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1.
J Ethnopharmacol ; 305: 116125, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36603786

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a major cause of morbidity and mortality due to repetitive remissions and relapses, and many severe complications, including colitis-associated cancer (CAC). The San-Qi-Xue-Shang-Ning (SQ) formula has been utilized in clinical practice to treat gut diseases, but its pharmacological evidence is limited and awaits elucidation. AIM OF THE STUDY: Here, we elucidated the molecular mechanisms of the SQ formula. MATERIALS AND METHODS: Its therapeutic value in combating UC and CAC was predicted from network pharmacology and weighted gene co-expression network analysis (WGCNA). Experimental colitis models were established by feeding dextran sodium sulfate (DSS) to C57BL/6N mice for 7 days, and they were subjected to the SQ formula for 14 days. High-throughput technologies and biochemical investigations were executed to corroborate the anti-colitis effect. RESULTS: Network pharmacology and WGCNA demonstrated that the targets of the SQ formula were associated with interleukin-17 (IL-17), tumor necrosis factor (TNF), IL-1b and peroxisome proliferators-activated receptor (PPAR) signaling pathways, and correlated with the survival in patients with colorectal cancer. In mice with colitis, the SQ treatment hindered colitis progression in a dose-dependent manner, as evidenced by the rescued colon length and weight loss, improved colonic epithelial integrity, and abolished crypt loss. In addition to the suppressed serum IL-17, TNFα, and IL-1b levels, the SQ-treated colitis mice exhibited decreased colonic protein abundance of hypoxia-inducible factor-1α (HIF-1 α), PPARα, and Caspase3 (Casp3) with an increased PPARγ expression. Concurrently, the high dose of SQ promoted the alternative activation of peritoneal macrophages by increasing Arg1 and inhibiting iNOS2, thereby facilitating the migration of NCM460 cells and controlling TNF-induced reactive oxygen species production and apoptosis in intestinal organoids. In colitis-accompanied dysbiosis, the SQ formula reversed the decreased microbiota diversity indexes and restored the microbiome profile in the murine colitis models. CONCLUSION: The SQ formula is a potent anti-colitis drug that facilitates inflammation resolution and restores gut microbiota homeostasis.


Assuntos
Colite Ulcerativa , Colite , Microbiota , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Interleucina-17/metabolismo , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colo , Homeostase , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
2.
Commun Biol ; 6(1): 95, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694043

RESUMO

Previous studies have conducted time course characterization of murine colitis models through transcriptional profiling of differential expression. We characterize the transcriptional landscape of acute and chronic models of dextran sodium sulfate (DSS) and adoptive transfer (AT) colitis to derive temporal gene expression and splicing signatures in blood and colonic tissue in order to capture dynamics of colitis remission and relapse. We identify sub networks of patient-derived causal networks that are enriched in these temporal signatures to distinguish acute and chronic disease components within the broader molecular landscape of IBD. The interaction between the DSS phenotype and chronological time-point naturally defines parsimonious temporal gene expression and splicing signatures associated with acute and chronic phases disease (as opposed to ordinary time-specific differential expression/splicing). We show these expression and splicing signatures are largely orthogonal, i.e. affect different genetic bodies, and that using machine learning, signatures are predictive of histopathological measures from both blood and intestinal data in murine colitis models as well as an independent cohort of IBD patients. Through access to longitudinal multi-scale profiling from disease tissue in IBD patient cohorts, we can apply this machine learning pipeline to generation of direct patient temporal multimodal regulatory signatures for prediction of histopathological outcomes.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Camundongos , Doenças Inflamatórias Intestinais/genética , Colite/induzido quimicamente , Colite/genética , Fenótipo , Sulfato de Dextrana/toxicidade
3.
Carbohydr Polym ; 302: 120329, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36604040

RESUMO

Starch from Pueraria lobata (PLS) had polyhedral or spherical granules, displaying a bimodal size distribution within 0.6-30 µm. It showed a trimodal distribution of different molecular weight peaks, with amylose fraction of 18.2 %. PLS had a high crystallinity degree of 37.76 % and consisted of C-type starch, which gelatinized at 64.46-79.61 °C, with a high range of gelatinization (15.15 °C) and high enthalpy (13.98 J/g). A 21-day supplementation of PLS presented a regulative effect on gut microbiota in normal mice, and alleviated DSS-induced murine colitis through attenuating colonic inflammation, maintaining barrier function, preventing gut dysbiosis, increasing the short-chain fatty acids production and inhibiting NF-κB/IL-1ß axis. The protective effect of PLS against colitis was in a gut microbiota-dependent manner. Notably, the amylose fraction was responsible for the prebiotic effect of PLS. The results would potentiate new application of PLS and the amylose fraction as functional prebiotics for prevention of colitis.


Assuntos
Colite , Pueraria , Camundongos , Animais , Amilose , Dextranos , Amido , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
4.
J Ethnopharmacol ; 305: 116067, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36586523

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is widely believed to be a leading risk factor of colorectal cancer. Gut microbiota is a known vital player in the progression of UC. Si-Ni-San (SNS) has been considered to effectively treat colitis in clinical practice during thousands of years, yet whether SNS ameliorated acute colitis mouse model by modulating intestinal flora has not been distinctly elucidated. AIM OF THE STUDY: Our study aimed to elucidate the effect of SNS against acute murine colitis and focused on the underlying mechanisms of SNS targeting gut microbiota. MATERIALS AND METHODS: 16S RNA sequencing, molecular biological analysis, and fecal microbiota transplants (FMT) were conducted to reveal the mechanisms of SNS in regulating gut microbiota. RESULTS: In our study, SNS dramatically inhibited DSS-induced acute inflammatory responses by improving gut microbiota dysbiosis, as evidenced by decreased abundance proinflammatory species, upregulated abundance of anti-inflammatory species and potentially altered microbiota metabolite metabolism. Additionally, intestinal flora knockout and FMT experiments confirmed that the therapeutic effect of SNS on colitis was dependent on gut microbiota, and specifically on favoring the growth of potential probiotics, Akkermansia genus. Furthermore, we found that SNS alone and SNS combined with Akkermansia muciniphila (A. muciniphila) increased Mucin 2 (MUC2) production, thus enhancing the competitive edge of A. muciniphila among pathogenic gut microbiota. CONCLUSION: Our study shed lights on the underlying mechanism of SNS in attenuating acute murine colitis from the perspective of intestinal flora and provides novel insights into the discovery of adjacent therapeutic strategy against colitis based on SNS and probiotics. CLASSIFICATION: Gastro-intestinal system.


Assuntos
Colite Ulcerativa , Colite , Medicamentos de Ervas Chinesas , Camundongos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/patologia , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Colo/patologia , Modelos Animais de Doenças
5.
Environ Pollut ; 317: 120819, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36481465

RESUMO

Chlorinated polyfluorinated ether sulfonate (F-53 B) is a distinct substitute for perfluorooctane sulphonate. It has been reported to be biologically toxic to mammals, causing enteric toxicity, liver toxicity and neurotoxicity. However, studies about the effects of F-53 B on patients with gastrointestinal diseases such as inflammatory bowel disease are very limited. In this study, whether the toxic impacts of F-53 B on the gut and liver can be exacerbated in mice with colitis was explored. The sensitivity of mice with acute colitis caused by dextran sulfate sodium salt (DSS) to F-53 B was compared with that of healthy mice. The mice were administered water containing F-53 B at doses of 10 and 100 µg/L sequentially for two weeks, respectively. F-53 B exposure exacerbated DSS-induced colonic inflammation, including inducing shortening of colon length, inflammatory cell infiltration and more severe histopathological symptoms. In addition, F-53 B administration significantly increased the levels of inflammatory cytokines, including interleukin (IL)-1, IL-6 and tumour necrosis factor-α, in the plasma of mice with enteritis compared with control group. F-53 B impaired intestinal integrity of mice with colitis by downregulating Claudin-1 and antimicrobial peptide-related genes while elevating serum lipopolysaccharide levels. In addition, in mice with colitis, F-53 B increased the levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, aspartate aminotransferase, and alanine aminotransferase, resulted in more severe liver inflammation and increased the level of genes related to the Gasdermin D-mediated pyrolysis. Conclusively, our results indicated that F-53 B delayed the self-healing of ulcerative colitis (UC) and caused liver inflammation in mice. This study provided some new insights into the health risks of F-53 B and raises concerns about the health of individuals with UC.


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite/induzido quimicamente , Colite/patologia , Inflamação , Colesterol , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Sulfato de Dextrana/toxicidade , Mamíferos
6.
Chem Biol Interact ; 370: 110316, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36543318

RESUMO

Ulcerative colitis (UC), a pathological condition of inflammatory bowel disease, is a chronic inflammatory disorder that involves an abnormal immune response and epithelial barrier dysfunction. Although we have previously reported the anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile (7-HMIA), a synthesized analog of arvelexin on macrophages and paw edema, its anti-colitis effect and its mechanism are not known. In this study, colitis was induced in mice model by 4% (w/v) dextran sodium sulfate (DSS) solution in drinking water for 9 days. At the same time, from the first day of administering drinking water containing DSS, the animals were treated with 5-aminosalicylic acid (5-ASA), 75 mg/kg/day, orally) or 7-HMIA (10 or 20 mg/kg/day, intraperitoneally), depending on the experimental group, respectively. The studies were terminated on the tenth day of the experiment. Our data showed that 7-HMIA reduced the disease activity index and spleen/body weight (S/B) ratio, and improved the shortened colon length comparable to the effects of 5-ASA observed in the DSS-exposed mice. 7-HMIA, like 5-ASA, inhibited the histological damage, such as a thickened colonic muscle layer and shortened crypt length in the colon of the mice with DSS-induced colitis. 7-HMIA restored the tight junction-related proteins (occludin, claudin-1, and claudin-2) and epithelial-mesenchymal transition-mediated proteins (E-cadherin, N-cadherin, and vimentin) in the colon tissue of mice with DSS-induced colitis. Additionally, 7-HMIA (20 mg/kg/day) showed the inhibitory effects similar to that of 5-ASA on the myeloperoxidase activity, interleukin (IL)-6 production, and expression levels of inducible nitric oxide synthase (iNOS), and even showed greater inhibition of IL-1ß production in the DSS-induced mice. Furthermore, the DSS-induced activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were effectively suppressed by 7-HMIA treatment like the effects of 5-ASA. Overall, our findings revealed that 7-HMIA decreased the severity of colitis by protecting the inflamed mucosal barrier by interfering with NF-κB and STAT3 activation.


Assuntos
Colite Ulcerativa , Colite , Água Potável , Camundongos , Animais , NF-kappa B/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Inflamação/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/patologia , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
7.
Biomed Pharmacother ; 158: 114136, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36535201

RESUMO

The gut-liver axis is a bidirectional relationship between the gut with its microbiota and the hepatic. Ulcerative colitis (UC) disrupts the intestinal barrier and influx of intestinal microorganisms and their products into the liver, which trigger liver injury. Tea consumption is associated with a low incidence of UC in Asian countries. In this study, we revealed the mechanisms of six types of tea water extracts (TWEs) obtained from the leaves of Camellia sinensis on the dextran sodium sulfate (DSS)-induced colitis and liver injury in mice. The TWEs significantly restored mucin production and increased the expression levels of tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), occluding, and claudin-1. In addition, TWEs also reduced the levels of pro-inflammatory cytokines in the colon and liver tissue by inactivating the NF-κB/NLRP3. Moreover, TEWs treatment promoted the integrity of the intestinal barrier to reduce serum lipopolysaccharide (LPS) levels, thereby reducing liver injury caused by intestinal microbial translocation and LPS induction. Analysis of 16 S rRNA microbial sequencing revealed that tea water extracts (TWEs) restored the DSS-induced gut dysbiosis. Interestingly, our results showed that the degree of fermentation of tea leaves was negatively associated with the alleviation of DSS-induced colitis effects, and there was also an overall negative trend with colitis-induced liver injury, except for black tea. Taken together, tea consumption mitigated DSS-induced colitis and liver injury in mice via inhibiting the TLR4/NF-κB/NLRP3 inflammasome pathway.


Assuntos
Camellia sinensis , Colite Ulcerativa , Colite , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Inflamassomos/metabolismo , Lipopolissacarídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Chá , Proteínas de Junções Íntimas/metabolismo , Receptor 4 Toll-Like
8.
Biomed Pharmacother ; 158: 114133, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36521243

RESUMO

Endoplasmic reticulum stress (ERS)-related autophagy is involved in the occurrence and development of ulcerative colitis (UC). Therefore, regulating ERS-related autophagy is a potential therapeutic target for the treatment of UC. Jianpi-Qingchang (JPQC) decoction, consisting of nine Chinese herbal medicines, is used to treat patients with UC. However, its mechanism of action has not been completely elucidated. Here, we aimed to reveal the therapeutic effects and mechanisms of JPQC in UC. We established a colitis model using dextran sulfate sodium (DSS) and an ERS model using thapsigargin (Tg) and administered JPQC. We systematically examined ERS-related autophagy associated protein expression, inflammatory cytokines, apoptotic cells, and autophagic flux. Moreover, the cellular ultrastructure was observed via transmission electron microscopy (TEM). We found that JPQC reduced disease activity index (DAI) scores, counteracted colonic tissue damage, decreased the number of autophagosomes, inhibited proinflammatory cytokines, enhanced anti-inflammatory cytokines, and dampened ERS-related autophagy associated protein gene expression.


Assuntos
Colite Ulcerativa , Colite , Humanos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite/tratamento farmacológico , Colo , Células Epiteliais , Citocinas/metabolismo , Autofagia , Estresse do Retículo Endoplasmático , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
9.
Biomed Pharmacother ; 158: 114148, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36580723

RESUMO

Colitis is a common and complex intestinal inflammatory disease in which lactate, a metabolite of anaerobic glycolysis, plays a crucial role. Our study aimed to investigate the alleviated effect of lactate in colitis, and to provide a nutritional measure to alleviate colitis injury. The variations in colonic lactate in piglets with DSS-induced colitis were investigated in Experiment 1 (Exp.1). Thirty weaned pigs were allotted into three groups and sampled at different stages of DSS-induced colitis (days 0, 5, and 7). The colonic level of lactate and interleukin 10 (IL-10) was significantly decreased on day 5 when compared to day 0. Colonic lactate, IL-10, and G protein receptor 81 (GPR81) levels were significantly increased on day 7 when compared to day 5. Sixty weaned piglets were assigned to control (basal diet), DSS (basal diet with DSS gavage), or lactate (2% lactate supplementation diet with DSS gavage) groups to investigate the effects of lactate on DSS-induced colitis in Experiment 2 (Exp.2). Lactate reduced the disease activity index (DAI), DSS-induced impairment of colonic structure in response to the critical inflammatory cytokines interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) when compared with the DSS group. Furthermore, GPR-81 levels, colonic M2 macrophages, and IL-10 levels, the colonic antioxidant capacity, colonic butyrate levels were increased, and eventually improved growth performance post-colitis. The results of this study show that lactate was decreased at the peak of colitis, accumulated in subsidized colitis. Furthermore, dietary lactate supplementation helped to alleviate DSS-induced colitis injury.


Assuntos
Colite , Suplementos Nutricionais , Ácido Láctico , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Interleucina-10 , Ácido Láctico/uso terapêutico , Suínos
10.
Life Sci ; 314: 121309, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563843

RESUMO

AIMS: Inflammatory bowel disease is a complex, refractory disorder characterised by chronic gastrointestinal inflammation. Studies have reported that Lactobacillus reuteri alleviates gastrointestinal inflammation and strengthens the intestinal barrier. However, further biochemical and genetic studies are required to correctly understand the therapeutic potential of L. reuteri. MATERIALS AND METHODS: This study sought to further understand the anti-colitis effect of L. reuteri isolated from faecal samples of healthy locals by focusing on biochemical (immunological, mechanical, chemical and biological barriers) and genetic studies. KEY FINDINGS: In this study, we assessed and compared the benefits and efficacy of L. reuteri FYNDL13 and FCQHC8L in the treatment of colitis and found strain FYNDL13 to be superior to FCQHC8L in this regard. Compared with FCQHC8L, FYNDL13 was associated with more diverse and powerful regulatory pathways. Meanwhile, it encouraged butyric acid formation, upregulated antimicrobial peptide-coding gene transcription and prevented hyperimmune reactions on the intestinal periphery and within the intestine. Moreover, it enhanced the abundance of beneficial bacteria (Bifidobacterium, Akkermansia, Blautia and Oscillospira), thereby limiting the relative abundance of harmful bacteria (Bacteroides and Sutterella). Furthermore, the advantage might be attributed to metabolism- and defence system-related genomic characteristics. SIGNIFICANCE: Taken together, our study compares and summarizes a pathway paradigm of these two L. reuteri strains in reinforcing the intestinal barrier against colitis and identifies candidate genes responsible for microbiota-immune axis balance.


Assuntos
Colite , Microbioma Gastrointestinal , Probióticos , Camundongos , Animais , Probióticos/uso terapêutico , Colite/induzido quimicamente , Colite/terapia , Colite/microbiologia , Inflamação , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL
11.
World J Gastroenterol ; 28(46): 6522-6536, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36569276

RESUMO

BACKGROUND: 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid (BCAA)-associated mammalian target of rapamycin complex 1 (mTORC1) activation. Previous studies have demonstrated the therapeutic effects of BT2 on arthritis, liver cancer, and kidney injury. However, the effects of BT2 on ulcerative colitis (UC) are unknown. AIM: To investigate the anti-UC effects of BT2 and the underlying mechanism. METHODS: Mouse UC models were created through the administration of 3.5% dextran sodium sulfate (DSS) for 7 d. The mice in the treated groups were administered salazosulfapyridine (300 mg/kg) or BT2 (20 mg/kg) orally from day 1 to day 7. At the end of the study, all of the mice were sacrificed, and colon tissues were removed for hematoxylin and eosin staining, immunoblot analyses, and immunohistochemical assays. Cytokine levels were measured by flow cytometry. The contents of BCAAs including valine, leucine, and isoleucine, in mouse serum were detected by liquid chromatography-tandem mass spectrometry, and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing. RESULTS: Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice. BT2 also reduced the production of the proinflammatory cytokines interleukin 6 (IL-6), IL-9, and IL-2 and increased the anti-inflammatory cytokine IL-10 level. In addition, BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice. Furthermore, high-throughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis. Compared with the DSS group, BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and Escherichia-Shigella. CONCLUSION: Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite/induzido quimicamente , Colo/patologia , Citocinas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Mamíferos
12.
Front Immunol ; 13: 1042549, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518763

RESUMO

Background: Dysfunction of intestinal epithelial cells (IECs) promotes inflammatory bowel disease (IBD) and associated colorectal cancer (CRC). AKR1B8 deficiency impairs the IEC barrier function, leading to susceptibility to chronic colitis induced by dextran sulfate sodium (DSS), yet it remains unclear how acute colitic response is in AKR1B8 deficient mice. Methods: AKR1B8 knockout (KO) and littermate wild type mice were exposed to oral 1.5% DSS in drinking water for 6 days. Disease activity index and histopathological inflammation scores by H&E staining were calculated for colitic severity; permeability was assessed by fluorescein isothiocyanate dextran (FITC-Dextran) probes and bacterial invasion and transmission were detected by in situ hybridization in mucosa or by culture in blood agar plates. Immunofluorescent staining and flow cytometry were applied for immune cell quantification. Toll-like receptor 4 (TLR4) and target gene expression was analyzed by Western blotting and qRT-PCR. Results: AKR1B8 KO mice developed severe acute colitis at a low dose (1.5%) of DSS in drinking water compared to wild type controls. In AKR1B8 KO mice, FITC-dextran was penetrated easily and luminal bacteria invaded to the surface of IEC layer on day 3, and excessive bacteria translocated into the colonic mucosa, mesenteric lymph nodes (MLNs) and liver on day 6, which was much mild in wild type mice. Hyper-infiltration of neutrophils and basophils occurred in AKR1B8 KO mice, and monocytes in spleen and macrophages in colonic mucosa increased markedly compared to wild type mice. TLR4 signaling in colonic epithelial cells of AKR1B8 KO mice was activated to promote great IL-1ß and IL-6 expression compared to wild type mice. Conclusions: AKR1B8 deficiency in IECs drives severe acute colitis induced by DSS at a low dose through activation of the innate immunity, being a novel pathogenic factor of colitis.


Assuntos
Oxirredutases do Álcool , Colite , Imunidade Inata , Animais , Camundongos , Bactérias , Colite/induzido quimicamente , Colite/genética , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor 4 Toll-Like , Oxirredutases do Álcool/deficiência , Oxirredutases do Álcool/genética
13.
World J Gastroenterol ; 28(43): 6109-6130, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36483152

RESUMO

BACKGROUND: Intestinal micro-ecological imbalances impair the intestinal barrier and induce intestinal inflammation, for example, ulcerative colitis (UC). According to the latest research, abnormalities in intestinal microbiota structure and their metabolites play a dominant role in UC progression; in addition, they could affect the mucus barrier based on different factors. Although numerous studies have confirmed the important role of intestinal microbiota in UC pathogenesis, the intricate connection between microbiota and metabolites and mucus barrier in UC occurrence remains unclear, and correlation analyses of differential microbiota and their metabolites under UC are relatively scarce. AIM: To reveal the differential intestinal microbiota and metabolites in UC pathogenesis and explore more sensitive biomarker compositions. METHODS: We used the antibiotic combination method to establish intestinal pseudo-aseptic mice; afterward, dextran sulfate sodium (DSS) was applied to establish an acute experimental colitis mice model. Colitis severity, assessed based on disease activity index, colorectal length, colorectal wet weight, and histological lesions, and mucus-related staining (mucopolysaccharide alcian blue and immunofluorescence of mucin), was compared between the pseudo-aseptic and bacterial colitis mice. Finally, differential intestinal microbiota, metabolites, and their association and correlations, were analyzed by 16s rDNA sequencing in combination with non-targeted metabolomics, through gas chromatography-mass spectrometry. RESULTS: Compared with the pseudo-aseptic mice, intestinal bacteria positive mice were more severely ill and their intestinal mucus loss was more pronounced in DSS-induced colitis (P < 0.05), suggesting that different microbiota and metabolites could cause the different degrees of colitis. Subsequently, we observed that in addition to Klebsiella, and Bacteroides, which were widely associated with colitis, Candidatus Stoquefichus, Anaerobiospirillum, Muribaculum, and Negativibacillus may be involved in protection against colitis. Furthermore, differential metabolites of the microbiota were mainly enriched in the synthesis-related pathways of key structural sequences of mucin. In combination with the mucin-related staining and immunofluorescence results, the findings indicate that the differential microbiota and their metabolites potentially regulate the composition and function of mucus under colitis. CONCLUSION: Microbiota and their metabolites are major factors regulating the composition and function of mucus, in turn influencing the function and structure of intestinal mucus barrier under colitis. The different microbiota and metabolites identified in the present study could be novel biomarkers for colitis.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Sulfato de Dextrana/toxicidade , Metabolômica , Mucinas
14.
Mar Drugs ; 20(12)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36547911

RESUMO

Polysaccharide from the edible alga Enteromorpha clathrata has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we illustrate that Enteromorpha clathrata polysaccharide (ECP) could alleviate body weight loss, reduce incidences of colonic bleeding, improve stool consistency and ameliorate mucosal damage in diseased mice. 16S rRNA high-throughput sequencing and bioinformatic analysis indicated that ECP significantly changed the structure of the gut microbiota and increased the abundance of Parabacteroides spp. in DSS-fed mice. In vitro fermentation studies further confirmed that ECP could promote the growth of Parabacteroides distasonis F1-28, a next-generation probiotic bacterium isolated from the human gut, and increase its production of short-chain fatty acids. Additionally, Parabacteroides distasonis F1-28 was also found to have anti-ulcerative colitis effects in DSS-fed mice. Altogether, our study demonstrates for the first time a beneficial effect of ECP on ulcerative colitis and provides a possible basis for understanding its therapeutic mechanisms from the perspective of symbiotic gut bacteria Parabacteroides distasonis.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Sulfato de Dextrana/toxicidade , RNA Ribossômico 16S , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Bactérias , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colo/microbiologia
15.
Int J Mol Sci ; 23(23)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36499169

RESUMO

Inflammatory bowel disease (IBD) is a worldwide chronic intestinal inflammatory immune-related disease. In this study, mice with dextran sulfate sodium (DSS)-induced colitis were used to evaluate the effect of Lactobacillus acidophilus on colitis. The results revealed that L. acidophilus CCFM137 and FAHWH11L56 show potential for relieving colitis symptoms, while L. acidophilus FGSYC48L79 did not show a protective effect. Moreover, L. acidophilus NCFM and FAHWH11L56 showed similar effects on various indicators of DSS-induced colitis, increasing the IL-10 and IL-17 in the colon, and modifying the CCL2/CCR2 axis and CCL3/CCR1 axis. For L. acidophilus CCFM137, its effects on colitis were different from the above two strains. Moreover, L. acidophilus FGSYC48L79 had negative effects on colitis by increasing the abundance of harmful bacteria in the gut microbiota and may promote the signaling of chemokines and their receptors. This may be related to its special genome compared to the other strains.


Assuntos
Colite , Probióticos , Camundongos , Animais , Lactobacillus acidophilus , Sulfato de Dextrana/toxicidade , Colite/induzido quimicamente , Colite/microbiologia , Probióticos/uso terapêutico , Colo/microbiologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Citocinas
16.
Oxid Med Cell Longev ; 2022: 1755608, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578522

RESUMO

Ulcerative colitis (UC) is a multifactor intestinal disease with increased morbidity. Recently, pleiotropic drugs with exact biosafety have been urgently needed. Honokiol (HKL) is the major bioactive component of traditional Chinese medicine "Houpu," with almost no toxic effects and approved anti-inflammation, antioxidant, antispasmodic, etc. effects. This study examined the therapeutic effect of HKL in dextran sulfate sodium- (DSS-) induced experimental colitis. In vivo, C57BL/6 mice received 3% DSS for seven days to generate UC, and HKL was pretreated for five days and given during the whole DSS-induced period. In vitro, RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) to induce inflammation, and mouse colon epithelial cells (MCEC) were treated with HKL or pretreated with HKL and then stimulated with LPS-induced macrophage supernate to investigate the barrier enhancement roles. HKL significantly ameliorated disease activity index (DAI), colon length, and histopathological scores in DSS-induced colitis. The inflammatory mediators of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) were decreased, and the tight conjunction proteins were increased in the HKL-treated group both in vivo and in vitro. Above all, HKL can relieve experimental UC through anti-inflammation, antioxidant, and epithelial barrier enhancement roles. These effects were associated with peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor-κB (NF-κB) p65, sirtuin3 (SIRT3)/adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), and nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO1) signaling pathways. In conclusion, after further clinical studies, HKL may be a promising drug for UC.


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Lipopolissacarídeos/efeitos adversos , Antioxidantes/metabolismo , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Inflamação/patologia , Colite Ulcerativa/induzido quimicamente , Colo , NF-kappa B/metabolismo , Anti-Inflamatórios/efeitos adversos , Interleucina-6/metabolismo , Estresse Oxidativo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
17.
Biochem Biophys Res Commun ; 636(Pt 2): 48-54, 2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36343490

RESUMO

Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the intestine with the pathogenesis to be largely unknown. We found that microRNA (miR)-10b knock-out mice displayed mild IBD symptoms, suggesting that miR-10b may be involved in the onset and development of IBD. This study focuses on elucidating the role of miR-10b in IBD. The colitis model was induced by feeding the mice with 2.5% dextran sodium sulfate (DSS), and the expression levels of miR-10b in colon tissue and blood samples were examined. The severity of colitis was assessed by disease activity index, colon length, histopathological damage, intestinal permeability and ELISA. Then, after transfection of Caco-2 cells with miR-10b mimic and inhibitor, qRT-PCR was used to detect the expression levels of intestinal barrier related genes in colon tissues and cells. miR-10b levels were significantly reduced in mice with DSS-induced acute colitis. Compared with wild-type (WT) mice, miR-10b knockout mice were more sensitive to DSS-induced colitis characterized by increased inflammatory cell infiltration and more severe disruption of colonic barrier function. In addition, by inhibiting miR-10b and thus increasing intestinal barrier gene expression in Caco-2 cells, we found that miR-10b suppressed inflammatory responses and enhanced intestinal barrier function both in vivo and in vitro. miR-10b inhibits the inflammatory response in DSS-induced acute colitis mice in vivo and enhances intestinal barrier function in vitro, suggesting that miR-10b plays a key role in the developmental process of IBD. Thus, miR-10b may be expected to be a new target for the treatment of IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , MicroRNAs , Animais , Humanos , Camundongos , Células CACO-2 , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo
18.
Folia Biol (Praha) ; 68(2): 50-58, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36384262

RESUMO

Ulcerative colitis is caused by various external factors and is an inflammatory disease that causes decreased intestinal function. Tenebrio molitor larvae contain more than 30 % fat, and the fat component consists of 45 % oleic acid, 20 % linoleic acid and 20 % polyunsaturated fatty acids. In this study, after administering Tenebrio molitor larva oil (TMLO) in a dextran sodium sulphate (DSS)-induced ulcerative colitis mouse model, the pathological findings and inflammatory markers of colitis were analysed to assess whether a colitis mitigation effect was achieved. In the TMLO-administered group, the colon length increased, the spleen weight decreased, and the body weight increased compared with that in the DSS group. In addition, the disease activity index level decreased, the mRNA expression level of inflammatory cytokines in the colon decreased, and the myeloperoxidase activity level significantly decreased. Also, the activity of the NF-κB pathway involved in the regulation of the inflammatory response was lower in the TMLO group than in the DSS group. Taken together, these results suggest that TMLO suppresses occurrence of acute ulcerative colitis in the DSS mouse model. Therefore, TMLO has the potential to be developed as a health food for the prevention and treatment of ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Tenebrio , Camundongos , Animais , Sulfato de Dextrana/toxicidade , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Larva , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
19.
BMC Vet Res ; 18(1): 405, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384756

RESUMO

BACKGROUND: Uncertain effects of probiotics and/or prebiotics have been reported in experimental and clinical colitis. This study aims to examine the effects of a synbiotic combination comprising Bacillus licheniformis DSM 17236 and Saccharomyces cerevisiae cell wall extract on dextran sulfate sodium (DSS)-induced colitis in Sprague Dawley rats. METHODS: Acute colitis was induced in rats by oral administration of DSS 3.5% for 7 days. Fifty rats were divided equally into five groups; one control group and the other groups were induced with colitis and treated with or without the tested synbiotic, mixed with diet, for 28 days and sulfasalazine (100 mg/kg) via intragastric tube once daily for 14 days. RESULTS: Symptomatically, the synbiotic administration raised the disease activity index (DAI) to comparable scores of the DSS group, specially from the 2nd to 7th days post DSS intoxication. It also induced a significant (p < 0.05) amplification of WBCs, myeloperoxidase (MPO), malondialdehyde (MDA), nuclear factor kappa B (NF-kB) expression and proinflammatory cytokines tumor necrosis factor alpha (TNFα), interferon gamma (INFγ), and interleukin-1 beta (IL-1ß) while depressed the antioxidant enzymes glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) when compared with the DSS and control groups. The DSS intoxicated and Synbiotic+DSS groups showed desquamations of the covering epithelium, noticeable diffuse leukocytic infiltrations, sever catarrhal enteritis, ischemic colitis with diffuse coagulative necrosis of the entire colonic mucosa. Contrarily, sulfasalazine proved to be effective in the reduction of the tested inflammatory markers and the pathological degenerative changes of the DSS ulcerative colitis. CONCLUSION: The examined synbiotic did not ameliorate but aggravated the DSS-induced colitis, so it should be subjected to intensive experimental and clinical testing before their use in animals and human.


Assuntos
Bacillus licheniformis , Colite , Doenças dos Roedores , Simbióticos , Humanos , Ratos , Animais , Sulfato de Dextrana/toxicidade , Saccharomyces cerevisiae , Sulfassalazina/efeitos adversos , Ratos Sprague-Dawley , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Colite/veterinária
20.
Gut Microbes ; 14(1): 2145843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398889

RESUMO

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Lactobacillus johnsonii , Receptor 1 Toll-Like , Animais , Camundongos , Anti-Inflamatórios , Colite/genética , Colite/microbiologia , Colite/terapia , Colite Ulcerativa/genética , Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Sulfato de Dextrana/toxicidade , Interleucina-10/genética , Macrófagos , RNA Ribossômico 16S , Receptor 1 Toll-Like/genética , Receptor 1 Toll-Like/metabolismo
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