Protective effect of Plumericin in inflammatory bowel disease: regulation of inflammatory and oxidative stress response in vitro and in vivo

2019 ◽  
Author(s):  
SF Rapa ◽  
B Waltenberger ◽  
R Di Paola ◽  
G Autore ◽  
S Cuzzocrea ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Bowel Disease ◽  
Stress Response ◽  
Protective Effect ◽  
Bowel Disease ◽  
Oxidative Stress Response ◽  
Inflammatory Bowel ◽  
And Oxidative Stress

scholarly journals Natural Product-Based Nanomedicine in Treatment of Inflammatory Bowel Disease

2020 ◽  
Vol 21 (11) ◽  
pp. 3956 ◽  
Author(s):  
Tripti Khare ◽  
Sushesh Srivatsa Palakurthi ◽  
Brijesh M. Shah ◽  
Srinath Palakurthi ◽  
Sharad Khare
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Bowel Disease ◽  
Natural Product ◽  
Bowel Disease ◽  
Synthetic Drugs ◽  
In Vivo Experiments ◽  
Inflammatory Bowel

Many synthetic drugs and monoclonal antibodies are currently in use to treat Inflammatory Bowel Disease (IBD). However, they all are implicated in causing severe side effects and long-term use results in many complications. Numerous in vitro and in vivo experiments demonstrate that phytochemicals and natural macromolecules from plants and animals reduce IBD-related complications with encouraging results. Additionally, many of them modify enzymatic activity, alleviate oxidative stress, and downregulate pro-inflammatory transcriptional factors and cytokine secretion. Translational significance of natural nanomedicine and strategies to investigate future natural product-based nanomedicine is discussed. Our focus in this review is to summarize the use of phytochemicals and macromolecules encapsulated in nanoparticles for the treatment of IBD and IBD-associated colorectal cancer.

scholarly journals Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53

2020 ◽  
Vol 295 (13) ◽  
pp. 4237-4251 ◽  
Author(s):  
Jie Zhang ◽  
Min Xu ◽  
Weihua Zhou ◽  
Dejian Li ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Epithelial Cell ◽  
Bowel Disease ◽  
Intestinal Epithelial Cell ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial ◽  
P53 Expression ◽  
Inflammatory Bowel

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1−/− mice, DJ-1−/−p53−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

scholarly journals Analysis of Functional Domains in Rho5, the Yeast Homolog of Human Rac1 GTPase, in Oxidative Stress Response

2019 ◽  
Vol 20 (22) ◽  
pp. 5550 ◽  
Author(s):  
Carolin Sterk ◽  
Lauren Gräber ◽  
Hans-Peter Schmitz ◽  
Jürgen J. Heinisch
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Hypervariable Region ◽  
Oxidative Stress Response ◽  
Small Gtpase ◽  
Rac1 Gtpase ◽  
Yeast Homolog ◽  
And Oxidative Stress ◽  
Polybasic Region

The small GTPase Rho5 of Saccharomyces cerevisiae is required for proper regulation of different signaling pathways, which includes the response to cell wall, osmotic, nutrient, and oxidative stress. We here show that proper in vivo function and intracellular distribution of Rho5 depends on its hypervariable region at the carboxyterminal end, which includes the CAAX box for lipid modification, a preceding polybasic region (PBR) carrying a serine residue, and a 98 amino acid–specific insertion only present in Rho5 of S. cerevisiae but not in its human homolog Rac1. Results from trapping GFP-Rho5 variants to the mitochondrial surface suggest that the GTPase needs to be activated at the plasma membrane prior to its translocation to mitochondria in order to fulfil its role in oxidative stress response. These findings are supported by heterologous expression of a codon-optimized human RAC1 gene, which can only complement a yeast rho5 deletion in a chimeric fusion with RHO5 sequences that restore the correct spatiotemporal distribution of the encoded protein.

scholarly journals The Effect of a Fennel Extract on the STAT Signaling and Intestinal Barrier Function

2021 ◽  
Author(s):  
John Rabalais ◽  
Philip Kozan ◽  
Tina Lu ◽  
Nassim Durali ◽  
Kevin Okamoto ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Protective Effect ◽  
Bowel Disease ◽  
Barrier Function ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Foeniculum Vulgare ◽  
Inflammatory Bowel ◽  
Stat Pathway

Background: Foeniculum vulgare, F. vulgare, commonly known as fennel, is believed to be one of the worlds oldest medicinal herbs and has been exploited by people for centuries as a nutritional aid for digestive disorders. In many southeast Asian countries it is ingested as an after-meal snack, mukhvas, due to its breath-freshening and digestive aid properties. F. vulgare is used in some countries, such as Iran, as a complementary and alternative treatment for inflammatory bowel disease (IBD). Methods: This study investigated the effects of F. vulgare on the barrier function of the intestinal epithelium Signal Transducer and Activator of Transcription (STAT) pathway, which is active in inflammatory bowel disease. To study the protective effects of F. vulgare extract in vitro, monolayers derived from the T84 colonic cell line were challenged with interferon-gamma (IFN-γ) and monitored with and without F. vulgare extract. To complement our in vitro studies, the dextran sodium sulfate induced murine colitis model was employed to ascertain whether the protective effect of F. vulgare extract can be recapitulated in vivo. Results: F. vulgare extract was shown to exert a protective effect on TEER in both T84 and murine models and showed increases in tight junction-associated mRNA in T84 cell monolayers. Both models demonstrated significant decreases in phosphorylated STAT1 (pSTAT1), indicating reduced activation of the STAT pathway. Additionally, mice treated with F. vulgare showed significantly lower ulcer indices than control mice. Conclusions: We conclude barrier function of the gastrointestinal tract is improved by F. vulgare, suggesting the potential utility of this agent as an alternative or adjunctive therapy in IBD.

scholarly journals In Vitro and in Vivo Evaluation of Pectin-based Melatonin Nanoparticles for the Treatment of Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Serkan Yener ◽  
Kazime Gonca Akbulut ◽  
Resul Karakuş ◽  
Deniz Erdoğan ◽  
Füsun Acartürk
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Histological Evaluation ◽  
Trinitrobenzene Sulfonic Acid ◽  
Colonic Tissue ◽  
In Vivo Evaluation ◽  
Promising Alternative ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease (IBD) is a general term including long-term inflammatory disorders of all or some parts of the digestive system. Nanoparticles (NPs) can accumulate in the inflamed zone independently of the polymers’ mucoadhesive character. The aim of this study was to prepare and investigate the melatonin loaded pectin-based nanoparticles for Inflammatory Bowel Disease (IBD). Melatonin (MEL) was loaded into nanoparticle system with a modified ionotropic-gelation method. In vitro characterization studies of the nanoparticles were carried out. The effectiveness of the oral and intracolonically administered nanoparticles were investigated in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. The indicators of oxidative stress in the colonic tissue like nitric oxide, malondialdehyde, glutathione, tumor necrosis factor-alpha, Interleukin (IL)-10, and IL-17 levels were investigated. In addition, the histological evaluation was performed. The mean diameter, zeta potential and polydispersity index values of the obtained nanoparticles were 75.3±3.3 nm, 24.24±1.03 mV and 0.109±0.067, respectively. The in vitro drug release studies showed that 84.0±0.7% of the drug was released from the nanoparticles for 8 h. MEL-loaded pectin nanoparticles ameliorated the TNBS-induced colitis. Treatment of the melatonin decreased the damage score by 73.2% in oral and by 67.1% in intracolonic route, respectively. A meaningful decrease was observed in colonic fibrosis, oxidative stress, and inflammatory parameters of the colon accompanying histologic injury. The results of the experiments and histological data showed that MEL-loaded calcium pectinate nanoparticle may be a promising alternative in colonic tissue damage which develops due to oxidative stress in IBD.

scholarly journals Inflammatory Bowel Disease–associated GP2 Autoantibodies Inhibit Mucosal Immune Response to Adherent-invasive Bacteria

2020 ◽  
Vol 26 (12) ◽  
pp. 1856-1868
Author(s):  
Stefanie Derer ◽  
Ann-Kathrin Brethack ◽  
Carlotta Pietsch ◽  
Sebastian T Jendrek ◽  
Thomas Nitzsche ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Ex Vivo ◽  
Expression Patterns ◽  
Mucosal Immune Response ◽  
Disease Manifestation ◽  
Inflammatory Bowel

Abstract Adherent-invasive Escherichia coli have been suggested to play a pivotal role within the pathophysiology of inflammatory bowel disease (IBD). Autoantibodies against distinct splicing variants of glycoprotein 2 (GP2), an intestinal receptor of the bacterial adhesin FimH, frequently occur in IBD patients. Hence, we aimed to functionally characterize GP2-directed autoantibodies as a putative part of IBD’s pathophysiology. Ex vivo, GP2-splicing variant 4 (GP2#4) but not variant 2 was expressed on intestinal M or L cells with elevated expression patterns in IBD patients. The GP2#4 expression was induced in vitro by tumor necrosis factor (TNF)-α. The IBD-associated GP2 autoantibodies inhibited FimH binding to GP2#4 and were decreased in anti-TNFα-treated Crohn’s disease patients with ileocolonic disease manifestation. In vivo, mice immunized against GP2 before infection with adherent-invasive bacteria displayed exacerbated intestinal inflammation. In summary, autoimmunity against intestinal expressed GP2#4 results in enhanced attachment of flagellated bacteria to the intestinal epithelium and thereby may drive IBD’s pathophysiology.

In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease

2016 ◽  
Vol 26 (19) ◽  
pp. 4587-4591 ◽  
Author(s):  
Suhrid Banskota ◽  
Han-eol Kang ◽  
Dong-Guk Kim ◽  
Sang Won Park ◽  
Hyeonjin Jang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inhibitory Activity ◽  
Inflammatory Bowel

scholarly journals Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

2015 ◽  
Vol 197 (20) ◽  
pp. 3329-3338 ◽  
Author(s):  
Michael I. Betteken ◽  
Edson R. Rocha ◽  
C. Jeffrey Smith
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Peritoneal Cavity ◽  
Bacteroides Fragilis ◽  
Oxidative Stress Response ◽  
Iron Storage ◽  
Content Type ◽  
Iron Storage Proteins

ABSTRACTBacteroides fragilisis a Gram-negative anaerobe and member of the human intestinal tract microbiome, where it plays many beneficial roles. However, translocation of the organism to the peritoneal cavity can lead to peritonitis, intra-abdominal abscess formation, bacteremia, and sepsis. During translocation,B. fragilisis exposed to increased oxidative stress from the oxygenated tissues of the peritoneal cavity and the immune response. In order to survive,B. fragilismounts a robust oxidative stress response consisting of an acute and a prolonged oxidative stress (POST) response. This report demonstrates that the ability to induce high levels of resistance totert-butyl hydroperoxide (tBOOH) after extended exposure to air can be linked to the POST response. Disk diffusion assays comparing the wild type to a Δdpsmutant and a ΔdpsΔbfrmutant showed greater sensitivity of the mutants to tBOOH after exposure to air, suggesting that Dps and DpsL play a role in the resistance phenotype. Complementation studies withdpsorbfr(encoding DpsL) restored tBOOH resistance, suggesting a role for both of these ferritin-family proteins in the response. Additionally, cultures treated with the iron chelator dipyridyl were not killed by tBOOH, indicating Dps and DpsL function by sequestering iron to prevent cellular damage. Anin vivoanimal model showed that the ΔdpsΔbfrmutant was attenuated, indicating that management of iron is important for survival within the abscess. Together, these data demonstrate a role for Dps and DpsL in the POST response which mediates survivalin vitroandin vivo.IMPORTANCEB. fragilisis the anaerobe most frequently isolated from extraintestinal opportunistic infections, but there is a paucity of information about the factors that allow this organism to survive outside its normal intestinal environment. This report demonstrates that the iron storage proteins Dps and DpsL protect against oxidative stress and that they contribute to survival bothin vitroandin vivo. Additionally, this work demonstrates an important role for the POST response inB. fragilissurvival and provides insight into the complex regulation of this response.

Oxidative stress and thromboxane-dependent platelet activation in inflammatory bowel disease: effects of anti-TNF-α treatment

2016 ◽  
Vol 116 (09) ◽  
pp. 486-495 ◽  
Author(s):  
Marco Guerci ◽  
Paola Simeone ◽  
Sandro Ardizzone ◽  
Alessandro Massari ◽  
Paolo Giuffrida ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Platelet Activation ◽  
Bowel Disease ◽  
Infliximab Treatment ◽  
Soluble Cd40 Ligand ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Vitro Effect

SummaryPatients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease despite having a lower burden of traditional risk factors. Platelets from IBD patients release more soluble CD40 ligand (CD40L), and this has been implicated in IBD platelet hyper-activation. We here measured the urinary F2-isoprostane 8-iso-prostaglandin (PG)2α (8-iso-PGF2α), urinary 11–dehydro–thromboxane (TX) B2 (11-dehydro–TXB2) and plasma CD40L in IBD patients, and explored the in vitro action of anti-tumour necrosis factor (TNF)–α antibody infliximab on IBD differentiating megakaryocytes. Urinary and blood samples were collected from 124 IBD patients and 37 healthy subjects. Thirteen IBD patients were also evaluated before and after 6–week infliximab treatment. The in vitro effect of infliximab on patient-derived megakaryocytes was evaluated by immunoflorescence microscopy and by flow cytometry. IBD patients had significantly (p<0.0001) higher urinary 8–iso–PGF2α and 11–dehydro–TXB2 as well as plasma CD40L levels than controls, with active IBD patients displaying higher urinary and plasma values when compared to inactive patients in remission. A 6-week treatment with infliximab was associated with a significant reduction of the urinary excretion of 8–iso–PGF2α and 11–dehydro–TXB2 (p=0.008) and plasma CD40L (p=0.001). Infliximab induced significantly rescued pro-platelet formation by megakaryocytes derived from IBD patients but not from healthy controls. Our findings provide evidence for enhanced in vivo TX–dependent platelet activation and lipid peroxidation in IBD patients. Anti-TNF–α therapy with infliximab down-regulates in vivo isoprostane generation and TX biosynthesis in responder IBD patients. Further studies are needed to clarify the implication of infliximab induced-proplatelet formation from IBD megakaryocytes.Supplementary Material to this article is available online at www.thrombosis-online.com.

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