RESUMO
Ulcerative colitis (UC) is a typical type of inflammatory bowl disease, which is accompanied by an increased risk of depression and anxiety-related psychological symptoms. Betaine is a naturally derived compound that can function as an anti-inflammatory drug and a neuromodulator. In-depth exploration of the potential role of betaine in treating UC-related depression and anxiety is crucial. This study aimed to elucidate the effects of betaine on UC-related depression and anxiety and clarify the underlying mechanisms. A dextran sulfate sodium (DSS)-induced mice model was established by 4% DSS drinking ad libitum for 7 days. The colonic injury was measured using hematoxylin-eosin (HE) staining and Alcian blue-periodic acid Schiff (AB-PAS) staining. Depression and anxiety-like behaviors were separately evaluated using a forced swimming test (FST), a tail suspension test (TST), a light-dark box test (LDBT), and an open field test (OFT). Immunohistochemistry was used to detect DNA damage and neurogenesis in the hippocampus. Western blotting was applied to detect the protein levels of macrophage polarization in mice colons and the alteration of mitochondrial dysfunction and the cGAS-STING pathway in the hippocampus. Betaine strongly alleviated mucosal structural disorder and mucin secretion reduction and promoted M2-macrophage polarization in the colon of DSS-treated mice. In addition, betaine could mitigate depression- and anxiety-like behaviors in DSS-treated mice, reduce the DNA damage and mitochondrial dysfunction, and inhibit the cGAS-STING signaling pathway. Our study reveals the antidepression/anxiety effects of betaine and further demonstrates the potential mechanism by which betaine inhibits DNA damage and mitochondrial dysfunction to block the cGAS-STING pathway, thereby repairing neurogenesis in the hippocampus.
Assuntos
Ansiedade , Betaína , Colite Ulcerativa , Depressão , Sulfato de Dextrana , Animais , Sulfato de Dextrana/efeitos adversos , Camundongos , Betaína/administração & dosagem , Betaína/farmacologia , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Depressão/metabolismo , Masculino , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Humanos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologiaRESUMO
Mammalian milk exosomal miRNAs play an important role in maintaining intestinal immune homeostasis and protecting epithelial barrier function, but the specific miRNAs and whether miRNA-mediated mechanisms are responsible for these benefits remain a matter of investigation. This study isolated sheep milk-derived exosomes (sheep MDEs), identifying the enriched miRNAs in sheep MDEs, oar-miR-148a, and oar-let-7b as key components targeting TLR4 and TRAF1, which was validated by a dual-luciferase reporter assay. In dextran sulfate sodium-induced colitis mice, administration of sheep MDEs alleviated colitis symptoms, reduced colonic inflammation, and systemic oxidative stress, as well as significantly increased colonic oar-miR-148a and oar-let-7b while reducing toll-like receptor 4 (TLR4) and TNF-receptor-associated factor 1 (TRAF1) level. Further characterization in TNF-α-challenged Caco-2 cells showed that overexpression of these miRNAs suppressed the TLR4/TRAF1-IκBα-p65 pathway and reduced IL-6 and IL-12 production. These findings indicate that sheep MDEs exert gastrointestinal anti-inflammatory effects through the miRNA-mediated modulation of TLR4 and TRAF1, highlighting their potential in managing colitis.
Assuntos
Colite , Sulfato de Dextrana , Exossomos , MicroRNAs , Leite , Fator 1 Associado a Receptor de TNF , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/imunologia , Sulfato de Dextrana/efeitos adversos , Leite/química , Leite/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Colite/metabolismo , Camundongos , Ovinos , Humanos , Exossomos/genética , Exossomos/metabolismo , Exossomos/química , Exossomos/imunologia , Fator 1 Associado a Receptor de TNF/genética , Fator 1 Associado a Receptor de TNF/metabolismo , Células CACO-2 , Masculino , Camundongos Endogâmicos C57BL , FemininoRESUMO
Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients' gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.
Assuntos
Colite , Sulfato de Dextrana , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Animais , Humanos , Camundongos , Colite/terapia , Colite/induzido quimicamente , Colite/imunologia , Colo/microbiologia , Colo/imunologia , Colo/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Macrófagos/imunologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologiaRESUMO
Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.
Assuntos
Apoptose , Mirtilos Azuis (Planta) , Colo , Sulfato de Dextrana , Estresse do Retículo Endoplasmático , Doenças Inflamatórias Intestinais , Extratos Vegetais , Animais , Mirtilos Azuis (Planta)/química , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Extratos Vegetais/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Masculino , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , HumanosRESUMO
Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.
Assuntos
Anti-Inflamatórios , Colite , Sulfato de Dextrana , Modelos Animais de Doenças , Peixe-Zebra , Animais , Sulfato de Dextrana/efeitos adversos , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismoRESUMO
Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics (S24-7 and Lactobacillaceae) while reducing harmful bacteria (Erysipelotrichi, Enterobacteriaceae). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.
Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Hesperidina , Mucosa Intestinal , Camundongos Endogâmicos C57BL , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/microbiologia , Colite Ulcerativa/imunologia , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Sulfato de Dextrana/efeitos adversos , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Hesperidina/farmacologia , Hesperidina/administração & dosagem , Hesperidina/análogos & derivados , Humanos , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/genética , NF-kappa B/metabolismo , NF-kappa B/genética , Colo/microbiologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/metabolismo , Colo/patologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológicoRESUMO
Currently, there is no known cause for ulcerative colitis (UC), an inflammatory bowel disease that is difficult to treat. This assay aimed to investigate the protective effects and mechanisms of Dendrobium officinale polysaccharide (DOP) in mice with acute UC induced by dextran sulphate sodium (DSS). We found that DOP could improve weight loss, decrease the disease activity index (DAI), and regulate the release of interleukin 2 (IL-2), IL-4, IL-6, and IL-10 in DSS-induced acute UC mice. Additionally, DOP preserved the integrity of the intestinal barrier in UC mice by increasing goblet cell density and maintaining tight junctions. DOP significantly enhanced total antioxidant capacity (T-AOC), and reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels in the bloodstream. In terms of serum biochemistry, DOP markedly elevated levels of bilirubin (BIL), alkaline phosphatase (ALP), total bile acid (TBA), creatinine (Crea), and creative kinase isoenzyme (CKMB). Furthermore, DOP increased the relative abundance of Lactobacillales. DOP also improved intestinal health and stimulated the synthesis of potent anti-inflammatory and antiviral substances by regulating the metabolism of purines, prostaglandins, and leukotrienes. Therefore, DOP can be considered a functional dietary supplement for the treatment of UC, as it improves the condition of DSS-induced UC mice.
Assuntos
Colite Ulcerativa , Dendrobium , Sulfato de Dextrana , Metaboloma , Polissacarídeos , Animais , Dendrobium/química , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Sulfato de Dextrana/efeitos adversos , Camundongos , Metaboloma/efeitos dos fármacos , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Citocinas/metabolismo , Antioxidantes/farmacologia , Modelos Animais de DoençasRESUMO
Bioactive components from Porphyra tenera (PT) have been reported to confer various health benefits. The role of PT in inflammatory bowel disease (IBD) has not been fully investigated. This study aimed to explore the anti-inflammatory properties of PT on dextran sodium sulfate (DSS)-treated mice. PT supplementation attenuated the severity of colitis in DSS-treated mice, evidenced by the reduction of disease activity index (DAI), restoration of colonic histological damage and suppression of abnormal inflammatory response. Sequencing analysis indicated that intake of PT alleviated DSS-induced gut microbiota dysbiosis, accompanied by reversing the generation of short-chain fatty acids (SCFAs) and bile acids (BAs). Overall, our findings demonstrated that supplementation of PT attenuated the severity of intestinal inflammation and ameliorated gut microbiota dysbiosis in a murine colitis model, which provided a rationale for further application of edible seaweeds for preventing inflammation-related disorders in humans.
Assuntos
Colite , Sulfato de Dextrana , Disbiose , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Animais , Camundongos , Sulfato de Dextrana/efeitos adversos , Colite/induzido quimicamente , Colite/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Disbiose/microbiologia , Disbiose/tratamento farmacológico , Humanos , Masculino , Modelos Animais de Doenças , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Porphyra/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ácidos Graxos Voláteis/metabolismo , Algas ComestíveisRESUMO
Proanthocyanidins (PA) have been proven to have an anti-inflammation effect in multiple models by regulating oxidative stress. ß-glucan (BG) could alleviate colitis from the perspectives of intestinal permeability and gut microbiota. In the present study, the synergistic anti-inflammatory function of PA and BG was explored from multiple aspects including immune response, intestinal barrier, gut microbiota, and differential metabolites. The results showed that the supplementation of PA and BG improved the colitis symptoms including atrophy of the colon, body weight loss, and organ index increase. Additionally, inflammatory cytokine levels and oxidative stress status were significantly regulated with the intake of PA and BG. Moreover, PA and BG intervention improved intestinal permeability and promoted the expression of barrier proteins. The microbiome and metabolic profile of cecal contents showed that PA and BG supplementation increased the abundance of anti-inflammatory bacteria and decreased the abundance of pro-inflammatory bacteria. Furthermore, some beneficial metabolites involved in amino acid metabolism, carbohydrate metabolism, and biosynthesis of other secondary metabolite pathways were increased. Overall, these findings have demonstrated the regulation of the inflammatory response and remodel of metabolite profiles by PA and BG complexes, indicating that it may serve as a new strategy for inflammatory bowel disease treatment in the future.
Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Proantocianidinas , beta-Glucanas , Animais , beta-Glucanas/administração & dosagem , beta-Glucanas/farmacologia , Sulfato de Dextrana/efeitos adversos , Camundongos , Proantocianidinas/administração & dosagem , Proantocianidinas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/imunologia , Masculino , Humanos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Anti-Inflamatórios/administração & dosagem , Sinergismo Farmacológico , Modelos Animais de Doenças , Colo/metabolismo , Colo/efeitos dos fármacos , Colo/imunologia , Colo/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Rice protein peptide (RPP) has been reported to alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis, but its potential protective effect and fundamental neurobiological mechanisms against DSS-induced inflammatory bowel disease (IBD), coupled with depression and cognitive impairment, remain unclear. In this study, RPP treatment in DSS-induced mice inhibited decreases in body weight and colon length and improved intestinal barrier function and behavioral performance. RPP treatment enhanced phenylalanine and tyrosine metabolism in the brains of mice, and it upregulated metabolites such as l-dopa, phenylethylamine, and 3,4-dihydroxyphenylacetate. Additionally, RPP treatment enhanced the brain-derived neurotrophic factor (BDNF) by upregulating the BDNF/TrkB/CREB signaling pathway. Spearman's correlation analysis revealed that the phenylalanine and tyrosine contents in the brain were significantly negatively correlated with the BDNF/TrkB/CREB signaling pathway and behavioral performance. In conclusion, this study suggested that RPP may serve as a unique nutritional strategy for preventing IBD and its associated cognitive impairment and depression symptoms.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Depressão , Sulfato de Dextrana , Oryza , Peptídeos , Fenilalanina , Transdução de Sinais , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Masculino , Fenilalanina/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Depressão/metabolismo , Depressão/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Peptídeos/administração & dosagem , Humanos , Oryza/química , Oryza/metabolismo , Sulfato de Dextrana/efeitos adversos , Proteínas de Plantas/metabolismo , Camundongos Endogâmicos C57BL , Receptor trkB/metabolismo , Colite/induzido quimicamente , Colite/metabolismo , Colite/tratamento farmacológico , Comportamento Animal/efeitos dos fármacosRESUMO
Intestinal barrier hemostasis is the key to health. As a resveratrol analogue, pterostilbene (PT) has been reported to prevent dextran sodium sulfate (DSS)-induced intestinal barrier dysfunction mainly associated with the intestinal NF-κB signaling pathway. However, the exact underlying mechanisms are not yet well-defined yet. In this study, we performed RNA-sequencing analysis and unexpectedly found that alarmin S100A8 sensitively responded to DSS-induced intestinal injury. Accordingly, histologic assessments suggested that the high expression of S100A8 was accompanied by increased intestinal infiltration of macrophages, upregulated intestinal epithelial Toll-like receptor 4 (TLR-4), and activated NF-κB signaling pathway. Interestingly, the above phenomena were effectively counteracted upon the addition of PT. Furthermore, by using a coculture system of macrophage THP-1 cells and HT-29 colon cells, we identified macrophage-secreted S100A8 activated intestinal epithelial NF-κB signaling pathway through TLR-4. Taken together, these findings suggested that PT ameliorated DSS-induced intestinal barrier injury through suppression of the macrophage S100A8-intestinal epithelial TLR-4-NF-κB signaling cascade.
Assuntos
Calgranulina A , Sulfato de Dextrana , Mucosa Intestinal , Camundongos Endogâmicos C57BL , NF-kappa B , Transdução de Sinais , Estilbenos , Receptor 4 Toll-Like , Sulfato de Dextrana/efeitos adversos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Humanos , Camundongos , Calgranulina A/genética , Calgranulina A/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Estilbenos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Masculino , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/genéticaRESUMO
BACKGROUND/AIM: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored. MATERIALS AND METHODS: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death. RESULTS: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1ß. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins. CONCLUSION: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD.
Assuntos
Apoptose , Colite , Citocinas , Sulfato de Dextrana , Modelos Animais de Doenças , Mesilato de Imatinib , Animais , Mesilato de Imatinib/farmacologia , Sulfato de Dextrana/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Mediadores da Inflamação/metabolismo , BiomarcadoresRESUMO
Inflammatory bowel disease (IBD) is a challenging condition to cure that can occur at any age. The gut microbiome and intestinal epithelial barrier play a crucial role in the development of IBD. 1,3-Dioleoyl-2-palmitoylglycerol (OPO), the predominant triglyceride in breast milk, is a structural lipid with multiple physiological functions. However, the protective effect of OPO on IBD and its underlying mechanism remains unclear. This study showed that oral administration of OPO markedly ameliorated dextran sulfate sodium (DSS)-induced colitis phenotypes. OPO treatment reduced inflammation levels by suppressing the TLR4-MyD88-NF-κB signaling pathway in colitis mice. Furthermore, OPO treatment improved intestinal epithelial barrier function via promoting epithelial cell proliferation and differentiation, inhibiting cell apoptosis, and upregulating tight junction protein expression. The 16S rRNA gene sequencing revealed that OPO treatment restored microbial alpha diversity and reshaped the microbiota of colitis mice. Therefore, our study revealed that OPO exhibited a protective role in DSS-induced colitis via maintaining intestinal epithelial barrier integrity and modulating gut microbiota. Our results highlight that OPO could be used as effective supplements for individuals with IBD or intestinal dysfunctions.
Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Mucosa Intestinal , Camundongos Endogâmicos C57BL , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Modelos Animais de Doenças , Receptor 4 Toll-Like/metabolismo , Triglicerídeos , NF-kappa B/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Substâncias Protetoras/farmacologiaRESUMO
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
Pleurotus eryngii, an edible mushroom recognized for its potent polysaccharides, demonstrates significant regulatory effects on metabolic processes. ß-glucan (WPEP) derived from P. eryngii has been noted for its therapeutic potential, exhibiting notable benefits in alleviating colonic inflammation and restructuring gut microbiota in mice treated with dextran sodium sulfate (DSS). This study focuses on utilizing DSS-induced colitis mice to explore the efficacy and underlying mechanisms of WPEP in ameliorating colitis, employing a metabolomics approach analyzing urine and serum. The findings reveal that WPEP administration effectively regulates metabolic imbalances in DSS mice, impacting purine metabolism, pentose and glucuronic acid interconversion, amino acid metabolism, primary bile acid biosynthesis, citric acid cycle, and lipid metabolism. Furthermore, WPEP demonstrates a capacity to modulate colitis by regulating diverse metabolic pathways, consequently influencing intestinal barrier integrity, motility, inflammation, oxidative stress, and immunity. These insights suggest that WPEP is a promising food component for managing inflammatory bowel diseases.
Assuntos
Colite , Sulfato de Dextrana , Metabolômica , Pleurotus , Animais , Pleurotus/química , Pleurotus/metabolismo , Sulfato de Dextrana/efeitos adversos , Camundongos , Colite/induzido quimicamente , Colite/metabolismo , Colite/tratamento farmacológico , Masculino , Camundongos Endogâmicos C57BL , Humanos , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Glicosídeos/administração & dosagem , Glicosídeos/metabolismo , Urina/química , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.
Assuntos
Anti-Inflamatórios , Bactérias , Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Phyllanthus emblica , Extratos Vegetais , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Sulfato de Dextrana/efeitos adversos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/administração & dosagem , Polissacarídeos/isolamento & purificação , Phyllanthus emblica/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/administração & dosagem , Masculino , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/microbiologia , Colite Ulcerativa/metabolismo , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/microbiologia , Modelos Animais de Doenças , Colo/microbiologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/imunologiaRESUMO
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
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
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
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.