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.

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.

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.

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 A Novel Curcumin-Mycophenolic Acid Conjugate Inhibited Hyperproliferation of Tumor Necrosis Factor-Alpha-Induced Human Keratinocyte Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 956
Author(s):  
Yonelian Yuyun ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Wiwat Supasena ◽  
Piyapan Suwattananuruk ◽  
Kemika Praengam ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Mycophenolic Acid ◽  
Tumor Necrosis ◽  
Molecular Mechanisms ◽  
Cellular Transport ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.

scholarly journals Multiple effects of tumor necrosis factor on lipoprotein lipase in vivo.

1987 ◽  
Vol 262 (17) ◽  
pp. 8390-8394 ◽  
Author(s):  
H Semb ◽  
J Peterson ◽  
J Tavernier ◽  
T Olivecrona
Keyword(s):  
Tumor Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Tumor Necrosis ◽  
Necrosis Factor
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