The Prostaglandin Analogs, Misoprostol and SC-46275, Potently Inhibit Cytokine Release from Activated Human Monocytes

Widomski, D. L.; Fretland, D. J.; Gasiecki, Alan F.; Collins, Paul W.

doi:10.3109/08923979709007656

Cited by 25 publications

(16 citation statements)

References 13 publications

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“…In addition to direct neuronal damage, PMNs contribute to secondary injury by causing microvessel occlusion and releasing oxygen radicals, cytolytic proteases, and proinflammatory cytokines, which may injure the endothelium [16,17]. Chopp et al reported that a reduction in the number of PMNs reduced post-ischemic tissue damage in the heart, intestine, lung, and liver [18].…”

Section: Resultsmentioning

confidence: 99%

Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study

Han

Wei

Guo

2011

BMC Complement Altern Med

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BackgroundThe roots of Sophora flavescens (Leguminosae) have been used in East Asian countries as an herbal medicine and a food ingredient for thousands of years. The aim of the present study was to investigate the effects of S. flavescens fermentation on endotoxin-induced uveitis (EIU) in rats.MethodsEIU was induced in rats via a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, fermented and non-fermented extracts of S. flavescens (FSE and NFSE, respectively) were administered orally, and the aqueous humor was collected from both eyes 24 hours later. The anti-inflammatory effects of FSE and NFSE were examined in terms of regulation of nuclear factor kappa B (NF-κB) activation and the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular cell adhesion molecule (ICAM)-1, and cyclooxygenase-2 (COX-2). The regulation of maleic dialdehyde (MDA) levels and polymorphonuclear cell (PMN) infiltration by FSE and NFSE were also examined.ResultsTreatment with FSE significantly inhibited LPS-induced increases in IL-1β and TNF-α production and the expression of iNOS, ICAM-1 and COX-2. Moreover, FSE suppressed LPS-induced NF-κB activation, and reduced both MDA levels and infiltration by PMN.ConclusionThese results indicate that solid state fermentation may enhance the anti-inflammatory effects of S. flavescens.

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Section: Resultsmentioning

confidence: 99%

Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study

Han

Wei

Guo

2011

BMC Complement Altern Med

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“…It also inhibits the release of inflammatory cytokines (222). In a small, placebo-controlled, semi-crossover study, tinnitus was improved (reduced severity, improved sleep and concentration) in 33% of subjects during misoprostol treatment (escalating to 800 μg/day), whereas no subjects improved in the placebo group (223).…”

Section: Drug Therapy For Tinnitus: Pharmacological Studiesmentioning

confidence: 99%

Pharmacological treatments for tinnitus: New and old

Salvi¹,

Lobariñas²,

Sun³

2009

Drugs Fut

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Subjective tinnitus, the phantom ringing or buzzing sensation that occurs in the absence of sound, affects 12–14% of adults; in some cases the tinnitus is so severe or disabling that patients seek medical treatment. However, although the economic and emotional impact of tinnitus is large, there are currently no FDA-approved drugs to treat this condition. Clinical trials are now underway to evaluate the efficacy of N-methyl-d-aspartate (NMDA) and dopamine D2 antagonists, selective serotonin reuptake inhibitors (SSRIs), γ-aminobutyric acid (GABA) agonists and zinc dietary supplements. Previous off-label clinical studies, while not definitive, suggest that patients with severe depression may experience improvement in their tinnitus after treatment with antidepressants such as nortriptyline or sertraline. A small subpopulation of patients with what has been described as “typewriter tinnitus” have been shown to gain significant relief from the anticonvulsant carbamazepine. Preliminary studies with misoprostol, a synthetic prostaglandin E1 analogue, and sulpiride, a dopamine D2 antagonist, have shown promise. Animal behavioral studies suggest that GABA transaminase inhibitors and potassium channel modulators can suppress tinnitus. Additionally, improvements in tinnitus have also been noted in patients taking melatonin for significant sleep disturbances. Like other complex neurological disorders, one drug is unlikely to resolve tinnitus in all patients; therapies targeting specific subgroups are likely to yield the greatest success.

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“…32) Signaling experiments revealed that MB28767 inhibited forskolin-induced cAMP concentrations in Chinese hamster ovary cells. 33) iv) EP4 agonists: ONO-AE1-329 and cicaprost 16,17) are well known selective EP4 agonists (Figures 1 F and G).…”

Section: Synthesized Ep Agonists I) Ep1 Agonistsmentioning

confidence: 99%

Roles of Prostaglandin E2 in Cardiovascular Diseases

et al. 2011

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SummaryProstaglandin E2 (PGE 2 ) is produced in inflammatory responses and regulates a variety of immunological reactions through 4 different receptor subtypes; EP1, 2, 3 and 4. However, the precise role of each receptor in cardiovascular disease has not yet been elucidated. Enhanced expression of some EPs has been observed in clinical and experimental cardiovascular diseases. EP agonists have been developed to clarify the role of each receptor. Recently, we developed a novel selective agonist to examine the effects of EP4 on cardiac transplantation, myocardial ischemia, and myocarditis. Of note, a selective EP4 agonist attenuated inflammatory cytokines and chemokines via attenuation of macrophage activation in inflammatory heart diseases. In this review article, we discuss the effects of PGE 2 receptor agonists on the development of cardiovascular diseases. (Int Heart J 2011; 52: 266-269) Key words: Prostaglandin, Receptors, Chemokine, Macrophage, Heart P rostanoids are known to be multifunctional physiologic factors. They are produced by various stimuli and participate in local homeostasis and physiologic responses. They are synthesized from arachidonic acid and quickly released to the extracellular medium to send signals via prostanoid receptors.1) The prostanoid receptors, DP, EP, FP, IP and TP, are bound to PGD 2 , PGE 2 , PGF 2α , PGI 2 , and TXA 2 , respectively. 2)In the cardiovascular system, these receptors are expressed on various cells, such as cardiomyocytes, vascular endothelium and smooth muscle cells.3) They play an important role in modulating homeostasis in the development of cardiovascular diseases, such as thrombosis and atherosclerosis.4) Recent studies revealed that prostanoids play an important role in both the occurrence and suppression of various cardiovascular diseases, such as myocardial ischemia, cardiac hypertrophy, cardiac fibrosis, and atherosclerosis. 5) However, the detailed roles of prostanoids in cardiovascular disease have not yet been completely elucidated. To clarify the mechanisms, selective receptor agonists have been developed.Among the prostanoids, PGE 2 is known to play a key role in the pathogenesis of cardiovascular diseases. It was reported that a deficiency of PGE 2 synthase-1 reduced plaque burden in fat-diet low-density lipoprotein receptor knockout mice.6) Another report revealed that PGE 2 synthase-1 knockout mice showed impaired left ventricular contraction after acute myocardial infarction.7) These studies indicate that PGE 2 plays a pivotal role in cardiovascular inflammation. 8, 9) PGE 2 exerts their effects via G-protein-coupled receptors, and PGE 2 -mediated cardioprotection is involved in the EP receptor subtypes. 10)Each receptor has their unique signaling pathways. EP1 couples to Gq and increases intracellular Ca . EP3 couples to Gi and inhibits the increase of cAMP. EP2 and EP4 receptors are coupled to stimulate adenylate cyclase, which leads to the elevation of intracellular cAMP.11) In these EP receptors, EP3 and EP4 are known to have cardioprote...

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The Prostaglandin Analogs, Misoprostol and SC-46275, Potently Inhibit Cytokine Release from Activated Human Monocytes

Cited by 25 publications

References 13 publications

Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study

Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study

Pharmacological treatments for tinnitus: New and old

Roles of Prostaglandin E2 in Cardiovascular Diseases

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