genética , Línea Celular , Citocinas/análisis , Citocinas/metabolismo , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Mucosa Gástrica/citología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/microbiología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Humanos , MicroARNs/genética , Proteínas de Unión al ARN/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Background Psyllium (Planta ovata, Ispaghul) seed and husk are used for treatment of altered bowel habit, i.âe. constipation and diarrhea. We studied the effect of Ispaghul extract on secretion of interleukin-1 beta (IL-1ß) by AGS (ATCC CRL 1739) and SW480 (ATCC CCL-227) epithelial cell lines and determined whether Ispaghul extract has an effect on IL-1ß secretion by Helicobacter pylori (H. pylori)-stimulated AGS cell and Escherichia coli K-12 (E. coli K-12)-stimulated SW480 cells in vitro. Methods The AGS cells and SW480 cells were pretreated with Ispaghul extract in concentrations, i.âe. 3.5 and 7âµg/mL prior to infection with H. pylori and E. coli K-12. Results DNA fragmentation in AGS and SW480 cells treated with Ispaghul extract was not significant (2.3±0.8â%) compared with untreated cells (2.2±0.6â%). Ispaghul extract decreased the H. pylori-stimulated secretion of IL-1ß by AGS cell (p<0.0001). This effect did not increase as the concentration of extract was increased. Ispaghul extract also decreased E. coli K-12-stimulated IL-1ß secretion by SW480 cell (p<0.0001). This effect increased as the concentration of extracts was increased. Conclusions Ispaghul extract had an effect on stimulated secretion of IL-1ß by the AGS and SW480 cell. It decreased pro-inflammatory reaction from both cell lines stimulated by bacteria.
Asunto(s)
Antiinflamatorios/farmacología , Células Epiteliales/efectos de los fármacos , Mucosa Gástrica/efectos de los fármacos , Bacterias Gramnegativas , Interleucina-1beta/metabolismo , Mucosa Intestinal/efectos de los fármacos , Psyllium , Línea Celular , Colon/citología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/microbiología , Células Epiteliales/metabolismo , Escherichia coli K12 , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Helicobacter pylori , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Extractos Vegetales/farmacología , Semillas , Estómago/citología , Estómago/efectos de los fármacos , Estómago/microbiologíaRESUMEN
BACKGROUND AND OBJECTIVES: A controversy developed between the benefits of energy drinks (EDs) versus the possible health threats since its revolution. Lack of information was a call to assess the effect of chronic consumption of Power Horse (PH) as one of the EDs, on the structure of pancreas and fundic mucosa of stomach in rats, and possible protective role of Omega-3. MATERIALS AND METHODS: Thirty two adult male albino rats were divided equally into 4 groups; control received group which only received a standard diet, Omega-3 group, PH group which given PH and PH plus Omega-3 group received both PH plus Omega-3 for 4 weeks. Biochemical assessment of blood glucose, serum insulin, gastrin, tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthetase (iNOS) was performed. The antioxidant activity and histopathological examination of both pancreatic tissue and fundic mucosa of stomach were assessed. RESULTS: Administration of PH significantly increased serum insulin and glucose levels while it significantly reduced serum gastrin level compared to control. PH also caused oxidants/antioxidants imbalance in both pancreas and fundic mucosa. The latter revealed degenerative changes and increased apoptosis which was evident by increased caspase-3 immunoexpression. Pancreas exhibited signs of ß-cells overstimulation. Fundic mucosa showed reduced number of parietal cells, gastrin hormone expression compared to control group. Omega-3 administration could alleviate, to some extent, these changes. It significantly decreased TNF-α, iNOS and reduced glutathione (GSH) as well as significantly increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities compared to the group which received PH alone. CONCLUSION: Power Horse intake significantly injures islet cells, pancreatic acini as well as the glandular cells of the fundic mucosa. Omega-3 decreases these detrimental effects mostly through its antioxidant and anti-inflammatory action.
Asunto(s)
Bebidas Energéticas , Mucosa Gástrica/metabolismo , Páncreas/citología , Páncreas/metabolismo , Estómago/citología , Animales , Antioxidantes/metabolismo , Glucemia , Peso Corporal , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Mucosa Gástrica/citología , Mucosa Gástrica/efectos de los fármacos , Gastrinas/sangre , Concentración de Iones de Hidrógeno , Insulina/sangre , Masculino , Óxido Nítrico Sintasa de Tipo II/sangre , Páncreas/efectos de los fármacos , Ratas , Estómago/efectos de los fármacos , Factor de Necrosis Tumoral alfa/sangreRESUMEN
The purposes of this study were to examine the characteristics of Helicobacter pylori and the effect of Rumex Aquaticus Herba extract on the expression of cytokines in H. pylori-infected gastric epithelial cells. Cultured human adenocarcinoma gastric cells (AGS) were infected by H. pylori in RPMI 1640 media. Cell growth was measured by trypan blue assay. Western blot analysis was performed to investigate effect of extract containing Quercetin-3-O-ß-d-glucuronopyranoside (ECQ) on the expression of inflammatory factors and the inhibition on cell growth. Furthermore, we compared the inhibitory effects with various combinations of clarithromycin, amoxicillin, omeprazole, and ECQ. The urease test with Christensen's Urea Agar was performed to identify the urease activity of H. pylori and the effect ECQ has on urease activity. When the cells were exposed to H. pylori, the trypan blue assay revealed a decrease in the rate of cell growth. Western blot analysis showed that H. pylori-infected cells had increased levels of degraded IκB-α and inflammatory factors. Pretreatment with ECQ inhibited interleukin expression induced by H. pylori in a dose-dependent manner. A combination of ECQ and antibiotics inhibited cytokine expression more effectively than other treatments. H. pylori displayed significant urease activity. ECQ did not significantly inhibit urease activity. These data suggest that H. pylori infection has cytotoxic effects against AGS cells, and ECQ may inhibit the production of proinflammatory cytokines in H. pylori-infected AGS cells.
Asunto(s)
Células Epiteliales/efectos de los fármacos , Mucosa Gástrica/efectos de los fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/inmunología , Helicobacter pylori/fisiología , Extractos Vegetales/farmacología , Rumex/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Células Epiteliales/citología , Células Epiteliales/inmunología , Mucosa Gástrica/citología , Mucosa Gástrica/inmunología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Humanos , Interleucina-8/genética , Interleucina-8/inmunologíaRESUMEN
Natural plant product Psyllium has anti-inflammatory activity that can modulate the function of cytokines. We determined the effect of Psyllium husk extract on interleukin (IL)-8 and NF-κB secretion by gastric epithelial cells in response to Helicobacter pylori Human gastric adenocarcinoma cell line (AGS) cells were pretreated with Psyllium extract in different concentrations before H pylori infection. Cell culture supernatant was analyzed for IL-8 and NF-κB by ELISA. RNA from cells was used for real-time polymerase chain reaction for messenger RNA expression of IL-8. Psyllium extract 5 and 10 µg/mL markedly (P < .001) lowered basal IL-8 by 64.71% and 74.51%, respectively, and H pylori-stimulated IL-8 was also (P < .001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10 µg/mL also reduced (P < .0001) cagA-positive H pylori-induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced (P = .0001) NF-κB in response to H pylori strains confirming its role as an anti-inflammatory agent.
Asunto(s)
Mucosa Gástrica/citología , Helicobacter pylori/efectos de los fármacos , Interacciones Huésped-Patógeno/efectos de los fármacos , Psyllium/farmacología , Línea Celular Tumoral , Fragmentación del ADN/efectos de los fármacos , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Humanos , Interleucina-8/metabolismo , FN-kappa B/metabolismo , Psyllium/químicaRESUMEN
Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.
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Mucositis/prevención & control , Pectinas/administración & dosificación , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/administración & dosificación , Células Madre/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Suplementos Dietéticos/análisis , Quinasas Similares a Doblecortina , Femenino , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Mucositis/dietoterapia , Mucositis/etiología , Mucositis/patología , Pectinas/farmacología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Traumatismos Experimentales por Radiación/dietoterapia , Traumatismos Experimentales por Radiación/patología , Protectores contra Radiación/farmacología , Células Madre/metabolismo , Células Madre/efectos de la radiación , Análisis de Supervivencia , Irradiación Corporal TotalRESUMEN
OBJECTIVE: To explore the molecular mechanism of moxibustion at stomach meridian acupoints for precancerous lesions of chronic atrophic gastritis (CAG). METHODS: Fifty male SD rats were randomly divided into a normal group, a model group, a stomach meridian group, a control point group and a vitacoenzyme group, 10 rats in each group. The CAG precancerous lesion model was made in all the groups except the normal group. The rats in the normal group and model group were bundled for 30 min per day; the rats in the stomach meridian group and control point group were bundled and treated with moxibustion at stomach meridian acupoints or control points for 30 min per day; the rats in the vitacoenzyme group were treated with intragastric administration of vitacoenzyme, once per day. All the treatment was given for 20 weeks. The pathological morphological change of gastric mucosa was observed under optical microscope; the expression of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), vascular endothelial growth factor (VEGF), gastric mucosal proliferatig cell nuclear antigen (PCNA), argyrophilic protein of nucleolar organizer regions (Ag-NORs) in gastric mucosal cells were detected by enzyme linked immuno sorbent assay (ELISA). RESULTS: Compared with the normal group, in the model group the gastric mucosal cells showed dysplasia and the expression of EGF, TGF-alpha, PCNA, VEGF, Ag-NORs in gastric mucosa cells in the model group was increased significantly (all P < 0.05). Compared with the model group, the gastric mucosa lesion gradually recovered and the expression of EGF, TGF-alpha, PCNA, VEGF, Ag-NORs in gastric mucosal cells was gradually decreased in the stomach meridian group, control point group and vitacoenzyme group, in which the stomach meridian group had the most significant effects (all P < 0.05). CONCLUSION: Moxibustion at stomach meridian acupoints can obviously decrease the expression of cell proliferative factors in gastric mucosa in rats with CAG precancerous lesions, inhibit the gastric mucosal cell dysplasia, and promote the recovery of gastric mucosa.
Asunto(s)
Factor de Crecimiento Epidérmico/metabolismo , Mucosa Gástrica/citología , Gastritis Atrófica/terapia , Hiperplasia/terapia , Moxibustión , Antígeno Nuclear de Célula en Proliferación/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Puntos de Acupuntura , Animales , Proliferación Celular , Factor de Crecimiento Epidérmico/genética , Gastritis Atrófica/genética , Gastritis Atrófica/metabolismo , Gastritis Atrófica/fisiopatología , Humanos , Hiperplasia/genética , Hiperplasia/metabolismo , Hiperplasia/fisiopatología , Masculino , Antígeno Nuclear de Célula en Proliferación/genética , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVE: The study is aimed to evaluate anti-inflammatory activity of Caesalpinia bonducella Fleming (Caesalpiniaceae) flower extract (CBFE) and to study its effect on radiographic outcome in adjuvant induced arthritis and authentication by high performance thin layer chromatography (HPTLC) chemical fingerprinting. MATERIALS AND METHODS: CBFE was administered orally (30, 100, and 300 mg/kg b.wt.) and tested for its anti-inflammatory activity in carrageenan-induced inflammation, cotton pellet induced chronic granulomatous inflammation and autacoids-induced inflammation. Effect on radiographic outcome was tested in adjuvant-induced arthritis. CBFE was HPTLC fingerprinted in suitable solvent system. RESULT: In carrageenan-induced inflammation, CBFE produced significant inhibition in edema volume at all the doses (30, 100 and 300 mg/kg b.wt.) and percentage of inhibition was 28.68, 31.00, and 22.48, respectively as compared to control at 5 h of its administration. In cotton pellet granuloma assay, CBFE significantly decreased the granuloma weight at 300 mg/kg dose level by 22.53%. CBFE (300 mg/kg) caused significant inhibition by 37.5, 44.44, and 35.29% edema volume, at ½, 1 and 3 h after 5-hydroxytryptamine injection, respectively. Radiographic score of animals treated with 300 mg/kg CBFE was significantly decreased when compared to arthritic control animals. CONCLUSION: The extract was found to possess significant anti-inflammatory activity. CBFE treatment improved the bony architecture in adjuvant-induced arthritis in rats. The developed HPTLC fingerprint would be helpful in the authentication of C. bonducella flower extract.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Experimental/prevención & control , Caesalpinia/química , Flores/química , Extractos Vegetales/uso terapéutico , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/química , Artritis Experimental/diagnóstico por imagen , Artritis Experimental/inmunología , Artritis Experimental/patología , Cromatografía en Capa Delgada , Relación Dosis-Respuesta a Droga , Etnofarmacología , Femenino , Mucosa Gástrica/citología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/inmunología , Mucosa Gástrica/patología , India , Masculino , Medicina Ayurvédica , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Radiografía , Distribución Aleatoria , Ratas Wistar , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad CrónicaRESUMEN
Coherent fiber imaging bundles can be used as passive probes for reflectance-mode endomicroscopy providing that the back-reflections from the fiber ends are efficiently rejected. We describe an approach specific to widefield endomicroscopy in which light is injected into a leached fiber bundle near the distal end, thereby avoiding reflections from the proximal face. We use this method to demonstrate the color widefield reflectance endomicroscopy of ex vivo animal tissue.
Asunto(s)
Endoscopía/instrumentación , Endoscopía/métodos , Tecnología de Fibra Óptica/instrumentación , Microscopía Fluorescente/instrumentación , Microscopía Fluorescente/métodos , Tejido Adiposo/química , Tejido Adiposo/citología , Animales , Mucosa Gástrica/química , Mucosa Gástrica/citología , Mucosa Intestinal/química , Mucosa Intestinal/citología , Modelos Biológicos , Cebollas/química , Cebollas/citología , Fantasmas de Imagen , PorcinosRESUMEN
BACKGROUND/AIMS: Although the gastroprotective properties of Ocimum gratissimum L. have been mentioned, the exact mechanism is yet to be explored. Since acid output plays a significant role in the pathogenesis of gastric ulceration, the present study was aimed at investigating the effect of leaf extract of Ocimum gratissimum on gastric luminal pH, acid output, parietal cell mass and gastric mucous cell population in rabbits. MATERIALS AND METHODS: The model of pyloric ligation for acid secretion and ulcer study was employed. Prior to the 4 h ligation, male New Zealand rabbits were treated orally with 75 mg/kg, 150 mg/kg and 250 mg/kg b.w aqueous leaf extract of Ocimum gratissimum twice daily for three weeks. The antisecretory and antiulcer effect of Ocimum gratissimum was compared with omeprazole (20 mg/kg p.o). Parietal cell mass and gastric mucous cell population were determined in the gastric samples by histometry. RESULTS: Aqueous leaf extract of Ocimum gratissimum caused significant reduction in ulcer formation, gastric secretion volume and acid output in a dose dependent manner (p<0.05). Percentage inhibition was recorded as 29%, 46.2%, 52.9% for ulcer; and 16.2%, 35.9%, 52.1% for acid output upon pretreatment with 75 mg/kg, 150 mg/kg and 250 mg/kg b.w respectively. Parietal cell mass was also reduced while gastric mucous cell population and luminal pH increased accordingly when compared to the control group. Data were comparable with the antisecretory effect of omeprazole. CONCLUSION: The results indicate that the anti-secretory activity of Ocimum gratissimum may be the anti-ulcer mechanism of this plant.
Asunto(s)
Tampones (Química) , Ácido Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Ocimum/química , Células Parietales Gástricas/efectos de los fármacos , Extractos Vegetales/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos/farmacología , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Concentración de Iones de Hidrógeno/efectos de los fármacos , Masculino , Omeprazol/farmacología , Hojas de la Planta , ConejosRESUMEN
ETHNOPHARMCOLOGICAL RELEVANCE: Helicobacter pylori induced oxidative stress represents an important mechanism leading to expression of inflammatory mediators. Korean red ginseng is used in traditional medicine to inhibit inflammation. However, the anti-inflammatory mechanism of red ginseng is still under investigation. Thus, we investigated whether Korean red ginseng extract (RGE) inhibits NADPH oxidase, a source of reactive oxygen species (ROS), and the Jak2/Stat3 pathway, which mediates the expression of inflammatory mediators, in Helicobacter pylori-infected gastric epithelial cells. MATERIALS AND METHODS: A standardized RGE was supplied by the Korea Ginseng Corporation. Human gastric epithelial cells (AGS) were treated with RGE and stimulated with Helicobacter pylori. NADPH oxidase activity, ROS levels, activation of Jak2/Stat3, and induction of MCP-1 and iNOS were determined. RESULTS: Helicobacter pylori infection resulted in an increase in ROS and activation of NADPH oxidase and Jak2/Stat3, which induced the expression of MCP-1 and iNOS in AGS cells. The induction of MCP-1 and iNOS was inhibited by both the Jak2/Stat3 inhibitor AG490 and RGE in Helicobacter pylori-infected cells. RGE suppressed NADPH oxidase activity by inhibiting translocation of cytosolic subunits p67phox and p47phox to the membrane and reduced ROS levels in Helicobacter pylori-infected cells. CONCLUSION: RGE inhibits the expression of MCP-1 and iNOS by suppressing the activation of NADPH oxidase and Jak2/Stat3 in Helicobacter pylori-infected gastric epithelial cells.
Asunto(s)
Quimiocina CCL2/antagonistas & inhibidores , Células Epiteliales/efectos de los fármacos , Infecciones por Helicobacter/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Panax , Extractos Vegetales/farmacología , Línea Celular , Quimiocina CCL2/genética , Células Epiteliales/metabolismo , Mucosa Gástrica/citología , Helicobacter pylori , Humanos , Janus Quinasa 2/metabolismo , NADPH Oxidasas/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of moxibustion-acupoint treatment with acupoints of Zusanli (ST 36) and Zhongwan (RN 12) on cell apoptosis and the expressions of heat shock protein (HSP) 60, HSP70 and second mitochondrial activator of caspase (Smac) in rat models of acute gastric mucosal lesion (AGML), and explore the mechanisms underlying protection of gastric mucosal lesion. METHODS: Twenty-four Sprague Dawley rats were divided into 3 groups, blank controlled group (group A), controlled-point group (group B) and acupoint group (group C), 8 for each. After 8-day moxibustion treatment in group B and C, gastric lavage of anhydrous ethanol was used to created AGML in all three groups. The Guth method was employed to measure the ulcer index (UI) of gastric mucosal lesion and immunohistochemistry used to measure apoptosis with apoptosis index (AI) and examine the expressions of HSP60, HSP70 and Smac. RESULTS: Compared with group A, the expressions of UI, AI, Smac and HSP60 were markedly elevated in group B (P < 0.05 or P < 0.01). However the expression of HSP70 showed no obvious change (P > 0.05); the expressions of UI, HSP60 and HSP70 were markedly elevated in group C (P < 0.01) while those of AI and Smac became obviously suppressed (P < 0.01). Compared with group B, the expressions of UI, AI and Smac decreased significantly in group C (P < 0.01) while those of HSP60 and HSP70 increased markedly (P < 0.01), and the expressions of HSP60 and HSP70 were considerably up-regulated (P < 0.01). CONCLUSION: The moxibustion treatment could alleviate the gastric mucosal lesion caused by anhydrous ethanol, induce the over-expressions of HSP60 and HSP70, and down-regulate the expression of Smac, which could suppress cell apoptosis.
Asunto(s)
Apoptosis , Proteínas Portadoras/genética , Chaperonina 60/genética , Gastritis/genética , Gastritis/terapia , Proteínas HSP70 de Choque Térmico/genética , Proteínas Mitocondriales/genética , Moxibustión , Animales , Proteínas Reguladoras de la Apoptosis , Proteínas Portadoras/metabolismo , Chaperonina 60/metabolismo , Femenino , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Gastritis/metabolismo , Gastritis/fisiopatología , Expresión Génica , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Masculino , Proteínas Mitocondriales/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Byrsonima crassa Niedenzu (Malpighiaceae) is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In a previous study, our group described the gastric protective effect of the methanolic extract from the leaves of B. crassa. The present study was carried out to investigate the effects of methanolic extract and its phenolic compounds on the respiratory burst of neutrophils stimulated by H. pylori using a luminol-based chemiluminescence assay as well as their anti-H. pylori activity. The suppressive activity on oxidative burst of H. pylori-stimulated neutrophils was in the order of methyl gallate > (+)-catechin > methanol extract > quercetin 3-O-α-l-arabinopyranoside > quercetin 3-O-ß-d-galactopyranoside > amentoflavone. Methyl gallate, compound that induced the highest suppressive activity with IC(50) value of 3.4 µg/mL, did not show anti-H. pylori activity. B. crassa could be considered as a potential source of natural antioxidant in gastric ulcers by attenuating the effects on the damage to gastric mucosa caused by neutrophil generated reactive oxygen species, even when H. pylori displays its evasion mechanisms.
Asunto(s)
Antioxidantes/farmacología , Helicobacter pylori/patogenicidad , Malpighiaceae/química , Fenoles/farmacología , Estallido Respiratorio/efectos de los fármacos , Antioxidantes/química , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Ácido Gálico/aislamiento & purificación , Ácido Gálico/farmacología , Mucosa Gástrica/citología , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Helicobacter pylori/efectos de los fármacos , Malpighiaceae/metabolismo , Metanol/química , Neutrófilos/inmunología , Neutrófilos/microbiología , Fenoles/química , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: To observe the effect of plasma derived from healthy volunteers undergoing moxibustion (moxibustion plasma) on alchol-injured human gastric epithelial GES-1 cells in vitro, and expression of heat shock protein 70 (HSP 70, cell apoptosis inhibitory protein), apoptosis inducing factor (AIF), Smac (a mitochondrial protein), and Caspase 3 and Caspase 9 (the latter 3 proteins are also involved in cell apoptosis) in order to study its mechanisms underlying protecting gastric mucous membrane. METHODS: Twenty-four healthy volunteer subjects (half men and half women) were randomized into acupoint-moximustion (A-M) [Zhongwan(CV 12), Guanyuan (CV 4) and Zusanli (ST 36)] group and non-acupoint-moxibustion (NA-M, 3 cun right to CV 12 and CV 4.1 cun medial to ST 36 ) group (n = 12/group). Moxibustion was applied to the above-mentioned 3 acupoints and non-acupoints for 30 min, once daily for 10 days. Venous blood of the subjects was collected before and after moxibustion. The cultured GES-1 cells were divided into: control group. ethanol-injury group (model), A-M plasma group (A-M-P, plasma got from volunteers undergoing A-M), and NA-M plasma group (NA-M-P,plasma got from volunteers accepting NA-M). The GES-1 cells of the latter 3 groups were treated with 8% ethanol for duplicating cell injury model. Apoptosis was detected by flowcytometry. Expression of HSP 70, second mitochondria-derived activator of Caspase (Smac) and AIF proteins of GES-1 cells were assayed by western blotting, and the immunoactivity of cysteinyl aspirate-specific proteinase-3 and 9 (Caspase-3, 9) was detected by immunocytochemistry. RESULTS: In comparison with the control group, the apoptosis rate, the expression of HSP 70, Smac and AIF proteins, and the immunoactivity of Caspase-3 and Caspase-9 of the model group were increased significantly (P < 0.01). Compared with the model group, the apoptosis rate of GES-1 cells, the expression of Smac and AIF proteins, and the immunoactivity of Caspase-3 and Caspase-9 in the A-M-P group, the apoptosis rate, the expression of Smac and the immunoactivity of Caspase-3 and Caspase-9 in the NA-M-P group were all down-regulated considerably (P < 0.05, P < 0.01). In comparison with the model group, HSP 70 expression of the A-M-P group was up-regulated significantly (P < 0.01). The apoptosis rate of GES-1 cells, the expression levels of Smac, AIF, Caspase-3 and Caspase-9 were significantly lower in the A-M-P group than in the NA-M-P group (P < 0.05, P < 0.01), while the expression of HSP 70 was apparently higher in the A-M-P group than in the NA-M-P group (P < 0.01). CONCLUSION: Plasma derived from the subjects undergoing moxibustion of Zusanli (ST 36), Zhongwan (CV 12) and Guanyuan (CV 4) can inhibit apoptosis of GES-1 cells in vitro, which is closely related to its effects in up-regulating intracellular HSP 70 expression and down-regulating mitochondrial apoptosis protein expression of AIF. Smac, Caspase-3 and Caspase-9.