scholarly journals Stereochemical Determination of Fistularins Isolated from the Marine Sponge Ecionemia acervus and Their Regulatory Effect on Intestinal Inflammation

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 170
Author(s):  
Yeong Kwang Ji ◽  
Seon Min Lee ◽  
Na-Hyun Kim ◽  
Nguyen Van Tu ◽  
Yun Na Kim ◽  
...  
Keyword(s):  
Marine Sponge ◽  
Intestinal Inflammation ◽  
Nuclear Translocation ◽  
Chemical Shifts ◽  
Stereochemical Structure ◽  
Mapk Phosphorylation ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Proton Chemical Shifts

By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2), six fistularin compounds (1–6) were isolated from the marine sponge Ecionemia acervus (order Astrophorida). Based on stereochemical structure determination using Mosher’s method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 (1) and -2 (2), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE2, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 (1) and 19-deoxyfistularin-3 (4) showed the highest activity. These findings suggest the potential use of the marine sponge E. acervus and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.

scholarly journals Isoquinolinequinone Derivatives from a Marine Sponge (Haliclona sp.) Regulate Inflammation in In Vitro System of Intestine

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 90
Author(s):  
Yun Kim ◽  
Yeong Ji ◽  
Na-Hyun Kim ◽  
Nguyen Van Tu ◽  
Jung-Rae Rho ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Marine Sponge ◽  
Nuclear Translocation ◽  
Hydroxyl Group ◽  
Subsequent Increase ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Key Functional Groups ◽  
Oxide Synthase

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1–8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.

1H Chemical Shifts of Protons Directly Bonded to Phosphorus

1970 ◽  
Vol 25 (5) ◽  
pp. 451-461 ◽  
Author(s):  
Doureid Houalla ◽  
Raymond Marty ◽  
Robert Wolf
Keyword(s):  
Chemical Shifts ◽  
Proton Chemical Shifts

Over 100 δH values of H- (P) obtained in our laboratory, as well as values from the literature, have been tabulated and discussed. These data are useful, not only in the study of molecules containing a P-H bond but also, more generally, in the determination of the factors which influence the value of proton chemical shifts.

scholarly journals Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 539
Author(s):  
Bahez Gareb ◽  
Antonius T. Otten ◽  
Henderik W. Frijlink ◽  
Gerard Dijkstra ◽  
Jos G. W. Kosterink
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Genetically Modified Organisms ◽  
Intestinal Inflammation ◽  
Systemic Exposure ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

scholarly journals Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase

2019 ◽  
Vol 316 (6) ◽  
pp. G692-G700 ◽  
Author(s):  
Emmeline Salameh ◽  
Mathieu Meleine ◽  
Guillaume Gourcerol ◽  
Jean-Claude do Rego ◽  
Jean-Luc do Rego ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Visceral Pain ◽  
Myeloperoxidase Activity ◽  
Therapeutic Approaches ◽  
Chronic Colitis ◽  
Functional Symptoms ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15–45 mg of TNBS) in 30 rats, whereas the control rats ( n = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced 1) a visceral hypersensitivity ( P = 0.03), 2) an increased colon weight-to-length ratio ( P = 0.01), 3) higher inflammatory and fibrosis scores ( P = 0.0390 and P = 0.0016, respectively), and 4) a higher colonic IL-6 and IL-10 production ( P = 0.008 and P = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae.NEW & NOTEWORTHY Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in the remission period. It might define novel therapeutic approaches to achieve a better inflammatory bowel disease-related sequelae management.

scholarly journals Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10

2019 ◽  
Vol 216 (2) ◽  
pp. 337-349 ◽  
Author(s):  
Peng Xiao ◽  
Huilun Zhang ◽  
Yu Zhang ◽  
Mingzhu Zheng ◽  
Rongbei Liu ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Interleukin 10 ◽  
Blood Monocytes ◽  
Stat3 Signaling ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Further Development

Inflammatory cytokines produced by activated macrophages largely contribute to the pathological signs of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is the predominant anti-inflammatory cytokine in the intestine, and its therapeutic efficacy for IBD has been clinically tested. Nevertheless, how the function of IL-10 is regulated in the intestinal microenvironment remains unknown, which largely hinders the further development of IL-10–based therapeutic strategies. Here, we found that the expression of phosphatase Shp2 was increased in colonic macrophages and blood monocytes from IBD patients compared with those from healthy controls. Shp2 deficiency in macrophages protects mice from colitis and colitis-driven colon cancer. Mechanistically, Shp2 disrupts IL-10–STAT3 signaling and its dependent anti-inflammatory response in human and mouse macrophages. Furthermore, a Shp2-inducing role of TNF-α is unveiled in our study. Collectively, our work identifies Shp2 as a detrimental factor for intestinal immune homeostasis and hopefully will be helpful in the future exploitation of IL-10 immunotherapy for IBD.

scholarly journals Immunomodulatory role of Parkinson’s disease 7 in inflammatory bowel disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rita Lippai ◽  
Apor Veres-Székely ◽  
Erna Sziksz ◽  
Yoichiro Iwakura ◽  
Domonkos Pap ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Ht 29

AbstractRecently the role of Parkinson’s disease 7 (PARK7) was studied in gastrointestinal diseases, however, the complex role of PARK7 in the intestinal inflammation is still not completely clear. Expression and localization of PARK7 were determined in the colon biopsies of children with inflammatory bowel disease (IBD), in the colon of dextran sodium sulphate (DSS) treated mice and in HT-29 colonic epithelial cells treated with interleukin (IL)-17, hydrogen peroxide (H2O2), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β or lipopolysaccharide (LPS). Effect of PARK7 on the synthesis of IBD related cytokines was determined using PARK7 gene silenced HT-29 cells and 3,4,5-trimethoxy-N-(4-(8-methylimidazo(1,2-a)pyridine-2-yl)phenyl)benzamide (Comp23)—compound increasing PARK7 activity—treated mice with DSS-colitis. PARK7 expression was higher in the mucosa of children with Crohn’s disease compared to that of controls. While H2O2 and IL-17 treatment increased, LPS, TNF-α or TGF-β treatment decreased the PARK7 synthesis of HT-29 cells. PARK7 gene silencing influenced the synthesis of IL1B, IL6, TNFA and TGFB1 in vitro. Comp23 treatment attenuated the ex vivo permeability of colonic sacs, the clinical symptoms, and mucosal expression of Tgfb1, Il1b, Il6 and Il10 of DSS-treated mice. Our study revealed the role of PARK7 in the regulation of IBD-related inflammation in vitro and in vivo, suggesting its importance as a future therapeutic target.

Determination of deuterium fraction in heavy water by proton chemical shifts

1979 ◽  
Vol 51 (8) ◽  
pp. 1335-1336
Author(s):  
Aarre. Kellomaki ◽  
Mirjami. Jutila
Keyword(s):  
Heavy Water ◽  
Chemical Shifts ◽  
Proton Chemical Shifts
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