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1.
J Ethnopharmacol ; 301: 115800, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36228890

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lagotis integra W. W. Smith (L. integra W. W. Smith) is an important origin plant of the famous Tibetan medicine HERBA LAGOTIS. It was documented to treat "Chi Ba" disease clinically, the symptoms of which are similar to ulcerative colitis (UC). AIMS OF THIS STUDY: To screen out the active components and study the mechanisms of L. integra W. W. Smith treating UC. MATERIALS AND METHODS: The components of L. integra W. W. Smith were comprehensively analyzed using UHPLC-Q-TOF/MS method. The mechanisms were investigated using network pharmacology method including target prediction, protein-protein interaction network analysis and gene enrichment analysis. Then, the mechanisms were verified using Dextran Sulfate Sodium (DSS)-induced UC model. Finally, the core active components were further screened out through molecular docking. RESULTS: The results showed that 32 major components were identified including 8 flavonoids, 9 phenylpropanoid glycosides, 13 iridoid glycosides and 1 phenolic acid. 76 potential core therapeutic targets and top 5 key targets, which were AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor (VEGFA), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), were screened out according to network pharmacology analysis. Animal experiments confirmed that those compounds could downregulate the expression levels of the 5 key target proteins in colonic tissue of mice to exert excellent anti-UC effect. Molecular docking results showed that the main active components were echinacoside, hemiphroside B, plantamajoside, plantainoside D, 10-O-trans-isoferuloyl catalpol and scutellarioside II. CONCLUSIONS: For the first time, our study provides insights into the effective materials and molecular mechanisms of L. integra W. W. Smith treating UC, which contributes to the understanding of its pharmacodynamics.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Plantas Medicinais , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Simulação de Acoplamento Molecular , Medicina Tradicional Tibetana , Medicina Herbária , Medicamentos de Ervas Chinesas/farmacologia , Fator A de Crescimento do Endotélio Vascular , Farmacologia em Rede , Tibet
2.
J Ethnopharmacol ; 301: 115765, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36195303

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mesua Assamica (King & prain) Kosterm. (MA) is an evergreen endemic medicinal tree available in Assam in India and other parts of south Asia. The bark of the plant is traditionally used for ant-malarial activity and treating fevers. It was reported to have anti-oxidant, anti-inflammatory, anti-diabetic, anti-cancer and anti-malarial properties, but no research findings have been reported about its protective activity on intestinal inflammatory disorders like ulcerative colitis (UC) yet. AIM OF THE STUDY: The aim of the current study is to evaluate the anti-ulcerative property of ethanolic extract of MA (MAE) in-vitro on GloResponse™ NF-кB-RE-luc2P HEK 293 cells for its anti-oxidant and anti-inflammatory activities and in-vivo chronic restraint stress aggravated dextran sodium sulfate (DSS)-induced UC model. MATERIALS AND METHODS: The chemical constituents of MAE were identified by LC-MS/MS. The in-vitro effects of MAE on GloResponse™ NF-кB-RE-luc2P HEK 293 cells stimulated with TNF-α 30 ng/ml were investigated for its potential therapeutic effects. Parameters such as body weights, behavioural, colonoscopy, colon lengths and spleen weights were measured and recorded in chronic restraint stress aggravated DSS-induced UC model in C57BL/6 mice. Histological, cytokines and immunoblotting analysis in the colon tissues were determined to prove its anti-inflammatory and anti-oxidant activities. RESULTS: MAE poses significant anti-oxidant and anti-inflammatory activity in-vitro in GloResponse™ NF-кB-RE-luc2P HEK 293 cells evidenced by DCFDA and immunoflourescence assay. MAE treatment at 100 mg/kg and 200 mg/kg for 14 consecutive days has reduced Disease activity Index (DAI), splenomegaly and improved the shortened colon length and sucrose preference in mice. MAE treatment has increased the levels of anti-oxidants like GSH and reduced the levels of MDA, MPO and nitrite levels in colon tissues. Moreover, MAE has ameliorated neutrophil accumulation, mucosal and submucosal inflammation and crypt density evidenced by histopathology. Furthermore, MAE treatment significantly reduced the increased pro-inflammatory cytokines like IL-6, IL-1ß and TNF-α. we found from immunoblotting that there is a concomitant decrease in protein expression of NF-κB, STAT3 signalling cascades and phosphorylation of IKBα with an increase in Nrf2, SOD2, HO-1 and SIRT1 in colon tissues. In addition, we have performed molecular docking studies confirming that phytochemicals present in the MAE have a stronger binding ability and druggability to the NF-κB, Nrf2 and SIRT1 proteins. CONCLUSIONS: MAE exhibited significant anti-colitis activity on chronic restraint stress aggravated DSS-induced ulcerative colitis via regulating NF-κB/STAT3 and HO-1/Nrf2/SIRT1 signaling pathways.


Assuntos
Colite Ulcerativa , NF-kappa B , Animais , Humanos , Camundongos , Anti-Inflamatórios , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Cromatografia Líquida , Colite Ulcerativa/induzido quimicamente , Colo , Citocinas/metabolismo , Sulfato de Dextrana , Células HEK293 , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Casca de Planta/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismo
3.
Talanta ; 252: 123834, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35985193

RESUMO

Ulcerative colitis, a kind of inflammatory bowel disease (IBD), is caused by dysregulated immune response of intestinal bacteria. This chronic disorder can lead to a deficiency of O2 (hypoxia) in the colon microenvironment. Nitroreductase (NTR) is a highly expressed endogenous enzyme under hypoxia, so the detection of NTR can provide diagnostic information about ulcerative colitis. Herein, an ultrasensitive NTR-triggered fluorescence probe (WS-1-NO2) is developed for hypoxia imaging in ulcerative colitis. The probe shows a significant fluorescence enhancement (45-fold) after reacting with NTR, with an extremely low detection limit of 0.096 ng/mL. Furthermore, we apply it for fluorescence imaging of hypoxia in living cells, tumors and dextran sulphate sodium (DSS)-induced ulcerative colitis mouse models. We believe that the probe may be investigated as an effective potential tool for gaining insight into the hypoxia-relevant diseases, such as cancer and ulcerative colitis.


Assuntos
Colite Ulcerativa , Corantes Fluorescentes , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/diagnóstico por imagem , Nitrorredutases , Imagem Óptica/métodos , Hipóxia/diagnóstico por imagem , Sulfato de Dextrana
4.
J Ethnopharmacol ; 300: 115741, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162543

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD), is an herbal formula commonly used for the treatment of ulcerative colitis (UC) in clinical practice, but the mechanism of PD alters the colitis remains elusive. AIM OF THE STUDY: To evaluate the intervention effect of PD on Dextran Sodium Sulfate (DSS)-induced UC based on gut microbiota and intestinal short-chain fatty acid (SCFAs) metabolism, and to investigate the mechanism of action of PD in treating UC. MATERIALS AND METHODS: A 3% (wt/vol) DSS-induced ulcerative colitis model in C57BL/6 male mice was used to evaluate the effect of oral PD in treating UC. The changes in gut microbiota in mice were analyzed by 16SrDNA gene sequencing, and the content of SCFAs in the intestinal contents of mice was determined by gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze the expression of inflammatory cytokines in serum and colonic tissues, and western blotting (WB) was applied to analyze the expression of tight junction proteins in colonic tissues. RESULTS: PD can alleviate the symptoms of UC mice, Pulsatilla Decoction high dose treatment group (PDHT) shows the best effect. Compared with the DSS group, the PDHT had significantly lower body mass, disease activity index (DAI) score, colonic macroscopic damage index (CMDI) score, and pathological damage score, at the phylum level, the relative abundance of Bacteroidetes increased while that of Firmicutes and Proteobacteria decreased, at the Genus level, the abundance of Bacteroides and Lachnospiraceae.NK4A136.group increased while that of Clostridium. sensu.stricto。, Escherichia. shigella and Turicibacter decreased. Compared with the DSS group, acetate, propionate, and total SCFAs in the PDHT with significantly higher levels. The concentrations of interleukin-1ß (L-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) decreased whereby the concentration of interleukin-10 (IL-10) increased in the PDHT group. The expression levels of Occludin, zonula occludens-1 (ZO-1), Claudin1, Claudin5, G protein-coupled receptor43 (GPR43) protein, and the relative expression of ZO-1 and Occludin mRNA were significantly increased PDHT group. CONCLUSIONS: PD has a good therapeutic effect on UC mice. The pharmacological mechanism is probably maintaining the homeostasis and diversity of gut microbiota, increasing the content of SCFAs, and repairing the colonic mucosal barrier.


Assuntos
Colite Ulcerativa , Colite , Pulsatilla , Animais , Bactérias/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Propionatos , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
J Ethnopharmacol ; 300: 115690, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075274

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear. AIM OF THE STUDY: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice. MATERIALS AND METHODS: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1ß, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4-/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms. RESULTS: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1ß, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4-/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis. CONCLUSIONS: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway.


Assuntos
Colite Ulcerativa , Fator 88 de Diferenciação Mieloide , Animais , Caspases/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Interleucina-18/uso terapêutico , Interleucina-6/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Drug Des Devel Ther ; 16: 3739-3776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324421

RESUMO

Background: Traditional Chinese medicine (TCM) has the advantage of multi-component and multi-target, which becomes a hot spot in the treatment of numerous diseases. Shaoyao decoction (SYD) is a TCM prescription, which is mainly used to treat damp-heat dysentery clinically, with small side effects and low cost. However, its mechanism remains elusive. The purpose of this study is to explore the mechanism of SYD in the treatment of mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through metabolomics and network pharmacology, and verify through molecular docking and immunohistochemistry, so as to provide a scientific basis for the role of SYD in the treatment of UC. Materials and Methods: Firstly, DSS-induced UC models were established and then untargeted metabolomics analysis of feces, livers, serum and urine was performed to determine biomarkers and metabolic pathways closely related to the role of SYD. Besides, network pharmacology was applied to screen the active components and UC-related targets, which was verified by molecular docking. Finally, metabonomics and network pharmacology were combined to draw the metabolite-pathway-target network and verified by immunohistochemistry. Results: Metabolomics results showed that a total of 61 differential metabolites were discovered in SYD-treated UC with 3 main metabolic pathways containing glycerophospholipid metabolism, sphingolipid metabolism and biosynthesis of unsaturated fatty acids, as well as 8 core targets involving STAT3, IL1B, IL6, IL2, AKT1, IL4, ICAM1 and CCND1. Molecular docking demonstrated that the first five targets had strong affinity with quercetin, wogonin, kaempferol and baicalein. Combined with metabolomics and network pharmacology, sphingolipid signaling pathway, PI3K/AKT-mTOR signaling pathway and S1P3 pathway were identified as the main pathways. Conclusion: SYD can effectively ameliorate various symptoms and alleviate intestinal mucosal damage and metabolic disorder in DSS induced UC mice. Its effect is mainly related to sphingolipid metabolism, PI3K/AKT-mTOR signaling pathway and S1P3 pathway.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Metabolômica , Serina-Treonina Quinases TOR , Esfingolipídeos
7.
J Med Food ; 25(11): 1021-1028, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36322892

RESUMO

This study investigated the effect of perilla oil (PO) on an ulcerative colitis mouse model. Five-week-old male C57BL/6J mice were divided into HD (high-fat diet control), HDD (high-fat diet along with dextran sodium sulfate [DSS] administration), HDD + FO, HDD + PO, and HDD + OO where HDD + FO, HDD + PO, and HDD + OO groups were treated with fish oil (FO), PO, and olive oil (OO), respectively. Biochemical analysis of serum, quantitative polymerase chain reaction, and western blotting of colon tissue were conducted to measure inflammatory marker levels. Administration of DSS resulted in colon shortening and a higher disease activity score than HD group. These symptoms were significantly reversed in the oil-treated groups. The body weight loss after DSS administration was significantly lower in the HDD + PO and HDD + OO groups than in the HDD and HDD + FO groups. PO significantly attenuated the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß in the serum and colon. The mRNA expression levels of proinflammatory markers in the colon were reduced, whereas those of tight junction proteins and epithelial defense barrier-associated markers were increased by PO treatment. The protein expression of p-p65 was significantly lower in the PO-treated group than the HDD group. In summary, this study revealed that PO improved colitis in the DSS-induced mouse model, indicating its potential role in managing conditions such as ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Masculino , Animais , Sulfato de Dextrana/efeitos adversos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo , Óleos de Peixe/efeitos adversos , Óleos de Peixe/metabolismo , Azeite de Oliva , Modelos Animais de Doenças
8.
Curr Microbiol ; 79(12): 393, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329273

RESUMO

Previously, we isolated a novel Phocaeicola strain, Phocaeicola faecalis FXJYN30E22, from the feces of a healthy human from China. Metagenomic analysis revealed that the distribution of FXJYN30E22 differed in the intestinal tract of different hosts. We aimed to determine whether FXJYN30E22 protects against ulcerative colitis by employing a mouse model. In this study, dextran sulfate sodium was used to construct the UC model. The disease activity index, colon length, body weight changes, and histological scores were used as the pathological indicators to assess the anti-inflammatory effect of P. faecalis FXJYN30E22. Further, cytokine levels, tight junction mRNA expression levels, and short-chain fatty acid (SCFA) concentrations were also analyzed. Phocaeicola faecalis FXJYN30E22 could reduce the DSS-induced increase in DAI score, and enhance the colon length and body weight. Phocaeicola faecalis FXJYN30E22 could enhance TJ protein concentration and modulate the level of cytokines to reach levels close to those of the control group. FXJYN30E22 could also upregulate the concentrations of SCFA, which include acetate and butyrate. Based on the correlation analysis, four factors, including interleukin (IL)-6, IL-10, IL-1ß levels, and propionate concentration, were related to the protective roles of FXJYN30E22 in UC mice to different degrees. According to an analysis of the genomic information, the potential protective effects of strain FXJYN30E22 may be associated with the secretion of SCFA by specific genes. These findings suggest that oral P. faecalis FXJYN30E22 could help maintain the epithelial barrier by regulating cytokine levels and secreting SCFA.


Assuntos
Colite Ulcerativa , Colite , Humanos , Camundongos , Animais , Sulfato de Dextrana/toxicidade , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Peso Corporal , Camundongos Endogâmicos C57BL
9.
BMC Gastroenterol ; 22(1): 469, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401221

RESUMO

BACKGROUND: Triclosan, an antimicrobial agent in personal care products, could be absorbed into the human body through the digestive tract. This animal experiment aimed to clarify the effects of triclosan exposure on the microbiome and intestinal immune functions in healthy and ulcerative colitis models. METHODS: Balb/c mice were maintained on an AIN-93G diet containing 80ppm triclosan dissolved in polyethylene as vehicle or vehicle alone for 1 week or 4 weeks. In the end, the mice were sacrificed, blood samples and colon tissues were collected for analysis of inflammation, and fecal samples were collected for 16 S rRNA sequencing of gut microbiota. To establish ulcerative colitis mice model, at the beginning of the 4th week, mice maintained on the diet with or without triclosan were treated with 2% Dextran sulfate sodium(DSS) in drinking water for 1 week. Then mice were sacrificed for analysis of colitis and gut microbiota. RESULTS: Triclosan exposure to common mice enhanced the levels of p-NF-κb and Toll-like receptor 4 (TLR4), and decreased the Occludin in the colon. Triclosan exposure to DSS-induced mice increased the level of inflammatory cytokines, reduced the levels of Occludin, and exacerbated the degree of damage to intestinal mucosa and crypt, infiltration of inflammatory cells and atypia of glandular cells. Low-grade intraepithelial neoplasia appeared. Both in common and DSS-induced mice, triclosan exposure changed the diversity and composition of gut microbiota. Fecal samples showed higher enrichment of sulfate-reducing bacteria and Bacteroides, and less butyrate-producing bacteria. CONCLUSION: Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice. And changes in the composition of gut microbiota were characterized by the increase of harmful bacteria, including sulfate-reducing bacteria and Bacteroides, and the reduction of protective probiotics, butyrate-producing bacteria.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Triclosan , Humanos , Camundongos , Animais , Microbioma Gastrointestinal/genética , Triclosan/efeitos adversos , Sulfato de Dextrana/efeitos adversos , Colite Ulcerativa/induzido quimicamente , Ocludina , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/microbiologia , Sulfatos/efeitos adversos , Butiratos/farmacologia
10.
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
11.
ACS Appl Mater Interfaces ; 14(45): 50692-50709, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36326017

RESUMO

Rhein (RH), a natural anthraquinone compound, is considered an effective treatment candidate for ulcerative colitis (UC), whose multiple biological activities contribute to UC, including anti-inflammation, antioxidation, intestinal barrier repair, and microflora regulation. However, the application of RH is severely limited by its low water solubility, low bioavailability, and poor colonic targeting. Although some nanoparticles have been developed for the oral delivery of RH, most of them mainly highlighted only one effect of some drug delivery strategies but the above multiple biological activities. Therefore, a multiple polysaccharide-based nanodelivery system, comprising chitosan (CS) and fucoidan (FU), with pH/reactive oxygen species (ROS) sensitivity and mucosal adhesion, was developed and first used to load RH as a comprehensive treatment for UC. Briefly, RH-F/C-NPs were prepared using the polyelectrolyte self-assembly method; the average size of RH-F/C-NPs was 233.1 ± 5.7 nm, and the encapsulation rate of RH was 93.67 ± 1.60%. And it could maintain gastric stability and release RH in the colon with the designed pH/ROS sensitivity contributed by the polysaccharide-based structures. Cellular uptake experiments showed that both NCM 460 cells and RAW 264.7 cells had a good uptake of RH-F/C-NPs. Importantly, the effects of RH were highlighted in in vivo experiments, the results of which showed that RH-F/C-NPs could significantly reduce DSS-induced inflammation by inhibiting the TLR4/NF-κB-mediated anti-inflammatory pathway, the Nrf2/HO-1-mediated antioxidant pathway, colonic mucosal barrier repair, and intestinal microflora regulation. In addition, pharmacokinetic studies have shown that F/C-NPs contribute to the increase in the plasma concentration and the accumulation of RH in the colon to some extent. In short, this study is the first to develop an oral multiple polysaccharide-based nanosystem with pH/ROS dual sensitivity to study the "one stone four birds" therapeutic effect of RH on UC.


Assuntos
Colite Ulcerativa , Nanopartículas , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Concentração de Íons de Hidrogênio , Nanopartículas/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
12.
Int J Nanomedicine ; 17: 5303-5314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406639

RESUMO

Aim: This study focuses on constructing of an anti-inflammatory drug delivery system by encapsulation of berberine in the ß-glucan nanoparticles and evaluates its effect on treating ulcerative colitis. Methods: ß-Glucan and the anti-inflammatory drug berberine (BER) are self-assembled into nanoparticles to construct a drug delivery system (GLC/BER). The interaction between the drug and the carrier was characterized by circular dichroism, ultraviolet-visible spectroscopy, and dynamic light scattering. The anti-inflammatory effect of the GLC/BER was evaluated through a lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation model and a sodium sulfate (DSS)-induced C57BL/6 mouse ulcerative colitis model. Results: The GLC/BER nanoparticles have a particle size of 80-120 nm and a high encapsulation efficiency of 37.8±4.21%. In the LPS-induced RAW264.7 macrophage inflammation model, GLC/BER significantly promoted the uptake of BER by RAW264.7 cells. RT-PCR and ELISA assay showed that it could significantly inhibit the inflammatory factors including IL-1ß, IL-6 and COX-2. Furthermore, GLC/BER shows inhibiting effect on the secretion of pro-inflammatory factors such as IL-1ß and IL-6, down-regulating the production of nitrite oxide; in animal studies, GLC/BER was found to exert a relieving effect on mice colitis. Conclusion: The study found that GLC/BER has an anti-inflammatory effect in vitro and in vivo, and the GLC carrier improves the potency and bioavailability of BER, providing a new type of nanomedicine for the treatment of colitis.


Assuntos
Berberina , Colite Ulcerativa , Colite , Nanopartículas , beta-Glucanas , Camundongos , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Lipopolissacarídeos , Interleucina-6 , Camundongos Endogâmicos C57BL , Macrófagos , Colite/induzido quimicamente , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico
13.
Oxid Med Cell Longev ; 2022: 6298662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36285298

RESUMO

Inflammatory bowel disease (IBD) is a complex inflammatory disorder characterized by chronic and spontaneously relapsing inflammation of the gastrointestinal tract. IBD includes two idiopathic disorders: Crohn's disease (CD) and ulcerative colitis (UC). In particular, UC causes inflammation and ulceration of the colon and rectum. There is no cure for UC. The pharmacological treatment is aimed at controlling and/or reducing the inflammatory process and promoting disease remission. The present study investigated the possible protective effects of soluble dietary fiber (SDF) isolated from yellow passion fruit peel in the dextran sulfate sodium- (DSS-) induced colitis model in mice, induced by 5% of DSS. The animals were treated with SDF (10, 30, or 100 mg/kg (po)), and the disease activity index was monitored. Colon tissues were collected, measured, and prepared for oxidative stress, inflammation, and histology analysis. SDF improved body weight loss, colon length, and disease activity index and prevented colonic oxidative stress by regulating GSH levels and SOD activity. Furthermore, SDF reduced colonic MPO activity, TNF-α, and IL-1ß levels and increased IL-10 and IL-6 levels. As observed by histological analysis, SDF treatment preserved the colonic tissue, the mucus barrier, and reduced inflammatory cell infiltration. Although this is a preliminary study, taken together, our data indicate that SDF may improve the course of DSS-UC. More studies are needed to explore and understand how SDF promotes this protection.


Assuntos
Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Passiflora , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colo , Citocinas , Sulfato de Dextrana/toxicidade , Fibras na Dieta/uso terapêutico , Modelos Animais de Doenças , Frutas , Inflamação/patologia , Doenças Inflamatórias Intestinais/patologia , Interleucina-10 , Interleucina-6 , Camundongos Endogâmicos C57BL , Polissacarídeos , Superóxido Dismutase/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
14.
Int Immunopharmacol ; 112: 109251, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36182875

RESUMO

Ulcerative colitis (UC) is a multifactorial, refractory chronic inflammatory disease. The primary factor leading to prolonged ulcerative colitis is the imbalance of the group 3 innate lymphoid cells (ILC3) subgroup resulting in the delayed reconstruction of damaged intestinal barrier. Previous studies show that luteolin had efficacy on UC, however, the potency of luteolin on restoring the balance of NCR-ILC3/NCR+ILC3 to repairing impaired intestinal barrier remains unclear. In this study, to investigate the potential mechanism of luteolin on ILC3 subgroup, we first evidenced that luteolin could promote transformation NCR-MNK3 to NCR+MNK3 in vitro. Then, a UC model was established in C57BL/6J mice to assess the efficacy of luteolin in restoring ILC3 subgroup balance and repairing intestinal barrier in chronic UC. Finally, the experiments in vitro validated the potential mechanism of luteolin in regulating ILC3 plasticity. The results showed that luteolin significantly alleviated the symptoms of DSS-induced UC in mice, including preventing body weight loss and decreasing the disease activity index (DAI) and intestinal damages. Additionally, luteolin increased NCR+ILC3 levels, promoted the production of IL-22 and decreased the levels of IL-17a and INF-γ in the intestine, and encourage intestinal barrier function recovery in UC mice by promoting the expression of ZO-1 and Occludin. Experiments in vitro revealed that luteolin facilitated the transformation of NCR-MNK3 to NCR+MNK3 and promoted the secretion of IL-22, which was linked to the Notch pathway. All results revealed that luteolin restored the balance of NCR-ILC3/NCR+ILC3 and contributed to repair of injured intestinal epithelium to alleviate ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Interleucina-17/metabolismo , Luteolina/farmacologia , Luteolina/uso terapêutico , Imunidade Inata , Ocludina/metabolismo , Camundongos Endogâmicos C57BL , Linfócitos/metabolismo , Intestinos , Mucosa Intestinal/metabolismo , Sulfato de Dextrana , Colite/induzido quimicamente , Modelos Animais de Doenças
15.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36232929

RESUMO

Several studies have indicated the beneficial anti-inflammatory effect of butyrate in inflammatory bowel disease (IBD) therapy implying attempts to increase butyrate production in the gut through orally administered dietary supplementation. Through the gut-liver axis, however, butyrate may reach directly the liver and influence the drug-metabolizing ability of hepatic enzymes, and, indirectly, also the outcome of applied pharmacotherapy. The focus of our study was on the liver microsomal cytochrome P450 (CYP) 2A5, which is a mouse orthologue of human CYP2A6 responsible for metabolism of metronidazole, an antibiotic used to treat IBD. Our findings revealed that specific pathogen-free (SPF) and germ-free (GF) mice with dextran sulfate sodium (DSS)-induced colitis varied markedly in enzyme activity of CYP2A and responded differently to butyrate pre-treatment. A significant decrease (to 50%) of the CYP2A activity was observed in SPF mice with colitis; however, an administration of butyrate prior to DSS reversed this inhibition effect. This phenomenon was not observed in GF mice. The results highlight an important role of gut microbiota in the regulation of CYP2A under inflammatory conditions. Due to the role of CYP2A in metronidazole metabolism, this phenomenon may have an impact on the IBD therapy. Butyrate administration, hence, brings promising therapeutic potential for improving symptoms of gut inflammation; however, possible interactions with drug metabolism need to be further studied.


Assuntos
Butiratos , Colite Ulcerativa , Microbioma Gastrointestinal , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Butiratos/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sistema Enzimático do Citocromo P-450/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Metronidazol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL
16.
Bioorg Chem ; 129: 106180, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36208500

RESUMO

Fifteen new triterpenoids (1-15), along with twenty known ones (16-35), were isolated from Pseudolarix amabilis. The triterpenoid structures include multiple skeleton types, such as 2,3-seco-cycloartane, 3,4-seco-cycloartane, 3,4:9,10-diseco-cycloartane, and 3,4:8,9:9,10-triseco-cycloartane, as elucidated by extensive spectroscopy (1D NMR, 2D NMR, HRESIMS, and IR) and single-crystal X-ray diffraction. The anti-inflammatory activities of compounds 1-35 were evaluated. Compounds 3, 11, 16, 24, 25, and 26 suppressed the transcription of the NF-κB-dependent reporter gene in LPS-induced 293T/NF-κB-Luc cells with IC50 values of 0.12, 0.10, 0.30, 0.09, 0.49, and 0.35 µM, respectively. In addition, compound 16 showed anti-inflammatory activity against xylene-induced ear swelling in vivo with an inhibition rate of 44.7 % (30 mg/kg). Compound 16 significantly improved the disease activity index (DAI) of ulcerative colitis at a dose of 400 mg/kg in a dextran sodium sulfate (DSS)-induced mouse model of experimental ulcerative colitis (P < 0.01).


Assuntos
Colite Ulcerativa , Pinaceae , Triterpenos , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , NF-kappa B , Lactonas , Triterpenos/química , Pinaceae/química , Anti-Inflamatórios/efeitos adversos , Sementes
17.
Ultrastruct Pathol ; 46(5): 439-461, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36221187

RESUMO

Testicular dysfunction is caused by the continuous inflammation and oxidative stress that are present at the local site in ulcerative colitis (UC) spreading to the testes via systemic circulation. The influence of ozone and naringine on colitis-mediated testicular dysfunction was investigated in this study. Forty-eight adult male rats were divided into four groups: I control group, II dextran sodium sulfate (DSS) UC-induced group, III DSS+naringine, and IV DSS+ozone groups. UC was induced in groups II, III, and IV using 0.1 ml of 4% DSS in their drinking water per day for 6 days by gastric gavage. All animals were sacrificed 45 days from the start. Blood samples were obtained to estimate serum testosterone hormone. Testicular tissues were processed for measurement of tissue malondialdehyde (MDA) and examined by light and electron microscopes. Ultrastructurally, group II revealed a relatively thick basement membrane enveloping the seminiferous tubule. Sertoli cell cytoplasm appears rarified with wide intracellular spaces, vacuoles, and multiple lysosomes; distorted spermatogonia with electron dense nuclei and cytoplasm; and primary spermatocytes with small nuclei and electron dense cytoplasm. Abnormal sperm profiles were visible in middle pieces, mid, principle, and end pieces that were markedly affected with disorganization of axoneme and outer dense fibers. Leydig cells revealed dilated cisternae of smooth endoplasmic reticulum. Morphometric and statistical analyses were performed. Group III showed some improvement; however, group IV showed more improvement. The results indicated that ozone caused marked improvement than naringine against UC-induced testicular damage via their antioxidant and anti-inflammatory properties.


Assuntos
Colite Ulcerativa , Água Potável , Ozônio , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Água Potável/efeitos adversos , Flavanonas , Masculino , Malondialdeído/efeitos adversos , Ozônio/toxicidade , Ratos , Sêmen , Testosterona
18.
Phytomedicine ; 107: 154460, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36182798

RESUMO

BACKGROUND: Qingchang Wenzhong Decoction (QCWZD), a chinese herbal prescription, is widely used for ulcerative colitis (UC). Nevertheless, the active ingredients and mechanism of QCWZD in UC have not yet been explained clearly. PURPOSE: This research focuses on the identification of the effective ingredients of QCWZD and the prediction and verification of their potential targets. METHODS: The UC mice were established by adding 3.0% dextran sulfate sodium (DSS) to sterile water for one week. Concurrently, mice in the treatment group were gavage QCWZD or mesalazine. LC-MS analyzed the main components absorbed after QCWZD treatment, and network pharmacology predicted their possible targets. ELISA, qPCR, immunohistochemistry and immunofluorescence experiments were used to evaluate the colonic inflammation level and the intestinal barrier completeness. The percentage of Th17 and Treg lymphocytes was detected by flow cytometry. RESULTS: After QCWZD treatment, twenty-seven compounds were identified from the serum. In addition, QCWZD treatment significantly reduced the increased myeloperoxidase (MPO) and inflammatory cell infiltration caused by DSS in the colonic. In addition, QCWZD can reduce the secretion of inflammatory factors in serum and promote the expression of mRNAs and proteins of occludin and ZO-1. Network pharmacology analysis indicated that inhibiting IL-6-STAT3 pathway may be necessary for QCWZD to treat UC. Flow cytometry analysis showed that QCWZD can restore the normal proportion of Th17 lymphocytes in UC mice. Mechanistically, QCWZD inhibited the phosphorylation of JAK2-STAT3 pathway, reducing the transcriptional activation of RORγT and IL-17A. CONCLUSIONS: Overall, for the first time, our work revealed the components of QCWZD absorbed into blood, indicated that the effective ingredients of QCWZD may inhibit IL-6-STAT3 pathway and inhibit the differentiation of Th17 lymphocytes to reduce colon inflammation.


Assuntos
Colite Ulcerativa , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Mesalamina/metabolismo , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ocludina/metabolismo , Peroxidase/metabolismo , Células Th17 , Água
19.
Phytomedicine ; 107: 154468, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36209702

RESUMO

BACKGROUND: Ulcerative colitis (UC) has affected an increasing number of people globally, with still limited clinical success. Huanglian Decoction (HLD) is a famous classical prescription documented for alleviating gastrointestinal disorders with unexplored therapeutic effects and mechanisms. PURPOSE: This study aimed to investigate the therapeutic effect and underlying mechanism of HLD in dextran sodium sulfate (DSS)-induced colitis mice. METHODS: The efficacy and safety of HLD were evaluated in a well-established DSS-induced colitis mice model. Disease progression was monitored via clinical symptoms, histopathological examination, biochemical assays, and epithelial barrier function evaluation. RESULTS: HLD alleviated DSS-induced colitis symptoms, reversed colon length reduction, reduced histological injury, downregulated the level of pro-inflammatory cytokines, maintained the tight distribution of ZO-1/occludin-1 and the normal level of ß-catenin, concurrent with apoptosis reduction in the colonic epithelium. After HLD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. CONCLUSION: This study demonstrates that HLD may present a potential remedy for UC treatment, providing evidence for further developing Chinese classical prescriptions.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Citocinas , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Camundongos , Camundongos Endogâmicos C57BL , Ocludina , Prescrições , beta Catenina
20.
Front Immunol ; 13: 966184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211446

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD's clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.


Assuntos
Colite Ulcerativa , Colite , Doença de Crohn , Doenças Inflamatórias Intestinais , Animais , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Doença de Crohn/genética , Sulfato de Dextrana/toxicidade , Doenças Inflamatórias Intestinais/genética , Camundongos
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