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1.
Food Funct ; 15(10): 5466-5484, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38690672

RESUMO

Inflammatory bowel disease (IBD) is difficult to cure, and formulating a dietary plan is an effective means to prevent and treat this disease. Wheat peptide contains a variety of bioactive peptides with anti-inflammatory and antioxidant functions. The results of this study showed that preventive supplementation with wheat peptide (WP) can significantly alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. WP can increase body weight, alleviate colon shortening, and reduce disease activity index (DAI) scores. In addition, WP improved intestinal microbial disorders in mice with colitis. Based on LC-MS, a total of 313 peptides were identified in WP, 4 of which were predicted to be bioactive peptides. The regulatory effects of WP and four bioactive peptides on the Keap1-Nrf2 signaling pathway were verified in Caco-2 cells. In conclusion, this study demonstrated that WP alleviates DSS-induced colitis by helping maintain gut barrier integrity and targeting the Keap1-Nrf2 axis; these results provided a rationale for adding WP to dietary strategies to prevent IBD.


Assuntos
Colite , Sulfato de Dextrana , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Peptídeos , Transdução de Sinais , Triticum , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Sulfato de Dextrana/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Humanos , Triticum/química , Células CACO-2 , Peptídeos/farmacologia , Masculino , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos
2.
Molecules ; 29(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731431

RESUMO

An excessive inflammatory response of the gastrointestinal tract is recognized as one of the major contributors to ulcerative colitis (UC). Despite this, effective preventive approaches for UC remain limited. Rosmarinic acid (RA), an enriched fraction from Perilla frutescens, has been shown to exert beneficial effects on disease-related inflammatory disorders. However, RA-enriched perilla seed meal (RAPSM) and perilla seed (RAPS) extracts have not been investigated in dextran sulfate sodium (DSS)-induced UC in mice. RAPSM and RAPS were extracted using the solvent-partitioning method and analyzed with high-pressure liquid chromatography (HPLC). Mice with UC induced using 2.5% DSS for 7 days were pretreated with RAPSM and RAPS (50, 250, 500 mg/kg). Then, the clinical manifestation, colonic histopathology, and serum proinflammatory cytokines were determined. Indeed, DSS-induced UC mice exhibited colonic pathological defects including an impaired colon structure, colon length shortening, and increased serum proinflammatory cytokines. However, RAPSM and RAPS had a protective effect at all doses by attenuating colonic pathology in DSS-induced UC mice, potentially through the suppression of proinflammatory cytokines. Concentrations of 50 mg/kg of RAPSM and RAPS were sufficient to achieve a beneficial effect in UC mice. This suggests that RAPSM and RAPS have a preventive effect against DSS-induced UC, potentially through alleviating inflammatory responses and relieving severe inflammation in the colon.


Assuntos
Colite Ulcerativa , Citocinas , Sulfato de Dextrana , Perilla , Extratos Vegetais , Sementes , Animais , Sulfato de Dextrana/efeitos adversos , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite Ulcerativa/prevenção & controle , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Citocinas/metabolismo , Citocinas/sangue , Sementes/química , Perilla/química , Modelos Animais de Doenças , Masculino , Depsídeos/farmacologia , Depsídeos/química , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Cinamatos/farmacologia , Cinamatos/química , Ácido Rosmarínico , Perilla frutescens/química
3.
J Agric Food Chem ; 72(19): 10923-10935, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691832

RESUMO

This study aimed to explore the ameliorative effects and potential mechanisms of Huangshan Umbilicaria esculenta polysaccharide (UEP) in dextran sulfate sodium-induced acute ulcerative colitis (UC) and UC secondary liver injury (SLI). Results showed that UEP could ameliorate both colon and liver pathologic injuries, upregulate mouse intestinal tight junction proteins (TJs) and MUC2 expression, and reduce LPS exposure, thereby attenuating the effects of the gut-liver axis. Importantly, UEP significantly downregulated the secretion levels of TNF-α, IL-1ß, and IL-6 through inhibition of the NF-κB pathway and activated the Nrf2 signaling pathway to increase the expression levels of SOD and GSH-Px. In vitro, UEP inhibited the LPS-induced phosphorylation of NF-κB P65 and promoted nuclear translocation of Nrf2 in RAW264.7 cells. These results revealed that UEP ameliorated UC and SLI through NF-κB and Nrf2-mediated inflammation and oxidative stress. The study first investigated the anticolitis effect of UEP, suggesting its potential for the treatment of colitis and colitis-associated liver disease.


Assuntos
Colite , Sulfato de Dextrana , Fator 2 Relacionado a NF-E2 , NF-kappa B , Polissacarídeos , Animais , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/administração & dosagem , Sulfato de Dextrana/efeitos adversos , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Humanos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/metabolismo , Células RAW 264.7 , NF-kappa B/metabolismo , NF-kappa B/genética , Camundongos Endogâmicos C57BL , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Estresse Oxidativo/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/imunologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Mucina-2/genética , Mucina-2/metabolismo
4.
J Tradit Chin Med ; 44(3): 427-436, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38767626

RESUMO

OBJECTIVE: To evaluate the protective effects of Chang'an decoction (, CAD) on colitis, and investigate the potential mechanisms underlying these effects from the perspectives of endoplasmic reticulum (ER) stress induced by mitofusin 2 (MFN2). METHODS: The composition of CAD was identified by liquid chromatography-mass spectrometry technology. A mice model of dextran sulfate sodium (DSS) induced colitis was established and therapeutic effects of CAD were determined by detecting body weight, disease activity index, colon length and histopathological changes. Then, the expression levels of MFN2, ER stress markers and Nucleotide-binding domain and leucine-rich repeat protein3 (NLRP3) relevant proteins were detected by polymerase chain reaction (PCR), Western blot, immunohistochemistry and immunofluorescence staining. Subsequently, knockdown and overexpression cell model were constructed to further investigate the underlying mechanism of MFN2 mediating ER stress and energy metabolism by PCR, Western blot, electron microscopy and reactive oxygen species (ROS) staining. Finally, inflammatory indicator and tight junction proteins were measured by PCR and immunofluorescence staining to evaluate the protective effects of CAD. RESULTS: Results showed that the indispensable regulatory role of MFN2 in mediating ER stress and mitochondrial damage was involved in the protective effects of CAD on colitis in mice fed with DSS. Network pharmacology analysis also revealed CAD may play a protective effect on colitis by affecting mitochondrial function. In addition, our data also suggested a causative role for MFN2 in the development of inflammatory responses and energy metabolic alterations by constructing a knockdown and overexpression cell model whereby alter proper ER-mitochondria interaction in Caco-2 cells. Furthermore, relative expression analyses of ER stress markers and NLRP3 inflammasome showed the onset of ER stress and activation of NLRP3 inflammasome, which is consistent with the above findings. In contrast, intervention of CAD could improve the mucosal barrier integrity and colonic inflammatory response effectively through inhibiting ER stress response mediated by MFN2. CONCLUSION: CAD could alleviate ER stress by regulating MFN2 to exert therapeutic effects on DSS-induced colitis, which might provide an effective natural therapeutic approach for the treatment of ulcerative colitis.


Assuntos
Colite , Medicamentos de Ervas Chinesas , Estresse do Retículo Endoplasmático , GTP Fosfo-Hidrolases , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Colite/tratamento farmacológico , Colite/metabolismo , Colite/genética , Colite/induzido quimicamente , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Sulfato de Dextrana/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Espécies Reativas de Oxigênio/metabolismo
5.
J Tradit Chin Med ; 44(3): 478-488, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38767631

RESUMO

OBJECTIVE: To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis (UC). METHODS: The bioinformatics method was used to predict the active ingredients and action targets of Shuangling extract against UC in mice. And the biological experiments such as serum biochemical indexes and histopathological staining were used to verify the pharmacological effect and mechanism of Shuangling extract against UC in mice. RESULTS: The Shuangling extract reduced the levels of seruminterleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-N), interleukin-6 (IL-6) and other inflammatory factors in UC mice and inhibited the inflammatory response. AKT Serine/threonine Kinase 1 and IL-6 may be the main targets of the anti-UC action of Shuangling extract, and the TNF signaling pathway, Forkhead box O signaling pathway and T-cell receptor signaling pathway may be the main signaling pathways. CONCLUSION: The Shuangling extract could inhibit the inflammatory response induced by UC and regulate intestinal immune function through multiple targets and multiple channels, which provided a new option and theoretical basis for anti-UC.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Fator de Necrose Tumoral alfa , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Camundongos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Sulfato de Dextrana/efeitos adversos , Masculino , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/imunologia , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos
6.
J Transl Med ; 22(1): 327, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566233

RESUMO

BACKGROUND: Regulatory T cells (Tregs) are crucial in maintaining immune homeostasis and preventing autoimmunity and inflammation. A proportion of Treg cells can lose Foxp3 expression and become unstable under inflammation conditions. The precise mechanisms underlying this phenomenon remain unclear. METHODS: The PI16 gene knockout mice (PI16fl/flFoxp3Cre) in Treg were constructed, and the genotypes were identified. The proportion and phenotypic differences of immune cells in 8-week-old mice were detected by cell counter and flow cytometry. Two groups of mouse Naïve CD4+T cells were induced to differentiate into iTreg cells to observe the effect of PI16 on the differentiation and proliferation of iTreg cells, CD4+CD25+Treg and CD4+CD25- effector T cells (Teff) were selected and co-cultured with antigen presenting cells (APC) to observe the effect of PI16 on the inhibitory ability of Treg cells in vitro. The effects of directed knockout of PI16 in Treg cells on inflammatory symptoms, histopathological changes and immune cell expression in mice with enteritis and autoimmune arthritis were observed by constructing the model of antigen-induced arthritis (AIA) and colitis induced by dextran sulfate sodium salt (DSS). RESULTS: We identified peptidase inhibitor 16 (PI16) as a negative regulator of Treg cells. Our findings demonstrate that conditional knock-out of PI16 in Tregs significantly enhances their differentiation and suppressive functions. The conditional knockout of the PI16 gene resulted in a significantly higher abundance of Foxp3 expression (35.12 ± 5.71% vs. 20.00 ± 1.61%, p = 0.034) in iTreg cells induced in vitro compared to wild-type mice. Mice with Treg cell-specific PI16 ablation are protected from autoimmune arthritis (AIA) and dextran sulfate sodium (DSS)-induced colitis development. The AIA model of PI16CKO is characterized by the reduction of joint structure and the attenuation of synovial inflammation and in DSS-induced colitis model, conditional knockout of the PI16 reduce intestinal structural damage. Additionally, we found that the deletion of the PI16 gene in Treg can increase the proportion of Treg (1.46 ± 0.14% vs. 0.64 ± 0.07%, p < 0.0001) and decrease the proportion of Th17 (1.00 ± 0.12% vs. 3.84 ± 0.64%, p = 0.001). This change will enhance the shift of Th17/Treg toward Treg cells in AIA arthritis model (0.71 ± 0.06% vs. 8.07 ± 1.98%, p = 0.003). In DSS-induced colitis model of PI16CKO, the proportion of Treg in spleen was significantly increased (1.40 ± 0.15% vs. 0.50 ± 0.11%, p = 0.003), Th17 (2.18 ± 0.55% vs. 6.42 ± 1.47%, p = 0.017), Th1 (3.42 ± 0.19% vs. 6.59 ± 1.28%, p = 0.028) and Th2 (1.52 ± 0.27% vs. 2.76 ± 0.38%, p = 0.018) in spleen was significantly decreased and the Th17/Treg balance swift toward Treg cells (1.44 ± 0.50% vs. 24.09 ± 7.18%, p = 0.012). CONCLUSION: PI16 plays an essential role in inhibiting Treg cell differentiation and function. Conditional knock out PI16 gene in Treg can promote the Treg/Th17 balance towards Treg dominance, thereby alleviating the condition. Targeting PI16 may facilitate Treg cell-based therapies for preventing autoimmune diseases and inflammatory diseases. The research provides us with novel insights and future research avenues for the treatment of autoimmune diseases, particularly arthritis and colitis.


Assuntos
Artrite , Doenças Autoimunes , Colite , Animais , Camundongos , Artrite/metabolismo , Artrite/patologia , Doenças Autoimunes/metabolismo , Diferenciação Celular , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Inflamação/patologia , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores , Células Th17
7.
Food Funct ; 15(8): 4109-4121, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38597225

RESUMO

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1ß, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.


Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Homeostase , Camundongos Endogâmicos C57BL , Riboflavina , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Riboflavina/farmacologia , Homeostase/efeitos dos fármacos , Masculino , Modelos Animais de Doenças , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo
8.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1266-1274, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621974

RESUMO

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.


Assuntos
Anexina A1 , Neoplasias Associadas a Colite , Colite , Medicamentos de Ervas Chinesas , Camundongos , Animais , Colite/complicações , Colite/tratamento farmacológico , Colite/genética , beta Catenina/genética , beta Catenina/metabolismo , Ciclina D1/metabolismo , Fusobacterium nucleatum/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Antígeno Ki-67/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Camundongos Endogâmicos C57BL , Caderinas/metabolismo , Peso Corporal , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Azoximetano
9.
Int J Mol Sci ; 25(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38674054

RESUMO

Neuregulin-1 (Nrg1, gene symbol: Nrg1), a ligand of the ErbB receptor family, promotes intestinal epithelial cell proliferation and repair. However, the dynamics and accurate derivation of Nrg1 expression during colitis remain unclear. By analyzing the public single-cell RNA-sequencing datasets and employing a dextran sulfate sodium (DSS)-induced colitis model, we investigated the cell source of Nrg1 expression and its potential regulator in the process of epithelial healing. Nrg1 was majorly expressed in stem-like fibroblasts arising early in mouse colon after DSS administration, and Nrg1-Erbb3 signaling was identified as a potential mediator of interaction between stem-like fibroblasts and colonic epithelial cells. During the ongoing colitis phase, a significant infiltration of macrophages and neutrophils secreting IL-1ß emerged, accompanied by the rise in stem-like fibroblasts that co-expressed Nrg1 and IL-1 receptor 1. By stimulating intestinal or lung fibroblasts with IL-1ß in the context of inflammation, we observed a downregulation of Nrg1 expression. Patients with inflammatory bowel disease also exhibited an increase in NRG1+IL1R1+ fibroblasts and an interaction of NRG1-ERBB between IL1R1+ fibroblasts and colonic epithelial cells. This study reveals a novel potential mechanism for mucosal healing after inflammation-induced epithelial injury, in which inflammatory myeloid cell-derived IL-1ß suppresses the early regeneration of intestinal tissue by interfering with the secretion of reparative neuregulin-1 by stem-like fibroblasts.


Assuntos
Colite , Sulfato de Dextrana , Fibroblastos , Mucosa Intestinal , Neuregulina-1 , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Colite/metabolismo , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Neuregulina-1/metabolismo , Neuregulina-1/genética , Receptor ErbB-3/metabolismo , Receptor ErbB-3/genética , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1/genética
10.
Int J Biol Macromol ; 267(Pt 1): 131482, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599423

RESUMO

The aim of this study was to explore the dynamic changes in the physicochemical properties of Laiyang pear residue polysaccharide (LPP) during in vitro digestion, as well as its protective effect on the intestines. Monosaccharide composition and molecular weight analysis showed that there was no significant change in LPP during the oral digestion stage. However, during the gastric and intestinal digestion stages, the glycosidic bonds of LPP were broken, leading to the dissociation of large molecular aggregates and a significant increase in reducing sugar content (CR) accompanied by a decrease in molecular weight. In addition, LPP exerted the intestinal protective ability via inhibiting gut inflammation, improving intestinal barrier, and regulating intestinal flora in DSS-induced mice. Specifically, LPP mitigated DSS-induced intestinal pathological damage of mice via enhancing intestinal barrier integrity and upregulating expressions of TJ proteins, and suppressed inflammation by inhibiting NF-κB signaling axis. Furthermore, LPP decreased the ratio of Firmicutes/Bacteroidetes, increased the relative abundance of Lactobacillus, and altered the diversity and the composition of gut microbiota in DSS-induced mice. Therefore, LPP had the potential to be a functional food that improved gut microbiota environment to enhance health and prevent diseases, such as a prebiotic.


Assuntos
Sulfato de Dextrana , Microbioma Gastrointestinal , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Camundongos , Sulfato de Dextrana/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Pyrus/química , Inflamação/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Digestão/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo
11.
Food Funct ; 15(9): 4970-4982, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38606509

RESUMO

Inhibition of ferroptosis in intestinal epithelial cells serves as an attractive target for the development of therapeutic strategies for colitis. Pinobanksin, one of the main flavonoids derived from propolis, possesses significant anti-inflammatory effects and inhibits the cell death of several cell lines. Here, we evaluated whether pinobanksin influenced colitis by modulation of epithelial ferroptosis. Mice treated with 2.5% DSS dissolved in sterile distilled water were established for an acute colitis model. The mitochondrial morphology, colonic iron level, lipid peroxidation products MDA/4-HNE, and lipid reactive oxygen species levels were measured to assess ferroptosis in epithelial cells. RNA-seq and functional analyses were performed to reveal key genes mediating pinobanksin-exerted modulation of ferroptosis. We found that pinobanksin, at different doses, induced significant anti-colitis effects and inhibited the elevated ferroptosis in colonic epithelial cells isolated from DSS-treated mice largely by activating GPX4 (negative regulator of ferroptosis). Furthermore, RNA-seq assays indicated that pinobanksin significantly increased the cystine transporter SLC7A11 in colonic tissues from mice with colitis. Depletion of SLC7A11 largely blocked pinobanksin-induced promotion of cystine uptake/glutathione biosynthesis and suppression of ferroptosis in epithelial cells from mice with colitis or IEC-6 cells pretreated with RSL3. Altogether, pinobanksin alleviated DSS-induced colitis largely by inhibition of ferroptosis in epithelial cells. Activation of SLC7A11 by pinobanksin resulted in the promotion of cystine uptake and enhancement of glutathione biosynthesis. This work will provide novel guidance for the clinical use of pinobanksin to treat colitis through inhibition of epithelial ferroptosis.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Colite , Ferroptose , Glutationa , Ferroptose/efeitos dos fármacos , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Glutationa/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Camundongos Endogâmicos C57BL , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Sulfato de Dextrana/efeitos adversos , Masculino , Flavonoides/farmacologia , Modelos Animais de Doenças , Humanos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
12.
J Food Sci ; 89(5): 3078-3093, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38605580

RESUMO

Human milk contains a variety of microorganisms that exert benefit for human health. In the current study, we isolated a novel Lactobacillus gasseri strain named Lactobacillus gasseri (L. gasseri) SHMB 0001 from human milk and aimed to evaluate the probiotic characteristics and protective effects on murine colitis of the strain. The results showed that L. gasseri SHMB 0001 possessed promising potential probiotic characteristics, including good tolerance against artificial gastric and intestinal fluids, adhesion to Caco-2 cells, susceptibility to antibiotic, no hemolytic activity, and without signs of toxicity or infection in mice. Administration of L. gasseri SHMB 0001 (1 × 108 CFU per gram of mouse weight per day) reduced weight loss, the disease activity index, and colon shortening in mice during murine colitis conditions. Histopathological analysis revealed that L. gasseri SHMB 0001 treatment attenuated epithelial damage and inflammatory infiltration in the colon. L. gasseri SHMB 0001 treatment increased the expression of colonic occludin and claudin-1 while decreasing the expression of pro-inflammatory cytokine genes. L. gasseri SHMB 0001 modified the composition and structure of the gut microbiota community and partially recovered the Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways altered by dextran sulfate sodium (DSS). Overall, our results indicated that the human breast milk-derived L. gasseri SHMB 0001 exhibited promising probiotic properties and ameliorative effect on DSS-induced colitis in mice. L. gasseri SHMB 0001 may be applied as a promising probiotic against intestinal inflammation in the future. PRACTICAL APPLICATION: L. gasseri SHMB 0001 isolated from human breast milk showed good tolerance to gastrointestinal environment, safety, and protective effect against DSS-induced mice colitis via enforcing gut barrier, downregulating pro-inflammatory cytokines, and modulating gut microbiota. L. gasseri SHMB 0001 may be a promising probiotic candidate for the treatment of intestinal inflammation.


Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Lactobacillus gasseri , Leite Humano , Probióticos , Probióticos/farmacologia , Animais , Humanos , Camundongos , Colite/induzido quimicamente , Colite/terapia , Colite/microbiologia , Sulfato de Dextrana/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Células CACO-2 , Feminino , Colo/microbiologia , Colo/patologia , Colo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças
13.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38612870

RESUMO

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut-brain interaction.


Assuntos
Disfunção Cognitiva , Colite , Eucommiaceae , Animais , Camundongos , Sulfato de Dextrana/efeitos adversos , Receptor 4 Toll-Like , Colite/induzido quimicamente , Colite/tratamento farmacológico , Ácido Clorogênico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico
14.
Nutrients ; 16(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38674835

RESUMO

Inflammatory bowel disease (IBD) has attracted much attention worldwide due to its prevalence. In this study, the effect of a solid-in-oil-in-water (S/O/W) emulsion with Caffeic acid phenethyl ester (CAPE, a polyphenolic active ingredient in propolis) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice was evaluated. The results showed that CAPE-emulsion could significantly alleviate DSS-induced colitis through its effects on colon length, reduction in the disease activity index (DAI), and colon histopathology. The results of ELISA and Western blot analysis showed that CAPE-emulsion can down-regulate the excessive inflammatory cytokines in colon tissue and inhibit the expression of p65 in the NF-κB pathway. Furthermore, CAPE-emulsion promoted short-chain fatty acids production in DSS-induced colitis mice. High-throughput sequencing results revealed that CAPE-emulsion regulates the imbalance of gut microbiota by enhancing diversity, restoring the abundance of beneficial bacteria (such as Odoribacter), and suppressing the abundance of harmful bacteria (such as Afipia, Sphingomonas). The results of fecal metabolome showed that CAPE-emulsion restored the DSS-induced metabolic disorder by affecting metabolic pathways related to inflammation and cholesterol metabolism. These research results provide a scientific basis for the use of CPAE-emulsions for the development of functional foods for treating IBD.


Assuntos
Ácidos Cafeicos , Colite , Emulsões , Animais , Masculino , Camundongos , Ácidos Cafeicos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/microbiologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Emulsões/química , Emulsões/farmacologia , Fezes/microbiologia , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Transdução de Sinais/efeitos dos fármacos
15.
Int J Biol Macromol ; 268(Pt 2): 131915, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679254

RESUMO

A water-soluble polysaccharide from the brown alga Ishige Okamurae, designated IOP-0, was obtained by preparative anion-exchange and size-exclusion chromatography. Chemical and spectroscopic investigations revealed that IOP-0 was a sulfated fucoidan with a backbone primarily composed of 3-linked and 4-linked-L-fucose with sulfate groups at C-2/C-4 of the 3-linked-L-fucose. The protective effect of IOP-0 on ulcerative colitis was evaluated in this work. The results showed that IOP-0 could significantly alleviate the symptoms of ulcerative colitis by preventing weight loss, preserving the structure of intestinal tissues, and ameliorating the dysregulation of inflammatory cytokines (TNF-α, IL-6, and IL-10). Meanwhile, IOP-0 protected the colonic mucosal barrier by promoting the tight junction protein ZO-1 and occludin expression. In addition, IOP-0 was able to maintain intestinal homeostasis and improve intestinal function by regulating the gut microbiota and their metabolites, such as short-chain fatty acids (SCFAs). These results suggest that IOP-0 might be a potential dietary supplement for the prevention and treatment of ulcerative colitis.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Polissacarídeos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Polissacarídeos/farmacologia , Polissacarídeos/química , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Sulfato de Dextrana/efeitos adversos , Camundongos , Phaeophyceae/química , Citocinas/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Inflamação/tratamento farmacológico , Sulfatos/química , Masculino
16.
J Transl Med ; 22(1): 369, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637862

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Fator de Transcrição STAT3 , Humanos , Camundongos , Animais , Colite Ulcerativa/terapia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Ácidos Graxos Voláteis/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Bactérias/metabolismo , Modelos Animais de Doenças , Inflamação , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Colo , Proteína Forkhead Box O3/metabolismo
17.
Food Funct ; 15(7): 3731-3743, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38489162

RESUMO

Pleurotus tuber-regium (PTR) has been proved to have obvious pharmacological properties. In this study, a polysaccharide was extracted from the mycelium of PTR and administered to DSS-induced colitis mice to clarify the protective effect and mechanism of the PTR polysaccharide (PTRP) on colitis. The results showed that PTRP significantly improved the clinical symptoms and intestinal tissue damage caused by colitis and inhibited the secretion of pro-inflammatory cytokines and myeloperoxidase activity, while the levels of oxidative stress factors in mice decreased and the antioxidant capacity increased. The 16S rRNA sequencing of the mouse cecum content showed that PTRP changed the composition of gut microbiota, and the diversity and abundance of beneficial bacteria increased. In addition, PTRP also enhanced the production of short-chain fatty acids by regulating gut microbiota. In conclusion, our study shows that PTRP has the potential to relieve IBD symptoms and protect intestinal function by regulating inflammatory cytokines, oxidative stress and gut microbiota.


Assuntos
Colite , Microbioma Gastrointestinal , Pleurotus , Camundongos , Animais , Citocinas/metabolismo , RNA Ribossômico 16S/genética , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Estresse Oxidativo , Antioxidantes/farmacologia , Polissacarídeos/farmacologia , Micélio/metabolismo , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo/metabolismo
18.
J Agric Food Chem ; 72(13): 7397-7410, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38528736

RESUMO

This study was designed to elucidate the colon microbiota-targeted release of nonextractable bound polyphenols (NEPs) derived from Fu brick tea and to further identify the possible anti-inflammatory mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. 1.5% DSS drinking water-induced C57BL/6J mice were fed rodent chow supplemented with or without 8% NEPs or dietary fibers (DFs) for 37 days. The bound p-hydroxybenzoic acid and quercetin in NEPs were liberated up to 590.5 ± 70.6 and 470.5 ± 51.6 mg/g by in vitro human gut microbiota-simulated fermentation, and released into the colon of the mice supplemented with NEPs by 4.4- and 1.5-fold higher than that of the mice supplemented without NEPs, respectively (p < 0.05). Supplementation with NEPs also enhanced the colonic microbiota-dependent production of SCFAs in vitro and in vivo (p < 0.05). Interestingly, Ingestion of NEPs in DSS-induced mice altered the gut microbiota composition, reflected by a dramatic increase in the relative abundance of Dubosiella and Enterorhabdus and a decrease in the relative abundance of Alistipes and Romboutsia (p < 0.05). Consumption of NEPs was demonstrated to be more effective in alleviating colonic inflammation and UC symptoms than DFs alone in DSS-treated mice (p < 0.05), in which the protective effects of NEPs against UC were highly correlated with the reconstruction of the gut microbiome, formation of SCFAs, and release of bound polyphenols. These findings suggest that NEPs as macromolecular carriers exhibit targeted delivery of bound polyphenols into the mouse colon to regulate gut microbiota and alleviate inflammation.


Assuntos
Colite Ulcerativa , Colite , Microbiota , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Inflamação/tratamento farmacológico , Fibras na Dieta , Polifenóis , Colo , Chá , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Colite/induzido quimicamente , Colite/tratamento farmacológico
19.
Food Funct ; 15(8): 4154-4169, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38482844

RESUMO

The consumption of dietary fiber is beneficial for gut health, but the role of bound polyphenols in dietary fiber has lacked systematic study. The aim of this study is to evaluate the ameliorative effect of mung bean coat dietary fiber (MDF) on DSS-induced ulcerative colitis in mice in the presence and absence of bound polyphenols. Compared to polyphenol-removed MDF (PR-MDF), MDF and formulated-MDF (F-MDF,backfilling polyphenols by the amount of extracted from MDF into PR-MDF) alleviated symptoms such as weight loss and colonic injury in mice with colitis, effectively reduced excessive inflammatory responses, and the bound polyphenols restored the integrity of the intestinal barrier by promoting the expression of tight junction proteins. Additionally, bound polyphenols restored the expression of autophagy-related proteins (mTOR, beclin-1, Atg5 and Atg7) and inhibited the excessive expression of apoptotic-related proteins (Bax, caspase-9, and caspase-3). Furthermore, bound polyphenols could ameliorate the dysregulation of the intestinal microbiota by increasing the abundance of beneficial bacteria and inhibiting the abundance of harmful bacteria. Thus, it can be concluded that the presence of bound polyphenols in MDF plays a key role in the alleviation of DSS-induced ulcerative colitis.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Fibras na Dieta , Microbioma Gastrointestinal , Polifenóis , Vigna , Animais , Polifenóis/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Fibras na Dieta/farmacologia , Sulfato de Dextrana/efeitos adversos , Vigna/química , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Humanos
20.
Food Funct ; 15(8): 4262-4275, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38526548

RESUMO

Changes in the chemical composition of white tea during storage have been studied extensively; however, whether such chemical changes impact the efficacy of white tea in ameliorating colitis remains unclear. In this study, we compared the effects of new (2021 WP) and 10-year-old (2011 WP) white tea on 3% dextrose sodium sulfate (DSS)-induced ulcerative colitis in mice by gavaging mice with the extracts at 200 mg kg-1 day-1. Chemical composition analysis showed that the levels of 50 compounds, such as flavanols, dimeric catechins, and amino acids, were significantly lower in the 2011 WP extract than in the 2021 WP extract, whereas the contents of 21 compounds, such as N-ethyl-2-pyrrolidinone-substituted flavan-3-ols, theobromine, and (-)-epigallocatechin-3-(3''-O-methyl) gallate, were significantly higher. Results of the animal experiments showed that 2011 WP ameliorated the pathological symptoms of colitis, which was superior to the activity of 2021 WP, and this effect was likely enhanced based on the decreasing of the relative abundance of the g_bacteroides and g_Escherichia-Shigella flora in mice with colitis and promoting the conversion of primary bile acids to secondary bile acids in the colon. These results will facilitate the development of novel functional products from white tea.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Chá , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Chá/química , Sulfato de Dextrana/efeitos adversos , Masculino , Extratos Vegetais/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Camellia sinensis/química , Catequina/farmacologia , Catequina/análogos & derivados , Colo/metabolismo , Colo/efeitos dos fármacos , Colo/microbiologia
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