RESUMO
Edible plant-derived nanovesicles (ePDNs) have shown potential as a non-pharmacological option for inflammatory bowel disease (IBD) by maintaining gut health and showing anti-inflammatory effects. However, the effects of Allium tuberosum-derived nanovesicles (ADNs) on colitis have not been studied to date. Here, we extracted exosome-like nanovesicles from Allium tuberosum and investigated whether they have an anti-inflammatory effect in RAW 264.7 cells and colitis mice. The results showed that ADNs reduced the elevated levels of inflammatory factors such as IL-1ß, IL-6, TNF-α, and NF-κB pathway-related proteins as a consequence of lipopolysaccharide (LPS) stimulation in RAW 264.7 cells. Furthermore, our mouse experiments demonstrated that ADNs could ameliorate dextran sulfate sodium (DSS)-induced colitis symptoms (e.g., increased disease activity index score, intestinal permeability, and histological appearance). Additionally, ADNs counteracted DSS-induced colitis by downregulating the expression of serum amyloid A (SAA), IL-1ß, IL-6, and TNF-α and increasing the expression of tight junction proteins (ZO-1 and occludin) and the anti-inflammatory cytokine IL-10. 16S rRNA gene sequencing showed that ADN intervention restored the gut microbial composition, which was similar to that of the DSS non-treated group, by decreasing the ratio of Firmicutes to Bacteroidetes and the relative abundance of Proteobacteria. Furthermore, ADNs induced acetic acid production along with an increase in the abundance of Lactobacillus. Overall, our findings suggest that ADN supplementation has a crucial role in maintaining gut health and is a novel preventive therapy for IBD.
Assuntos
Anti-Inflamatórios , Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Camundongos Endogâmicos C57BL , Masculino , Modelos Animais de Doenças , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagemRESUMO
This study is to investigate the protective effects of Eurotium cristatum intracellular polysaccharides (ECIP) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). The oral administration of ECIP could downregulate the disease activity index (DAI) and ameliorate the colonic shortening, immune stress, and damage caused by DSS. In addition, ECIP treatment increased the colonic contents of SCFAs including acetic, propionic, and butyric acids in UC mice. Targeted and untargeted metabolic analysis suggested that ECIP dramatically altered the tryptophan metabolism in the feces of UC mice and promoted the conversion of tryptophan into indole metabolites including indolepyruvate and indole-3-acetic acid (IAA) and indolealdehyde (IAId). Moreover, ECIP observably increased the content of colonic IL-22 and stimulated the relative concentration and relative expression of tight junction molecules in mRNA and proteins levels. Conclusively, consumption of ECIP can improve colon damage and its related effects of UC by promoting the production of IAA and IAId to reinforce intestinal barriers.
Assuntos
Colite Ulcerativa , Colo , Camundongos Endogâmicos C57BL , Polissacarídeos , Triptofano , Animais , Camundongos , Triptofano/metabolismo , Masculino , Colite Ulcerativa/metabolismo , Colite Ulcerativa/tratamento farmacológico , Humanos , Colo/metabolismo , Colo/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Polissacarídeos/química , Polissacarídeos/administração & dosagem , Sulfato de Dextrana/efeitos adversos , Ácidos Indolacéticos/metabolismo , Interleucina 22 , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
The polysaccharide glucan was extracted from Gastrodia elata Blume, and its structural characterizations and beneficial effects against acute dextran sulfate sodium (DSS)-induced ulcerative colitis were investigated. The results showed that a polysaccharide GP with a molecular weight of 811.0 kDa was isolated from G. elata Blume. It had a backbone of α-D-1,4-linked glucan with branches of α-d-glucose linked to the C-6 position. GP exhibited protective effects against DSS-induced ulcerative colitis, and reflected in ameliorating weight loss and pathological damages in mice, increasing colon length, inhibiting the expression of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), decreasing the levels of inflammatory related proteins NLRP3 and ASC, and elevating the anti-inflammatory cytokine interleukin-10 (IL-10) level in mouse colon tissues. GP supplementation also reinforced the intestinal barrier by promoting the expression of ZO-1, Occludin, and MUC2 of colon tissues, and positively regulated intestinal microbiota. Thus, GP treatment possessed a significant improvement in ulcerative colitis in mice, and it was expected to be developed as a functional food.
Assuntos
Sulfato de Dextrana , Gastrodia , Glucanos , Animais , Sulfato de Dextrana/efeitos adversos , Glucanos/química , Glucanos/farmacologia , Camundongos , Gastrodia/química , Colite/tratamento farmacológico , Colite/induzido quimicamente , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Citocinas/metabolismo , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Peso MolecularRESUMO
Miao sour soup (MSS), a daily fermented food in Guizhou, China, is rich in microorganisms with various beneficial activities, including anti-inflammatory and antioxidant activities. However, the therapeutic effects of MSS on IBD remain unexplored. This study aimed to investigate the protective effect of MSS against colitis in mice. In this study, we examined the microbial community structure of MSS by metagenomic sequencing and also explored the protective effect of MSS on DSS-induced colitis in mice. We investigated the effects of MSS on intestinal inflammatory response and intestinal barrier function in mice. Finally, the changes in intestinal flora were analyzed based on the 16S rRNA gene sequencing results. Significantly, the experiment result shows that MSS ameliorated the severity of DSS-induced disease in mice by mitigating colitis-associated weight loss, reducing the disease activity index of IBD, alleviating colonic hemorrhagic lesions, increasing colon length, and improving colonic tissue damage. Moreover, MSS preserved intestinal barrier integrity and restored intestinal epithelial function in mice. Additionally, MSS modulated the structure and composition of the intestinal flora. Furthermore, MSS downregulated pro-inflammatory factors and attenuated the NF-κB p65 expression, thereby mitigating the inflammatory response. These findings highlight the protective effect of MSS against DSS-induced colitis, providing substantial scientific support for potential applications of MSS as a functional food.
Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Mucosa Intestinal , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Masculino , Mucosa Intestinal/microbiologia , Camundongos Endogâmicos C57BL , Alimentos Fermentados , Modelos Animais de Doenças , Colo/microbiologia , Colo/metabolismo , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Função da Barreira IntestinalRESUMO
3,5-Dimethyl-8-methoxy-3,4-dihydro-1H-isochromen-6-ol (DMD) is a polyketide compound obtained from the endophytic fungus Penicillium sp. HJT-A-10 of Rhodiola tibetica. R. tibetica is a nourishing food and also used in traditional Chinese medicine and Xizang medicine. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice, DMD significantly alleviated the pathological symptom of UC. Network pharmacology studies have shown that nucleotide-binding domain-like receptor family pyrin domain containing (NLRP) 3 is the primary target protein of DMD associated with anti-UC. In molecular biology studies, DMD suppressed the activation of NLRP3 and decreased the expression of downstream inflammatory proteins and pro-inflammatory cytokines in UC. The finding was further verified in knockout mice. DMD lost the effect of attenuating DSS-induced UC in NLRP3-/- mice. In conclusion, this study demonstrates that DMD reduces inflammatory response and balances the barrier integrity to attenuate UC via targeting NLRP3, and DMD is a potential natural agent or dietary supplement for attenuating UC.
Assuntos
Colite Ulcerativa , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/genética , Camundongos , Humanos , Masculino , Penicillium/química , Benzopiranos/farmacologia , Benzopiranos/química , Sulfato de Dextrana/efeitos adversosRESUMO
Extracellular vesicles released by probiotics have been demonstrated to effectively alleviate intestinal inflammation, yet the precise underlying mechanisms remain unclear. In this research, for the first time, Lactobacillus plantarum UJS001 (LP-UJS) was isolated from fermented sauerkraut in Zhenjiang, China. Thereafter, the therapeutic effect of LP-UJS-derived extracellular vesicles (LP-UJS-EVs) on dextran sulfate sodium-induced ulcerative colitis (UC) in mice was analyzed to elucidate the immune mechanisms. According to our findings, LP-UJS-EVs played a pivotal role in restoring the intestinal barrier and alleviating intestinal inflammation. Notably, LP-UJS-EVs induced M2 polarization of macrophages, promoted the release of IL-10 and TGF-ß, inhibited the release of histamine, IL-6, and TNF-α, and exerted regulatory effects on intestinal microflora, as evidenced by the reduced abundances of Coprococcus, Parabacteroides, Staphylococcus, and Allobaculum, alongside the enhanced abundance of Prevotella. Furthermore, both LP-UJS and LP-UJS-EVs affected the lysine degradation pathway and significantly increased the abundance of related metabolites, especially oxoadipic acid. In summary, our results underscore the substantial therapeutic potential of LP-UJS and its secreted EVs in the treatment of UC.
Assuntos
Colite Ulcerativa , Vesículas Extracelulares , Microbioma Gastrointestinal , Lactobacillus plantarum , Macrófagos , Camundongos Endogâmicos C57BL , Probióticos , Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/imunologia , Lactobacillus plantarum/metabolismo , Animais , Camundongos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/química , Macrófagos/imunologia , Macrófagos/metabolismo , Probióticos/farmacologia , Probióticos/administração & dosagem , Masculino , Humanos , Homeostase , Interleucina-10/metabolismo , Interleucina-10/genética , Interleucina-10/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/genética , Sulfato de Dextrana/efeitos adversos , Fator de Crescimento Transformador beta/metabolismoRESUMO
Fucoidan has shown better effects on the improvement of acute ulcerative colitis (UC). However, the specific mechanisms by which fucoidan improves UC-related behavioral disorders in aged mice, especially its effect on the gut-brain axis, remain to be further explored. C57BL/6 male mice aged 8 months were gavaged with 400 or 100 mg/kg bw day fucoidan for five consecutive weeks, with UC being induced by ad libitum to dextran sulfate sodium (DSS) solution in the fifth week. The results showed that fucoidan ameliorated UC and accompanying anxiety- and depressive-like behaviors with downregulated expressions of (NOD)-like receptor family and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteine aspartate-specific protease-1 (Caspase-1) and interlekin-1ß (IL-1ß), and elevated mRNA levels of brain-derived neurotrophic factor (Bdnf) and postsynaptic-density protein 95 (Psd-95) in cortex and hippocampus. Furthermore, fucoidan improved the permeability of intestinal barrier and blood-brain barrier and restored the abnormal structure of the gut microbiota with a significantly decreased ratio of Firmicutes to Bacteroidota (F/B) and obviously increased abundance of Akkermansia. As a diet-derived bioactive ingredient, fucoidan might be a better alternative for the prevention of UC and accompanying anxiety- and depressive-like behaviors.
Assuntos
Ansiedade , Colite Ulcerativa , Depressão , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Polissacarídeos , Animais , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Polissacarídeos/química , Masculino , Sulfato de Dextrana/efeitos adversos , Camundongos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/metabolismo , Ansiedade/tratamento farmacológico , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Caspase 1/metabolismo , Caspase 1/genética , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacosRESUMO
Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease, characterized by dysregulated immune response. HDAC3 is reported to be an epigenetic brake in inflammation, playing critical roles in macrophages. However, its role in IBD is unclear. In our study, we found HDAC3 was upregulated in CX3CR1-positive cells in the mucosa from IBD mice. Conditional knockout (cKO) of Hdac3 in CX3CR1 positive cells attenuated the disease severity of Dextran Sulfate Sodium (DSS)-induced colitis. In addition, inhibition of HDAC3 with RGFP966 could also alleviate the DSS-induced tissue injury and inflammation in IBD. The RNA sequencing results revealed that Hdac3 cKO restrained DSS-induced upregulation of genes in the pathways of cytokine-cytokine receptor interaction, complement and coagulation cascades, chemokine signaling, and extracellular matrix receptor interaction. We also identified that Guanylate-Binding Protein 5 (GBP5) was transcriptionally regulated by HDAC3 in monocytes by RNA sequencing. Inhibition of HDAC3 resulted in decreased transcriptional activity of interferon-gamma-induced expression of GBP5 in CX3CR1-positive cells, such as macrophages and microglia. Overexpression of HDAC3 upregulated the transcriptional activity of GBP5 reporter. Lastly, conditional knockout of Hdac3 in macrophages (Hdac3 mKO) attenuated the disease severity of DSS-induced colitis. In conclusion, inhibition of HDAC3 in macrophages could ameliorate the disease severity and inflammatory response in colitis by regulating GBP5-NLRP3 axis, identifying a new therapeutic avenue for the treatment of colitis.
Assuntos
Colite , Sulfato de Dextrana , Histona Desacetilases , Macrófagos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais , Animais , Sulfato de Dextrana/toxicidade , Sulfato de Dextrana/efeitos adversos , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Camundongos , Macrófagos/metabolismo , Macrófagos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Colite/induzido quimicamente , Colite/genética , Colite/patologia , Colite/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/antagonistas & inibidores , Modelos Animais de Doenças , Receptor 1 de Quimiocina CX3C/metabolismo , Receptor 1 de Quimiocina CX3C/genética , Camundongos Endogâmicos C57BL , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Acrilamidas , FenilenodiaminasRESUMO
Although only Saccharomyces boulardii has been studied for ulcerative colitis (UC), probiotic yeasts have immense therapeutic potential. Herein, we evaluated the kefir yeast Kluyveromyces marxianus A4 (Km A4) and its anti-inflammatory effect with sulfasalazine in BALB/c mice with dextran sulfate sodium (DSS)-induced colitis. Oral administration continued for 7 days after the mice were randomly divided into seven groups: control (CON, normal mice administered with saline), DSS-induced colitis mice administered saline (DSS), and DSS-induced colitis mice administered sulfasalazine only (S), Km A4 only (A4), Km A4 plus sulfasalazine (A4 + S), S. boulardii ATCC MYA-796 (Sb MYA-796) only (Sb), and Sb MYA-796 plus sulfasalazine (Sb + S). The ß-glucan content of Km A4 was significantly higher than that of Sb MYA-796 (P < 0.05). Body weight gain (BWG) significantly correlated with colon length, cyclooxygenase-2 (Cox-2) levels, and Bacteroides abundance (P < 0.05). In colitis-induced mice, the A4 + S group had the lowest histological score (6.00) compared to the DSS group (12.67), indicating the anti-inflammatory effects of this combination. The A4 + S group showed significantly downregulated expression of interleukin (Il)-6, tumor necrosis factor-α (Tnf-α), and Cox-2 and upregulated expression of Il-10 and occludin (Ocln) compared to the DSS group. Mice treated with A4 + S had enhanced Bacteroides abundance in their gut microbiota compared with the DSS group (P < 0.05). Bacteroides were significantly correlated with all colitis biomarkers (BWG, colon length, Il-6, Tnf-α, Il-10, Cox-2, and Ocln; P < 0.05). The anti-inflammatory effects of Km A4 could be attributed to high ß-glucan content and gut microbiota modulation. Thus, treatment with Km A4 and sulfasalazine could alleviate UC.
Assuntos
Anti-Inflamatórios , Colite Ulcerativa , Microbioma Gastrointestinal , Kluyveromyces , Camundongos Endogâmicos BALB C , Probióticos , Sulfassalazina , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Colite Ulcerativa/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Sulfassalazina/farmacologia , Camundongos , Anti-Inflamatórios/farmacologia , Probióticos/farmacologia , Masculino , Kefir/microbiologia , Sulfato de Dextrana/efeitos adversos , Humanos , Colo/microbiologia , Colo/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Modelos Animais de Doenças , FemininoRESUMO
We previously confirmed that tannic acid could delay the metabolism of resistant starch in vitro, which suggested that tannic acid might deliver resistant starch to the distal colon in vivo. Accordingly, co-supplementation of resistant starch and tannic acid might be beneficial for keeping the distal colon healthy. Thus, this study compared the effects of resistant starch, tannic acid and their mixtures on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. It was found that the mixtures had a more profound effect on ameliorating DSS-induced ulcerative colitis than resistant starch or tannic acid. In particular, the mixtures reversed the histology damage of the distal colon induced by DSS, while resistant starch or tannic acid alone did not. The mixtures also had a stronger ability to resist oxidative stress and inhibit inflammation in the distal colon. These results suggested that resistant starch and tannic acid synergistically alleviated DSS-induced ulcerative colitis, particularly in the distal colon. On the other hand, DSS decreased the production of short-chain fatty acids and induced significant microbial disorder, while the administration of resistant starch, tannic acid and their mixtures reversed the above shifts caused by DSS. In particular, the mixtures exhibited stronger prebiotic activity, as indicated by the microbial composition and production of short-chain fatty acids. Therefore, it was inferred that tannic acid delivered resistant starch to the distal colon of mice, and thus the mixtures had stronger prebiotic activity. As a result, the mixtures effectively alleviated ulcerative colitis in the whole colon.
Assuntos
Colite Ulcerativa , Colo , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Taninos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Animais , Taninos/farmacologia , Sulfato de Dextrana/efeitos adversos , Camundongos , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Masculino , Amido/farmacologia , Modelos Animais de Doenças , Amido Resistente/farmacologia , Sinergismo Farmacológico , Ácidos Graxos Voláteis/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PolifenóisRESUMO
Large-leaf yellow tea (LYT)-derived peptides (TPP) are rich in amino acids required for damage repair, such as Glu, Arg, and Pro, and can be used to alleviate acute colitis. However, its effect and mechanisms against colitis remain unclear. This study utilized TPP to intervene in dextran sodium sulfate-induced acute colitis in C57BL/6 J mice. Results confirmed that TPP ameliorated acute colitis symptoms by inhibiting pro-inflammatory cytokines, restoring gut microbiota dysbiosis, particularly by increasing the abundance of beneficial bacteria Akkermansia and Lactobacillus while declining harmful microbiota Escherichia-Shigella. Besides, TPP intervention reshaped the gut microbiota phenotype by increasing the aerobic phenotype and reducing the potentially pathogenic phenotype. Levels of short-chain fatty acids, including acetic acid, propanoic acid, isobutyric acid, and butyric acid, were also enhanced in a dose-dependent manner to help restore gut microbiota equilibrium. This study supports using TPP as a viable plant protein-derived dietary resource for alleviating inflammatory bowel disease.
Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Peptídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Sulfato de Dextrana/efeitos adversos , Camundongos , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Peptídeos/química , Masculino , Humanos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Proteínas de Plantas/química , Proteínas de Plantas/administração & dosagem , Chá/química , Camellia sinensis/química , Modelos Animais de DoençasRESUMO
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 fármacosRESUMO
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/químicaRESUMO
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/metabolismoRESUMO
Probiotics are increasingly used to manage gut dysbiosis-related conditions due to their robust ability to manipulate the gut microbial community. However, few studies have reported that probiotics can specifically modulate individual gut microbes. This study demonstrated that administering the probiotic, Lactiplantibacillus fermentum F6, could ameliorate dextran sulfate sodium-induced colitis in a rat model, evidenced by the decreases in the disease activity index score, histopathology grading, and serum pro-inflammatory cytokine levels, as well as the increase in the serum anti-inflammatory cytokine levels. Shotgun metagenomics revealed that the fecal metagenomic of colitis rats receiving the probiotic intervention contained substantially fewer Akkermansia muciniphila than the dextran sulfate sodium group. Thus, the probiotic mechanism might be exerted by reducing specific gut microbial species associated with disease pathogenesis. A new paradigm for designing probiotics that manage diseases through direct and precise manipulation of gut microbes has been provided through this study.
Assuntos
Akkermansia , Colite , Microbioma Gastrointestinal , Limosilactobacillus fermentum , Probióticos , Animais , Masculino , Ratos , Colite/induzido quimicamente , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Disbiose/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Limosilactobacillus fermentum/fisiologia , Probióticos/farmacologia , Probióticos/administração & dosagem , Ratos Sprague-DawleyRESUMO
Ulcerative colitis is a chronic, spontaneous inflammatory bowel disease that primarily affects the colon. This study aimed to explore how Porphyra haitanensis porphyran (PHP) modulates the immune response and the associated mechanisms that alleviate dextran sulphate sodium-induced colitis in mice. Histological assessments via H&E staining and AB-PAS staining revealed that PHP intervention partially restored the number of goblet cells and improved intestinal mucosal function. Immunohistochemical and Western blot analyses of claudin-1, occludin, and MUC-2 demonstrated that PHP could repair the intestinal barrier and reduce colon damage by upregulating the expression of these proteins. PHP intervention was associated with a decrease in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokine expression. Moreover, the expression of proteins involved in intestinal immune homing, such as CCR-9, CCL-25, MAdCAM-1, and α4ß7, was significantly suppressed in response to PHP treatment. Conversely, PHP upregulates the expression of CD40 and TGF-ß1, both of these can promote healing and reduce inflammation in the gut lining. This study demonstrates that PHP can ameliorate ulcerative colitis by enhancing the intestinal barrier and modulating immune responses. These findings offer valuable insights into the potential utility of P. haitanensis as a promising natural product for managing ulcerative colitis.
Assuntos
Sulfato de Dextrana , Porphyra , Animais , Porphyra/química , Sulfato de Dextrana/toxicidade , Sulfato de Dextrana/efeitos adversos , Camundongos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Citocinas/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Masculino , Inflamação/tratamento farmacológico , Inflamação/patologia , Modelos Animais de Doenças , Colo/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Sefarose/análogos & derivadosRESUMO
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 fármacosRESUMO
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/metabolismoRESUMO
Ulcerative colitis (UC) is a common chronic inflammatory disease that causes serious harm to human health. Probiotics have the effect of improving UC. This study evaluated the preventative potential of water-in-oil-in-water (W1/O/W2) emulsions containing both probiotics and fish oil on UC and associated anxiety-like behavior using a mice model. UC model was established in mice by administering dextran sulfate sodium salt (DSS). Free probiotics, probiotic-loaded emulsions, or fish oil and probiotic co-loaded emulsions were then orally administered to the mice. Various bioassays, histological studies, 16s rDNA gene sequencing, and behavioral experiments were conducted to assess changes in the intestinal environment, microbiota, and anxiety-like behavior of the mice. The fish oil and probiotic co-loaded emulsions significantly reduced the inflammatory response by enhancing tight junction protein secretion (ZO-1, Occludin, and Claudin-1), inhibiting pro-inflammatory factors (TNF-α, and IL-1ß), and promoting short-chain fatty acids (SCFAs) production. These emulsions also modified the gut microbiota by promoting beneficial bacteria and suppressing pathogenic bacteria, thereby restoring a balanced gut microbiota. Notably, the emulsions containing both probiotics and fish oil also ameliorated anxiety-like behavior in the mice. The co-delivery of probiotics and fish oil using W1/O/W2 emulsions has shown significant promise in relieving UC and its associated anxiety-like behavior. These findings provide novel insights into the development of advanced therapeutic strategies for treating UC.
Assuntos
Colite Ulcerativa , Emulsões , Óleos de Peixe , Microbioma Gastrointestinal , Probióticos , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Emulsões/química , Probióticos/farmacologia , Óleos de Peixe/farmacologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Água , Sulfato de Dextrana/efeitos adversos , HumanosRESUMO
The prophylactic and adjunctive impacts of compound prebiotics (CP), comprising galacto-oligosaccharides, fructo-oligosaccharides, and isomalto-oligosaccharides, on colitis remain unclear. This study aimed to elucidate the effects of CP on dextran sodium sulfate (DSS)-induced colitis via modulation of the gut microbiota. Mice received prophylactic CP (PCP) for three weeks and DSS in the second week. In the third week, therapeutic CP, mesalazine, and a combination of CP and mesalazine (CPM) were administered to mice with DSS-induced colitis. The administration of PCP and CPM was found to ameliorate colitis, as evidenced by increases in body weight and colon length, elevation of the anti-inflammatory cytokine IL-10, and reductions in the disease activity index, histological scores, and levels of pro-inflammatory cytokines in mice with DSS-induced colitis on days 14 or 21. Furthermore, an increase in the relative abundance of probiotics (Ligilactobacillus, Bifidobacterium, and Limosilactobacillus), alpha diversity indices, short-chain fatty acids (SCFA) contents, and microbial network complexity was observed following PCP or CPM treatment. Correlation analysis revealed positive associations between these probiotics and both SCFA and IL-10, and negative associations with pro-inflammatory cytokines. This study highlighted the potential of CP as novel prophylactic and adjunctive treatments for alleviating DSS-induced intestinal inflammation and maintaining gut microbiota homeostasis.