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1.
Biomed Res Int ; 2021: 5561221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414236

RESUMO

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1ß in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.


Assuntos
Brucea/química , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Óleos Vegetais/administração & dosagem , Quassinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Quassinas/farmacologia , Resultado do Tratamento , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
2.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445403

RESUMO

Natural smectites have demonstrated efficacy in the treatment of diarrhea. The present study evaluated the prophylactic effect of a diosmectite (FI5pp) on the clinical course, colon damage, expression of tight junction (TJ) proteins and the composition of the gut microbiota in dextran sulfate sodium (DSS) colitis. Diosmectite was administered daily to Balb/c mice from day 1 to 7 by oral gavage, followed by induction of acute DSS-colitis from day 8 to 14 ("Control", n = 6; "DSS", n = 10; "FI5pp + DSS", n = 11). Mice were sacrificed on day 21. Clinical symptoms (body weight, stool consistency and occult blood) were checked daily after colitis induction. Colon tissue was collected for histological damage scoring and quantification of tight junction protein expression. Stool samples were collected for microbiome analysis. Our study revealed prophylactic diosmectite treatment attenuated the severity of DSS colitis, which was apparent by significantly reduced weight loss (p = 0.022 vs. DSS), disease activity index (p = 0.0025 vs. DSS) and histological damage score (p = 0.023 vs. DSS). No significant effects were obtained for the expression of TJ proteins (claudin-2 and claudin-3) after diosmectite treatment. Characterization of the microbial composition by 16S amplicon NGS showed that diosmectite treatment modified the DSS-associated dysbiosis. Thus, diosmectites are promising candidates for therapeutic approaches to target intestinal inflammation and to identify possible underlying mechanisms of diosmectites in further studies.


Assuntos
Bactérias/classificação , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Microbiota/efeitos dos fármacos , Silicatos/administração & dosagem , Administração Oral , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , DNA Bacteriano/genética , DNA Ribossômico/genética , Fezes/microbiologia , Masculino , Camundongos Endogâmicos BALB C , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Índice de Gravidade de Doença , Silicatos/farmacologia , Proteínas de Junções Íntimas/metabolismo , Resultado do Tratamento
3.
J Agric Food Chem ; 69(36): 10592-10605, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34460244

RESUMO

Ripened pu-erh tea has the biological activity of antioxidation and anti-inflammation, which inhibits the related parameters of colitis. However, the role of storage-induced changes in bioactive ingredients of ripened pu-erh tea in colitis remains unclear. In this study, 3.5% dextran sulfate sodium-induced colitis mice were treated with 10 mg/kg bw/day extracts, aged 14 years (P2006) and unaged (P2020) ripened pu-erh tea, respectively, for 1 week. We found that ripened pu-erh tea, especially P2006, inhibited the intestinal oxidative stress-mediated inflammation pathway (TLR4/MyD88/ROS/p38MAPK/NF-κB p65), upregulated the expression of intestinal tight junction proteins (Mucin-2, ZO-1, occludin), promoted M2 polarization of macrophages, and in turn, improved the intestinal immune barrier, which stemmed from the reshaping of intestinal microbiota (e.g., increased Lachnospiraceae_NK4A136_group and Akkermansia levels). Our results speculate that drinking aged ripe pu-erh tea (10 mg/kg bw/day in mice, a human equivalent dose of 7 g/60 kg bw/day) has a practical effect on alleviating and preventing the development of intestinal inflammation.


Assuntos
Colite , Chá , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Sulfato de Dextrana/efeitos adversos , Inflamação/tratamento farmacológico , Inflamação/genética , Camundongos , Estresse Oxidativo
4.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201918

RESUMO

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Mice lacking PTPN2 in dendritic cells (DCs) develop skin and liver inflammation by the age of 22 weeks due to a generalized loss of tolerance leading to uncontrolled immune responses. The effect of DC-specific PTPN2 loss on intestinal health, however, is unknown. The aim of this study was to investigate the DC-specific role of PTPN2 in the intestine during colitis development. PTPN2fl/flxCD11cCre mice were subjected to acute and chronic DSS colitis as well as T cell transfer colitis. Lamina propria immune cell populations were analyzed using flow cytometry. DC-specific PTPN2 deletion promoted infiltration of B and T lymphocytes, macrophages, and DCs into the lamina propria of unchallenged mice and elevated Th1 abundance during acute DSS colitis, suggesting an important role for PTPN2 in DCs in maintaining intestinal immune cell homeostasis. Surprisingly, those immune cell alterations did not translate into increased colitis susceptibility in acute and chronic DSS-induced colitis or T cell transfer colitis models. However, macrophage depletion by clodronate caused enhanced colitis severity in mice with a DC-specific loss of PTPN2. Loss of PTPN2 in DCs affects the composition of lamina propria lymphocytes, resulting in increased infiltration of innate and adaptive immune cells. However, this did not result in an elevated colitis phenotype, likely because increased infiltration of macrophages in the intestine upon loss of PTPN2 loss in DCs can compensate for the inflammatory effect of PTPN2-deficient DCs.


Assuntos
Colite/etiologia , Colite/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 2/deficiência , Animais , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Transgênicos , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo , Fator de Transcrição STAT1/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia
5.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199466

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with an incompletely understood pathogenesis. Long-standing colitis is associated with increased risk of colon cancer. Despite the availability of various anti-inflammatory and immunomodulatory drugs, many patients fail to respond to pharmacologic therapy and some experience drug-induced adverse events. Dietary supplements, particularly saffron (Crocus sativus), have recently gained an appreciable attention in alleviating some symptoms of digestive diseases. In our study, we investigated whether saffron may have a prophylactic effect in a murine colitis model. Saffron pre-treatment improved the gross and histopathological characteristics of the colonic mucosa in murine experimental colitis. Treatment with saffron showed a significant amelioration of colitis when compared to the vehicle-treated mice group. Saffron treatment significantly decreased secretion of serotonin and pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, in the colon tissues by suppressing the nuclear translocation of NF-κB. The gut microbiome analysis revealed distinct clusters in the saffron-treated and untreated mice in dextran sulfate sodium (DSS)-induced colitis by visualization of the Bray-Curtis diversity by principal coordinates analysis (PCoA). Furthermore, we observed that, at the operational taxonomic unit (OTU) level, Cyanobacteria were depleted, while short-chain fatty acids (SCFAs), such as isobutyric acid, acetic acid, and propionic acid, were increased in saffron-treated mice. Our data suggest that pre-treatment with saffron inhibits DSS-induced pro-inflammatory cytokine secretion, modulates gut microbiota composition, prevents the depletion of SCFAs, and reduces the susceptibility to colitis.


Assuntos
Bactérias/classificação , Produtos Biológicos/administração & dosagem , Colite/tratamento farmacológico , Crocus/química , Sulfato de Dextrana/efeitos adversos , Microbiota/efeitos dos fármacos , Administração Oral , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Produtos Biológicos/farmacologia , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Filogenia , Profilaxia Pré-Exposição , Serotonina/metabolismo , Resultado do Tratamento
6.
J Agric Food Chem ; 69(27): 7663-7674, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34182753

RESUMO

In this study, the preventive effect of tangeretin (TAN), a natural flavonoid derivative from citrus fruits, on the dextran sulfate sodium (DSS)-induced colitis in mice was evaluated. Our results showed that dietary TAN (0.04% and 0.08% w/w in the diet) significantly reduced the severity of colitis caused by DSS treatment in mice, evidenced by the increased colon length, the reduced disease activity index, and the attenuated colonic tissue damages. Moreover, dietary TAN inhibited the inflammatory response via down-regulating the overexpression of colonic inflammatory cytokines. Immunohistochemical analysis revealed that the intestinal barrier function was restored by TAN through enhancing claudin-1 and ZO-1 expressions. Additionally, dietary TAN modulated gut microbiota in colitic mice via enhancing gut microbiota diversity, ascending the level of beneficial bacteria, e.g., Lachnospiraceae and Lactobacillaceae, and descending the level of harmful bacteria, e.g., Enterobacteriaceae and Alistipes. Besides, dietary TAN promoted short-chain fatty acids production in DSS-treated mice. Altogether, these findings provided scientific evidence for the rational utilization of TAN as a preventive agent against colonic inflammation and related diseases.


Assuntos
Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo , Citocinas , Sulfato de Dextrana/efeitos adversos , Dieta , Modelos Animais de Doenças , Flavonas , Camundongos , Camundongos Endogâmicos C57BL
7.
Phytomedicine ; 87: 153570, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34062350

RESUMO

BACKGROUND: Croton crassifolius Geisel (CCG, also known as Ji-Gu-Xiang in Traditional Chinese Medicine), is traditionally prescribed for the therapy of rheumatic arthritis and gastrointestinal ulcer. However, the effect of CCG on ulcerative colitis (UC) has not been investigated. PURPOSE: To explore the therapeutic potential and underlying mechanism of CCG extract against UC by colonic and serum metabolomics. METHODS: In order to standardize the CCG extract, UPLC-QTOF-MS was used for quantitative and qualitative analysis of the representative terpenoids. C57BL/6J mice were divided into control, Dextran Sulfate Sodium (DSS), mesalazine (100 mg•kg-1), CCG extract (150 and 600 mg•kg-1) groups. The mice were provided 3% DSS dissolved in distilled water ad libitum for 7 days except control group. Weight change, disease activity index (DAI), colon lengths and expression of inflammatory mediators iNOS and COX-2 in colonic tissue were determined. Serum and colon metabolomics using UPLC-QTOF-MS technology coupled with multivariate data analysis were performed to reveal the underlying mechanism. RESULTS: Thirty-five terpenoids in CCG were identified by fingerprint, in which ten representative terpenes were quantified. CCG could relieve the weight loss, the degree of bloody stool and ulcer of colon, as well as significantly lowering the expression level of iNOS and COX-2. Metabolomics analysis showed that 25 biomarkers were obviously interfered by CCG treatment and 16 of them were highly correlated with the efficacy of CCG. The analysis of metabolic pathway showed that the anti-UC effect of CCG was associated with the regulation on linoleic acid metabolism, sphingolipid metabolism, α-linolenic acid metabolism, and glycerophospholipids metabolism. CONCLUSIONS: The oral administration of CCG significantly alleviated DSS-induced UC symptoms by reducing inflammation and rectifying the metabolic disorder. CCG may provide a new strategy for the management of UC.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Croton/química , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Colite Ulcerativa/induzido quimicamente , Colo/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana/efeitos adversos , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos
8.
Biomolecules ; 11(5)2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947113

RESUMO

Cardamonin is a naturally occurring chalcone, majorly from the Zingiberaceae family, which includes a wide range of spices from India. Herein, we investigated the anti-inflammatory property of cardamonin using different in vitro and in vivo systems. In RAW 264.7 cells, treatment with cardamonin showed a reduced nitrous oxide production without affecting the cell viability and decreased the expression of iNOS, TNF-α, and IL-6, and inhibited NF-kB signaling which emphasizes the role of cardamonin as an anti-inflammatory molecule. In a mouse model of dextran sodium sulfate (DSS)-induced colitis, cardamonin treatment protected the mice from colitis. Subsequently, we evaluated the therapeutic potential of this chalcone in a colitis-associated colon cancer model. We performed microRNA profiling in the different groups and observed that cardamonin modulates miRNA expression, thereby inhibiting tumor formation. Together, our findings indicate that cardamonin has the potential to be considered for future therapy against colorectal cancer.


Assuntos
Anti-Inflamatórios/administração & dosagem , Chalconas/administração & dosagem , Colite/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , MicroRNAs/genética , Animais , Anti-Inflamatórios/farmacologia , Azoximetano/efeitos adversos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chalconas/farmacologia , Colite/induzido quimicamente , Colite/complicações , Colite/metabolismo , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Camundongos , Óxido Nitroso/metabolismo , Células RAW 264.7 , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Células THP-1
9.
Food Funct ; 12(13): 6102-6116, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34047732

RESUMO

Fermented foods provide essential nutritional components and bioactive molecules that have beneficial effects on several gastrointestinal disorders. In the present investigation, the potential protective effects of whey fermented with probiotic Lactobacillus rhamnosus MTCC-5897 on gastrointestinal health in a murine ulcerative colitis model induced by dextran sulfate sodium (DSS) were evaluated. Pre-consumption of whey fermented with probiotic L. rhamnosus (PFW) before colitis induction significantly reduced (p < 0.01) the disease activity index and improved (p < 0.05) the hematological parameters and histological scores. The considerably diminished levels (p < 0.01) of pro-inflammatory markers (IL-4, TNF-α, CRP and MPO activity) and the enhanced (p < 0.05) levels of the anti-inflammatory cytokine TGF-ß with IgA in the intestine upon feeding PFW appeared to prevent inflammation on colitis induction. Transcriptional modulations in pathogen recognition receptors (TLR-2/4) and tight junctional genes (ZO-1, occludin, claudin-1) along with localized distribution of junctional (claudin-1, occludin and ZO-1) and cytoskeleton (actin) proteins improved immune homeostasis and intestinal barrier integrity. Besides, significantly reduced (p < 0.05) levels of the FITC-dextran marker in serum upon consumption of PFW directly confirmed the healthy status of the host gut.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Fermentação , Mucosa Intestinal/efeitos dos fármacos , Lactobacillus rhamnosus , Probióticos/farmacologia , Soro do Leite/química , Actinas/metabolismo , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Carbohydr Polym ; 265: 118041, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33966825

RESUMO

Aloe polysaccharides (APs) are indigestible bioactive polysaccharides, while can be fermented by colonic microbiota. Although plant polysaccharides can alleviate subacute ulcerative colitis (SUC), the mechanisms APs regulated SUC via colonic microbiota have not been fully explored. Hence, to elucidate the complex interactions between the novel APs, colonic microbiota, SCFAs, and inflammation, the SUC mouse model and in-depth analysis were performed, including multiple bioinformatics analysis and structural equation modeling (SEM). After APs intervention, SCFAs and SCFAs-producing genus, including Akkermansia and Blautia, were increased in colon, and the colonic inflammation and barrier dysfunction were alleviated significantly in SUC mice. Spearman analysis found positive correlations between microbiota and SCFAs. PICRUSt2 and KEGG analysis revealed 6-pyruvoyltetra hydropterin synthase in folate biosynthesis metabolism pathway was activated, while phosphotransferase system was inhibited. SEM results further proved APs was beneficial to gut micro-ecological balance in mice via SCFAs metabolism and anti-inflammatory functions. Together, APs could be exploited to alleviate SUC as dietary therapeutics.


Assuntos
Aloe/química , Colite Ulcerativa/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Akkermansia/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/metabolismo , Colo/efeitos dos fármacos , Biologia Computacional/métodos , Sulfato de Dextrana/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Análise de Classes Latentes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fósforo-Oxigênio Liases/metabolismo , Polissacarídeos/química
11.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946346

RESUMO

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1ß) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.


Assuntos
Anti-Inflamatórios/farmacologia , Sulfato de Dextrana/efeitos adversos , Extratos Vegetais/farmacologia , Estilbenos/farmacologia , Animais , Biomarcadores , Colite/tratamento farmacológico , Colite/etiologia , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia
12.
Methods Mol Biol ; 2299: 385-403, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34028756

RESUMO

Mouse models are essential for investigation of underlying disease mechanisms that drive intestinal fibrosis, as well as assessment of potential therapeutic approaches to either prevent or resolve fibrosis. Here we describe several common mouse models of intestinal inflammation and fibrosis, including chemically driven colitis models, a bacterially triggered colitis model, and spontaneous intestinal inflammation in genetically susceptible mouse strains. Detailed protocols are provided for dextran sodium sulfate (DSS) colitis, 2,4,6-trinitro-benzene sulfonic acid (TNBS) colitis, adherent-invasive Escherichia coli (AIEC)-triggered colitis, the interleukin-10 knockout (IL-10KO) mouse model of spontaneous colitis, and the SAMP/YitFc model of spontaneous ileocolitis.


Assuntos
Colite/etiologia , Colite/patologia , Interleucina-10/genética , Animais , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Escherichia coli/patogenicidade , Humanos , Masculino , Camundongos , Camundongos Knockout , Ácido Trinitrobenzenossulfônico/efeitos adversos
13.
Front Immunol ; 12: 648162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868283

RESUMO

Tremella fuciformis is an edible medicinal mushroom, and its polysaccharide components are found to confer various health benefits. This study identified the protective effects of polysaccharides of Tremella fuciformis (TPs) against dextran sulfate sodium (DSS)-induced colitis in mice. High dose of TPs (HTPs) could prevent the colon from shortening, reduce activity of colonic myeloperoxidase and serum diamine oxidase (DAO), decrease the concentration of D-lactate, and alleviate the colonic tissue damage in colitic mice. HTPs treatment stimulated Foxp3+T cells, and promoted the production of anti-inflammatory cytokines whereas it reduced the production of pro-inflammatory and the portion of immunoglobulin A (IgA)-coated bacteria, which was related to modulation of immune responses. 16S rRNA sequencing analysis showed that TPs could significantly increase gut community diversity, and restore the relative abundances of Lactobacillus, Odoribacter, Helicobacter, Ruminococcaceae, and Marinifilaceae. According to metabolomic analysis, HTPs induced specific microbial metabolites akin to that in normal mice. Tyrosine biosynthesis, tryptophan metabolism, and bile acid metabolism were influenced in the HTPs group compared with those in the DSS group. HTPs could alleviate DSS-induced colitis by immunoregulation and restored the gut microbiota and microbial metabolites. The results indicated that HTPs have potential to be developed as a food supplement to ameliorate intestinal diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Basidiomycota/química , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Fatores de Transcrição Forkhead/metabolismo , Polissacarídeos Fúngicos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/metabolismo , Substâncias Protetoras/administração & dosagem , Linfócitos T Reguladores/imunologia , Animais , Basidiomycota/genética , Ácidos e Sais Biliares/metabolismo , Colite/imunologia , Colite/microbiologia , Modelos Animais de Doenças , Feminino , Polissacarídeos Fúngicos/química , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , RNA Ribossômico 16S/genética , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Resultado do Tratamento , Triptofano/metabolismo , Tirosina/biossíntese
14.
Front Immunol ; 12: 586930, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828545

RESUMO

The Epstein-Barr virus (EBV) commonly infects humans and is highly associated with different types of cancers and autoimmune diseases. EBV has also been detected in inflamed gastrointestinal mucosa of patients suffering from prolonged inflammation of the digestive tract such as inflammatory bowel disease (IBD) with no clear role identified yet for EBV in the pathology of such diseases. Since we have previously reported immune-stimulating capabilities of EBV DNA in various models, in this study we investigated whether EBV DNA may play a role in exacerbating intestinal inflammation through innate immune and regeneration responses using the Drosophila melanogaster model. We have generated inflamed gastrointestinal tracts in adult fruit flies through the administration of dextran sodium sulfate (DSS), a sulfated polysaccharide that causes human ulcerative colitis- like pathologies due to its toxicity to intestinal cells. Intestinal damage induced by inflammation recruited plasmatocytes to the ileum in fly hindguts. EBV DNA aggravated inflammation by enhancing the immune deficiency (IMD) pathway as well as further increasing the cellular inflammatory responses manifested upon the administration of DSS. The study at hand proposes a possible immunostimulatory role of the viral DNA exerted specifically in the fly hindgut hence further developing our understanding of immune responses mounted against EBV DNA in the latter intestinal segment of the D. melanogaster gut. These findings suggest that EBV DNA may perpetuate proinflammatory processes initiated in an inflamed digestive system. Our findings indicate that D. melanogaster can serve as a model to further understand EBV-associated gastroinflammatory pathologies. Further studies employing mammalian models may validate the immunogenicity of EBV DNA in an IBD context and its role in exacerbating the disease through inflammatory mediators.


Assuntos
DNA Viral , Suscetibilidade a Doenças , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4 , Doenças Inflamatórias Intestinais/etiologia , Animais , Biomarcadores , Contagem de Células , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Drosophila melanogaster , Hemócitos , Herpesvirus Humano 4/genética , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Regeneração , Células-Tronco/imunologia , Células-Tronco/metabolismo
15.
Am J Chin Med ; 49(3): 661-676, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33683190

RESUMO

Ulcerative Colitis (UC) is a chronic inflammation disease, and the incidence of UC is increasing recently. Both clinical trials and animal experiments show that moxibustion is a complementary and alternative treatment for UC. Previous studies showed that moxibustion can improve UC by regulating the balance of Tregs and Th17 (Sun et al., 2017). Treg cells is one subset of CD4[Formula: see text] T cells that exert the immunosuppressive function. CD39 and CD73, expressed on the surface of Tregs, hydrolyze ATP to AMP and are further involved in the immunosuppressive function of Tregs. In this study, we investigated the effect of moxibustion on CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in dextran sulfate sodium (DSS) induced UC mice. The A2a receptor (A2aR), one of the targets of adenosine, was also detected. The results showed that moxibustion could increase the expression of CD39, CD73, and A2aR in colonic tissue and improve the proportion of CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in peripheral blood, inguinal draining lymph nodes and spleen in the UC model. Additionally, A2aR agonists enhanced the cell viability of colonic epithelial cells and inhibit the production of cytokines IL-6 and TNF-[Formula: see text] in vitro, which may further influence the pathway of ATP purine signal metabolism and alleviates the gut inflammation of UC mice. Taken together, this study provides supplemental evidence to reveal the immune related mechanism of moxibustion in the treatment of UC.


Assuntos
5'-Nucleotidase/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Sulfato de Dextrana/efeitos adversos , Moxibustão/métodos , Receptor A2A de Adenosina/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Animais , Sobrevivência Celular , Colite Ulcerativa/etiologia , Colite Ulcerativa/metabolismo , Colo/citologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Interleucina-6/metabolismo , Camundongos , Fator de Necrose Tumoral alfa/metabolismo
16.
J Nanobiotechnology ; 19(1): 85, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766052

RESUMO

BACKGROUND: Graphene oxide (GO), a novel carbon-based nanomaterial, has promising applications in biomedicine. However, it induces potential cytotoxic effects on the gastrointestinal (GI) tract cells, and these effects have been largely uncharacterized. The present study aimed to explore the toxic effects of GO on the intestinal tract especially under pre-existing inflammatory conditions, such as inflammatory bowel disease (IBD), and elucidate underlying mechanisms. RESULTS: Our findings indicated that oral gavage of GO worsened acute colitis induced by 2.5% dextran sodium sulfate (DSS) in mice. In vitro, GO exacerbated DSS-induced inflammation and apoptosis in the FHC cell line, an ideal model of intestinal epithelial cells (IECs). Further, the potential mechanism underlying GO aggravated mice colitis and cell inflammation was explored. Our results revealed that GO treatment triggered apoptosis in FHC cells through the activation of reactive oxygen species (ROS)/AMP-activated protein kinase (AMPK)/p53 pathway, as evidenced by the upregulation of cytochrome c (Cytc), Bax, and cleaved caspase-3 (c-cas3) and the downregulation of Bcl-2. Interestingly, pretreatment with an antioxidant, N-acetyl-L-cysteine, and a specific inhibitor of AMPK activation, Compound C (Com.C), effectively inhibited GO-induced apoptosis in FHC cells. CONCLUSIONS: Our data demonstrate that GO-induced IECs apoptosis via ROS/AMPK/p53 pathway activation accounts for the exacerbation of colitis in vivo and aggravation of inflammation in vitro. These findings provide a new insight into the pathogenesis of IBD induced by environmental factors. Furthermore, our findings enhance our understanding of GO as a potential environmental toxin, which helps delineate the risk of exposure to patients with disturbed intestinal epithelial barrier/inflammatory disorders such as IBD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Grafite/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Animais , Caspase 3 , Sobrevivência Celular , Colite/patologia , Colo , Citocinas , Feminino , Grafite/química , Inflamação , Doenças Inflamatórias Intestinais , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2
17.
Med Sci Monit ; 27: e928478, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33686049

RESUMO

BACKGROUND Bifidobacterium is a potentially effective and safe treatment for patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease. However, information on the influence of B. bifidum on gut microbial diversity of treated and pretreated IBD patients is limited. MATERIAL AND METHODS Our study investigated therapeutic and preventive effects of B. bifidum ATCC 29521 on C57BL/6 mice with dextran sulfate sodium (DSS)-induced acute colitis via 16S ribosomal ribonucleic acid (rRNA) gene sequencing. RESULTS Treatment and pretreatment of mice with B. bifidum ATCC 29521 significantly alleviated the severity of acute colitis on the basis of clinical and pathologic indicators. 16S rRNA gene sequencing showed that administration of B. bifidum shifted composition of the gut microbiome in mice with DSS-induced colitis in both treated and pretreated groups. Mice pretreated with B. bifidum ATCC 29521 for 21 days exhibited a significant increase in diversity of the gut microbiome. Principal coordinate analysis showed that gut microbiota structure was shaped by different treatments and time points. On the basis of linear discriminant analysis of effect size, the abundance of the genus Escherichia-Shigella, belonging to the family Enterobacteriaceae, was reduced in the B. bifidum-treated group, indicating that pathogens were inhibited by the B. bifidum treatment. Furthermore, the genera Intestinimonas and Bacteroides were significantly associated with the B. bifidum-pretreated group. CONCLUSIONS 16S rRNA gene sequencing showed that pretreatment with B. bifidum ATCC 29521 reduced intestinal inflammation and altered the gut microbiota to favor the genera Intestinimonas and Bacteroides.


Assuntos
Bifidobacterium bifidum/metabolismo , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Bactérias/genética , Colite/microbiologia , Colite Ulcerativa/genética , Colo/patologia , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Doenças Inflamatórias Intestinais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Probióticos/uso terapêutico , RNA Ribossômico 16S/genética
18.
Front Immunol ; 12: 619366, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708211

RESUMO

Ulcerative colitis is an inflammatory disease of the colon that is associated with colonic neutrophil accumulation. Recent evidence indicates that diet alters the composition of the gut microbiota and influences host-pathogen interactions. Specifically, bacterial fermentation of dietary fiber produces metabolites called short-chain fatty acids (SCFAs), which have been shown to protect against various inflammatory diseases. However, the effect of fiber deficiency on the key initial steps of inflammation, such as leukocyte-endothelial cell interactions, is unknown. Moreover, the impact of fiber deficiency on neutrophil recruitment under basal conditions and during inflammation in vivo is unknown. Herein, we hypothesized that a fiber-deficient diet promotes an inflammatory state in the colon at baseline and predisposes the host to more severe colitis pathology. Mice fed a no-fiber diet for 14 days showed significant changes in the gut microbiota and exhibited increased neutrophil-endothelial interactions in the colonic microvasculature. Although mice fed a no-fiber diet alone did not have observable colitis-associated symptoms, these animals were highly susceptible to low dose (0.5%) dextran sodium sulphate (DSS)-induced model of colitis. Supplementation of the most abundant SCFA, acetate, prevented no-fiber diet-mediated enrichment of colonic neutrophils and colitis pathology. Therefore, dietary fiber, possibly through the actions of acetate, plays an important role in regulating neutrophil recruitment and host protection against inflammatory colonic damage in an experimental model of colitis.


Assuntos
Quimiotaxia de Leucócito/imunologia , Colite/etiologia , Fibras na Dieta/deficiência , Microbioma Gastrointestinal , Infiltração de Neutrófilos/imunologia , Animais , Biomarcadores , Adesão Celular , Colite/metabolismo , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Dieta , Modelos Animais de Doenças , Células Endoteliais , Contagem de Leucócitos , Masculino , Metagenômica/métodos , Camundongos , RNA Ribossômico 16S
19.
J Tradit Chin Med ; 41(1): 68-78, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33522199

RESUMO

OBJECTIVE: To investigate the effects of Qingre Jianpi decoction (,QRJPD) on dextran sulfate sodium (DSS)-induced colitis mice and explore its mechanism. METHODS: All mice were randomly divided into six groups. Weight changes, disease activity index values, and histological damage were detected. Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC) method. The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were detected by western blot analysis, IHC, and quantitative reverse transcription polymerase chain reaction. RESULTS: QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis (UC), reduced the secretion of inflammatory cytokines, and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the NLRP3 inflammasome. CONCLUSION: QRJPD exerts protective effects by inhibiting DSS-induced NLRP3 inflammasome activation.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Sulfato de Dextrana/efeitos adversos , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamassomos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/química , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas NLR/química , Proteínas NLR/genética , Proteínas NLR/imunologia , Domínio Pirina
20.
Am J Pathol ; 191(5): 872-884, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33607043

RESUMO

Defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease. To date, no effective therapies that specifically target the intestinal TJ barrier are available. The purpose of this study was to identify probiotic bacterial species or strains that induce a rapid and sustained enhancement of intestinal TJ barrier and protect against the development of intestinal inflammation by targeting the TJ barrier. After high-throughput screening of >20 Lactobacillus and other probiotic bacterial species or strains, a specific strain of Lactobacillus acidophilus, referred to as LA1, uniquely produced a marked enhancement of the intestinal TJ barrier. LA1 attached to the apical membrane surface of intestinal epithelial cells in a Toll-like receptor (TLR)-2-dependent manner and caused a rapid increase in enterocyte TLR-2 membrane expression and TLR-2/TLR-1 and TLR-2/TLR-6 hetero-complex-dependent enhancement in intestinal TJ barrier function. Oral administration of LA1 caused a rapid enhancement in mouse intestinal TJ barrier, protected against a dextran sodium sulfate (DSS) increase in intestinal permeability, and prevented the DSS-induced colitis in a TLR-2- and intestinal TJ barrier-dependent manner. In conclusion, we report for the first time that a specific strain of LA causes a strain-specific enhancement of intestinal TJ barrier through a novel mechanism that involves the TLR-2 receptor complex and protects against the DSS-induced colitis by targeting the intestinal TJ barrier.


Assuntos
Colite/prevenção & controle , Inflamação/prevenção & controle , Lactobacillus acidophilus/fisiologia , Probióticos , Receptor 2 Toll-Like/metabolismo , Animais , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Células Epiteliais/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/patologia , Receptor 2 Toll-Like/genética
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