scholarly journals Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. Morsy ◽  
Snehal S. Patel ◽  
Azza A. K. El-Sheikh ◽  
Jignasa K. Savjani ◽  
Anroop B. Nair ◽  
...  
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Withaferin A ◽  
Boswellic Acid ◽  
Cotton Pellet ◽  
Anti Inflammatory ◽  
Necrosis Factor

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

scholarly journals Potential anti-inflammatory activity of low molecular weight heparin in patients with exacerbations of COPD – short report

2014 ◽  
Vol 124 (1) ◽  
pp. 46-48 ◽  
Author(s):  
Barabara Rybacka-Chabros ◽  
Aldona Pietrzak ◽  
Paweł Chabros ◽  
Janusz Milanowski
Keyword(s):  
Tumor Necrosis ◽  
Serum Levels ◽  
Tnf Alpha ◽  
Interleukin 12 ◽  
Low Molecular Weight ◽  
Necrosis Factor Alpha ◽  
Daily Dose ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

AbstractIntroduction. Anti-inflammatory, separate from anti-thrombotic activity of low molecular weight heparin, is still not well documented. Aim. We estimated the influence of enoxaparin on serum levels of tumor necrosis factor alpha, as the pro-inflammatory cytokine, and interleukin-12, as the heparin-binding, anti-inflammatory cytokine, in patients with exacerbations of chronic obstructive pulmonary disease. Material and methods. Seventy-three consecutive patients (48 males, 25 females) aged 56-75 years without thromboembolic history, were enrolled into the study. They were randomized to group who received enoxaparin in one daily dose 40 mg, or to group who did not receive it. Patients receiving oral anti-coagulants were excluded from the study. Using ELISA approach, we evaluated serum levels of tumor necrosis factor-alpha and interleukin-12 at the following periods: before the first dose of enoxaparin, after 7 days of treatment and 14 days of treatment. Serum level of the C-reactive protein was evaluated simultaneously. Results. In enoxaparin recipients statistically significant (p<0.01) decreasing of TNF-alpha serum levels (from 168.33 pg/ml in admission, to 85.67 pg/ml in the end of study) to compare enoxaparine non-recipients, was observed. Interleukin-12 serum levels were significantly higher in enoxaparine recipients both after 7 days (67.46 pg/ml) and 14 days (89.32 pg/ml) of the study (p<0.05). C-reactive proteins serum levels were significantly higher in enoxaparine non-recipients than recipients (p<0.05) in all study period. Conclusions. Enoxaparin in daily dose 40 mg, significantly depressed serum levels of TNF-alpha and promote serum levels of interleukin-12. Enoxaparin administration may be beneficial for the patients with COPD exacerbation during the first 14 days of treatment

In Vitro and In Vivo Anti-inflammatory Effects of Struthanthus vulgaris

Planta Medica ◽  
2017 ◽  
Vol 83 (09) ◽  
pp. 770-777 ◽  
Author(s):  
Franciane Marques ◽  
Maycow da Costa ◽  
Cátia Vittorazzi ◽  
Luciane Gramma ◽  
Thiago Barth ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leaf Extract ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Struthanthus vulgaris is probably the most common medicinal mistletoe plant in Brazil, and has been used in folk medicine as an anti-inflammatory agent and for cleaning skin wounds. Our proposal was to evaluate the anti-inflammatory activity of S. vulgaris ethanol leaf extract and provide further insights of how this biological action could be explained using in vitro and in vivo assays. In vitro anti-inflammatory activity was preliminarily investigated in lipopolysaccharide/interferon gamma-stimulated macrophages based on their ability to inhibit nitric oxide production and tumor necrosis factor-alpha. In vivo anti-inflammatory activity of S. vulgaris ethanol leaf extract was investigated in the mice carrageenan-induced inflammation air pouch model. The air pouches were inoculated with carrageenan and then treated with 50 and 100 mg/kg of S. vulgaris ethanol leaf extract or 1 mg/kg of dexamethasone. Effects on the immune cell infiltrates, pro- and anti-inflammatory mediators such as tumor necrosis factor-alpha, interleukin 1, interleukin 10, and nitric oxide, were evaluated. The chemical composition of S. vulgaris ethanol leaf extract was characterized by LC-MS/MS. In vitro S. vulgaris ethanol leaf extract significantly decreased the production of nitric oxide and tumor necrosis factor-alpha in macrophages and did not reveal any cytotoxicity. In vivo, S. vulgaris ethanol leaf extract significantly suppressed the influx of leukocytes, mainly neutrophils, protein exudation, nitric oxide, tumor necrosis factor-alpha, and interleukin 1 concentrations in the carrageenan-induced inflammation air pouch. In conclusion, S. vulgaris ethanol leaf extract exhibited prominent anti-inflammatory effects, thereby endorsing its usefulness as a medicinal therapy against inflammatory diseases, and suggesting that S. vulgaris ethanol leaf extract may be a source for the discovery of novel anti-inflammatory agents.

A Comparison of the Anti-Inflammatory Effects of Four Combined Statin and Antiplatelet Therapies on Tumor Necrosis Factor-Mediated Acute Inflammation in vivo

Pharmacology ◽  
2019 ◽  
Vol 104 (1-2) ◽  
pp. 21-27 ◽  
Author(s):  
Okki Cho ◽  
Han-Sol Kim ◽  
Kyung-Yeon Park ◽  
Tae-Hwe Heo
Keyword(s):  
Tumor Necrosis Factor ◽  
Combination Therapy ◽  
Tumor Necrosis ◽  
Acute Inflammation ◽  
Therapeutic Effects ◽  
Combination Therapies ◽  
Beneficial Effects ◽  
Anti Inflammatory ◽  
Necrosis Factor

Background: Combination therapy has been administered to patients with chronic or complex diseases due to its improved therapeutic effects compared with the results of monotherapy. Due to the pleiotropic effects of statins and antiplatelets, these drugs have been studied in combination with other drugs, but not all combinations exerted obvious beneficial effects compared with individual drugs. In this study, we aimed to compare the anti-inflammatory effects of 4 different combination therapies of statins and antiplatelets on the tumor necrosis factor (TNF)-mediated inflammation in vivo. Methods: Mice were orally administered cilostazol plus pravastatin (CILOP) or cilostazol plus rosuvastatin (CILOR), clopidogrel plus pravastatin (CLOP), or clopidogrel plus rosuvastatin (CLOR); then, acute inflammation was induced by the injection of lipopolysaccharide (LPS) or TNF. Serum TNF levels, macrophage accumulation in the lesioned aortas, and mouse mortality were observed to be comparable to the anti-inflammatory effects of the combination therapies. Results: In mice with LPS-induced inflammation, CILOP and CILOR substantially reduced macrophage infiltration of aortic lesions and the serum TNF levels compared with CLOP and CLOR. Moreover, among the 4 combinations, CILOP significantly improved the survival rate of mice with TNF-mediated acute lethal inflammation. Conclusions: The combination therapy comprising cilostazol and statins, particularly pravastatin, exerted the best anti-TNF effect compared with clopidogrel and statin therapy; thus, a suitable combination therapy, such as CILOP, can be a potential remedy to cure TNF-related diseases.

scholarly journals Intraperitoneal Administration of Rosuvastatin Prevents Postoperative Peritoneal Adhesions by Decreasing the Release of Tumor Necrosis Factor

2018 ◽  
Vol 91 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Stefan Chiorescu ◽  
Octavian Aurel Andercou ◽  
Nicolae Ovidiu Grad ◽  
Ion Aurel Mironiuc
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Intraperitoneal Administration ◽  
Serum Levels ◽  
Control Group ◽  
Peritoneal Adhesions ◽  
Group I ◽  
Anti Inflammatory ◽  
Necrosis Factor

Objectives. The purpose of this experimental study was to demonstrate the reduction of peritoneal adhesions formation in rats after intraperitoneal administration of rosuvastatin, due to its anti-inflammatory effect.Method. Peritoneal adhesions were induced in 120 Wistar-Bratislava rats divided into 4 groups (n=30), using a parietal and visceral (cecal) abrasion model. Group I was designated as control group; in group II, a saline solution was administered intraperitoneally; in groups III and IV, a single dose of rosuvastatin solution, 10 mg/kg and 5 mg/kg respectively, was injected intraperitoneally. The serum values of tumor necrosis factor (TNF-α) and interleukin-1 (IL-1α) were determined on day 1 and day 7 postoperatively (ELISA). Macroscopic assessment of the peritoneal adhesions was conducted on day 14.Results. Rosuvastatin therapy induced a significant decrease of tumor necrosis factor serum levels in groups III and IV, on day 1 and day 7 (p<0.01). Intraperitoneal administration of rosuvastatin correlated with a decrease of mean interleukin-1α levels on postoperative day 1 in groups III (p=0.0013) and IV (p=0.00011), but not on day 7, where the differences were no longer statistically significant (p=0.8) The reduction of postoperative peritoneal adhesions in the experimental rat model is supported by the anti-inflammatory effect of rosuvastatin, mediated mainly by the tumor necrosis factor.Conclusions. Rosuvastatin prevents the formation of postoperative peritoneal adhesions in rats. This effect may be linked to the inhibition of proinflammatory cytokines release in the early stages of adhesions formation. The present study suggests that rosuvastatin may be an efficient pharmacological agent in the prevention of postoperative peritoneal adhesions development, and requires further studies as it has a promising application value.

scholarly journals In vivo induction of gamma interferon and tumor necrosis factor by interleukin-2 infusion following intensive chemotherapy or autologous marrow transplantation

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1374-1380 ◽  
Author(s):  
HE Heslop ◽  
DJ Gottlieb ◽  
AC Bianchi ◽  
A Meager ◽  
HG Prentice ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Marrow Transplantation ◽  
Tumor Necrosis ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Gamma Interferon ◽  
Granulocyte Function ◽  
Necrosis Factor

Abstract Interleukin-2 (IL-2) therapy may improve immune reconstitution and reduce the risk of leukemic relapse in the setting of minimal residual disease by augmenting cytotoxic effector mechanisms directed at residual malignant cells. In addition, IL-2 in vitro promotes the release of cytokines including gamma-interferon (gamma-IFN) and tumor necrosis factor (TNF), which also possess antileukemic activity and can enhance granulocyte function. To determine if IL-2 infusion induces release of gamma-IFN and TNF in vivo in sufficient quantity to mediate these effects, we have measured serum levels of these cytokines and secretion by lymphocytes obtained from patients receiving this cytokine in a phase 1 trial. Serum gamma-IFN was undetectable pre-IL-2 and increased to 1.5 to 17 U/mL during IL-2 infusion (P less than .05). Culture of patient lymphocytes for 48 hours produced 1.2 U gamma-IFN/2 x 10(6) cells/mL pre-IL-2 rising to 50 U/2 x 10(6) cells/mL when the lymphocytes were obtained during therapy (P less than .05). Lymphocyte subset analysis showed that both CD3+ and CD16+ cells secreted gamma- IFN in response to IL-2. TNF secretion by lymphocytes also rose during IL-2 infusion from a mean of 5 U/mL to 14.4 U/mL (P less than .01) although no rise was seen in serum levels. The material secreted by IL- 2-stimulated lymphocytes is bioactive as addition of supernatants from lymphocytes obtained during IL-2 therapy to cultures of myeloid blasts significantly inhibited clonogenic growth. IL-2-induced secretion of these cytokines mediated this inhibition as it could be partially blocked by either anti-gamma-IFN or anti-TNF antibodies. Preincubation of granulocytes with the same supernatants produced enhanced oxidative metabolism, measured by chemiluminescence in response to N-formyl- methionyl-leucyl-phenylalanine (FMLP). This effect also could be partially abrogated by anti-gamma-IFN and anti-TNF antibodies. Therefore, secondary cytokine secretion may boost granulocyte function and contribute to the antileukemic effects of IL-2 infusion in patients following bone marrow transplantation or chemotherapy.

Corticosteroid-independent inhibition of tumor necrosis factor production by the neuropeptide urocortin

1998 ◽  
Vol 275 (5) ◽  
pp. E757-E762 ◽  
Author(s):  
Davide Agnello ◽  
Riccardo Bertini ◽  
Silvano Sacco ◽  
Cristina Meazza ◽  
Pia Villa ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inhibitory Effect ◽  
Direct Inhibitory Effect ◽  
Anti Inflammatory ◽  
Camp Levels ◽  
Tnf Inhibition ◽  
Pituitary Adrenal Axis ◽  
Necrosis Factor

Urocortin (UCN) is a neuropeptide homologous with corticotropin-releasing factor (CRF), which has anti-inflammatory activities not all mediated by corticosteroids. In mice, UCN (1 μg/mouse sc) significantly reduced lipopolysaccharide (LPS)-induced serum tumor necrosis factor (TNF) and interleukin (IL)-1β levels in vivo but did not affect serum IL-6. These effects were paralleled by a rise in corticosterone (CS) levels. Blockade of the CS increase by cyanoketone did not prevent TNF inhibition by UCN, suggesting the neuropeptide has anti-inflammatory mechanisms independent of the hypothalamus-pituitary-adrenal axis. In fact UCN had a direct inhibitory effect on LPS-induced TNF in rat Kupffer cells at concentrations between 10−10 and 10−16 M, and this effect was related to increased cAMP levels. However, the in vivo inhibition of LPS-induced IL-1β by UCN was reversed by cyanoketone, indicating that the increase of endogenous glucocorticoids might be more important in IL-1β inhibition than in TNF inhibition by UCN.

scholarly journals Terpene Glycosides from Sanguisorba officinalis and Their Anti-Inflammatory Effects

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2906 ◽  
Author(s):  
Da-Le Guo ◽  
Jin-Feng Chen ◽  
Lu Tan ◽  
Meng-Ying Jin ◽  
Feng Ju ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
High Resolution Mass Spectrometry ◽  
Experimental Platform ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Sanguisorba Officinalis ◽  
Factor Α ◽  
Necrosis Factor

Two new terpene glycosides (1–2) along with two known analogs (3–4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1–4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-α

2002 ◽  
Vol 282 (5) ◽  
pp. R1429-R1435 ◽  
Author(s):  
Brian N. Finck ◽  
Rodney W. Johnson
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Epididymal Adipose Tissue ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Leptin Expression ◽  
Necrosis Factor

Tumor necrosis factor (TNF)-α stimulates the secretion of the adipocyte-derived hormone leptin. However, the cellular mechanisms by which TNF-α influences leptin production are poorly understood. To examine this issue, epididymal fat pads were isolated from mice and cultured in recombinant murine TNF-α (100 ng/ml). Compared with medium-treated controls, steady-state leptin expression was increased in TNF-α-treated explants. Culture with inhibitors of translation (cycloheximide) or transcription (actinomycin-D) abrogated the induction of leptin following TNF-α. Explants were also cultured in the presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor (SB-203580) or PG J2 metabolite [15-deoxy-Δ12,14-PG J2 (PGJ)] and then exposed to TNF-α. Both compounds completely abolished TNF-α-induced increases in leptin production. To test the relevance of this in vivo, mice were pretreated with PGJ and then given TNF-α. PGJ treatment markedly blunted the TNF-α-induced increase in leptin, TNF-α, and interleukin-6 gene expression in epididymal adipose tissue. Collectively, these data indicate that TNF-α acutely activates leptin expression and that anti-inflammatory agents can abrogate TNF-α-induced hyperleptinemia.

scholarly journals In vivo induction of gamma interferon and tumor necrosis factor by interleukin-2 infusion following intensive chemotherapy or autologous marrow transplantation

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1374-1380 ◽  
Author(s):  
HE Heslop ◽  
DJ Gottlieb ◽  
AC Bianchi ◽  
A Meager ◽  
HG Prentice ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Marrow Transplantation ◽  
Tumor Necrosis ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Gamma Interferon ◽  
Granulocyte Function ◽  
Necrosis Factor

Interleukin-2 (IL-2) therapy may improve immune reconstitution and reduce the risk of leukemic relapse in the setting of minimal residual disease by augmenting cytotoxic effector mechanisms directed at residual malignant cells. In addition, IL-2 in vitro promotes the release of cytokines including gamma-interferon (gamma-IFN) and tumor necrosis factor (TNF), which also possess antileukemic activity and can enhance granulocyte function. To determine if IL-2 infusion induces release of gamma-IFN and TNF in vivo in sufficient quantity to mediate these effects, we have measured serum levels of these cytokines and secretion by lymphocytes obtained from patients receiving this cytokine in a phase 1 trial. Serum gamma-IFN was undetectable pre-IL-2 and increased to 1.5 to 17 U/mL during IL-2 infusion (P less than .05). Culture of patient lymphocytes for 48 hours produced 1.2 U gamma-IFN/2 x 10(6) cells/mL pre-IL-2 rising to 50 U/2 x 10(6) cells/mL when the lymphocytes were obtained during therapy (P less than .05). Lymphocyte subset analysis showed that both CD3+ and CD16+ cells secreted gamma- IFN in response to IL-2. TNF secretion by lymphocytes also rose during IL-2 infusion from a mean of 5 U/mL to 14.4 U/mL (P less than .01) although no rise was seen in serum levels. The material secreted by IL- 2-stimulated lymphocytes is bioactive as addition of supernatants from lymphocytes obtained during IL-2 therapy to cultures of myeloid blasts significantly inhibited clonogenic growth. IL-2-induced secretion of these cytokines mediated this inhibition as it could be partially blocked by either anti-gamma-IFN or anti-TNF antibodies. Preincubation of granulocytes with the same supernatants produced enhanced oxidative metabolism, measured by chemiluminescence in response to N-formyl- methionyl-leucyl-phenylalanine (FMLP). This effect also could be partially abrogated by anti-gamma-IFN and anti-TNF antibodies. Therefore, secondary cytokine secretion may boost granulocyte function and contribute to the antileukemic effects of IL-2 infusion in patients following bone marrow transplantation or chemotherapy.

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