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Sample records for anti-inflammatory treatment strategies

  1. Anti-inflammatory strategies in the treatment of schizophrenia.

    PubMed

    Andrade, Chittaranjan

    2016-01-01

    Schizophrenia is a major mental illness with a lifetime prevalence of about 1%. Antipsychotic drugs, with a primary mechanism of action that involves dopamine receptor blockade, are the mainstay in the treatment of the disorder. However, despite optimum antipsychotic treatment, few patients return to pre-morbid levels; the treatment deficit includes refractory positive symptoms, negative symptoms, mood impairments, cognitive impairments, social impairments, and/or a variety of medication-related adverse effects, including extrapyramidal symptoms, metabolic disturbances, hyperprolactinemia, and others. To address these, antipsychotic treatment has been augmented with psychosocial interventions, cognitive rehabilitation, different kinds of electrical and magnetic brain stimulation, and a large range of drugs from the neuropsychiatric as well as, surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of schizophrenia includes abnormalities in immunological and inflammatory pathways, and so it is not surprising that anti-inflammatory drugs have also been trialed as augmentation agents in schizophrenia. This article critically examines the outcomes after augmentation with conventional anti-inflammatory interventions; results from randomized controlled trials do not encourage the use of either aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied for this indication during the past decade and a half.

  2. Anti-inflammatory Strategies to Prevent Diabetic Cardiovascular Disease.

    PubMed

    Jialal, I; Devaraj, S

    2015-08-01

    Diabetes is a proinflammatory state and inflammation is crucial in the genesis of vascular complications. While there are many anti-inflammatory strategies, most of which have been shown to reduce inflammation in diabetes, there is sparse data on reduction in cardiovascular events (CVEs). To date, the only anti-inflammatory strategies that have been shown to reduce CVE in diabetes include statins, angiotensin receptor blockers, metformin, and pioglitazone. We also discuss the role of novel emerging therapies.

  3. [Effect of anti-inflammatory therapy on the treatment of dry eye syndrome].

    PubMed

    Mrukwa-Kominek, Ewa; Rogowska-Godela, Anna; Gierek-Ciaciura, Stanisława

    2007-01-01

    Dry eye syndrome is a common chronic disease; agents and strategies for its effective management are still lacking. The syndrome tends to be accompanied by ocular surface inflammation; therefore, the use of anti-inflammatory agents might prove beneficial. The authors present up-to-date guidelines, strategies, and efficacy of dry eye syndrome management, including anti-inflammatory treatment. As no diagnostic tests are now available to assess ocular surface inflammation severity, the right timing to launch an anti-inflammatory agent is difficult to determine. Patients with mild intermittent bouts of symptoms which can be alleviated with ophthalmic lubricants do not typically require anti-inflammatory therapy. The latter should be considered in those who do not respond to lubricating drops, obtain poor results on clinical tests, and show symptoms of ocular surface irritation (eg. conjunctivae redness). Anti-inflammatory treatment of dry eye syndrome may include short-term corticosteroids, cyclosporine A emulsion, oral tetracycline therapy, oral omega-3 fatty acid supplements, and autologous serum eye drops. Anti-inflammatory treatment should be safe and effective; potential benefits should be evaluated for each individual patient. The authors have reviewed the advantages of anti-inflammatory treatment in dry eye syndrome, presented in literature.

  4. Glycosaminoglycan analogs as a novel anti-inflammatory strategy

    PubMed Central

    Severin, India C.; Soares, Adriano; Hantson, Jennifer; Teixeira, Mauro; Sachs, Daniela; Valognes, Delphine; Scheer, Alexander; Schwarz, Matthias K.; Wells, Timothy N. C.; Proudfoot, Amanda E. I.; Shaw, Jeffrey

    2012-01-01

    Heparin, a glycosaminoglycan (GAG), has both anti-inflammatory and anti-coagulant properties. The clinical use of heparin against inflammation, however, has been limited by concerns about increased bleeding. While the anti-coagulant activity of heparin is well understood, its anti-inflammatory properties are less so. Heparin is known to bind to certain cytokines, including chemokines, small proteins which mediate inflammation through their control of leukocyte migration and activation. Molecules which can interrupt the chemokine-GAG interaction without inhibiting coagulation could therefore, represent a new class of anti-inflammatory agents. In the present study, two approaches were undertaken, both focusing on the heparin-chemokine relationship. In the first, a structure based strategy was used: after an initial screening of potential small molecule binders using protein NMR on a target chemokine, binding molecules were optimized through structure-based design. In the second approach, commercially available short oligosaccharides were polysulfated. In vitro, these molecules prevented chemokine-GAG binding and chemokine receptor activation without disrupting coagulation. However, in vivo, these compounds caused variable results in a murine peritoneal recruitment assay, with a general increase of cell recruitment. In more disease specific models, such as antigen-induced arthritis and delayed-type hypersensitivity, an overall decrease in inflammation was noted, suggesting that the primary anti-inflammatory effect may also involve factors beyond the chemokine system. PMID:23087686

  5. Anti-inflammatory treatment in schizophrenia.

    PubMed

    Müller, Norbert; Myint, Aye-Mu; Krause, Daniela; Weidinger, Elif; Schwarz, Markus J

    2013-04-05

    Antipsychotics, which act predominantly as dopamine D2 receptor antagonists, have several shortcomings. The exact pathophysiological mechanism leading to dopaminergic dysfunction in schizophrenia is still unclear, but inflammation has been postulated to be a key player in the pathophysiology of the disorder. A dysfunction in activation of the type 1 immune response seems to be associated with an imbalance in tryptophan/kynurenine metabolism; the degrading enzymes involved in this metabolism are regulated by cytokines. Kynurenic acid (KYNA), an N-methyl-d-aspartate antagonist, was found to be increased in critical regions of the central nervous system (CNS) in schizophrenia, resulting in reduced glutamatergic neurotransmission. The differential activation of microglial cells and astrocytes as functional carriers of the immune system in the CNS may also contribute to this imbalance. The immunological effects of many existing antipsychotics, however, rebalance in part the immune imbalance and overproduction of KYNA. The immunological imbalance results in an inflammatory state combined with increased prostaglandin E(2) production and increased cyclo-oxygenase-2 (COX-2) expression. Growing evidence from clinical studies with COX-2 inhibitors points to favorable effects of anti-inflammatory therapy in schizophrenia, in particular in an early stage of the disorder. Further options for immunomodulating therapies in schizophrenia will be discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases

    PubMed Central

    Scott, David A; Martin, Michael

    2006-01-01

    Discoveries in the first few years of the 21st century have led to an understanding of important interactions between the nervous system and the inflammatory response at the molecular level, most notably the acetylcholine (ACh)-triggered, α7-nicotinic acetylcholine receptor (α7nAChR)-dependent nicotinic anti-inflammatory pathway. Studies using the α7nAChR agonist, nicotine, for the treatment of mucosal inflammation have been undertaken but the efficacy of nicotine as a treatment for inflammatory bowel diseases remains debatable. Further understanding of the nicotinic anti-inflammatory pathway and other endogenous anti-inflammatory mechanisms is required in order to develop refined and specific therapeutic strategies for the treatment of a number of inflammatory diseases and conditions, including periodontitis, psoriasis, sarcoidosis, and ulcerative colitis. PMID:17167832

  7. Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases.

    PubMed

    Scott, David A; Martin, Michael

    2006-12-14

    Discoveries in the first few years of the 21st century have led to an understanding of important interactions between the nervous system and the inflammatory response at the molecular level, most notably the acetylcholine (ACh)-triggered, alpha7-nicotinic acetylcholine receptor (alpha7nAChR)-dependent nicotinic anti-inflammatory pathway. Studies using the alpha7nAChR agonist, nicotine, for the treatment of mucosal inflammation have been undertaken but the efficacy of nicotine as a treatment for inflammatory bowel diseases remains debatable. Further understanding of the nicotinic anti-inflammatory pathway and other endogenous anti-inflammatory mechanisms is required in order to develop refined and specific therapeutic strategies for the treatment of a number of inflammatory diseases and conditions, including periodontitis, psoriasis, sarcoidosis, and ulcerative colitis.

  8. Novel anti-inflammatory therapies for the treatment of atherosclerosis.

    PubMed

    Khan, Razi; Spagnoli, Vincent; Tardif, Jean-Claude; L'Allier, Philippe L

    2015-06-01

    The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis

    PubMed Central

    Lobatto, Mark E.; Fayad, Zahi A.; Silvera, Stephane; Vucic, Esad; Calcagno, Claudia; Mani, Venkatesh; Dickson, Stephen D.; Nicolay, Klaas; Banciu, Manuela; Schiffelers, Raymond M.; Metselaar, Josbert M; van Bloois, Louis; Wu, Hai-Shan; Fallon, John T.; Rudd, James H.; Fuster, Valentin; Fisher, Edward A.; Storm, Gert; Mulder, Willem J.M.

    2012-01-01

    Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. 18F-fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of non-invasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy. PMID:21028895

  10. Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis.

    PubMed

    Lobatto, Mark E; Fayad, Zahi A; Silvera, Stephane; Vucic, Esad; Calcagno, Claudia; Mani, Venkatesh; Dickson, Stephen D; Nicolay, Klaas; Banciu, Manuela; Schiffelers, Raymond M; Metselaar, Josbert M; van Bloois, Louis; Wu, Hai-Shan; Fallon, John T; Rudd, James H; Fuster, Valentin; Fisher, Edward A; Storm, Gert; Mulder, Willem J M

    2010-12-06

    Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy.

  11. [Chemokines a hope of specific anti-inflammatory treatment].

    PubMed

    Schedvins, Per; Hjelmström, Peter

    2002-03-07

    Inflammation is a serious medical problem that causes suffering in many common diseases such as rheumatoid arthritis and asthma. Despite the fact that the clinical signs of inflammation--rubor, tumor, calor and dolor--have been known for almost two thousand years, our knowledge of the molecular pathways that mediate inflammation is still limited. Today's anti-inflammatory drugs are non-specific and have many undesirable side effects. The discovery of chemokines as small specific regulatory proteins of the immune system has increased our understanding of the inflammatory process. We have reason to believe that chemokines and their receptors are going to be targets for a new kind of anti-inflammatory therapy.

  12. The Promise and Limitations of Anti-Inflammatory Agents for the Treatment of Major Depressive Disorder.

    PubMed

    Raison, Charles L

    2017-01-01

    This review provides a critical perspective on recent meta-analyses suggesting that several anti-inflammatory modalities, including nonsteroidal anti-inflammatory drugs (NSAIDs), omega-3 fatty acids, and cytokine antagonist, possess generalizable antidepressant properties. By examining confounds and limitations in the available literature it is suggested that current data suggest that only a sub-group of individuals with major depressive disorder (MDD) have evidence of increased inflammatory biomarkers and it is in these individuals that anti-inflammatory agents show promise for reducing depressive symptoms. The treatment implications of this cautionary perspective are discussed.

  13. Conservative Nonhormonal Options for the Treatment of Male Infertility: Antibiotics, Anti-Inflammatory Drugs, and Antioxidants

    PubMed Central

    Condorelli, Rosita A.

    2017-01-01

    The nonhormonal medical treatment can be divided into empirical, when the cause has not been identified, and nonempirical, if the pathogenic mechanism causing male infertility can be solved or ameliorated. The empirical nonhormonal medical treatment has been proposed for patients with idiopathic or noncurable oligoasthenoteratozoospermia and for normozoospermic infertile patients. Anti-inflammatory, fibrinolytic, and antioxidant compounds, oligo elements, and vitamin supplementation may be prescribed. Infection, inflammation, and/or increased oxidative stress often require a specific treatment with antibiotics, anti-inflammatory drugs, and/or antioxidants. Combined therapies can contribute to improve sperm quality. PMID:28164122

  14. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus.

    PubMed

    Li, Zheng; Geng, Ya-Na; Jiang, Jian-Dong; Kong, Wei-Jia

    2014-01-01

    Oxidative stress and inflammation are proved to be critical for the pathogenesis of diabetes mellitus. Berberine (BBR) is a natural compound isolated from plants such as Coptis chinensis and Hydrastis canadensis and with multiple pharmacological activities. Recent studies showed that BBR had antioxidant and anti-inflammatory activities, which contributed in part to its efficacy against diabetes mellitus. In this review, we summarized the antioxidant and anti-inflammatory activities of BBR as well as their molecular basis. The antioxidant and anti-inflammatory activities of BBR were noted with changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines after BBR administration in diabetic animals. BBR inhibited oxidative stress and inflammation in a variety of tissues including liver, adipose tissue, kidney and pancreas. Mechanisms of the antioxidant and anti-inflammatory activities of BBR were complex, which involved multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear factor- κ B (NF- κ B) pathway. Detailed mechanisms and pathways for the antioxidant and anti-inflammatory activities of BBR still need further investigation. Clarification of these issues could help to understand the pharmacology of BBR in the treatment of diabetes mellitus and promote the development of antidiabetic natural products.

  15. Anti-inflammatory treatment of meconium aspiration syndrome: benefits and risks.

    PubMed

    Mokra, Daniela; Mokry, Juraj; Tonhajzerova, Ingrid

    2013-06-01

    Meconium aspiration syndrome (MAS) is a major cause of respiratory insufficiency in the term and post-term newborns. There are several pathomechanisms participating in this disorder, particularly the airway obstruction, surfactant dysfunction, inflammation, lung edema, pulmonary vasoconstriction and bronchoconstriction. Inflammatory changes resulting from meconium aspiration cause severe impairment of lung parenchyma and surfactant, and influence the reactivity of both vascular and airway smooth muscle. Therefore, anti-inflammatory drugs may be of benefit in the management of MAS. This article reviews the pharmacological actions and side effects of various anti-inflammatory drugs used up to now in the experimental models of MAS and in the treatment of newborns with meconium aspiration.

  16. Effects of heat treatment on antioxidative and anti-inflammatory properties of orange by-products

    USDA-ARS?s Scientific Manuscript database

    This study investigated the changes in functional components, antioxidative activities, antibacterial activities, anti-inflammatory activities of orange (Citrus sinensis (L.) Osbeck) by-products (OBP) by heat treatment at 50 and 100 degrees C (hereafter, 50D and 100D extracts, respectively). Optimal...

  17. [Treatment of chronic obstructive pulmonary disease--traditional bronchodilatation and targeted anti-inflammatory therapy].

    PubMed

    Mróz, Robert M; Skopiński, Tomasz; Hołownia, Adam; Chyczewska, Elżbieta; Braszko, Jan J

    2011-01-01

    Currently available pharmacological treatment of COPD relies mostly on prophylaxis (smoking cessation) and symptomatic treatment, i.e. inhaled anticholinergic agents, β2-agonists and phosphodiesterase inhibitors, aiming in their bronchodilatation capacity. Inhaled corticosteroid therapy is mainly prescribed in far advanced stages of the disease and its role in disease modification is still controversial. The authors analize currently available treatment modalities with regards to their potential anti-inflammatory and pleiotropic mode of action, which may lead to disease course modification.

  18. Potential Novel Treatments for Bipolar Depression: Ketamine, Fatty Acids, Anti-inflammatory Agents, and Probiotics.

    PubMed

    Vázquez, G H; Camino, S; Tondo, L; Baldessarini, Ross J

    2017-07-28

    Treatments for depression in bipolar disorder (BD) are far less well developed than for unipolar major depressive disorder. Several innovative and experimental approaches have been emerging recently, including use of the dissociative anesthetic ketamine and other antagonists of central NMDA glutamate receptors, as well as unsaturated fatty acids, anti-inflammatory agents, and possibly probiotic methods. We reviewed relevant reports from the past decade. Ketamine, a phencyclidine-like NMDA-glutamate receptor antagonist, has emerged as a highly innovative, experimental treatment for treatment-resistant unipolar major depression, possibly in bipolar depression, and with brief antisuicidal effects. Its limitations include poor bioavailability, rapid but short-lived effects, and little information about long-term benefits and safety of repeated administration. Polyunsaturated fatty acids critical for the structure and functioning of neuronal and other cell membranes have some evidence of benefit as experimental treatments for depression including in BD. There also is evidence of altered expression of peptides associated with inflammation in mood disorder patients, encouraging experimental treatment with anti-inflammatory agents; of these, the COX-II inhibitor celecoxib has shown some evidence of benefit. The concept of altering intestinal flora with probiotic treatments to treat mood disorders remains speculative. Ketamine represents an innovative, rapidly acting, experimental treatment for bipolar depression with practical limitations. Unsaturated fatty acids and anti-inflammatory agents have inconsistent support; probiotic treatments lack evidence. These innovative approaches require much more clinical investigation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Inflammatory Kinetics and Efficacy of Anti-inflammatory Treatments on Human Nucleus Pulposus Cells

    PubMed Central

    Walter, Benjamin A; Purmessur, Devina; Likhitpanichkul, Morakot; Weinberg, Alan; Cho, Samuel K.; Qureshi, Sheeraz A.; Hecht, Andrew C.; Iatridis, James C.

    2015-01-01

    Study Design Human nucleus pulposus (NP) cell culture study investigating response to tumor necrosis factor-α (TNFα), effectiveness of clinically available anti-inflammatory drugs, and interactions between pro-inflammatory cytokines. Objective To characterize the kinetic response of pro-inflammatory cytokines released by human NP cells to TNFα stimulation and the effectiveness of multiple anti-inflammatories with 3 sub-studies: Timecourse, Same-time blocking, Delayed blocking. Summary of Background Data Chronic inflammation is a key component of painful intervertebral disc (IVD) degeneration. Improved efficacy of anti-inflammatories requires better understanding of how quickly NP cells produce pro-inflammatory cytokines and which pro-inflammatory mediators are most therapeutically advantageous to target. Methods Degenerated human NP cells (n=10) were cultured in alginate with or without TNFα (10ng/mL). Cells were incubated with one of four anti-inflammatories (anti-IL-6 receptor/atlizumab, IL-1 receptor anatagonist, anti-TNFα/infliximab and sodium pentosan polysulfate/PPS) in two blocking-studies designed to determine how intervention timing influences drug efficacy. Cell viability, protein and gene expression for IL-1β, IL-6 & IL-8 were assessed. Results Timecourse: TNFα substantially increased the amount of IL-6, IL-8 & IL-1β, with IL-1β and IL-8 reaching equilibrium within ~72 hours (IL-1β: 111±40pg/mL, IL-8: 8478±957pg/mL), and IL-6 not reaching steady state after 144 hours (1570±435 pg/mL). Anti-TNFα treatment was most effective at reducing the expression of all cytokines measured when added at the same time as TNFα stimulation. Similar trends were observed when drugs were added 72 hours after TNFα stimulation, however, no anti-inflammatories significantly reduced cytokine levels compared to TNF control. Conclusion IL-1β, IL-6 and IL-8 were expressed at different rates and magnitudes suggesting different roles for these cytokines in disease

  20. Potential of anti-inflammatory treatment for cystic fibrosis lung disease

    PubMed Central

    Taylor-Cousar, Jennifer L; Von Kessel, Kelsey A; Young, Robert; Nichols, David P

    2010-01-01

    Cystic fibrosis (CF) is the most common life-shortening genetic disorder in Caucasians. With improved diagnosis and treatment, survival has steadily increased. Unfortunately, the overwhelming majority of patients still die from respiratory failure caused by structural damage resulting from airway obstruction, recurrent infection, and inflammation. Here, we discuss the role of inflammation and the development of anti-inflammatory therapies to treat CF lung disease. The inflammatory host response is the least addressed component of CF airway disease at this time. Current challenges in both preclinical and clinical investigation make the identification of suitable anti-inflammatory drugs more difficult. Despite this, many researchers are making significant progress toward this goal and the CF research community has reason to believe that new therapies will emerge from these efforts. PMID:22096358

  1. Assessing the Value of Botanical Anti-Inflammatory Agents in an OTC Acne Treatment Regimen.

    PubMed

    Draelos, Zoe Diana

    2015-12-01

    Over-the-counter acne treatments have assumed more importance for the dermatologist as access and affordability of prescription acne medications has decreased. This research evaluated the efficacy of a three step acne treatment regimen containing stabilized botanical anti-inflammatory ingredients as compared to a currently marketed acne regimen. 80 female/male subjects 12+ years with mild to moderate acne (at least 10 inflammatory and 10 non-inflammatory lesions) were enrolled for 12 weeks and randomized to use the study botanical anti-inflammatory acne regimen or the traditional benzoyl peroxide comparator. Evaluations included investigator global assessment, investigator tolerability assessment, acne lesion characteristics (erythema, lesion height, diameter of inflammation, and amount of pus), subject product assessment, and digital photos at baseline, 2, 4, and 12 weeks. The botanical regimen outperformed the comparator in terms of target lesion erythema, height, inflammation, and pus at weeks 2 and 4, perhaps due to anti-inflammatory ingredients, however parity was reached between the two products by week 12. No difference in lesion counts between the two groups was noted at week 2, however by week 4, there was a lower lesion count with the study regimen in terms of closed comedones (P<0.001) and inflammatory (P=0.016) lesions than the comparator. This statistically significant difference continued into week 12 with a reduction in closed comedones (P=0.006) for the study regimen. Modern OTC cosmetic formulation ingredients including emollients, anti-inflammatory/antioxidants, and sensitive skin modulators provided an improved skin appearance, less lesional erythema, and a better overall appearance in subjects with acne treated for 12 weeks.

  2. The role of nonsteroidal anti-inflammatory medications and exercise in the treatment of ankylosing spondylitis.

    PubMed

    Elyan, Mazen; Khan, Muhammad Asim

    2006-08-01

    Ankylosing spondylitis (AS) is a chronic systemic rheumatic disease that primarily affects the sacroiliac joints and spine. Even with the development of tumor necrosis factor-alpha inhibitors, which have revolutionized the treatment of this disease, the combination of nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and a life-long exercise program still form the first step in its management. Multiple clinical trials have addressed the efficacy and safety of both nonselective and selective NSAIDs. Gastrointestinal toxicity remains their major side effect, with increased concern about the potential of cardiovascular toxicity, especially with the selective cyclooxygenase-2 inhibitors. A specific set of recommendations has been proposed for the management of AS.

  3. Induction of Mincle by Helicobacter pylori and consequent anti-inflammatory signaling denote a bacterial survival strategy.

    PubMed

    Devi, Savita; Rajakumara, Eerappa; Ahmed, Niyaz

    2015-10-12

    Evasion of innate immune recognition is one of the key strategies for persistence of Helicobacter pylori, by virtue of its ability to modulate or escape the host innate immune receptors and signaling pathways. C-type lectin receptors (CLRs) predominantly expressed by macrophages are pivotal in tailoring immune response against pathogens. The recognition of glyco or carbohydrate moieties by Mincle (Macrophage inducible C-type lectin) is emerging as a crucial element in anti-fungal and anti-mycobacterial immunity. Herein, we demonstrate the role of Mincle in modulation of innate immune response against H. pylori infection. Our results revealed an upregulated expression of Mincle which was independent of direct host cell contact. Upon computational modelling, Mincle was observed to interact with the Lewis antigens of H. pylori LPS and possibly activating an anti-inflammatory cytokine production, thereby maintaining a balance between pro- and anti-inflammatory cytokine production. Furthermore, siRNA mediated knockdown of Mincle in human macrophages resulted in up regulation of pro-inflammatory cytokines and consequent down regulation of anti-inflammatory cytokines. Collectively, our study demonstrates a novel mechanism employed by H. pylori to escape clearance by exploiting functional plasticity of Mincle to strike a balance between pro-and anti-inflammatory responses ensuring its persistence in the host.

  4. Anti-inflammatory Diets.

    PubMed

    Sears, Barry

    2015-01-01

    Chronic disease is driven by inflammation. This article will provide an overview on how the balance of macronutrients and omega-6 and omega-3 fatty acids in the diet can alter the expression of inflammatory genes. In particular, how the balance of the protein to glycemic load of a meal can alter the generation of insulin and glucagon and the how the balance of omega-6 and omega-3 fatty acids can effect eicosanoid formation. Clinical results on the reduction of inflammation following anti-inflammatory diets are discussed as well as the molecular targets of anti-inflammatory nutrition. To overcome silent inflammation requires an anti-inflammatory diet (with omega-3s and polyphenols, in particular those of Maqui). The most important aspect of such an anti-inflammatory diet is the stabilization of insulin and reduced intake of omega-6 fatty acids. The ultimate treatment lies in reestablishing hormonal and genetic balance to generate satiety instead of constant hunger. Anti-inflammatory nutrition, balanced 40:30:30 with caloric restriction, should be considered as a form of gene silencing technology, in particular the silencing of the genes involved in the generation of silent inflammation. To this anti-inflammatory diet foundation supplemental omega-3 fatty acids at the level of 2-3 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day should be added. Finally, a diet rich in colorful, nonstarchy vegetables would contribute adequate amounts of polyphenols to help not only to inhibit nuclear factor (NF)-κB (primary molecular target of inflammation) but also activate AMP kinase. Understanding the impact of an anti-inflammatory diet on silent inflammation can elevate the diet from simply a source of calories to being on the cutting edge of gene-silencing technology.

  5. Prevention and treatment of ulcers induced by nonsteroidal anti-inflammatory drugs: an update.

    PubMed

    Dajani, E Z; Agrawal, N M

    1995-03-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are most frequently used for the treatment of rheumatic disease due to their anti-inflammatory and analgesic properties. All NSAIDs have the potential to cause damage to the gastrointestinal (GI) tract and have been associated with the induction of peptic ulcers and massive life-threatening bleeding. The therapeutic approaches for the treatment and prevention of NSAID-induced ulcers is critically reviewed using data derived from carefully controlled, world-wide clinical studies with anti-ulcer drugs. Histamine (H2) antagonists, omeprazole, sucralfate and E-prostaglandin (PGE) analogs are effective for the treatment of NSAID-induced gastric and duodenal ulcers, if NSAIDs are discontinued. However, if NSAIDs are continued while GI damage is present, the PGE analogs misoprostol, arbaprostil and enprostil have shown efficacy in healing NSAID-induced ulcers. Furthermore, one limited clinical study demonstrated that omeprazole has efficacy in healing NSAID-associated ulcers. Neither H2 antagonists, sucralfate and sulglycotide (a cytoprotective drug) have shown efficacy in preventing NSAID-induced gastric ulcers. However H2 antagonists have shown efficacy in preventing NSAID-induced duodenal ulcers. In contrast, only misoprostol prevents the development of NSAID-induced gastric and duodenal ulcers. Such pharmacological observations suggest that the pathophysiologic mechanisms for the induction of NSAID-induced gastric ulcer are distinctly different from those of NSAID-induced duodenal ulcers. Mild diarrhea and GI intolerance were the predominant adverse reactions experienced by patients receiving synthetic PGEs, particularly enprostil and arbaprostil. From the published data, we conclude that misoprostol is the only anti-ulcer drug proven to be well tolerated and effective for the treatment and prevention of NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAIDs therapy.

  6. Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia.

    PubMed

    Costa, José Fernando Oliveira; Barbosa-Filho, José Maria; Maia, Gabriela Lemos de Azevedo; Guimarães, Elisalva Teixeira; Meira, Cássio Santana; Ribeiro-dos-Santos, Ricardo; de Carvalho, Lain Carlos Pontes; Soares, Milena Botelho Pereira

    2014-12-01

    Betulinic acid (BA) is a lupane-type triterpene with a number of biological activities already reported. While potent anti-HIV and antitumoral activities were attributed to BA, it is considered to have a moderate anti-inflammatory activity. Here we evaluated the effects of BA in a mouse model of endotoxic shock. Endotoxemia was induced through intraperitoneally LPS administration, nitric oxide (NO) and cytokines were assessed by Griess method and ELISA, respectively. Treatment of BALB/c mice with BA at 67 mg/kg caused a 100% survival against a lethal dose of lipopolysaccharide (LPS). BA treatment caused a reduction in TNF-α production induced by LPS but did not alter IL-6 production. Moreover, BA treatment increased significantly the serum levels of IL-10 compared to vehicle-treated, LPS-challenged mice. To investigate the role of IL-10 in BA-induced protection, wild-type and IL-10(-/-) mice were studied. In contrast to the observations in IL-10(+/+) mice, BA did not protect IL-10(-/-) mice against a lethal LPS challenge. Addition of BA inhibited the production of pro-inflammatory mediators by macrophages stimulated with LPS, while promoting a significant increase in IL-10 production. BA-treated peritoneal exudate macrophages produced lower concentrations of TNF-α and NO and higher concentrations of IL-10 upon LPS stimulation. Similarly, macrophages obtained from BA-treated mice produced less pro-inflammatory mediators and increased IL-10 when compared to non-stimulated macrophages obtained from vehicle-treated mice. In conclusion, we have shown that BA has a potent anti-inflammatory activity in vivo, protecting mice against LPS by modulating TNF-α production by macrophages in vivo through a mechanism dependent on IL-10.

  7. Anti-inflammatory glycosylated flavonoids as therapeutic agents for treatment of diabetes-impaired wounds.

    PubMed

    Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet; Serna-Saldívar, Sergio O

    2015-01-01

    Diabetes is a chronic disease that affects more than 387 million people worldwide. About 20% of patients diagnosed with diabetes develop diabetic foot ulcerations (DFU). Standard treatment of DFU includes wound debridement, infection control, revascularization and, in general, the acceleration of the healing process. Topical ointments containing flavonoids exert beneficial effects in wound healing process. Flavonoids increase the migration and proliferation of fibroblasts and collagen synthesis. Furthermore, most flavonoids exert antibacterial and astringent activities that help in infection control. Additionally, flavonoids possess antioxidant and anti-inflammatory activities reducing the reactive oxygen species and modulating the inflammatory pathways, respectively. Bioactivity of flavonoids can vary according to source, chemical structure and glycosylation pattern. In summary, topical application of flavonoids reduces epithelialization and wound closure time of DFU in diabetic patients.

  8. Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis.

    PubMed

    Rosenblat, Joshua D; Kakar, Ron; Berk, Michael; Kessing, Lars V; Vinberg, Maj; Baune, Bernhard T; Mansur, Rodrigo B; Brietzke, Elisa; Goldstein, Benjamin I; McIntyre, Roger S

    2016-03-01

    Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Interaction of Salicylates and the Other Nonsteroidal Anti-Inflammatory Agents With Breast Cancer Endocrine Treatment: Systematic Review.

    PubMed

    Ch Yiannakopoulou, Eugenia

    2015-12-01

    Despite advances in breast cancer treatment, mortality from breast cancer is still high. Undoubtedly, novel treatment strategies are needed for chemoprevention of high-risk women and for the treatment of receptor-negative breast cancer. An appealing strategy would be the combination of breast endocrine treatment with salicylates and the other nonsteroidal anti-inflammatory agents (NSAIDs). This systematic review aimed to synthesize evidence on the possible synergistic antitumor effect of breast cancer endocrine treatment with salicylates and the other NSAIDs. Electronic databases were searched with the appropriate search terms. Most of the identified studies investigated the possible synergistic effect of exemestane with celecoxib in different clinical settings including metastatic treatment, adjuvant treatment, ductal carcinoma in situ. The possible synergistic effect of tamoxifen with celecoxib was investigated in one experimental study and the possible synergistic effect of exemestane with aspirin was investigated in another experimental study. Synergistic effect was detected in the majority of the studies. In conclusion, existing limited evidence suggests synergistic interaction of salicylates and the other NSAIDs in the treatment of estrogen responsive breast cancer with clinical implications in the reversal of acquired resistance to breast cancer endocrine treatment and in chemoprophylaxis.

  10. Anti-inflammatory treatment in dysfunction of pulmonary surfactant in meconium-induced acute lung injury.

    PubMed

    Mokra, D; Drgova, A; Kopincova, J; Pullmann, R; Calkovska, A

    2013-01-01

    Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal). Thirty minutes later, meconium-instilled animals were treated by glucocorticoids budesonide (0.25 mg/kg, i.t.) and dexamethasone (0.5 mg/kg, i.v.), or phosphodiesterase inhibitors aminophylline (2 mg/kg, i.v.) and olprinone (0.2 mg/kg, i.v.), or the antioxidant N-acetylcysteine (10 mg/kg, i.v.). Healthy, non-ventilated animals served as controls (Con). At the end of experiments, left lung was lavaged and a differential leukocyte count in sediment was estimated. The supernatant of lavage fluid was adjusted to a concentration of 0.5 mg phospholipids/ml. Surfactant quality was evaluated by capillary surfactometer and expressed by initial pressure and the time of capillary patency. The right lung was used to determine lung edema by wet/dry (W/D) weight ratio. Total antioxidant status (TAS) in blood plasma was evaluated. W/D ratio increased and capillary patency time shortened significantly, whereas the initial pressure increased and TAS decreased insignificantly in Sal vs. Con groups. Meconium instillation potentiated edema formation and neutrophil influx into the lungs, reduced capillary patency and TAS, and decreased the surfactant quality compared with both Sal and Con groups (p > 0.05). Each of the anti-inflammatory agents reduced lung edema and neutrophil influx into the lung and partly reversed surfactant dysfunction in the MAS model, with a superior effect observed after glucocorticoids and the antioxidant N-acetylcysteine.

  11. Cost-effectiveness of Strategies for Primary Prevention of Nonsteroidal Anti-inflammatory Drug-induced Peptic Ulcer Disease

    PubMed Central

    Ko, Cynthia W; Deyo, Richard A

    2000-01-01

    OBJECTIVE Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of peptic ulcer disease by 5- to 7-fold in the first 3 months of treatment. This study examined the relative cost-effectiveness of different strategies for the primary prevention of NSAID-induced ulcers in patients that are starting NSAID treatment. MEASUREMENTS AND MAIN RESULTS A decision analysis model was developed to compare the cost-effectiveness of 6 prophylactic strategies relative to no prophylaxis for patients 65 years of age starting a 3-month course of NSAIDs: (1) testing for Helicobacter pylori infection and treating those with positive tests; (2) empiric treatment of all patients for Helicobacter pylori; (3) conventional-dose histamine2receptor antagonists; (4) high-dose histamine2receptor antagonists; (5) misoprostol; and (6) omeprazole. Costs were estimated from 1997 Medicare reimbursement schedules and the Drug Topics Red Book. Empiric treatment of Helicobacter pylori with bismuth, metronidazole, and tetracycline was cost-saving in the baseline analysis. Selective treatment of Helicobacter pylori, misoprostol, omeprazole, and conventional-dose or high-dose histamine2receptor antagonists cost $23,800, $46,100, $34,400, and $15,600 or $21,500 per year of life saved, respectively, relative to prophylaxis. The results were sensitive to the probability of an ulcer, the probability and mortality of ulcer complications, and the cost of, efficacy of, and compliance with prophylaxis. The cost-effectiveness estimates did not change substantially when costs associated with antibiotic resistance of Helicobacter pylori were incorporated. CONCLUSIONS Several strategies for primary prevention of NSAID-induced ulcers in patients starting NSAIDs were estimated to have acceptable cost-effectiveness relative to prophylaxis. Empirically treating all patients for Helicobacter pylori with bismuth, metronidazole, and tetracycline was projected to be cost-saving in older patients. PMID:10886475

  12. Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

    PubMed

    Safioleas, Konstantinos; Giamarellos-Bourboulis, Evangelos J; Carrer, Dionyssia-Pinelopi; Pistiki, Aikaterini; Sabracos, Lambros; Deliveliotis, Charalambos; Chrisofos, Michael

    2016-05-01

    Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Efficacies of Acupuncture and Anti-inflammatory Treatment for Carpal Tunnel Syndrome.

    PubMed

    Hadianfard, Mohammadjavad; Bazrafshan, Esmaeel; Momeninejad, Hadi; Jahani, Navid

    2015-10-01

    This study compared the efficacies of acupuncture and anti-inflammatory treatment in patients with carpal tunnel syndrome (CTS). Fifty patients with mild to moderate CTS were randomly divided into two groups. Both groups received night wrist splints as the standard conservative treatment for 1 month. The acupuncture group also received eight sessions of acupuncture therapy (twice a week for 4 weeks). The control group received 400 mg of ibuprofen three times a day for 10 days. The visual analog scale (VAS) score, the score on the Boston Carpal Tunnel Questionnaire for Functional Status and Symptom Severity (BCTQ FUNCT and SYMPT), and the electrodiagnostic findings were evaluated at baseline and 1 month after treatment. At the final follow up, significant improvements were found in both groups (p < 0.05). Statistically significant improvements were observed in the VAS score, the score on the global BCTQ FUNCT and SYMPT, and the electrodiagnostic findings, but not in the distal motor latency (DML), in the acupuncture group (p < 0.05). Our findings indicate that acupuncture affected the score on the global BCTQ FUNCT and SYMPT, the VAS score, and the electrodiagnostic findings, except the DML, more than ibuprofen did and that acupuncture might be an effective treatment for CTS.

  14. Formulation strategies to modulate the topical delivery of anti-inflammatory compounds.

    PubMed

    Puglia, Carmelo; Rizza, Luisa; Offerta, Alessia; Gasparri, Franco; Giannini, Valentina; Bonina, Francesco

    2013-01-01

    The aim of this study was to assess the ability of some vehicles (emulsion and emulgel), containing hydrogenated lecithin as penetration enhancer, in increasing the percutaneous absorption of the two model compounds dipotassium glycyrrhizinate (DG) and stearyl glycyrrhetinate (SG). Furthermore SG-loaded solid lipid nanoparticles (SLNs) were prepared and the effect of this vehicle on SG permeation profile was evaluated as well. Percutaneous absorption has been studied in vitro, using excised human skin membranes (i.e., stratum corneum epidermis or [SCE]), and in vivo, determining their anti-inflammatory activity. From the results obtained, the use of both penetration enhancers and SLNs resulted in being valid tools to optimize the topical delivery of DG and SG. Soy lecithin guaranteed an increase in the percutaneous absorption of the two activities and a rapid anti-inflammatory effect in in vivo experiments, whereas SLNs produced an interesting delayed and sustained release of SG.

  15. Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Retinal Diseases.

    PubMed

    Rodrigues, Eduardo Büchele; Farah, Michel Eid; Bottós, Juliana Mantovani; Bom Aggio, Fabio

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of drugs in medicine and ophthalmology. Several NSAIDs have been commercially available for many years: diclofenac, flurbiprofen, indomethacin, ketorolac and suprofen. The purpose of this chapter is to review the clinical use of earlier and newer pharmacologic agents of the NSAID class. NSAIDs may have a modulating effect on ocular inflammation and pain through the prevention of prostaglandin synthesis via cyclooxygenase inhibition. Newer-generation NSAIDs have emerged in recent years for the treatment of ocular pain and inflammation. Nepafenac ophthalmic suspension 0.1% is a new topical NSAID prodrug that has been approved by the Food and Drug Administration for the treatment of pain and inflammation after cataract surgery. Preliminary data suggest nepafenac may also provide unique efficacy in the posterior segment, since its corneal permeability characteristics are superior to those of other NSAIDs. Nevanac, diclofenac, ketorolac and bromfenac are some notable NSAID candidates which should be investigated intravitreally or topically for retinal pharmacotherapy. In addition, for intraocular surgery, NSAIDs can help to prevent intraoperative miosis, reduce ocular pain, decrease postoperative inflammation and prevent cystoid macular edema. Retinal, choroidal and vitreous diseases may be the target of future nepafenac studies, either as monotherapy or as combination treatments.

  16. Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis

    PubMed Central

    Williams, Patricia B; Crandall, Elizabeth; Sheppard, John D

    2010-01-01

    Over 50% of patients who seek treatment for allergies present with ocular symptoms. Our current ability to control ocular allergic symptoms is greater than ever before. Newer dual-acting topical eyedrops attack multiple facets of the allergic cascade. Azelastine has antihistaminic effects providing immediate relief, mast cell stabilization providing early-phase intervention, and inhibition of expression and activation of anti-inflammatory mediators which characterize the late phase of the immune reaction. The ophthalmic eyedrop formulation is approved for treatment of allergic conjunctivitis in adults and children aged over 3 years. In clinical trials comparing azelastine with other dual-acting eyedrops, such as levocabastine and olopatadine, azelastine was reported to be slightly less efficacious and to sting briefly upon administration. Even so, many patients experienced the full benefit of symptom relief, and preferred azelastine. As a broad-spectrum drug, azelastine offers many desirable properties for management of ocular allergies. Because it can often produce maximal effect with just twice-daily dosing, azelastine is a particularly good choice for the allergic population in whom minimizing exposure to topical products and preservatives is a key concern. PMID:20856595

  17. Biopeptides with antioxidant and anti-inflammatory potential in the prevention and treatment of diabesity disease.

    PubMed

    Martínez Leo, Edwin Enrique; Acevedo Fernández, Juan José; Segura Campos, Maira Rubi

    2016-10-01

    Diabesity is the leading cause of modern, chronic disease. In 2012, diabetes killed 1.2 million people worldwide and its global prevalence exceeded 347 million people, and it is expected that it will increase to 540 million by 2030. Because of this health imperative, it is also linked to increasing obesity. The role of the inflammatory process and oxidative stress in the pathophysiology of these diseases is widely documented. This paper review, using data from major databases, the role of biopeptides with antioxidant and anti-inflammatory activity as a potential aid for the prevention and treatment of diabesity, since the mechanisms of action mentioned directly affect oxidative stress and the characteristic imbalance of the inflammatory process of this disease. Some of these studies have demonstrated beneficial results in relation to oxidative stress and proinflammatory markers. However, the role of biopeptides, in relation to oxidative stress and inflammatory biomarkers, remains unclear and represents a potentially fruitful area for further research in the health area.

  18. Anti-inflammatory polymer electrodes for glial scar treatment: bringing the conceptual idea to future results.

    PubMed

    Asplund, Maria; Boehler, Christian; Stieglitz, Thomas

    2014-01-01

    Conducting polymer films offer a convenient route for the functionalization of implantable microelectrodes without compromising their performance as excellent recording units. A micron thick coating, deposited on the surface of a regular metallic electrode, can elute anti-inflammatory drugs for the treatment of glial scarring as well as growth factors for the support of surrounding neurons. Electro-activation of the polymer drives the release of the substance and should ideally provide a reliable method for controlling quantity and timing of release. Driving signals in the form of a constant potential (CP), a slow redox sweep or a fast pulse are all represented in literature. Few studies present such release in vivo from actual recording and stimulating microelectronic devices. It is essential to bridge the gap between studies based on release in vitro, and the intended application, which would mean release into living and highly delicate tissue. In the biological setting, signals are limited both by available electronics and by the biological safety. Driving signals must not be harmful to tissue and also not activate the tissue in an uncontrolled manner. This review aims at shedding more light on how to select appropriate driving parameters for the polymer electrodes for the in vivo setting. It brings together information regarding activation thresholds for neurons, as well as injury thresholds, and puts this into context with what is known about efficient driving of release from conducting polymer films.

  19. Anti-inflammatory polymer electrodes for glial scar treatment: bringing the conceptual idea to future results

    PubMed Central

    Asplund, Maria; Boehler, Christian; Stieglitz, Thomas

    2014-01-01

    Conducting polymer films offer a convenient route for the functionalization of implantable microelectrodes without compromising their performance as excellent recording units. A micron thick coating, deposited on the surface of a regular metallic electrode, can elute anti-inflammatory drugs for the treatment of glial scarring as well as growth factors for the support of surrounding neurons. Electro-activation of the polymer drives the release of the substance and should ideally provide a reliable method for controlling quantity and timing of release. Driving signals in the form of a constant potential (CP), a slow redox sweep or a fast pulse are all represented in literature. Few studies present such release in vivo from actual recording and stimulating microelectronic devices. It is essential to bridge the gap between studies based on release in vitro, and the intended application, which would mean release into living and highly delicate tissue. In the biological setting, signals are limited both by available electronics and by the biological safety. Driving signals must not be harmful to tissue and also not activate the tissue in an uncontrolled manner. This review aims at shedding more light on how to select appropriate driving parameters for the polymer electrodes for the in vivo setting. It brings together information regarding activation thresholds for neurons, as well as injury thresholds, and puts this into context with what is known about efficient driving of release from conducting polymer films. PMID:24860493

  20. Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

    PubMed Central

    Cho, Hongsik; Walker, Andrew; Williams, Jeb; Hasty, Karen A.

    2015-01-01

    Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA) mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo. PMID:26000299

  1. Intra-articular Treatment of Knee Osteoarthritis: from Anti-inflammatories to Products of Regenerative Medicine

    PubMed Central

    Richards, Masters M.; Maxwell, Joshua Shane; Weng, Lihui; Angelos, Mathew G.; Golzarian, Jafar

    2016-01-01

    Objectives Knee osteoarthritis (OA)1 is a debilitating condition that may ultimately require total knee arthroplasty (TKA)2. Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI)3. The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment. Methods A literature search was executed using Medline, Cochrane, and Embase with keywords ”knee osteoarthritis” and “injection.” Specifically, articles discussing intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP)4 and mesenchymal stem cells (MSC)5, were analyzed. Results Forty-five publications were scrutinized. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5. Papers included animal models. Local anesthetics have potential side effects and may only be effective for four hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to one months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation. Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint. Conclusions Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they

  2. Could Pyelonephritic Scarring Be Prevented by Anti-Inflammatory Treatment? An Experimental Model of Acute Pyelonephritis

    PubMed Central

    Bahat Özdoğan, Elif; Özdemir, Tuğba; Arslansoyu Çamlar, Seçil; İmamoğlu, Mustafa; Çobanoğlu, Ümit; Sönmez, Bircan; Tosun, İlknur; Doğan, İsmail

    2014-01-01

    Objectives. This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. Methods. Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, “ceftriaxone + ketoprofen,” methylprednisolone, and “ceftriaxone + methylprednisolone” were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. Results. When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in “ceftriaxone + ketoprofen” group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in “ceftriaxone + methylprednisolone” group (P = 0.041). Renal scar score was declined in “ceftriaxone + ketoprofen” group and “ceftriaxone + methylprednisolone” group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in “ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone” (P = 0.011, P = 0.023). Conclusion. It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys. PMID:25105116

  3. Could pyelonephritic scarring be prevented by anti-inflammatory treatment? An experimental model of acute pyelonephritis.

    PubMed

    Bahat Özdoğan, Elif; Özdemir, Tuğba; Arslansoyu Çamlar, Seçil; Imamoğlu, Mustafa; Cobanoğlu, Ümit; Sönmez, Bircan; Tosun, İlknur; Doğan, Ismail

    2014-01-01

    This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, "ceftriaxone + ketoprofen," methylprednisolone, and "ceftriaxone + methylprednisolone" were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in "ceftriaxone + ketoprofen" group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in "ceftriaxone + methylprednisolone" group (P = 0.041). Renal scar score was declined in "ceftriaxone + ketoprofen" group and "ceftriaxone + methylprednisolone" group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in "ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone" (P = 0.011, P = 0.023). It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys.

  4. Anti-Inflammatory Targets for the Treatment of Reperfusion Injury in Stroke

    PubMed Central

    Mizuma, Atsushi; Yenari, Midori A.

    2017-01-01

    While the mainstay of acute stroke treatment includes revascularization via recombinant tissue plasminogen activator or mechanical thrombectomy, only a minority of stroke patients are eligible for treatment, as delayed treatment can lead to worsened outcome. This worsened outcome at the experimental level has been attributed to an entity known as reperfusion injury (R/I). R/I is occurred when revascularization is delayed after critical brain and vascular injury has occurred, so that when oxygenated blood is restored, ischemic damage is increased, rather than decreased. R/I can increase lesion size and also worsen blood barrier breakdown and lead to brain edema and hemorrhage. A major mechanism underlying R/I is that of poststroke inflammation. The poststroke immune response consists of the aberrant activation of glial cell, infiltration of peripheral leukocytes, and the release of damage-associated molecular pattern (DAMP) molecules elaborated by ischemic cells of the brain. Inflammatory mediators involved in this response include cytokines, chemokines, adhesion molecules, and several immune molecule effectors such as matrix metalloproteinases-9, inducible nitric oxide synthase, nitric oxide, and reactive oxygen species. Several experimental studies over the years have characterized these molecules and have shown that their inhibition improves neurological outcome. Yet, numerous clinical studies failed to demonstrate any positive outcomes in stroke patients. However, many of these clinical trials were carried out before the routine use of revascularization therapies. In this review, we cover mechanisms of inflammation involved in R/I, therapeutic targets, and relevant experimental and clinical studies, which might stimulate renewed interest in designing clinical trials to specifically target R/I. We propose that by targeting anti-inflammatory targets in R/I as a combined therapy, it may be possible to further improve outcomes from pharmacological thrombolysis or

  5. Nonsteroidal anti-inflammatory drugs and 5-HT₃ serotonin receptor antagonists as innovative antipsychotic augmentation treatments for schizophrenia.

    PubMed

    Andrade, Chittaranjan

    2014-07-01

    Antipsychotic treatment is the mainstay in the management of schizophrenia. However, despite optimum use of antipsychotic drugs, many schizophrenia patients continue to exhibit residual positive, negative, cognitive, and other symptoms. Various antipsychotic augmentation strategies have been studied using non-antipsychotic augmenting agents; 2 innovative classes of drugs examined have been nonsteroidal anti-inflammatory drugs (NSAIDs) and 5-HT₃ serotonin receptor antagonists. Meta-analysis of the NSAID studies in schizophrenia patients with positive symptoms (8 randomized controlled trials [RCTs], pooled N = 774) shows that NSAID augmentation is associated with a significant decrease in positive symptom ratings (standardized mean difference [SMD] = 0.19), with no significant change in negative or total symptom ratings. Meta-analysis of the 5-HT₃ antagonist studies in stable schizophrenia patients (6 RCTs, pooled N = 311) shows that 5-HT₃ antagonist augmentation is associated with significant reduction in negative symptom (SMD = 1.10), general psychopathology (SMD = 0.70), and total symptom (SMD = 1.03) ratings without reduction in positive symptom ratings. Neither NSAID nor 5-HT₃ antagonist augmentation increases the dropout rate. Whereas the benefits with NSAID augmentation are, perhaps, too small to be clinically meaningful, antipsychotic augmentation with 5-HT₃ antagonists may be a possible strategy to reduce persistent negative symptoms in schizophrenia. Both fields of inquiry require further investigation.

  6. Antioxidant and anti-inflammatory effects of Schisandra and Paeonia extracts in the treatment of asthma

    PubMed Central

    CHEN, XIA; HUANG, YI; FENG, JING; JIANG, XIAO-FANG; XIAO, WAN-FEI; CHEN, XIAO-XI

    2014-01-01

    The aim of the present study was to investigate the antioxidant and anti-inflammatory effects of Paeonia and Schisandra extracts in asthmatic rats. An ethanol extraction method was used to prepare the Schisandra and Paeonia extracts, and the levels of hydroxyl radical, total antioxidant activity and total phenolic content were detected. The rats were divided into three groups: Treatment (group A), model (group B) and control (group C). The treatment group received traditional Chinese antiasthmatic medicine (mixed extract, 2 ml/day) for 10 days. Levels of malondialdehyde (MDA), Cu-Zn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected in the serum, while interleukin (IL)-4, IL-6, interferon (IFN)-γ, IL-13 and IL-22 levels were analyzed in the serum, bronchoalveolar lavage fluid and lung tissue homogenates of the three groups. In addition, pathological changes of the tracheal tissues were observed via biopsies and the NF-κB p65 level was measured in the lung tissue using immunohistochemistry. Total antioxidant activity, hydroxyl radical levels and total phenolic content in the mixed herbal extracts were higher than those in the single herbal extracts. At day 5 following the treatment, the number of eosinophils was significantly reduced in the tracheal tissues. At day 10 following the treatment, the mucosa was significantly repaired. In vivo antioxidant levels revealed that the serum and erythrocyte SOD activity and GSH-Px were higher in group A as compared with group B, while the level of MDA in group A was lower than that in group B (P<0.05). The levels of serum and erythrocyte SOD activity and GSH-Px in group B were lower than those in group C, while the level of MDA in group B was higher than that in group C (P<0.05). IL-4, IL-6 and IL-13 levels in the serum, bronchoalveolar lavage fluid and lung tissue in group A were not significantly different from those in group B (P>0.05). However, IFN-γ levels in group A significantly increased as

  7. Antioxidant and anti-inflammatory effects of Schisandra and Paeonia extracts in the treatment of asthma.

    PubMed

    Chen, Xia; Huang, Yi; Feng, Jing; Jiang, Xiao-Fang; Xiao, Wan-Fei; Chen, Xiao-Xi

    2014-11-01

    The aim of the present study was to investigate the antioxidant and anti-inflammatory effects of Paeonia and Schisandra extracts in asthmatic rats. An ethanol extraction method was used to prepare the Schisandra and Paeonia extracts, and the levels of hydroxyl radical, total antioxidant activity and total phenolic content were detected. The rats were divided into three groups: Treatment (group A), model (group B) and control (group C). The treatment group received traditional Chinese antiasthmatic medicine (mixed extract, 2 ml/day) for 10 days. Levels of malondialdehyde (MDA), Cu-Zn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected in the serum, while interleukin (IL)-4, IL-6, interferon (IFN)-γ, IL-13 and IL-22 levels were analyzed in the serum, bronchoalveolar lavage fluid and lung tissue homogenates of the three groups. In addition, pathological changes of the tracheal tissues were observed via biopsies and the NF-κB p65 level was measured in the lung tissue using immunohistochemistry. Total antioxidant activity, hydroxyl radical levels and total phenolic content in the mixed herbal extracts were higher than those in the single herbal extracts. At day 5 following the treatment, the number of eosinophils was significantly reduced in the tracheal tissues. At day 10 following the treatment, the mucosa was significantly repaired. In vivo antioxidant levels revealed that the serum and erythrocyte SOD activity and GSH-Px were higher in group A as compared with group B, while the level of MDA in group A was lower than that in group B (P<0.05). The levels of serum and erythrocyte SOD activity and GSH-Px in group B were lower than those in group C, while the level of MDA in group B was higher than that in group C (P<0.05). IL-4, IL-6 and IL-13 levels in the serum, bronchoalveolar lavage fluid and lung tissue in group A were not significantly different from those in group B (P>0.05). However, IFN-γ levels in group A significantly increased as

  8. An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report

    PubMed Central

    2014-01-01

    Background The Anti-Inflammatory Diet (IBD-AID) is a nutritional regimen for inflammatory bowel disease (IBD) that restricts the intake of certain carbohydrates, includes the ingestion of pre- and probiotic foods, and modifies dietary fatty acids to demonstrate the potential of an adjunct dietary therapy for the treatment of IBD. Methods Forty patients with IBD were consecutively offered the IBD-AID to help treat their disease, and were retrospectively reviewed. Medical records of 11 of those patients underwent further review to determine changes in the Harvey Bradshaw Index (HBI) or Modified Truelove and Witts Severity Index (MTLWSI), before and after the diet. Results Of the 40 patients with IBD, 13 patients chose not to attempt the diet (33%). Twenty-four patients had either a good or very good response after reaching compliance (60%), and 3 patients’ results were mixed (7%). Of those 11 adult patients who underwent further medical record review, 8 with CD, and 3 with UC, the age range was 19–70 years, and they followed the diet for 4 or more weeks. After following the IBD-AID, all (100%) patients were able to discontinue at least one of their prior IBD medications, and all patients had symptom reduction including bowel frequency. The mean baseline HBI was 11 (range 1–20), and the mean follow-up score was 1.5 (range 0–3). The mean baseline MTLWSI was 7 (range 6–8), and the mean follow-up score was 0. The average decrease in the HBI was 9.5 and the average decrease in the MTLWSI was 7. Conclusion This case series indicates potential for the IBD-AID as an adjunct dietary therapy for the treatment of IBD. A randomized clinical trial is warranted. PMID:24428901

  9. Anti-inflammatory ingredients.

    PubMed

    Wu, Jessica

    2008-07-01

    There is a growing public awareness and concern among individuals regarding the condition of their skin, with a concomitant desire to use natural products to treat skin conditions. The increased interest in these products has spurred scientific and clinical studies evaluating the composition and clinical usefulness of natural products in the treatment of inflammatory skin dermatoses. There are numerous natural ingredients that have been demonstrated to possess anti-inflammatory properties that make formulations containing these ingredients attractive treatment options. This article summarizes the active ingredients, anti-inflammatory properties, clinical effects, and therapeutic potential of colloidal oatmeal, feverfew, licorice, aloe vera, chamomile, and turmeric. Potential therapeutic indications include erythema induced by ultraviolet light, rosacea, atopic dermatitis, sensitive and irritated skin, drug-induced skin eruptions, and psoriasis. These products may be particularly well suited as alternatives to pharmacologic therapies in chronic conditions for which long-term use is required.

  10. Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

    PubMed Central

    Farney, Jaymelynn K.; Mamedova, Laman K.; Coetzee, Johann F.; KuKanich, Butch; Sordillo, Lorraine M.; Stoakes, Sara K.; Minton, J. Ernest; Hollis, Larry C.

    2013-01-01

    Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation. PMID:23678026

  11. Polymeric nanoparticles modified with fatty acids encapsulating betamethasone for anti-inflammatory treatment.

    PubMed

    Silva, Catarina Oliveira; Rijo, Patrícia; Molpeceres, Jesús; Figueiredo, Isabel Vitória; Ascensão, Lia; Fernandes, Ana Sofia; Roberto, Amílcar; Reis, Catarina Pinto

    2015-09-30

    Topical glucocorticosteroids were incorporated into nanocarrier-based formulations, to overcome side effects of conventional formulations and to achieve maximum skin deposition. Nanoparticulate carriers have the potential to prolong the anti-inflammatory effect and provide higher local concentration of drugs, offering a better solution for treating dermatological conditions and improving patient compliance. Nanoparticles were formulated with poly-ϵ-caprolactone as the polymeric core along with stearic acid as the fatty acid, for incorporation of betamethasone-21-acetate. Oleic acid was applied as the coating fatty acid. Improvement of the drug efficacy, and reduction in drug degradation with time in the encapsulated form was examined, while administering it locally through controlled release. Nanoparticles were spherical with mean size of 300 nm and negatively charged surface. Encapsulation efficiency was 90%. Physicochemical stability in aqueous media of the empty and loaded nanoparticles was evaluated for six months. Drug degradation was reduced compared to free drug, after encapsulation into nanoparticles, avoiding the potency decline and promoting a controlled drug release over one month. Fourier transform infrared spectroscopy and thermal analysis confirmed drug entrapment, while cytotoxicity studies performed in vitro on human keratinocytes, Saccharomyces cerevisiae models and Artemia salina, showed a dose-response relationship for nanoparticles and free drug. In all models, drug loaded nanoparticles had a greater inhibitory effect. Nanoparticles increased drug permeation into lipid membranes in vitro. Preliminary safety and permeation studies conducted on rats, showed betamethasone-21-acetate in serum after 48 h application of a gel containing nanoparticles. No skin reactions were observed. In conclusion, the developed nanoparticles may be applied as topical treatment, after encapsulation of betamethasone-21-acetate, as nanoparticles promote prolonged drug

  12. The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

    PubMed Central

    Wang, Y; Wang, V M; Chan, C-C

    2011-01-01

    Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. PMID:21183941

  13. Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies

    PubMed Central

    Zhao, Gang; Dharmadhikari, Gitanjali; Maedler, Kathrin; Meyer-Hermann, Michael

    2014-01-01

    Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from in vitro experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting glucose bear the potential of stopping progression from pre-diabetes to overt type 2 diabetes. However, once in overt type 2 diabetes, these treatments have to be complemented by adjuvant anti-inflammatory therapies in order to stop or decelerate disease progression. Moreover, the model suggests that while glucose-lowering therapy needs to be continued all the way, dose and duration of the anti-inflammatory therapy needs to be specifically controlled. The model proposes a framework for the discussion of clinical trial outcomes. PMID:25167060

  14. [Proteolytic enzymes as an alternative in comparison with nonsteroidal anti-inflammatory drugs (NSAID) in the treatment of degenerative and inflammatory rheumatic disease: systematic review].

    PubMed

    Heyll, Uwe; Münnich, Uwe; Senger, Volker

    2003-11-15

    The comparably high number of severe side effects due to treatment with nonsteroidal anti-inflammatory drugs (NSAID) calls for better tolerated substances. One possible alternative is seen in the systemic treatment with proteolytic enzyme preparations for oral administration. The aim of this study was to determine whether the results from controlled randomized trials on enzyme therapy prove equal anti-inflammatory effectiveness compared to NSAID in the treatment of degenerative or inflammatory rheumatic disease. All drug preparations registered in Germany as having anti-inflammatory properties were listed. Among these preparations, a systematic search was carried out for randomized clinical therapeutic trials giving evidence for the anti-inflammatory effectiveness of enzyme preparations or their components. The anti-inflammatory effectiveness of three out of eight registered enzyme preparations was investigated in randomized trials. In total, seven trials were judged to be sufficiently documented and to allow valuation. All studies show severe methodical deficits, and the standard trial design (clinical trials during inpatient rehabilitation in combination with extensive accompanying treatment) does not allow clear-cut conclusions. According to the present state of knowledge, oral proteolytic enzyme treatment does not offer a justified alternative in comparison with NSAID in the anti-inflammatory treatment of rheumatic disease.

  15. Regular physical exercise as a strategy to improve antioxidant and anti-inflammatory status: benefits in type 2 diabetes mellitus.

    PubMed

    de Lemos, Edite Teixeira; Oliveira, Jorge; Pinheiro, João Páscoa; Reis, Flávio

    2012-01-01

    Over the last 30 years the combination of both a sedentary lifestyle and excessive food availability has led to a significant increase in the prevalence of obesity and aggravation of rates of metabolic syndrome and type 2 diabetes mellitus (T2DM). Several lines of scientific evidence have been demonstrating that a low level of physical activity and decreased daily energy expenditure leads to the accumulation of visceral fat and, consequently, the activation of the oxidative stress/inflammation cascade, which underlies the development of insulin resistant T2DM and evolution of micro, and macrovascular complications. This paper focuses on the pathophysiological pathways associated with the involvement of oxidative stress and inflammation in the development of T2DM and the impact of regular physical exercise (training) as a natural antioxidant and anti-inflammatory strategy to prevent evolution of T2DM and its serious complications.

  16. Regular Physical Exercise as a Strategy to Improve Antioxidant and Anti-Inflammatory Status: Benefits in Type 2 Diabetes Mellitus

    PubMed Central

    Teixeira de Lemos, Edite; Oliveira, Jorge; Páscoa Pinheiro, João; Reis, Flávio

    2012-01-01

    Over the last 30 years the combination of both a sedentary lifestyle and excessive food availability has led to a significant increase in the prevalence of obesity and aggravation of rates of metabolic syndrome and type 2 diabetes mellitus (T2DM). Several lines of scientific evidence have been demonstrating that a low level of physical activity and decreased daily energy expenditure leads to the accumulation of visceral fat and, consequently, the activation of the oxidative stress/inflammation cascade, which underlies the development of insulin resistant T2DM and evolution of micro, and macrovascular complications. This paper focuses on the pathophysiological pathways associated with the involvement of oxidative stress and inflammation in the development of T2DM and the impact of regular physical exercise (training) as a natural antioxidant and anti-inflammatory strategy to prevent evolution of T2DM and its serious complications. PMID:22928086

  17. Effect of modern surgical treatment on the inflammatory/anti-inflammatory balance in patients with obstructive sleep apnoea.

    PubMed

    Binar, M; Akcam, T M; Karakoc, O; Sagkan, R I; Musabak, U; Gerek, M

    2017-08-01

    To investigate the inflammatory/anti-inflammatory cytokine balance - T helper 1/T helper 2 ratios - in obstructive sleep apnoea patients, before and after treatment. Twenty-eight patients received continuous positive airway pressure treatment and 29 patients who could not tolerate continuous positive airway pressure were scheduled for surgery. Serum levels of interleukins 2, 4 and 10, tumour necrosis factor-alpha, and interferon gamma were analysed by enzyme-linked immunosorbent assays before and three months after treatment. The success rate of surgical treatment was 65.5 per cent. Mean compliance for the continuous positive airway pressure group was 40.9 per cent. The apnoea/hypopnoea index significantly decreased in both groups after treatment (p < 0.001). The interferon gamma/interleukin-4 ratio decreased following surgical treatment (p = 0.014), and the interleukin-2/interleukin-4 ratio decreased after treatment in 57 patients in the overall cohort (p = 0.032). After treatment for obstructive sleep apnoea, some ratios reflecting T helper 1/T helper 2 cytokine balance favoured the T helper 2 direction, suggesting a shift to an anti-inflammatory state. Successful surgery and better continuous positive airway pressure compliance can help ameliorate inflammation in obstructive sleep apnoea patients, which may reduce associated morbidities.

  18. Non-steroidal anti-inflammatory drug gastropathy: causes and treatment.

    PubMed

    Hawkey, C J

    1996-01-01

    Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) almost invariably cause acute gastroduodenal injury and probably account for approximately 12,000 ulcer bleeding episodes and 1200 deaths per annum in the United Kingdom. Clinically significant intestinal toxicity is also recognized but less clearly defined. The main risk factors for NSAID-related peptic ulcer complications are age, past history, use of higher risk individual NSAIDs, drug dose, concurrent use of warfarin or corticosteroids. The underlying reason for NSAID use and Helicobacter pylori status is not clearly associated with increased risk. Whether NSAIDs cause drug-induced non-ulcer dyspepsia is also controversial. Acute injury occurs more readily with aspirin than with non-aspirin NSAIDs, and the spectrum of acute injury is of little value in predicting clinically significant end points in comparison with different NSAIDs. However, acute studies of co-prescribed protective agents are highly predictive of performance in clinical practice. Gastric mucosal integrity is maintained by the interplay of three protective networks: prostaglandin synthesis, nitric oxide synthesis and the activity of the enteric nervous system. Aspirin and NSAIDs act by inhibiting prostaglandin synthesis catalysed by two cyclooxygenase enzymes. Most existing NSAIDs are unselective and inhibit the activity of the constitutive cyclooxygenase (COX) 1 enzyme in the stomach as much as the cyclooxygenase (COX) 2 enzyme which is induced at sites of inflammation such as joint disease. There are, however, prospects for selective cyclooxygenase 2 inhibitors. Some NSAIDs, particularly aspirin, have additional topical toxicity, which may in part reflect mucosal trapping. Some data favor an effect of NSAIDs in inhibiting mitochondrial oxidative phosphorylation. The principal physiological mechanisms which are compromised by NSAID use are mucosal blood flow, secretion of mucus and bicarbonate and maintenance of a

  19. Bronchodilatory and anti-inflammatory effects of ASM-024, a nicotinic receptor ligand, developed for the treatment of asthma.

    PubMed

    Assayag, Evelyne Israël; Beaulieu, Marie-Josée; Cormier, Yvon

    2014-01-01

    Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145 ± 0.032 mg/kg for ASM 024-treated group as compared to 0.088 ± 0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD.

  20. Small-molecule anti-inflammatory drug compositions for the treatment of asthma: a patent review (2013 - 2014).

    PubMed

    Glossop, Paul; Whitlock, Gavin; Gibson, Karl

    2015-07-01

    Asthma is a chronic condition affecting 235 million people worldwide, with prevalence continuing to increase. A significant number of patients have poorly controlled asthma but despite this, a new mechanistic class of small-molecule asthma therapy has not emerged over the past 15 years. In this article, the authors review the published patent literature from 2013 to 2014 that describes the discovery of novel small-molecule anti-inflammatory agents for the treatment of asthma. This patent analysis was performed using multiple search engines including SciFinder and Free Patents Online. This review highlights that significant research is still directed towards the development of novel anti-inflammatory agents for the treatment of asthma. Current standard-of-care therapies are given topically to the lung via an inhaled dose, which the authors believe can offer significant advantages in terms of efficacy and therapeutic index, compared with an oral dose. Several of the patents reviewed disclose preferred compounds and data that suggest an inhaled approach is being specifically pursued. The patents reviewed target a wide range of inflammatory pathways, although none have yet delivered an approved novel medicine for asthma; this gives an indication of both the opportunity and challenge involved in such an endeavor.

  1. Evolving guidelines in the use of topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis

    PubMed Central

    2014-01-01

    Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to an elevated risk for cardiovascular and gastrointestinal adverse events and renal toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to oral formulations while reducing widespread systemic drug exposure, which may provide a benefit in terms of safety and tolerability. As a result, European treatment guidelines have, for many years, recommended the use of topical NSAIDs as a safe and effective treatment option for OA. Following the recent approval of several topical NSAID formulations by the US Food and Drug Administration, US treatment guidelines are increasingly recommending the use of topical NSAIDs as an alternative therapy and, in some cases, as a first-line option for OA. This commentary summarizes OA treatment guidelines that are currently available and discusses their potential evolution with regard to the increased inclusion of topical NSAIDs. PMID:24444047

  2. Hypoglycemic agents and potential anti-inflammatory activity

    PubMed Central

    Kothari, Vishal; Galdo, John A; Mathews, Suresh T

    2016-01-01

    Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor-γ agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium–glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds. PMID:27114714

  3. Combination of oral zinc gluconate and topical triclosan: An anti-inflammatory treatment modality for initial hidradenitis suppurativa.

    PubMed

    Hessam, Schapoor; Sand, Michael; Meier, Nina Mareike; Gambichler, Thilo; Scholl, Lisa; Bechara, Falk G

    2016-11-01

    Hidradenitis suppurativa (HS) is often a therapeutic challenge with relapses and chronicity which can severely impact patients' quality of life. To evaluate the efficacy of anti-inflammatory oral zinc gluconate, 90mg/day, combined with topical triclosan, 2% twice daily. We retrospectively evaluated the medical records of HS patients in our HS Center of the Department of Dermatology, Venereology, and Allergology, Ruhr-University Bochum, regarding change of disease severity and quality of life. Secondary outcome measures were the number of nodules and fistulas, the number of boils or flair-ups, and the intensity of pain. Sixty-six patients in Hurley stage I and II were included. After 3 months of combination therapy, the modified HS Score and the Dermatology Life Quality Index improved significantly (p<0.0001 and p=0.0386, respectively). The number of inflammatory nodules, new boils or flare-ups, and erythema scores decreased significantly. Fistula count and the visual analogue scale score showed no significant difference. Side-effects (mostly abdominal pain and nausea) were reported by 12 (22.2%) patients. The combination therapy of zinc gluconate and topical triclosan can be considered as an anti-inflammatory treatment for HS patients in Hurley stage I and initial Hurley stage II. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    PubMed Central

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    neuroprotection of brain tissue through anti-inflammatory and anti-apoptotic effects in a mouse model of SWI. These results suggest a new strategy for promoting neuronal survival and function after CED to improve long-term patient outcome. PMID:27445818

  5. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion.

    PubMed

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    through anti-inflammatory and anti-apoptotic effects in a mouse model of SWI. These results suggest a new strategy for promoting neuronal survival and function after CED to improve long-term patient outcome.

  6. Utilization of gastroprotective strategies for nonsteroidal anti-inflammatory drug-induced gastrointestinal events in a major teaching hospital.

    PubMed

    Lee, Hooi Leng; Chua, Siew Siang; Mahadeva, Sanjiv

    2016-01-01

    Clinical guidelines recommend the prescribing of gastroprotective strategies in nonsteroidal anti-inflammatory drug (NSAID) users with risk factors for gastrointestinal (GI) ulcer or ulcer complications. However, these guidelines are not often translated into clinical practice. Therefore, the aim of this study was to investigate the utilization of gastroprotective strategies for NSAID-induced upper GI events in at-risk users in a major teaching hospital. A cross-sectional, observational, pharmacy-based study was conducted in a major Asian institution with both primary and secondary health care services. This study involved the screening of prescriptions for regular NSAIDs, and patients who met the inclusion criteria were recruited and interviewed using a questionnaire. Of the 409 participants recruited, 83.1% had at least one GI risk factor, of whom 70.3% did not receive appropriate gastroprotection. The most common GI risk factor was the use of high-dose NSAIDs (69.2%), followed by participants aged 65 years and older (22%) and concomitant use of low-dose aspirin (11.7%). Appropriate gastroprotective strategies utilized consisted of the use of a cyclooxygenase (COX)-2 inhibitor alone or a nonselective NSAID plus a proton pump inhibitor (PPI) in the moderate-risk group and a COX-2 inhibitor plus a PPI in the high-risk group. Gastroprotective strategies were underutilized in 67.1% of at-risk participants and overutilized in 59.4% of those without risk factors. Co-prescription of a histamine-2 receptor antagonist at lower-than-recommended doses constituted 59% of the inappropriate gastroprotective agents used. Logistic regression analysis revealed patients aged 65 years and older (odds ratio, 1.89; 95% CI =1.15-3.09) as a predictor for the prescribing of gastroprotection by the clinicians. Approximately 70% of at-risk NSAID users, mainly on high-dose NSAIDs, were not prescribed appropriate gastroprotective strategies. Further measures are warranted to improve the

  7. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    PubMed

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

  8. A strategy to discover decoy chemokine ligands with an anti-inflammatory activity

    PubMed Central

    Abboud, Dayana; Daubeuf, François; Do, Quoc Tuan; Utard, Valérie; Villa, Pascal; Haiech, Jacques; Bonnet, Dominique; Hibert, Marcel; Bernard, Philippe; Galzi, Jean-Luc; Frossard, Nelly

    2015-01-01

    Excessive signaling by chemokines has been associated with chronic inflammation or cancer, thus attracting substantial attention as promising therapeutic targets. Inspired by chemokine-clearing molecules shaped by pathogens to escape the immune system, we designed a generic screening assay to discover chemokine neutralizing molecules (neutraligands) and unambiguously distinguish them from molecules that block the receptor (receptor antagonists). This assay, called TRIC-r, combines time-resolved intracellular calcium recordings with pre-incubation of bioactive compounds either with the chemokine or the receptor-expressing cells. We describe here the identification of high affinity neutraligands of CCL17 and CCL22, two chemokines involved in the Th2-type of lung inflammation. The decoy molecules inhibit in vitro CCL17- or CCL22-induced intracellular calcium responses, CCR4 endocytosis and human T cell migration. In vivo, they inhibit inflammation in a murine model of asthma, in particular the recruitment of eosinophils, dendritic cells and CD4+T cells. Altogether, we developed a successful strategy to discover as new class of pharmacological tools to potently control cell chemotaxis in vitro and in vivo. PMID:26442456

  9. Treatment of experimental asthma using a single small molecule with anti-inflammatory and BK channel-activating properties

    PubMed Central

    Goldklang, Monica P.; Perez-Zoghbi, Jose F.; Trischler, Jordis; Nkyimbeng, Takwi; Zakharov, Sergey I.; Shiomi, Takayuki; Zelonina, Tina; Marks, Andrew R.; D'Armiento, Jeanine M.; Marx, Steven O.

    2013-01-01

    Large conductance voltage- and calcium-activated potassium (BK) channels are highly expressed in airway smooth muscle (ASM). Utilizing the ovalbumin (OVA) and house dust mite (HDM) models of asthma in C57BL/6 mice, we demonstrate that systemic administration of the BK channel agonist rottlerin (5 μg/g) during the challenge period reduced methacholine-induced airway hyperreactivity (AHR) in OVA- and HDM-sensitized mice (47% decrease in peak airway resistance in OVA-asthma animals, P<0.01; 54% decrease in HDM-asthma animals, P<0.01) with a 35–40% reduction in inflammatory cells and 20–35% reduction in Th2 cytokines in bronchoalveolar lavage fluid. Intravenous rottlerin (5 μg/g) reduced AHR within 5 min in the OVA-asthma mice by 45% (P<0.01). With the use of an ex vivo lung slice technique, rottlerin relaxed acetylcholine-stimulated murine airway lumen area to 87 ± 4% of the precontracted area (P<0.01 vs. DMSO control). Rottlerin increased BK channel activity in human ASM cells (V50 shifted by 73.5±13.5 and 71.8±14.6 mV in control and asthmatic cells, respectively, both P<0.05 as compared with pretreatment) and reduced the frequency of acetylcholine-induced Ca2+ oscillations in murine ex vivo lung slices. These findings suggest that rottlerin, with both anti-inflammatory and ASM relaxation properties, may have benefit in treating asthma.—Goldklang, M. P., Perez-Zoghbi, J. F., Trischler, J., Nkyimbeng, T., Zakharov, S. I., Shiomi, T., Zelonina, T., Marks, A. R., D'Armiento, J. M., Marx, S. O. Treatment of experimental asthma using a single small molecule with anti-inflammatory and BK channel-activating properties. PMID:23995289

  10. Utilization of gastroprotective strategies for nonsteroidal anti-inflammatory drug-induced gastrointestinal events in a major teaching hospital

    PubMed Central

    Lee, Hooi Leng; Chua, Siew Siang; Mahadeva, Sanjiv

    2016-01-01

    Background and purpose Clinical guidelines recommend the prescribing of gastroprotective strategies in nonsteroidal anti-inflammatory drug (NSAID) users with risk factors for gastrointestinal (GI) ulcer or ulcer complications. However, these guidelines are not often translated into clinical practice. Therefore, the aim of this study was to investigate the utilization of gastroprotective strategies for NSAID-induced upper GI events in at-risk users in a major teaching hospital. Patients and methods A cross-sectional, observational, pharmacy-based study was conducted in a major Asian institution with both primary and secondary health care services. This study involved the screening of prescriptions for regular NSAIDs, and patients who met the inclusion criteria were recruited and interviewed using a questionnaire. Results Of the 409 participants recruited, 83.1% had at least one GI risk factor, of whom 70.3% did not receive appropriate gastroprotection. The most common GI risk factor was the use of high-dose NSAIDs (69.2%), followed by participants aged 65 years and older (22%) and concomitant use of low-dose aspirin (11.7%). Appropriate gastroprotective strategies utilized consisted of the use of a cyclooxygenase (COX)-2 inhibitor alone or a nonselective NSAID plus a proton pump inhibitor (PPI) in the moderate-risk group and a COX-2 inhibitor plus a PPI in the high-risk group. Gastroprotective strategies were underutilized in 67.1% of at-risk participants and overutilized in 59.4% of those without risk factors. Co-prescription of a histamine-2 receptor antagonist at lower-than-recommended doses constituted 59% of the inappropriate gastroprotective agents used. Logistic regression analysis revealed patients aged 65 years and older (odds ratio, 1.89; 95% CI =1.15–3.09) as a predictor for the prescribing of gastroprotection by the clinicians. Conclusion Approximately 70% of at-risk NSAID users, mainly on high-dose NSAIDs, were not prescribed appropriate

  11. [Comparative characteristic of the local application of anti-inflammatory agents for the treatment of otitis externa and otitis media].

    PubMed

    Magomedov, M M; Starostina, A E; Magomedov, M G

    2012-01-01

    The objective of the present work was the clinical study of candibiotic exhibitic antibacterial, antimycotic, anti-inflammatory, and anesthetic properties when applied for the treatment of otitis externa and otitis media. This agent was included together with traditionally used systemic medications in the combined treatment of 26 patients. It was applied in the form of endoaural drops, transtubal administration through a catheter, and transtympanic pumping by the Politzer balloon technique (in case of perforation). In the patients with otomycosys, the preparation was used for the treatment of the external acoustic canal after the removal of fungal masses thrice daily for 1 month. Good clinical effect achieved in all the patients was manifest as the normal otoscopic picture and less frequent complaints on days 8-10 after the onset of therapy. Its maximum duration was 21 days. Positive dynamics (pain relief) was apparent within the first 2 days of the treatment. Fungal mycelium was absent after 14-16 days of the treatment in 100% of the patients initially presenting with yeast-like fungi.

  12. Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile.

    PubMed

    Heemskerk, Mattijs M; Dharuri, Harish K; van den Berg, Sjoerd A A; Jónasdóttir, Hulda S; Kloos, Dick-Paul; Giera, Martin; van Dijk, Ko Willems; van Harmelen, Vanessa

    2014-12-01

    Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment.

  13. Aczone, a topical gel formulation of the antibacterial, anti-inflammatory dapsone for the treatment of acne.

    PubMed

    Scheinfeld, Noah

    2009-05-01

    Allergen Inc has launched Aczone, a topical gel formulation of the antibacterial, anti-inflammatory agent dapsone, for the potential treatment of acne vulgaris. Oral dapsone has demonstrated efficacy in acne, but was associated with severe side effects such as anemia, which was particularly serious in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Aczone was developed to overcome this limitation, and is formulated using solvent-microparticle technology for improved absorption and action and for fewer side effects. In a phase I clinical trial, systemic exposure to dapsone was 126-fold lower following treatment with Aczone compared with oral dapsone. Aczone significantly reduced lesion counts in patients with acne in phase III trials, and was particularly effective in reducing inflammatory lesions. In a phase IV trial, Aczone was safely applied to patients with G6PD deficiency without inducing anemia. Phase IV trials in patients with acne were ongoing at the time of publication to assess safety and to compare Aczone monotherapy with combinations of Aczone and other anti-acne therapeutics. At the time of publication, Allergen was also developing Aczone for the treatment of rosacea; the drug was undergoing phase II trials for this indication. Aczone appears to be a novel promising anti-acne therapeutic option, particularly for patients with inflammatory acne.

  14. The effectiveness of nonsteroidal anti-inflammatory agents in the treatment of pelvic inflammatory disease: a systematic review.

    PubMed

    Dhasmana, Divya; Hathorn, Emma; McGrath, Racheal; Tariq, Anjum; Ross, Jonathan Dc

    2014-07-22

    Pelvic inflammatory disease (PID) is the result of infection ascending through the endocervix to the uterus and fallopian tubes. Inflammation driven by infected host cells appears to be central to the development of tissue damage and associated reproductive complications. Nonsteroidal anti-inflammatory agents (NSAIDs) therefore have the potential to reduce the sequelae associated with pelvic infection. A search of four electronic reference databases, an internet search for relevant grey literature and a review of the bibliographies of identified publications was used to identify studies evaluating NSAIDs in the management of PID. A predefined search strategy was used to identify studies that included women with PID aged over 16 and diagnosed after 1980. Randomized controlled trials, nonrandomized controlled trials, and cohort studies with comparison group data were included without language restriction. Two reviewers independently assessed the studies against agreed criteria and extracted relevant data using a standardized pro forma. A meta-analysis to calculate the relative risk associated with NSAID use was planned if appropriate. Forty-three studies were identified. After reviewing abstracts or full texts, two randomized controlled trials were found to meet the selection criteria for inclusion. The use of NSAIDs was reported to improve tubal patency, reduce pelvic adhesions and reduce suprapubic pain but the studies were of poor quality with a high risk of bias. Meta-analysis of the data was not performed. Insufficient data is available to support or refute the efficacy of NSAIDs in the prevention of short or long-term complications of PID.

  15. Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial.

    PubMed

    Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S; Lyketsos, Constantine G

    2012-04-01

    We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright © 2011 John Wiley & Sons, Ltd.

  16. [Feasibility and assessment of combined anti-inflammatory, antibacterial and immunocorrective treatment in periodontal disease].

    PubMed

    Pleskanovskaia, N V; Ippolitov, E V; Tsarev, V N; Pimenova, M P; Martirosian, V G; Arutiunov, S D

    2013-01-01

    The article presents the experience of using medical dressings of combined action based on antibiotic Spiramycin and antiseptic Triclosan. Investigation and treatment of 79 patients with moderate chronic periodontitis proved the given drug formulation to be highly clinically effective for local treatment of periodontal disease.

  17. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

    PubMed

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-02-28

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  18. Effect of topical anti-inflammatory treatment on the outcome of laser trabeculoplasty. The Fluorometholone-Laser Trabeculoplasty Study Group.

    PubMed

    Shin, D H; Frenkel, R E; David, R; Cheetham, J K

    1996-09-01

    We investigated the effect of anti-inflammatory treatment on the outcome of argon laser trabeculoplasty. In this multicenter, double-masked, randomized, placebo-controlled, parallel comparison study, 140 chronic open-angle glaucoma patients received either 0.25% fluorometholone or vehicle four times a day unilaterally, beginning 24 hours before and continuing one week after argon laser trabeculoplasty. The laser surgeon placed 50 to 60 burns over the inferior 180 degrees of the trabecular meshwork. The patients were followed up frequently for five weeks after the procedure. Following argon laser trabeculoplasty, signs of anterior chamber inflammation were significantly lower in the fluorometholone group. However, there was no significant difference between the fluorometholone and the vehicle groups in the incidence of increased intraocular pressure in the immediate post-argon laser trabeculoplasty period. Intraocular pressure decreased significantly in both groups from day 1 throughout the follow-up period. A significant between-group difference in intraocular pressure decrease was found only at week 5 (7.83 +/- 6.27 [S.D.] mm Hg for the fluorometholone group vs 6.63 +/- 5.79 mm Hg for the vehicle group, P = .046). No drug-related clinically significant adverse events were observed. Use of fluorometholone is effective in attenuating inflammation and has no clinically significant impact on the outcome of argon laser trabeculoplasty or on the incidence of intraocular pressure spikes during the immediate post-argon laser trabeculoplasty period.

  19. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment

    PubMed Central

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-01-01

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer. PMID:28264501

  20. PPARγ Agonists as an Anti-Inflammatory Treatment Inhibiting Rotavirus Infection of Small Intestinal Villi

    PubMed Central

    Gómez, Dory; Muñoz, Natalia; Guerrero, Rafael; Acosta, Orlando; Guerrero, Carlos A.

    2016-01-01

    Rotavirus infection has been reported to induce an inflammatory response in the host cell accompanied by the increased expression or activation of some cellular molecules including ROS, NF-κB, and COX-2. PPARγ stimulation and N-acetylcysteine (NAC) treatment have been found to interfere with viral infections including rotavirus infection. Small intestinal villi isolated from in vivo infected mice with rotavirus ECwt were analyzed for the percentage of ECwt-infected cells, the presence of rotavirus antigens, and infectious virion yield following treatment with pioglitazone. Isolated villi were also infected in vitro and treated with PPARγ agonists (PGZ, TZD, RGZ, DHA, and ALA), all-trans retinoic acid (ATRA), and NAC. After treatments, the expression of cellular proteins including PPARγ, NF-κB, PDI, Hsc70, and COX-2 was analyzed using immunochemistry, ELISA, immunofluorescence, and Western blotting. The results showed that rotavirus infection led to an increased accumulation of the cellular proteins studied and ROS. The virus infection-induced accumulation of the cellular proteins studied and ROS was reduced upon pioglitazone treatment, causing also a concomitant reduction of the infectious virion yield. We hypothesized that rotavirus infection is benefiting from the induction of a host cell proinflammatory response and that the interference of the inflammatory pathways involved leads to decreased infection. PMID:27382365

  1. [Treatment of erosive gastropathy caused by nonsteroidal anti-inflammatory agents using low doses of antacids].

    PubMed

    Rybár, I; Rovenský, J; Orlovská, M

    2000-10-01

    In an open clinical, endoscopy controlled study involving 31 patients with erosive NSAIDs-induced gastropathy without Helicobacter pylori infection, the effect of low dose of antacids (120 mmol/l) with aluminium oxide and magnesium oxide (Maalox) administered for 4 weeks was followed. The administration of NSAIDs was not interrupted during the time of treatment. Healing rate of the gastric erosions after four weeks reached 65% (20/31) and endoscopic score in the gastric mucosa proved significant improvement (0.97 +/- 0.49 compared to 0.07 +/- 0.25, p < 0.01). Our results suggest efficacy of low dose antacids containing aluminium in the treatment of NSAIDs-induced gastric erosions.

  2. [Profile of prescription and adequacy of treatment with non-steroidal anti-inflammatory drugs in diabetic patients].

    PubMed

    Navarro-Martínez, A; Vidal-Martínez, M; García-Rosa, I; Lázaro-Gómez, M J; Brotons-Román, J

    2015-01-01

    The aim of this study was to quantify and describe the prescription profile, as well as to assess the adequacy of treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in the diabetic population of a health district. This is a descriptive, cross-sectional study aimed at a target population of 2,795 diabetic patients. Data were collected from the computerised clinical records of a sample of 380 individuals. The adequacy of treatment was assessed using the recommendations proposed by the Spanish societies of Rheumatology, Cardiology and Gastroenterology. More than one-quarter (28%) of the diabetic patients received treatment with NSAIDs. The most commonly used ones were ibuprofen, naproxen, and dexketoprofen, with a defined daily dose per 1,000 inhabitants per day of 35.3, 17.2, and 13.2, respectively. In patients with a history of chronic kidney disease and cardiovascular high risk, fewer NSAIDs were prescribed, while they were used most frequently in patients with a risk for gastrointestinal adverse events. The prescription was considered adequate in 46.5% of diabetic patients. The main causes of inappropriate use were the inadequate prescription of NSAIDs (25.2%), and the use of any NSAID other than naproxen (20.6%). The most prescribed NSAIDs were those showing a low cardiovascular risk profile. Treatment with NSAIDs was inadequate in more than half of the patients. Risk factors for cardiovascular, and especially gastrointestinal, events must be considered in order to avoid its use when not indicated, as well as the use of any NSAIDs other than naproxen. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  3. Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease.

    PubMed

    Maczurek, Annette; Hager, Klaus; Kenklies, Marlene; Sharman, Matt; Martins, Ralph; Engel, Jürgen; Carlson, David A; Münch, Gerald

    2008-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that destroys patient memory and cognition, communication ability with the social environment and the ability to carry out daily activities. Despite extensive research into the pathogenesis of AD, a neuroprotective treatment - particularly for the early stages of disease - remains unavailable for clinical use. In this review, we advance the suggestion that lipoic acid (LA) may fulfil this therapeutic need. A naturally occurring cofactor for the mitochondrial enzymes pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, LA has been shown to have a variety of properties which can interfere with the pathogenesis or progression of AD. For example, LA increases acetylcholine (ACh) production by activation of choline acetyltransferase and increases glucose uptake, thus supplying more acetyl-CoA for the production of ACh. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione. In addition, LA down-regulates the expression of redox-sensitive pro-inflammatory proteins including TNF and inducible nitric oxide synthase. Furthermore, LA can scavenge lipid peroxidation products such as hydroxynonenal and acrolein. In human plasma, LA exists in an equilibrium of free and plasma protein bound form. Up to 150 muM, it is bound completely, most likely binding to high affinity fatty acid sites on human serum albumin, suggesting that one large dose rather than continuous low doses (as provided by "slow release" LA) will be beneficial for delivery of LA to the brain. Evidence for a clinical benefit for LA in dementia is yet limited. There are only two published studies, in which 600 mg LA was given daily to 43 patients with AD (receiving a standard treatment with choline-esterase inhibitors) in an open-label study over an observation period of up to 48 months. Whereas

  4. Targeted delivery of siRNA to macrophages for anti-inflammatory treatment.

    PubMed

    Kim, Sang-Soo; Ye, Chunting; Kumar, Priti; Chiu, Isaac; Subramanya, Sandesh; Wu, Haoquan; Shankar, Premlata; Manjunath, N

    2010-05-01

    Inflammation mediated by tumor necrosis factor-alpha (TNF-alpha) and the associated neuronal apoptosis characterizes a number of neurologic disorders. Macrophages and microglial cells are believed to be the major source of TNF-alpha in the central nervous system (CNS). Here, we show that suppression of TNF-alpha by targeted delivery of small interfering RNA (siRNA) to macrophage/microglial cells dramatically reduces lipopolysaccharide (LPS)-induced neuroinflammation and neuronal apoptosis in vivo. Because macrophage/microglia express the nicotinic acetylcholine receptor (AchR) on their surface, we used a short AchR-binding peptide derived from the rabies virus glycoprotein (RVG) as a targeting ligand. This peptide was fused to nona-D-arginine residues (RVG-9dR) to enable siRNA binding. RVG-9dR was able to deliver siRNA to induce gene silencing in macrophages and microglia cells from wild type, but not AchR-deficient mice, confirming targeting specificity. Treatment with anti-TNF-alpha siRNA complexed to RVG-9dR achieved efficient silencing of LPS-induced TNF-alpha production by primary macrophages and microglia cells in vitro. Moreover, intravenous injection with RVG-9dR-complexed siRNA in mice reduced the LPS-induced TNF-alpha levels in blood as well as in the brain, leading to a significant reduction in neuronal apoptosis. These results demonstrate that RVG-9dR provides a tool for siRNA delivery to macrophages and microglia and that suppression of TNF-alpha can potentially be used to suppress neuroinflammation in vivo.

  5. [Influence of the anti-inflammatory, anti-bacterial and anti-oxidative treatment combined with the dietary supplementation on sperm parameters].

    PubMed

    Grygoruk, Cezary; Mrugacz, Grzegorz; Ratomski, Karol; Grusza, Mirosław; Kanczuga-Koda, Luiza; Pietrewicz, Piotr

    2012-12-01

    The severe oligospermia and lukocytospermia is diagnosed among 25-40% of the infertile patients despite the absence of any clinical manifestation of the inflammatory process. The white blood cells are the main source of the free oxidative radicals, which can injure the cell membranes and the sperm DNA integrity influencing the reproductive potential of the male gametes. The aim of study was to assess the influence of the anti-inflammatory anti-bacterial and anti-oxidative treatment combined with the dietary supplementation on sperm parameters in the patients with severe oligospermia and lukocytospermia. 100 patients with a severe oligospermia and leukocytospermia were qualified into the study. The anti-inflammatory anti-bacterial and anti-oxidative treatment combined with dietary supplementation was applied for 90 days. The sperm analysis was performed before and after the treatment. The mean volume of sperm samples and spermatozoa concentration were comparable before and after treatment. The leukocyte concentration was significantly lower after the therapy. There were significantly more spermatozoa in the fast and slow forward movement, less spermatozoa without movements and comparable concentration in spermatozoa in slow undirected movement after applied treatment. The present study demonstrated that the anti-inflammatory, anti-bacterial and anti-oxidative treatment combined with dietary supplementation in the patients with severe oligospermia and lukocytospermia improves the sperm movement parameters and reduces the inflammatory response. Therefore, it might be beneficial to patient suffering from the infertility.

  6. The effectiveness of nonsteroidal anti-inflammatory agents in the treatment of pelvic inflammatory disease: a systematic review

    PubMed Central

    2014-01-01

    Background Pelvic inflammatory disease (PID) is the result of infection ascending through the endocervix to the uterus and fallopian tubes. Inflammation driven by infected host cells appears to be central to the development of tissue damage and associated reproductive complications. Nonsteroidal anti-inflammatory agents (NSAIDs) therefore have the potential to reduce the sequelae associated with pelvic infection. Methods A search of four electronic reference databases, an internet search for relevant grey literature and a review of the bibliographies of identified publications was used to identify studies evaluating NSAIDs in the management of PID. A predefined search strategy was used to identify studies that included women with PID aged over 16 and diagnosed after 1980. Randomized controlled trials, nonrandomized controlled trials, and cohort studies with comparison group data were included without language restriction. Two reviewers independently assessed the studies against agreed criteria and extracted relevant data using a standardized pro forma. A meta-analysis to calculate the relative risk associated with NSAID use was planned if appropriate. Results Forty-three studies were identified. After reviewing abstracts or full texts, two randomized controlled trials were found to meet the selection criteria for inclusion. The use of NSAIDs was reported to improve tubal patency, reduce pelvic adhesions and reduce suprapubic pain but the studies were of poor quality with a high risk of bias. Meta-analysis of the data was not performed. Conclusions Insufficient data is available to support or refute the efficacy of NSAIDs in the prevention of short or long-term complications of PID. PMID:25052765

  7. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  8. The Isothiocyanate Isolated from Moringa oleifera Shows Potent Anti-Inflammatory Activity in the Treatment of Murine Subacute Parkinson's Disease.

    PubMed

    Giacoppo, Sabrina; Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2017-02-01

    The present study was aimed at estimating a possible neuroprotective effect of glucomoringin (GMG) [4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate] bioactivated with the enzyme myrosinase to form the corresponding isothiocyanate [4-(α-L-rhamnopyranosyloxy)benzyl C; moringin] in the treatment or prevention of Parkinson's disease (PD). In this study, the beneficial effects of moringin were compared with those of pure GMG, not enzymatically activated, in an in vivo experimental mouse model of subacute PD. Subacute PD was induced in C57BL/6 mice by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were pretreated daily for 1 week with moringin (10 mg/kg +5 μL myrosinase/mouse) and with GMG (10 mg/kg). Behavioral evaluations were also performed to assess motor deficits and bradykinesia in MPTP mice. Besides, assuming that pretreatment with moringin could modulate the triggering of inflammatory cascade with a correlated response, we tested its in vitro anti-inflammatory activity by using a model of RAW 264.7 macrophages stimulated with lipopolysaccharide. Achieved results in vivo showed a higher efficacy of moringin compared with GMG not only to modulate the inflammatory pathway but also oxidative stress and apoptotic pathways. In addition, the greater effectiveness of moringin in countering mainly the inflammatory pathway has been corroborated by the results obtained in vitro. The relevance and innovation of the present study lie in the possible use of a safe formulation of a bioactive compound, resulting from exogenous myrosinase hydrolysis of the natural phytochemical GMG, which can be used in clinical practice as a useful drug for the treatment or prevention of PD.

  9. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    PubMed Central

    Schwier, Nicholas; Tran, Nicole

    2016-01-01

    Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy. PMID:27023565

  10. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

    PubMed Central

    Lionberger, David R; Brennan, Michael J

    2010-01-01

    The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions. PMID:21197326

  11. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy

    PubMed Central

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi AJO; Moriguchi-Jeckel, Cristina M; de Vries, Erik FJ

    2017-01-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants. PMID:28653857

  12. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy.

    PubMed

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi Ajo; Moriguchi-Jeckel, Cristina M; de Vries, Erik Fj

    2017-09-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30-50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic-pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants.

  13. Devil's Claw (Harpagophytum procumbens): no evidence for anti-inflammatory activity in the treatment of arthritic disease.

    PubMed Central

    Whitehouse, L. W.; Znamirowska, M.; Paul, C. J.

    1983-01-01

    Devil's Claw (Harpagophytum procumbens), an herbal product being marketed in Canada as a home remedy for the relief of arthritic disease, was screened for efficacy with standard preclinical screening methods. At doses 100 times or greater than the recommended daily dose for humans, Devil's Claw was completely ineffective in reducing edema of the rat hind foot induced by either lambda-carrageenan or Mycobacterium butyricum. At concentrations of up to 1 x 10(5) microgram/ml, Devil's Claw was also ineffective as an in-vitro inhibitor of prostaglandin synthetase. These results indicate that Devil's Claw lacks the anti-inflammatory properties possessed by all antiarthritic drugs of the nonsteroidal, anti-inflammatory analgesic type. PMID:6407745

  14. Evaluation of anti-inflammatory effect of silver-coated glass beads in mice with experimentally induced colitis as a new type of treatment in inflammatory bowel disease.

    PubMed

    Siczek, Krzysztof; Zatorski, Hubert; Chmielowiec-Korzeniowska, Anna; Kordek, Radzisław; Tymczyna, Leszek; Fichna, Jakub

    2017-06-01

    Recent studies point at the anti-inflammatory action of silver through induction of apoptosis of inflammatory cells via oxidative stress, promotion of wound healing as well as antimicrobial effect. Our aim was to design a new formulation based on silver and validate its anti-inflammatory activity in the mouse models of colitis. Silver-coated glass beads were prepared using a magnetron sputtering method and a standard magnetron sputtering gun equipped with pure silver target. Colitis was induced by the ic administration of TNBS into colon (to mimic Crohn's disease) and addition of DSS to drinking water (to imitate ulcerative colitis). Evaluation of inflammation was performed based on macroscopic and microscopic scoring, quantification of the myeloperoxidase activity and colonic microflora analysis. Silver-coated glass beads administered ic alleviated intestinal inflammation in mouse models of colitis, induced by TNBS and DSS. This alleviation of colitis resulted principally from changes in the gut microflora. The anti-inflammatory action of the new formulation was associated predominantly with the presence of the silver nanolayer on the beads, and to a lesser extent the size of glass polymer units. The application of the newly developed formulation employing silver-coated glass beads has the potential to be translated to clinical conditions for the efficient treatment of IBD. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Anti-inflammatory activities of colloidal oatmeal (Avena sativa) contribute to the effectiveness of oats in treatment of itch associated with dry, irritated skin.

    PubMed

    Reynertson, Kurt A; Garay, Michelle; Nebus, Judith; Chon, Suhyoun; Kaur, Simarna; Mahmood, Khalid; Kizoulis, Menas; Southall, Michael D

    2015-01-01

    Oat (Avena sativa) in colloidal form is a centuries-old topical treatment for a variety of skin conditions, including skin rashes, erythema, burns, itch, and eczema; however, few studies have investigated the exact mechanism of action for the anti-inflammatory activity of colloidal oatmeal. Four extracts of colloidal oatmeal were made with various solvents and tested in anti-inflammatory and antioxidant assays. In addition, an investigator blind study was performed with twenty-nine healthy female subjects who exhibited bilateral mild to moderate itch with moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. Extracts of colloidal oatmeal diminished pro-inflammatory cytokines in vitro and the colloidal oat skin protectant lotion showed significant clinical improvements in skin dryness, scaling, roughness, and itch intensity. These results demonstrate that colloidal oat extracts exhibit direct anti-oxidant and anti-inflammatory activities, which may provide the mechanisms for observed dermatological benefits while using the colloidal oatmeal skin protectant lotion.

  16. Synthesis and biological evaluation of a novel class of curcumin analogs as anti-inflammatory agents for prevention and treatment of sepsis in mouse model.

    PubMed

    Zhao, Chengguang; Zhang, Yali; Zou, Peng; Wang, Jian; He, Wenfei; Shi, Dengjian; Li, Huameng; Liang, Guang; Yang, Shulin

    2015-01-01

    A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs) were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 MAPK and suppressed IκBα degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-κB) and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure-activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases.

  17. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  18. Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea.

    PubMed

    Del Rosso, James Q; Webster, Guy F; Jackson, Mark; Rendon, Marta; Rich, Phoebe; Torok, Helen; Bradshaw, Mark

    2007-05-01

    Doxycycline monotherapy at antimicrobial doses has been shown to be effective for the treatment of rosacea. To evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea. In two phase III, parallel-group, multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count. The mean lesion count at baseline was approximately 20 in each study arm. At week 16, the mean change from baseline in lesion count in the active-treatment groups was -11.8 in study 301 and -9.5 in study 302 compared with -5.9 and -4.3, respectively, in the placebo groups (P < .001 for both comparisons). Anti-inflammatory dose doxycycline was well tolerated; the most common adverse events were nasopharyngitis (4.8%), diarrhea (4.4%), and headache (4.4%). In both studies, the reduction of inflammatory lesion counts did not plateau within the 16-week time frame in either treatment group. Rosacea is often treated for a period of months or years. The duration of the studies did not allow for assessment of safety beyond 16 weeks or whether the progressive improvement seen with active treatment would continue beyond 16 weeks. Neither study assessed the effect of treatment in patients with only erythematotelangiectatic (subtype 1) rosacea. Once-daily anti-inflammatory dose doxycycline appears to be effective and safe for the treatment of rosacea.

  19. The Effects of Anti-inflammatory Drug Treatment in Gastric Cancer Prevention: an Update of a Meta-analysis

    PubMed Central

    Kong, Pengfei; Wu, Ruiyan; Liu, Xuechao; Liu, Jianjun; Chen, Shangxiang; Ye, Minting; Yang, Chenlu; Song, Ze; He, Wenzhuo; Yin, Chenxi; Yang, Qiong; Jiang, Chang; Liao, Fangxin; Peng, Roujun; Zhou, Zhiwei; Xu, Dazhi; Xia, Liangping

    2016-01-01

    Gastric cancer has high incidence and fatality rates, making chemoprevention agents necessary. There is an ongoing debate about aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) use can significant reduce the risk of GC. We conducted a meta-analysis of existing studies evaluating the association of anti-inflammatory drug and GC. We performed a systematic literature search of PubMed, Web of Science, Embase, OVID, Cochrane Library and Clincialtrials.gov up to August 31, 2015. Either a fixed-effects or a random-effects model using was based on the result of homogeneity analysis. Subgroup, sensitivity, meta-regression, and publication bias analyses were evaluated. Forty-seven studies were finally included in this meta-analysis. The overall GC risk reduction benefit associated with anti-inflammatory drug use represented an RR of 0.78 (95% CI 0.71 to 0.85) and an adjusted RR of 0.74 (95% CI 0.71 to 0.77). Besides, the prevention benefit of aspirin/NSAIDs ingestion appeared to be confined to those patients with regiment of short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day). Further, our data also suggest that COX-2 inhibitors use is a more effective approach in GC prevention (RR, 0.45; 95% CI, 0.29-0.70). In this meta-analysis, our finding support short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day) aspirin/NSAIDs intake is a well method for GC prevention and also confirm the inverse association between aspirin/NSAIDs use and GC risk. Additionally, selective COX-2 inhibitors use probably a more effective approach to reduce GC risk. PMID:27994661

  20. Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR-γ agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson's disease.

    PubMed

    Pisanu, Augusta; Lecca, Daniela; Mulas, Giovanna; Wardas, Jadwiga; Simbula, Gabriella; Spiga, Saturnino; Carta, Anna R

    2014-11-01

    Neuroinflammatory changes play a pivotal role in the progression of Parkinson's disease (PD) pathogenesis. Recent findings have suggested that activated microglia may polarize similarly to peripheral macrophages in the central nervous system (CNS), assuming a pro-inflammatory M1 phenotype or the alternative anti-inflammatory M2 phenotype via cytokine production. A skewed M1 activation over M2 has been related to disease progression in Alzheimer disease, and modulation of microglia polarization may be a therapeutic target for neuroprotection. By using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-probenecid (MPTPp) mouse model of progressive PD, we investigated dynamic changes in the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and anti-inflammatory cytokines, such as transforming growth factor (TGF)-β and IL-10, within Iba-1-positive cells in the substantia nigra compacta (SNc). In addition, to further characterize changes in the M2 phenotype, we measured CD206 in microglia. Moreover, in order to target microglia polarization, we evaluated the effect of the peroxisome-proliferator-activated receptor (PPAR)-γ agonist rosiglitazone, which has been shown to exert neuroprotective effects on nigral dopaminergic neurons in PD models, and acts as a modulator of cytokine production and phenotype in peripheral macrophages. Chronic treatment with MPTPp induced a progressive degeneration of SNc neurons. The neurotoxin treatment was associated with a gradual increase in both TNF-α and IL-1β colocalization with Iba-1-positive cells, suggesting an increase in pro-inflammatory microglia. In contrast, TGF-β colocalization was reduced by the neurotoxin treatment, while IL-10 was mostly unchanged. Administration of rosiglitazone during the full duration of MPTPp treatment reverted both TNF-α and IL-1β colocalization with Iba-1 to control levels. Moreover, rosiglitazone induced an increase in TGF-β and IL-10

  1. [Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective].

    PubMed

    De Lossada, A; Oteo-Álvaro, Á; Giménez, S; Oyagüez, I; Rejas, J

    2016-01-01

    To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (p<.001), with mean incremental cost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  2. The role of pro-inflammatory and anti-inflammatory adipokines on exercise-induced bronchospasm in obese adolescents undergoing treatment.

    PubMed

    da Silva, Patrícia Leão; de Mello, Marco Túlio; Cheik, Nadia Carla; Sanches, Priscila Lima; Piano, Aline; Corgosinho, Flávia Campos; Campos, Raquel Munhoz da Silveira; Carnier, June; Inoue, Daniela; do Nascimento, Claudia Mo; Oyama, Lila M; Tock, Lian; Tufik, Sérgio; Dâmaso, Ana R

    2012-04-01

    Recent studies have demonstrated a greater prevalence in exercise-induced bronchospasm (EIB) in obese adolescents. However, the role of pro-/anti-inflammatory adipokines and the repercussions of obesity treatment on EIB need to be explored further. Therefore, the objective of this study was to evaluate the role of pro-/anti-inflammatory adipokines on EIB in obese adolescents evaluated after long-term interdisciplinary therapy. Thirty-five post-pubertal obese adolescents, including 20 non-EIB (body mass index [BMI] 36 ± 5 kg/m(2)) and 15 EIB (BMI 36 ± 5 kg/m(2)), were enrolled in this study. Body composition was measured by plethysmography, using the BOD POD body composition system, and visceral fat was analyzed by ultrasound. Serum levels of adiponectin and leptin were analyzed. EIB and lung function were evaluated according to the American Thoracic Society criteria. Patients were recruited to a 1-year interdisciplinary intervention of weight loss, consisting of medical, nutritional, exercise, and psychological components. Anthropometrics and lung function variables improved significantly after the therapy in both groups. Furthermore we observed a reduction in EIB occurrence in obese adolescents after treatment. There was an increase in adiponectin levels and a reduction in leptin levels after the therapy. In addition, a low FEV(1) value was a risk factor associated with EIB occurrence at baseline, and was correlated after treatment with changes in anthropometric and maximal O(2) consumption values as well as the adipokines profile. In the present study it was demonstrated that 1 year of interdisciplinary therapy decreased EIB frequency in obese adolescents, paralleled by an increase in lung function and improvement in pro-/anti-inflammatory adipokines.

  3. Anti-Inflammatory Iridoids of Botanical Origin

    PubMed Central

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  4. [Role of anti-inflammatory drugs in the treatment of acute coronary syndromes. From athero-inflammation to athero-thrombosis].

    PubMed

    Altman, Raúl; Scazziota, Alejandra

    2003-01-01

    Coronary thrombosis is the most important cause of morbidity and mortality and the most severe manifestation of atherosclerosis. Knowledge of the pathophysiology of atheroma formation and the causes of atheroma accidents have allowed the development of new therapeutic measures for reducing thrombotic events after a coronary episode. Treating the thrombosis after plaque rupture is useful, but a late measure once coronary flow is disturbed. Therefore, treatment at an earlier stage, which we call athero-inflammation, a central event in atheroma progression leading to atherothrombosis, seems wise. There is evidence of an inflammatory component in the pathogenesis of atheroma rupture in acute coronary events. Earlier studies of anti-inflammatory medication have not demonstrated a reduction in thrombotic complications after an acute coronary episode. However, there are pathophysiological arguments and clinical findings that suggest that it would be advisable to include anti-inflammatory medications, especially those that inhibit preferentially COX-2, in the therapeutic arsenal for this pathology. We postulated that blocking athero-inflammation could prevent thrombosis. A pilot study was carried out in 120 patients with acute coronary syndrome without ST-segment elevation in which 60 patients were treated with meloxicam, a preferential COX-2 inhibitor. All patients received heparin and aspirin. During the stay in the coronary care unit, as well as after 90 days, meloxicam lowered composite outcomes (myocardial infarction, death and revascularization procedures) compared with the control group. These results and available pathophysiological and clinical evidence support the hypothesis of potential benefits of non-steroidal anti-inflammatory drugs with preferential inhibitory activity on COX-2 in patients with acute coronary syndromes. More trials are needed to confirm their preventive effect.

  5. Circumcision plus antibiotic, anti-inflammatory, and α-blocker therapy for the treatment for chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized, multicenter trial.

    PubMed

    Zhao, Yuyang; Zhao, Wei; Lang, Genqiang; Chen, Yaowu; Liu, Jianxin; Wang, Guozeng; Ma, Xiaobing; Gong, Min; Xu, Dongliang; Xia, Shujie

    2015-05-01

    The purpose of the study was to evaluate the efficacy of circumcision combined with antibiotic, anti-inflammatory, and α-blocker therapy for the treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Subjects assigned to the circumcision group were given antibiotic, anti-inflammatory, and α-blocker medications and scheduled for surgery the same period in each site by study clinicians. Subjects assigned to the control group were asked to only take the same medications and remain uncircumcised until the end of the 3-month study period. The primary outcome was a reduction of at least four points on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). A total of 774 eligible participants underwent randomization, and the ratio of men with a decrease of at least four points on the total NIH-CPSI score from baseline to 12 weeks was 84.6% in the circumcision group and 68.5% in the control group (P < 0.001). Of the 713 men who completed the trial, the median total NIH-CPSI score decreased significantly from 21.0 ± 7.0 to 12.0 ± 8.0 (P < 0.001) in the circumcision group, and in the control group, the change was from 21.0 ± 8.0 to 15.0 ± 7.0 (P < 0.001). Comparison of the changes in the total and three subdomain NIH-CPSI scores over time revealed significant differences between the circumcision and control groups (P < 0.001). Our findings show that circumcision plus antibiotic, anti-inflammatory, and α-blocker therapy for CP/CPPS patients resulted in improved NIH-CPSI scores compared with medication therapy only.

  6. The anti-inflammatory and analgesic action of transdermal glyceryltrinitrate in the treatment of infusion-related thrombophlebitis.

    PubMed

    Berrazueta, J R; Poveda, J J; Ochoteco, J; Amado, J A; Puebla, F; Salas, E; Sarabia, M

    1993-01-01

    We have carried out a prospective double-blind randomized study in 40 patients with infusion-related thrombophlebitis. Twenty-two patients were included in the glyceryltrinitrate (GTN) ointment group and 18 patients in the control heparinoid group. Pain was assessed by an analogue scale. At 48 hours the analgesic index was 84.6 +/- 18 units with GTN and 49 +/- 45 units with heparinoid ointment (P < 0.01). Faster relief of oedema was also observed in the GTN-treated group. All signs of thrombophlebitis were relieved in less than 4 days in the GTN group compared with 9 days in the controls (P < 0.005). We conclude that transdermal GTN is useful therapy for infusion-related thrombophlebitis showing evidence of anti-inflammatory and analgesic effect.

  7. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain.

    PubMed

    Younger, Jarred; Parkitny, Luke; McLain, David

    2014-04-01

    Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.

  8. The anti-inflammatory and analgesic action of transdermal glyceryltrinitrate in the treatment of infusion-related thrombophlebitis.

    PubMed Central

    Berrazueta, J. R.; Poveda, J. J.; Ochoteco, J.; Amado, J. A.; Puebla, F.; Salas, E.; Sarabia, M.

    1993-01-01

    We have carried out a prospective double-blind randomized study in 40 patients with infusion-related thrombophlebitis. Twenty-two patients were included in the glyceryltrinitrate (GTN) ointment group and 18 patients in the control heparinoid group. Pain was assessed by an analogue scale. At 48 hours the analgesic index was 84.6 +/- 18 units with GTN and 49 +/- 45 units with heparinoid ointment (P < 0.01). Faster relief of oedema was also observed in the GTN-treated group. All signs of thrombophlebitis were relieved in less than 4 days in the GTN group compared with 9 days in the controls (P < 0.005). We conclude that transdermal GTN is useful therapy for infusion-related thrombophlebitis showing evidence of anti-inflammatory and analgesic effect. PMID:8383319

  9. Antimycobacterial, anti-inflammatory and genotoxicity evaluation of plants used for the treatment of tuberculosis and related symptoms in South Africa.

    PubMed

    Madikizela, B; Ndhlala, A R; Finnie, J F; Van Staden, J

    2014-04-28

    Emergence of drug-resistant tuberculosis strains and long duration of treatment has established an urgent need to search for new effective agents. The great floral diversity of South Africa has potential for producing new bioactive compounds, therefore pharmacological screening of plant extracts within this region offers much potential. To assess the in vitro antimycobacterial, anti-inflammatory and genotoxicity activity of selected plants that are used for the treatment of TB and related symptoms in South Africa. Ground plant materials from 10 plants were extracted sequentially with four solvents (petroleum ether, dichloromethane, 80% ethanol and water) and a total of 68 extracts were produced. A broth microdilution method was used to screen extracts against Mycobacterium tuberculosis H37Ra. The cyclooxygenase-2 (COX-2) enzyme was used to evaluate the anti-inflammatory activity of the extracts and the Salmonella microsome assay using two Salmonella typhimurium strains (TA98 and TA100) to establish genotoxicity. Six out of 68 extracts showed good antimycobacterial activity. Three extracts showed good inhibition (>70%) of COX-2 enzyme. All the extracts tested were non-genotoxic against the tested Salmonella strains. The results observed in this study indicate that some of the plants such as Abrus precatorius subsp. africanus, Ficus sur, Pentanisia prunelloides and Terminalia phanerophlebia could be investigated further against drug-resistant TB strains. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Antioxidant and anti-inflammatory medicinal plants have potential role in the treatment of cardiovascular disease: a review.

    PubMed

    Adegbola, Peter; Aderibigbe, Ifewumi; Hammed, Wasiu; Omotayo, Tolulope

    2017-01-01

    Cardiovascular disease is a compound name for clusters of disorders afflicting the heart and blood vessels; it is assuming an increasing role as a major cause of morbidity and mortality. Unhealthy practices such as smoking, high intake of saturated fat and cholesterol, diabetes and physical inactivity are predisposing factors. The risk factors cause alteration in vascular integrity, compromised membrane integrity, increase free radical generation and reduced endogenous antioxidant system resulting in oxidative stress. Substance with ability to maintain vascular integrity, prevent, or reduce radical formation are able to treat cardiovascular disease. Conventional drugs in use to this effect are with side effect and as alternative, medicinal plants are increasingly gaining acceptance from the public and medical professionals. Reports have shown that bioactive compounds in plants with antioxidant, anti-inflammatory, ability to protect vascular endothelium, prevent lipid oxidation, and augment endogenous antioxidant system are cardioprotective. Phenolics and flavonoids in medicinal plants have been widely reported to play these major roles. This study reviewed the role of bioactive compounds in medicinal plants using a wide range database search.

  11. Protection against murine endotoxemia by treatment with Ruta chalepensis L., a plant with anti-inflammatory properties.

    PubMed

    Iauk, Liliana; Mangano, Katia; Rapisarda, Antonio; Ragusa, Salvatore; Maiolino, Luigi; Musumeci, Rosario; Costanzo, Rosaria; Serra, Agostino; Speciale, Annamaria

    2004-02-01

    The anti-inflammatory effect of the extract of Ruta Chalepensis L. (Rutaceae) on the course of lethal endotoxemia in BALB/c mice was studied. When administered by gavage as 1 g/kg per day starting 14 or 7 days prior to injection of 0.75 mg endotoxin (LPS: lipopolysaccharide), the extract markedly reduced lethality (32.5% in both experiments versus approximately 85% of the control mice). A delay in lethality, but not cumulative lethality, was observed when prophylaxis was given 24 and 1 h prior to LPS challenge. The effect was associated with reduced LPS-induced blood levels of nitrite, an indicator of nitric oxide production. In contrast, the blood levels of tumour necrosis factor, interleukin 6 and interleukin 10 did not differ significantly from those of controls given LPS alone. These data show that Ruta Chalepensis L. possesses powerful immunopharmacological properties that make it capable of counteracting the lethal effects of high doses of LPS in vivo.

  12. Pharmacokinetics of non-steroidal anti-inflammatory drugs in male rabbits after acute and chronic administration and effect of chronic treatment on seminal prostaglandins, sperm quality and fertility.

    PubMed

    Löscher, W; Lüttgenau, H; Schlegel, W; Krüger, S

    1988-01-01

    The pharmacokinetics of various non-steroidal anti-inflammatory drugs were determined to find dosage regimens by which drug concentrations known as active from human anti-inflammatory therapy could be reached and maintained in rabbits during continued administration. Based on the pharmacokinetics and side-effects of the different drugs, phenylbutazone was selected for the fertility experiments. Treatment of male rabbits with phenylbutazone for 9 consecutive days significantly reduced seminal concentrations of PGE-2 and PGF-2 alpha and tended to increase ejaculate volumes, sperm motility, and fertility. These results indicate that, at least in rabbits, inhibition of PG synthesis by prolonged treatment with non-steroidal anti-inflammatory drugs does not impair male fertility. Instead, chronic treatment with the drugs at non-toxic doses may improve sperm quality and fertility.

  13. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

    Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking.

  14. [Non-steroidal anti-inflammatory drugs and tramadol in the treatment of osteoarthrosis deformans in patients with arterial hypertension].

    PubMed

    Lazebnik, L B; Kotsiubinskaia, O B; Konev, Iu V; Drozdov, V N

    2004-01-01

    The prohypertensive effect of non-steroidal anti-inflammatory drugs (NSAIDs) can be manifested by the decreased efficiency of antihypertensive therapy. The tactics of their differential use in relation to the its effect on blood pressure (BP) in patients with osteoarthrosis (OA) and arterial hypertension (AH) has not been developed for the most effective and safe therapy. In this connection, it is extremely urgent to study the comparative safety of used NSAIDs as to their prohypertensive effect and to work out the management of patients with AH and OA. Ninety-eight patients with second-third degree OA of the knee and hip joints concurrent with the pain syndrome and first-second grade AH were followed up. Diclofenac, ketoprofen, arthrotec, nimesulide, and meloxicam were used. In a control group, the analgesic tramadol was supplemented to the therapy. AH was controlled by enalapril monotherapy. In groups of patients receiving diclofenac, arthrotec, meloxicam, and ketoprofen, there was a trend for the number of cases of an adequate nocturnal BP lowering (Dipper) to reduce and for those of an inadequate nocturnal BP decrease (Non-dipper), which may be accounted for by the prohypertensive effect of these drugs; this trend was most pronounced in the diclofenac and arthrotec groups. Despite its marked prohypertensive effect, nimesulide did not impair circadian BP variations. The central-acting analgesic tramadol exerted no prohypertensive effect and it did not increase BP values. The prohypertensive effect of the tested NSAIDs and tramadol increases in the following order: tramadol, ketoprofen, meloxicam, nimesulide, arthrotec, diclofenac.

  15. Anti-inflammatory and anti-allergic effects and underlying mechanisms of Huang-Lian-Jie-Du extract: Implication for atopic dermatitis treatment.

    PubMed

    Chen, Yunlong; Xian, Yanfang; Lai, Zhengquan; Loo, Steven; Chan, Wood Yee; Lin, Zhi-Xiu

    2016-06-05

    Huang-Lian-Jie-Du Decoction (HLJDD), a well-known Chinese herbal formula recorded in the Tang dynasty, is composed of Coptidis rhizoma (Huang-Lian), Scutellariae radix (Huang-Qin), Phellodendri Chinensis cortex (Huang-Bai) and Gardenia fructus (Zhi-Zi). It has clinical efficacy of purging fire for removing toxin and is commonly used for the treatment of disease including Alzheimer's disease, stroke and gastrointestinal disorders. HLJDD is also frequently applied for the treatment of various skin diseases, such as atopic dermatitis (AD) and various types of eczema. The aim of this study is to investigate the anti-inflammatory and anti-allergic actions of Huang-Lian-Jie-Du ethanolic extract (HLJDE) and to elucidate underlying molecular mechanisms of action using relevant in vitro experimental models. The anti-inflammatory effects of HLJDE were investigated through evaluating the change of nitric oxide (NO) and the production of several cytokines and chemokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cell line. Expression of mitogen-activated protein kinases (MAPKs), NF-κB p65 phosphorylation, inhibitor-κBα (IκBα) degradation were further investigated to elucidate its anti-inflammatory molecular mechanisms. Meanwhile, the anti-allergic activities of HLJDE was also evaluated using antigen-induced RBL-2H3 cell line. β-hexosaminidase and histamine release and selected cytokines and chemokines were measured to evaluate the anti-allergic activities of HLJDE. In addition, intracellular Ca(2+)level, MAPKs and Lyn phosphorylation were further investigated to reveal its anti-allergic molecular mechanisms. HLJDE could significantly suppress the secretion of NO, IL-1β, IL-4, MCP-1 and GM-CSF in RAW264.7 cells in a dose-dependent manner. In addition, HLJDE also markedly reduced the phosphorylation of MAPKs, and inhibited the transcriptional activity of NF-κB and IκBα degradation. Furthermore, HLJDE exerted marked anti-allergic activity through inhibiting the

  16. The Role of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Treatment of Patients With Hepatic Disease: A Review Article

    PubMed Central

    Soleimanpour, Maryam; Imani, Farnad; Safari, Saeid; Sanaie, Sarvin; Soleimanpour, Hassan; Ameli, Hoorolnesa; Alavian, Seyed Moayed

    2016-01-01

    Context Patients with hepatic dysfunction suffer from many problems and associated complications in organs other than the liver. Therefore, it is very important to investigate the effects of different drugs in the treatment of these patients. Due to the high consumption of non-steroidal anti-inflammatory drugs (NSAIDs), studying the effects of these drugs in patients with hepatic dysfunction is particularly important. Evidence Acquisition Research studies published from 1958 to 2014 were investigated in the present study. The literature search was conducted based on the following keywords: non-steroidal anti-inflammatory drugs (NSAIDs), liver dysfunction, cirrhosis, pharmaceutical complications, drug-induced liver injury (DILI), and similar words from reliable resources. In total, 63 articles and two books (out of 179 initially identified resources) were included in the study. Results In addition to significant hemostatic disorders and cardiovascular disorders, disorders of the renal, respiratory, and gastrointestinal systems, as well as disorders of the central nervous system, occur in patients with hepatic dysfunction. The various NSAIDs have different effects on different bodily systems. Therefore, the appropriate drug should be chosen based on both the condition of the disease and the severity of the dysfunction. Conclusions Due to the potential adverse effects of NSAIDs in patients with hepatic disease, their impact on all bodily systems should be emphasized when determining whether their use is necessary. Further, the appropriate medication should be selected after a careful assessment of the severity of the disease and any associated complications. It is logical that medicines should only be prescribed by a qualified physician. PMID:27843779

  17. The multifunctional anti-inflammatory drugs used in the therapy of Alzheimer's disease.

    PubMed

    Shi, S; Wang, Z; Qiao, Z

    2013-01-01

    Inflammation has recently been implicated as a critical mechanism in Alzheimer's disease (AD). Microglia are the resident immune cells in the central nervous system (CNS), and they mediate the inflammatory response in the AD brain. Thus, suppression of microglial activation and subsequent neuroinflammation may be a potential therapeutic approach against AD. In the following review, we briefly discuss the limitations and advantages of current drug targets for AD and then summarize several anti-inflammatory drugs in trial, including natural nonsteroidal anti-inflammatory drugs (NSAIDs), polyphenols and new drugs synthesized based on multi-target directed ligand (MTDL) design. In addition to their anti-inflammatory effects, these drugs can act as anti-oxidants and reduce microglial activation or amyloid-β (Aβ) plaques. Thus, the studies focused on multiple factors in AD processes might reveal the best potential treatment strategy for the future.

  18. Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy.

    PubMed

    Thiele, Jan R; Habersberger, Jonathon; Braig, David; Schmidt, Yvonne; Goerendt, Kurt; Maurer, Valentin; Bannasch, Holger; Scheichl, Amelie; Woollard, Kevin J; von Dobschütz, Ernst; Kolodgie, Frank; Virmani, Renu; Stark, G Bjoern; Peter, Karlheinz; Eisenhardt, Steffen U

    2014-07-01

    The relevance of the dissociation of circulating pentameric C-reactive protein (pCRP) to its monomeric subunits (mCRP) is poorly understood. We investigated the role of conformational C-reactive protein changes in vivo. We identified mCRP in inflamed human striated muscle, human atherosclerotic plaque, and infarcted myocardium (rat and human) and its colocalization with inflammatory cells, which suggests a general causal role of mCRP in inflammation. This was confirmed in rat intravital microscopy of lipopolysaccharide-induced cremasteric muscle inflammation. Intravenous pCRP administration significantly enhanced leukocyte rolling, adhesion, and transmigration via localized dissociation to mCRP in inflamed but not noninflamed cremaster muscle. This was confirmed in a rat model of myocardial infarction. Mechanistically, this process was dependent on exposure of lysophosphatidylcholine on activated cell membranes, which is generated after phospholipase A2 activation. These membrane changes could be visualized intravitally on endothelial cells, as could the colocalized mCRP generation. Blocking of phospholipase A2 abrogated C-reactive protein dissociation and thereby blunted the proinflammatory effects of C-reactive protein. Identifying the dissociation process as a therapeutic target, we stabilized pCRP using 1,6-bis(phosphocholine)-hexane, which prevented dissociation in vitro and in vivo and consequently inhibited the generation and proinflammatory activity of mCRP; notably, it also inhibited mCRP deposition and inflammation in rat myocardial infarction. These results provide in vivo evidence for a novel mechanism that localizes and aggravates inflammation via phospholipase A2-dependent dissociation of circulating pCRP to mCRP. mCRP is proposed as a pathogenic factor in atherosclerosis and myocardial infarction. Most importantly, the inhibition of pCRP dissociation represents a promising, novel anti-inflammatory therapeutic strategy. © 2014 American Heart

  19. Combined Anti-Inflammatory and Anti-AGE Drug Treatments Have a Protective Effect on Intervertebral Discs in Mice with Diabetes

    PubMed Central

    Illien-Junger, Svenja; Grosjean, Fabrizio; Laudier, Damien M.; Vlassara, Helen; Striker, Gary E.; Iatridis, James C.

    2013-01-01

    Objective Diabetes and low back pain are debilitating diseases and modern epidemics. Diabetes and obesity are also highly correlated with intervertebral disc (IVD) degeneration and back pain. Advanced-glycation-end-products (AGEs) increase reactive-oxygen-species (ROS) and inflammation, and are one cause for early development of diabetes mellitus. We hypothesize that diabetes results in accumulation of AGEs in spines and associated spinal pathology via increased catabolism. We present a mouse model showing that: 1) diabetes induces pathological changes to structure and composition of IVDs and vertebrae; 2) diabetes is associated with accumulation of AGEs, TNFα, and increased catabolism spinal structures; and 3) oral-treatments with a combination of anti-inflammatory and anti-AGE drugs mitigate these diabetes-induced degenerative changes to the spine. Methods Three age-matched groups of ROP-Os mice were compared: non-diabetic, diabetic (streptozotocin (STZ)-induced), or diabetic mice treated with pentosan-polysulfate (anti-inflammatory) and pyridoxamine (AGE-inhibitor). Mice were euthanized and vertebra-IVD segments were analyzed by μCT, histology and Immunohistochemistry. Results Diabetic mice exhibited several pathological changes including loss in IVD height, decreased vertebral bone mass, decreased glycosaminoglycan content and morphologically altered IVDs with focal deposition of tissues highly expressing TNFα, MMP-13 and ADAMTS-5. Accumulation of larger amounts of methylglyoxal suggested that AGE accumulation was associated with these diabetic degenerative changes. However, treatment prevented or reduced these pathological effects on vertebrae and IVD. Conclusion This is the first study to demonstrate specific degenerative changes to nucleus pulposus (NP) morphology and their association with AGE accumulation in a diabetic mouse model. Furthermore, this is the first study to demonstrate that oral-treatments can inhibit AGE-induced ROS and inflammation in

  20. Antidepressant augmentation with anti-inflammatory agents.

    PubMed

    Andrade, Chittaranjan

    2014-09-01

    Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression.

  1. Influence of Hydrothermal Treatment on Physicochemical Properties and Drug Release of Anti-Inflammatory Drugs of Intercalated Layered Double Hydroxide Nanoparticles

    PubMed Central

    Gu, Zi; Wu, Aihua; Li, Li; Xu, Zhi Ping

    2014-01-01

    The synthesis method of layered double hydroxides (LDHs) determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. We synthesised MgAl–LDHs intercalated with non-steroidal anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen) using a co-precipitation method with or without hydrothermal treatment (150 °C, 4 h). After being hydrothermally treated, LDH–drug crystallites increased in particle size and crystallinity, but did not change in the interlayer anion orientation, gallery height and chemical composition. The drug release patterns of all studied LDH–drug hybrids were biphasic and sustained. LDHs loaded with diclofenac had a quicker drug release rate compared with those with naproxen and ibuprofen, and the drug release from the hydrothermally-treated LDH–drug was slower than the freshly precipitated LDH–drug. These results suggest that the drug release of LDH–drugs is influenced by the crystallite size of LDHs, which can be controlled by hydrothermal treatment, as well as by the drug molecular physicochemical properties. PMID:24858732

  2. Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain.

    PubMed

    Tomazoni, Shaiane Silva; Leal-Junior, Ernesto Cesar Pinto; Frigo, Lúcio; Pallotta, Rodney Capp; Teixeira, Simone; de Almeida, Patricia; Bjordal, Jan Magnus; Lopes-Martins, Rodrigo Álvaro Brandão

    2016-10-01

    Osteoarthritis (OA) is a chronic inflammatory disease and is characterized as a degenerative process. This study aimed to evaluate and compare the effects of a topical nonsteroidal anti-inflammatory drug (NSAID), physical activity, and photobiomodulation therapy (PBMT) applied alone and/or in combination between them in an experimental model of knee OA. OA was induced by injection of papain in the knees of rats. After 21 days, the animals started to be treated with the above treatment. Histological analysis shows that the experimental model of OA induction causes morphological changes consistent with the disease, and among treatments, the PBMT is the most effective for reducing these changes. Moreover, the results demonstrate that PBMT and NSAID reduce the total number of cells in the inflammatory infiltrate (p<0.05) and PBMT was the most effective for reducing the activity of myeloperoxidase (p<0.05). Finally, we observed that both NSAID and PBMT were effective for reducing the gene expression of MMP-3 (p<0.05), but in relation to the gene expression of MMP-13, PBMT was the most effective treatment (p<0.05). The results of this study indicate that PBMT is the most effective therapy in stopping disease progression, and improving inflammatory conditions observed in OA.

  3. Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain

    NASA Astrophysics Data System (ADS)

    Tomazoni, Shaiane Silva; Leal-Junior, Ernesto Cesar Pinto; Frigo, Lúcio; Pallotta, Rodney Capp; Teixeira, Simone; de Almeida, Patricia; Bjordal, Jan Magnus; Lopes-Martins, Rodrigo Álvaro Brandão

    2016-10-01

    Osteoarthritis (OA) is a chronic inflammatory disease and is characterized as a degenerative process. This study aimed to evaluate and compare the effects of a topical nonsteroidal anti-inflammatory drug (NSAID), physical activity, and photobiomodulation therapy (PBMT) applied alone and/or in combination between them in an experimental model of knee OA. OA was induced by injection of papain in the knees of rats. After 21 days, the animals started to be treated with the above treatment. Histological analysis shows that the experimental model of OA induction causes morphological changes consistent with the disease, and among treatments, the PBMT is the most effective for reducing these changes. Moreover, the results demonstrate that PBMT and NSAID reduce the total number of cells in the inflammatory infiltrate (p<0.05) and PBMT was the most effective for reducing the activity of myeloperoxidase (p<0.05). Finally, we observed that both NSAID and PBMT were effective for reducing the gene expression of MMP-3 (p<0.05), but in relation to the gene expression of MMP-13, PBMT was the most effective treatment (p<0.05). The results of this study indicate that PBMT is the most effective therapy in stopping disease progression, and improving inflammatory conditions observed in OA.

  4. Helicobacter pylori does not play a part in the dyspeptic complaints of rheumatology patients receiving long term treatment with non-steroidal anti-inflammatory drugs

    PubMed Central

    Calvet, X; Gratacos, J; Font, J; Larrosa, M; Sanfeliu, I; Roque, M

    2002-01-01

    Objective: To determine the variables related to dyspepsia in rheumatology patients requiring NSAID treatment, assessing in particular the role of Helicobacter pylori infection. Methods: One hundred and eighty six consecutive patients with a rheumatological disorder requiring NSAID treatment (68 male, 118 female; mean (SD) age 55 (15) years) were included in a cross sectional study; dyspeptic symptoms were measured by a previously validated scale. Helicobacter pylori infection was determined by serology. Variables related to the severity of symptoms and the need for antisecretory drugs were determined by multivariate analysis. Results: No relation was found between Helicobacter pylori infection and dyspepsia or any of its surrogate markers (antisecretory drug use or NSAID intolerance). Female sex and treatment with antisecretory drugs were found to be independent predictors for the appearance and severity of dyspeptic symptoms. The only independent predictive variables of the requirement for antisecretory drugs were age, previous ulcer disease, taking NSAIDs with a medium or high anti-inflammatory potential, and the symptoms score. Conclusion: Helicobacter pylori infection does not seem to play any part in the gastric symptoms of patients treated long term with NSAIDs. PMID:12079909

  5. Treatment of radiculopathies: a study of efficacy and tollerability of paravertebral oxygen-ozone injections compared with pharmacological anti-inflammatory treatment.

    PubMed

    Melchionda, D; Milillo, P; Manente, G; Stoppino, L; Macarini, L

    2012-01-01

    The study was performed to evaluate the effectiveness of lumbar paravertebral injections of a gas mixture of Oxygen and Ozone in patients with lumbar radiculopathies caused by L4-L5 or L5-S1 disk herniations compared to a pharmacological therapy based on non-steroidal anti-inflammatory drugs. Lumbar radiculopathy caused by disc herniation is widely spread. Many therapeutic options are available before steering patients to the surgery. Low back pain and sciatica represent some of the most frequent causes of antinflammatory-analgesic drugs overuse. Recent findings have shown that medical Ozone can be used in the treatment of radicular syndrome caused by herniated intervertebral discs. Although widely spread, there are insufficient published data supporting the effectiveness of this approach in clinical practice. We studied 38 affected patients with acute L5 or S1 radicolopathy. The patients were randomly divided in two groups: A) 20 patients treated with lumbar paravertebral injections of Oxygen and Ozone; B) 18 patients treated pharmacologically with antinflammatory-analgesic drugs. All patients underwent a clinical and neurological examination at baseline (T1) and after 1 (T2), 2 (T3), 4 weeks (T4) and after 3 (T5) and 6 months (T6). An MRI and EMG examination were performed at baseline and after 6 months. The intensity of pain and the outcome of treatments were evaluated in all patients with the Visual Analogue Scale and with the Oswestry Disability Index. We found a reduction of pain and discomfort soon after one week with oxygen-ozone injections compared with pharmacological treatment, but this difference of response became statistically significant after two weeks (50 percent vs 16.6 percent) and is confirmed after 3 and 6 months, when 80 percent of patients treated with injections turned out pain free compared with half of the patients treated pharmacologically. No statistical difference were found in MRI and EMG examinations. No adverse effects were found in

  6. The effect of prolonged whole-body cryostimulation treatment with different amounts of sessions on chosen pro- and anti-inflammatory cytokines levels in healthy men.

    PubMed

    Lubkowska, Anna; Szyguła, Zbigniew; Chlubek, Dariusz; Banfi, Giuseppe

    2011-09-01

    Cryotherapy is used in the early treatment of acute injuries (sprains, strains, fractures) yet only a few papers discuss the possible influence of whole-body cryostimulation on inflammation mechanisms or immunology. It is postulated that cold exposure can have an immunostimulating effect related to enhanced noradrenaline response and can be connected with paracrine effects. The aim of this study was to examine the effect of different sequences of whole-body cryostimulations on the level of pro- and anti-inflammatory cytokines in healthy individuals. The research involved 45 healthy men divided into three groups. The groups were subjected to 5, 10 or 20, 3-minute long whole-body cryostimulations each day at -130°C. Blood was collected for analysis before the stimulations, after completion of the whole series, and 2 weeks after completion of the series, for the examination of any long-term effect. The analysis of results showed that in response to cryostimulation, the level of ani-inflammatory cytokines IL-6 and IL-10 increased while Il-1α cytokine level decreased. It seems that the most advantageous sequence was the series of 20 cryostimulations due to the longest lasting effects of stimulation after the completion of the whole series of treatments.

  7. Α-aryl-N-alkyl nitrones, as potential agents for stroke treatment: synthesis, theoretical calculations, antioxidant, anti-inflammatory, neuroprotective, and brain-blood barrier permeability properties.

    PubMed

    Chioua, Mourad; Sucunza, David; Soriano, Elena; Hadjipavlou-Litina, Dimitra; Alcázar, Alberto; Ayuso, Irene; Oset-Gasque, María Jesús; González, María Pilar; Monjas, Leticia; Rodríguez-Franco, María Isabel; Marco-Contelles, José; Samadi, Abdelouahid

    2012-01-12

    We report the synthesis, theoretical calculations, the antioxidant, anti-inflammatory, and neuroprotective properties, and the ability to cross the blood-brain barrier (BBB) of (Z)-α-aryl and heteroaryl-N-alkyl nitrones as potential agents for stroke treatment. The majority of nitrones compete with DMSO for hydroxyl radicals, and most of them are potent lipoxygenase inhibitors. Cell viability-related (MTT assay) studies clearly showed that nitrones 1-3 and 10 give rise to significant neuroprotection. When compounds 1-11 were tested for necrotic cell death (LDH release test) nitrones 1-3, 6, 7, and 9 proved to be neuroprotective agents. In vitro evaluation of the BBB penetration of selected nitrones 1, 2, 10, and 11 using the PAMPA-BBB assay showed that all of them cross the BBB. Permeable quinoline nitrones 2 and 3 show potent combined antioxidant and neuroprotective properties and, therefore, can be considered as new lead compounds for further development in specific tests for potential stroke treatment.

  8. Anti-inflammatory properties of bioactive titanium metals.

    PubMed

    Yang, Bangcheng; Gan, Lu; Qu, Yang; Yue, Chongxia

    2010-09-01

    Anti-inflammatory properties of bioactive titanium metals prepared by anodic oxidation (AO-Ti) and alkali-heat (AH-Ti) treatments were studied by bacterial adhesion test and myeloperoxidase (MPO) activity assay methods. The bioactivities of the metals were also evaluated by apatite formation ability and osteoblasts culture experiments. Both metals could induce apatite formation and support osteoblasts proliferation. At the condition with normal incandescent light shine, both bioactive titanium metals had antibacterial adhesion properties compared with the titanium metal without treatment. The MPO activity assay proved that they both showed anti-inflammatory properties in vivo. The bioactive AO-Ti had better anti-inflammatory properties than the AH-Ti. It indicated that it is possible to optimize the anti-inflammatory properties of the bioactive titanium metals by different preparation methods. (c) 2010 Wiley Periodicals, Inc.

  9. Morinda citrifolia (Noni) as an Anti-Inflammatory Treatment in Women with Primary Dysmenorrhoea: A Randomised Double-Blind Placebo-Controlled Trial.

    PubMed

    Fletcher, H M; Dawkins, J; Rattray, C; Wharfe, G; Reid, M; Gordon-Strachan, G

    2013-01-01

    Introduction. Noni (Morinda citrifolia) has been used for many years as an anti-inflammatory agent. We tested the efficacy of Noni in women with dysmenorrhea. Method. We did a prospective randomized double-blind placebo-controlled trial in 100 university students of 18 years and older over three menstrual cycles. Patients were invited to participate and randomly assigned to receive 400 mg Noni capsules or placebo. They were assessed for baseline demographic variables such as age, parity, and BMI. They were also assessed before and after treatment, for pain, menstrual blood loss, and laboratory variables: ESR, hemoglobin, and packed cell volume. Results. Of the 1027 women screened, 100 eligible women were randomized. Of the women completing the study, 42 women were randomized to Noni and 38 to placebo. There were no significant differences in any of the variables at randomization. There were also no significant differences in mean bleeding score or pain score at randomization. Both bleeding and pain scores gradually improved in both groups as the women were observed over three menstrual cycles; however, the improvement was not significantly different in the Noni group when compared to the controls. Conclusion. Noni did not show a reduction in menstrual pain or bleeding when compared to placebo.

  10. Effect of topical anti-inflammatory treatment on the long-term outcome of laser trabeculoplasty. Fluorometholone-Laser Trabeculoplasty Study Group.

    PubMed

    Kim, Y Y; Glover, B K; Shin, D H; Lee, D; Frenkel, R E; Abreu, M M

    1998-11-01

    To investigate the effect of anti-inflammatory treatment on the long-term outcome of argon laser trabeculoplasty, we extended the short-term study of the Fluorometholone-Laser Trabeculoplasty Study Group. Among the chronic open-angle glaucoma patients randomly assigned to the 0.25% fluorometholone or placebo eyedrops four times daily before and after argon laser trabeculoplasty in the Fluorometholone-Laser Trabeculoplasty Study, the long-term records of 27 patients (13 eyes in the fluorometholone group and 14 eyes in the placebo group) were available for our review and analysis. There were no statistically significant differences in the success rate of argon laser trabeculoplasty between the fluorometholone and control groups over the follow-up period of 4.6 +/- 3.4 years. While it decreased ocular inflammation and discomfort during the early postoperative period, peri-argon laser trabeculoplasty use of a topical corticosteroid did not influence the long-term intraocular pressure outcome of argon laser trabeculoplasty.

  11. Morinda citrifolia (Noni) as an Anti-Inflammatory Treatment in Women with Primary Dysmenorrhoea: A Randomised Double-Blind Placebo-Controlled Trial

    PubMed Central

    Fletcher, H. M.; Dawkins, J.; Rattray, C.; Wharfe, G.; Reid, M.; Gordon-Strachan, G.

    2013-01-01

    Introduction. Noni (Morinda citrifolia) has been used for many years as an anti-inflammatory agent. We tested the efficacy of Noni in women with dysmenorrhea. Method. We did a prospective randomized double-blind placebo-controlled trial in 100 university students of 18 years and older over three menstrual cycles. Patients were invited to participate and randomly assigned to receive 400 mg Noni capsules or placebo. They were assessed for baseline demographic variables such as age, parity, and BMI. They were also assessed before and after treatment, for pain, menstrual blood loss, and laboratory variables: ESR, hemoglobin, and packed cell volume. Results. Of the 1027 women screened, 100 eligible women were randomized. Of the women completing the study, 42 women were randomized to Noni and 38 to placebo. There were no significant differences in any of the variables at randomization. There were also no significant differences in mean bleeding score or pain score at randomization. Both bleeding and pain scores gradually improved in both groups as the women were observed over three menstrual cycles; however, the improvement was not significantly different in the Noni group when compared to the controls. Conclusion. Noni did not show a reduction in menstrual pain or bleeding when compared to placebo. PMID:23431314

  12. Practical experience with the treatment of recipient mares with a non-steroidal anti-inflammatory drug in an equine embryo transfer programme.

    PubMed

    Koblischke, P; Budik, S; Müller, J; Aurich, C

    2010-12-01

    As part of a commercial embryo transfer programme, 20 embryos were transferred to spontaneously synchronous or synchronized recipient mares. In 14 cases, embryo recipients were treated with non-steroidal anti-inflammatory drugs (NSAID), receiving flunixin meglumine i.v. at the time of transfer and vedaprofen orally twice a day on the 3 days after embryo transfer, while six embryos were transferred to untreated mares that served as controls. Out of the 14 recipient mares treated with NSAID, 11 (79%) were pregnant at 6-8 days after transfer and in 10 mares, the pregnancy was continued. From the six untreated recipients, only one became pregnant but underwent early embryonic death between day 14 and 35 after ovulation. In conclusion, pregnancy rate in NSAID-treated recipients is higher than that in untreated recipients and above reported average values, indicating that treatment of recipient mares with NSAID helps to increase pregnancy rates after transcervical transfer and can be recommended for equine embryo transfer.

  13. Pathway Analysis of Skin from Psoriasis Patients after Adalimumab Treatment Reveals New Early Events in the Anti-Inflammatory Mechanism of Anti-TNF-α

    PubMed Central

    Langkilde, Ane; Olsen, Lene C.; Sætrom, Pål; Drabløs, Finn; Besenbacher, Søren; Raaby, Line; Johansen, Claus; Iversen, Lars

    2016-01-01

    Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood. We investigated early events in skin from psoriasis patients after treatment with anti-TNF-α antibodies by use of bioinformatics tools. We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new very early events in psoriasis after adalimumab treatment. Some of these events have been described after longer periods of anti-TNF-α treatment when clinical and histological changes appear, suggesting that effects of anti-TNF-α treatment on gene expression appear very early before clinical and histological changes. Combining microarray data on biopsies from psoriasis patients with pathway analysis allowed us to integrate in vitro findings into the identification of mechanisms that may be important in vivo. Furthermore, these results may reflect primary effect of anti-TNF-α treatment in contrast to studies of gene expression changes following clinical and histological changes, which may reflect secondary changes correlated to the healing of the skin. PMID:28005985

  14. Pathway Analysis of Skin from Psoriasis Patients after Adalimumab Treatment Reveals New Early Events in the Anti-Inflammatory Mechanism of Anti-TNF-α.

    PubMed

    Langkilde, Ane; Olsen, Lene C; Sætrom, Pål; Drabløs, Finn; Besenbacher, Søren; Raaby, Line; Johansen, Claus; Iversen, Lars

    2016-01-01

    Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood. We investigated early events in skin from psoriasis patients after treatment with anti-TNF-α antibodies by use of bioinformatics tools. We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new very early events in psoriasis after adalimumab treatment. Some of these events have been described after longer periods of anti-TNF-α treatment when clinical and histological changes appear, suggesting that effects of anti-TNF-α treatment on gene expression appear very early before clinical and histological changes. Combining microarray data on biopsies from psoriasis patients with pathway analysis allowed us to integrate in vitro findings into the identification of mechanisms that may be important in vivo. Furthermore, these results may reflect primary effect of anti-TNF-α treatment in contrast to studies of gene expression changes following clinical and histological changes, which may reflect secondary changes correlated to the healing of the skin.

  15. Adjunctive treatment of decompression illness with a non-steroidal anti-inflammatory drug (tenoxicam) reduces compression requirement.

    PubMed

    Bennett, M; Mitchell, S; Dominguez, A

    2003-01-01

    We report a randomized trial examining adjunctive administration of the NSAID, tenoxicam, to divers suffering with DCI. 180 subjects were graded for severity on admission and randomized according to a stratified random number schedule. Subjects were recompressed and treatment continued daily until symptom stabilization or complete resolution. Tenoxicam 20 mg or a placebo preparation was administered at the first air break during the initial recompression and continued daily for seven days. The subjects were assessed using a recovery status score at the completion of treatment and at 4-6 weeks. The proportion of patients with mild residual symptoms at discharge and final follow-up was not significantly different (discharge placebo 30% versus tenoxicam 37%, P=0.41; six weeks placebo 20% versus tenoxicam 17%, P=0.58). There was a significant reduction in the number of treatments required to achieve discharge (median treatments placebo 3, tenoxicam 2, P=0.01). 61% of patients in the tenoxicam group required less than 3 compressions, versus 40% in the placebo group (P=0.01, RRR 33 % [95%CI 9%-56%], NNT=5 [95%CI 3-18]). There was no evidence of increased complications of treatment in the tenoxicam group. When given this NSAID, patients with DCI require fewer hyperbaric oxygen (HBO2) sessions to achieve a standard clinical end-point and there is likely to be an associated cost saving.

  16. Update on rosacea and anti-inflammatory-dose doxycycline.

    PubMed

    Berman, Brian; Perez, Oliver A; Zell, Deborah

    2007-01-01

    Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have been used to treat rosacea; however, high-dose antibiotics or long-term, low-dose antibiotics commonly used for the treatment of rosacea flares or for rosacea maintenance therapy, respectively, can lead to the development of antibiotic-resistant organisms. The first oral medication approved by the U.S. Food and Drug Administration for the treatment of rosacea in the United States is Oracea (CollaGenex Pharmaceuticals Inc., Newtown, PA, USA). Oracea is a 40 mg capsule of doxycycline monohydrate, containing 30 mg immediate-release and 10 mg delayed-release doxycycline beads ("anti-inflammatory-dose doxycycline"). Anti-inflammatory-dose doxycycline is not an antibiotic and does not lead to the development of antibiotic-resistant organisms. Each capsule of anti-inflammatory-dose doxycycline contains a total of 40 mg of anhydrous doxycycline as 30 mg of immediate-release and 10 mg of delayed-release beads. In contrast to other oral therapies, anti-inflammatory-dose doxycycline is taken once daily, which may increase treatment compliance. The results of two phase III trials have been encouraging, leading to the recent release (summer 2006) of Oracea for the treatment of rosacea in the United States. Anti-inflammatory-dose doxycycline should not be used by individuals with known hypersensitivity to tetracyclines or increased photosensitivity, or by pregnant or nursing women (anti-inflammatory-dose doxycycline is a pregnancy category-D medication). The risk of permanent teeth discoloration and decreased bone growth rate make anti-inflammatory-dose doxycycline contraindicated in infants and children. However, when used appropriately in patients with rosacea, anti-inflammatory-dose doxycycline may help prolong the effectiveness and life span of our most precious antibiotics.

  17. In vitro modeling of repetitive motion strain and manual medicine treatments: potential roles for pro- and anti-inflammatory cytokines.

    PubMed

    Standley, Paul R; Meltzer, Kate

    2008-07-01

    Despite positive clinical outcomes documented post-treatment with a variety of manual medicine treatments (MMT), the underlying cellular mechanisms responsible remain elusive. We have developed an in vitro human fibroblast cell system used to model various biomechanical strains that human fibroblasts might undergo in response to repetitive motion strain (RMS) and MMT. Our data utilizing this system suggest that RMS induces disruption of cell-cell and cell-matrix contacts, which appear are reversed when a modeled MMT is also added to the treatment protocol. Similarly, while RMS induces secretion of several inflammatory cytokines, modeled MMT attenuates this secretory response. In terms of strain direction, fibroblasts strained equiradially exhibit unique cytokine secretory profiles vs. those strained heterobiaxially. Taken together, these data suggest that this cell model may prove useful in identifying the cellular mechanisms by which various fascial strains used clinically to treat somatic dysfunctions yield positive clinical outcomes such as reduced pain, reduced analgesic use and improved range of motion.

  18. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain.

    PubMed

    Schnitzer, Thomas J; Ekman, Evan F; Spierings, Egilius L H; Greenberg, H Scott; Smith, Michael D; Brown, Mark T; West, Christine R; Verburg, Kenneth M

    2015-06-01

    To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs. Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient's Global Assessment (PGA) of OA. Safety assessments included adverse events, physical and neurological examinations, laboratory tests and vital signs. Although all tanezumab treatments provided significant improvements in WOMAC Pain and Physical Function over either NSAID alone, only tanezumab+NSAIDs were significant versus NSAIDs with PGA and met the prespecified definition of superiority. Combination treatment did not substantially improve pain or function over tanezumab monotherapy. Adverse event frequency was higher with tanezumab than with NSAIDs and highest with combination therapy. Higher incidence of all-cause total joint replacements occurred with tanezumab+NSAID versus tanezumab monotherapy or NSAIDs. Rapidly progressive OA incidence was significantly greater versus NSAID in all tanezumab groups except tanezumab 5 mg monotherapy. Subjects receiving partial symptomatic relief of OA pain with NSAIDs may receive greater benefit with tanezumab monotherapy. While only coadministration of tanezumab with NSAIDs met the definition of superiority, combination treatment did not provide important benefits over tanezumab monotherapy; small differences in efficacy were negated by treatment-limiting or irreversible safety outcomes. NCT00809354. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S

    PubMed Central

    Heemskerk, Mattijs M.; Dharuri, Harish K.; van den Berg, Sjoerd A. A.; Jónasdóttir, Hulda S.; Kloos, Dick-Paul; Giera, Martin; van Dijk, Ko Willems; van Harmelen, Vanessa

    2014-01-01

    Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the “biosynthesis of unsaturated fatty acids” pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment. PMID:25320342

  20. High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs--pharmacological mechanisms and clinical relevance.

    PubMed

    Hohlfeld, T; Saxena, A; Schrör, K

    2013-05-01

    Inhibition of platelet function by aspirin results from irreversible inhibition of platelet cyclooxygenase (COX)-1. While sufficient inhibition is obtained at antiplatelet doses (75-325 mg/day) in most (≥95%) treated patients, the antiplatelet effect of aspirin and subsequent cardiovascular risk reduction is much less in clinical settings and disease-dependent. Several reasons for this "high on treatment platelet reactivity" are known. This paper reviews the evidence for an interaction between aspirin and other COX inhibitors, namely non-steroidal anti-inflammatory drugs (NSAIDs). Numerous experimental studies demonstrated a pharmacodynamic interaction between aspirin and NSAIDs. This likely occurs within the hydrophobic substrate channel of platelet COX-1 and might be explained by molecular competition between inhibitor drugs and substrate (arachidonic acid) at overlapping binding sites. This interaction is found with some compounds, notably ibuprofen and dipyrone (metamizole), but not with others, such as diclofenac and acetaminophen (paracetamol). Hence, this interaction is not a class effect of NSAIDs and/or non-steroidal analgesics but rather due to specific structural requirements which still remain to be defined. In vivo studies on healthy subjects and patients tend to confirm this type of interaction as well as large differences between NSAIDs and non-steroidal analgesics, respectively. These interactions may be clinically relevant and may increase the cardiovascular risk in long-term treatment for primary and secondary cardiovascular prevention in patients with chronic inflammation, such as rheumatoid arthritis. These patients have an elevated risk for myocardial infarctions and may require chronic antiplatelet treatment by aspirin in addition to treatment of inflammatory pain.

  1. Recurrent nephrogenic adenoma: a case report of resolution after treatment with antibiotics and nonsteroidal anti-inflammatory medication.

    PubMed

    Voss, Katherine; Peppas, Dennis

    2013-11-01

    Nephrogenic adenoma is an uncommon urothelial lesion that has been associated with chronic inflammation and surgical manipulation of the urinary tract. Several cases of vesical nephrogenic adenoma in patients with a history of renal transplantation have been reported. The present case report reviewed the management of recurrent nephrogenic adenoma in a 6-year-old boy with history of renal transplantation 3 years before the diagnosis of nephrogenic adenoma. After multiple surgical resections for recurrent nephrogenic adenoma, the lesion finally resolved with long-term treatment with ibuprofen (Motrin) and trimethoprim and sulfamethoxazole (Septra). Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis

    PubMed Central

    Coquerelle, C; Oldenhove, G; Acolty, V; Denoeud, J; Vansanten, G; Verdebout, J-M; Mellor, A; Bluestone, J A; Moser, M

    2010-01-01

    Background and aims Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to act as a negative regulator of T cell function and has been implicated in the regulation of T helper 1 (Th1)/Th2 development and the function of regulatory T cells. Tests were carried out to determine whether anti-CTLA-4 treatment would alter the polarisation of naive T cells in vivo. Methods Mice were treated with anti-CTLA-4 monoclonal antibody (mAb) (UC10-4F10) at the time of immunisation or colonic instillation of trinitrobenzene sulfonic acid (TNBS). The cytokines produced by lymph node cells after in vitro antigenic stimulation and the role of indoleamine 2,3 dioxygenase (IDO) and of interleukin-10 (IL-10) were tested, and the survival of mice was monitored. Results Injection of anti-CTLA-4 mAb in mice during priming induced the development of adaptive CD4+ regulatory T cells which expressed high levels of ICOS (inducible co-stimulator), secreted IL-4 and IL-10. This treatment inhibited Th1 memory responses in vivo and repressed experimental intestinal inflammation. The anti-CTLA-4-induced amelioration of disease correlated with IDO expression and infiltration of ICOShigh Foxp3+ T cells in the intestine, suggesting that anti-CTLA-4 acted indirectly through the development of regulatory T cells producing IL-10 and inducing IDO. Conclusions These observations emphasise the synergy between IL-10 and IDO as anti-inflammatory agents and highlight anti-CTLA-4 treatment as a potential novel immunotherapeutic approach for inducing adaptive regulatory T cells. PMID:19505881

  3. Topical delivery of leflunomide for rheumatoid arthritis treatment: evaluation of local tissue deposition of teriflunomide and its anti-inflammatory effects in an arthritis rat model.

    PubMed

    Bae, Joonho; Park, Jin Woo

    2016-01-01

    We investigated whether leflunomide can be delivered topically and metabolized into teriflunomide through the skin, and evaluated the therapeutic effect of topical leflunomide. Permeation of leflunomide across and formation of its active metabolite within the skin was examined ex vivo. Deposition of teriflunomide in micropig knee joints after applying topical and transdermal patches containing leflunomide was investigated by determining the plasma and joint tissue concentrations. Finally, the anti-inflammatory effects and inhibition of skin sensitization by topical leflunomide were evaluated in a rat adjuvant arthritis model and mice with delayed-type induced hypersensitivity. We found that after topical application of leflunomide on freshly excised mouse, rat and guinea pig skin, ∼24% of the permeated drug existed as teriflunomide. In micropigs treated topically with leflunomide on the knee joint, significantly lower teriflunomide concentrations were found in plasma, but its concentrations in the knee joint were 3.4-fold to 54.6-fold higher than those after oral administration. In a rat arthritis model, the plasma concentration of teriflunomide after treatment with 10% leflunomide topical solution was 7.54-fold lower than that after 10 mg/kg oral leflunomide. However, topical leflunomide was nearly as effective as oral in inhibiting paw edema (37% versus 56%, respectively). The values for hypersensitized mouse ear weight after treatment with topical leflunomide decreased significantly by 26% compared to vehicle. These results demonstrate that topically applied leflunomide can be delivered effectively and deposited as teriflunomide in an arthritic joint, possibly allowing better compliance in rheumatoid arthritis patients by avoiding leflunomide's side effects.

  4. Expression of pleiotrophin, an important regulator of cell migration, is inhibited in intestinal epithelial cells by treatment with non-steroidal anti-inflammatory drugs

    USDA-ARS?s Scientific Manuscript database

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the suppression of inflammation and pain. However, the analgesic properties of NSAIDs are also associated with significant negative side effects, most notably in the gastrointestinal (GI) tract. Increasingly, evi...

  5. Anti-allergic, anti-inflammatory and antioxidant activities of the different extracts of Thai traditional remedy called prabchompoothaweep for allergic rhinitis treatment.

    PubMed

    Jai-aue, Areeratna; Makchuchit, Sunita; Juckmeta, Thana; Itharat, Arunporn

    2014-08-01

    Prabchompoothaweep remedy (PT) has long been used in Thai traditional medicine to treat allergic rhinitis and asthma. It is composed of 23 plants. It is on National herbal drug list of Thailand, but there is no reportfor anti-allergic, anti-inflammatory and antioxidant activities. To investigate anti-allergic, anti-inflammatory and antioxidant activities of the crude extract from PTby different extraction method. The method of extract used was maceration in 95% ethanol and 50% ethanol; the residue of these extracts were continued extracted by boiling water, they obtained PTE95, PTE50, PTR95 andPTR50, respectively. The other method of extraction was boiling and drying by lyophilizer that obtained PTW Five crude extracts were determined anti- allergic activity by the inhibition of β-hexosaminidase release from RBL-2H3 cell lines, anti-inflammatory activity were determined by the inhibition ofnitric oxide (NO) production from RA W264. 7 cell lines induced by lipopolysaccharide (LPS) and antioxidant activity were tested by DPPH radical scavenging assay. PTE95 showed the most potent ofanti-allergic activity, anti-inflammatory activity and antioxidant activity (IC5 = 12.97, 22.51 and EC50 = 14.62 μg/ml, respectively). These results suggest that the method of extraction PT that showed the best anti-allergy, anti-inflamation and antioxidant activity was maceration in 95% ethanol.

  6. The diagnostic value of small bowel wall vascularity after sulfur hexafluoride-filled microbubble injection in patients with Crohn's disease. Correlation with the therapeutic effectiveness of specific anti-inflammatory treatment.

    PubMed

    Quaia, Emilio; Migaleddu, Vincenzo; Baratella, Elisa; Pizzolato, Riccardo; Rossi, Alexia; Grotto, Maurizio; Cova, Maria Assunta

    2009-03-01

    To assess the value of small bowel wall vascularity after microbubble contrast agent injection in evaluating the therapeutic effectiveness of specific anti-inflammatory treatment in patients with Crohn's disease. Fifteen patients (7 male and 8 female; mean age+/-SD, 40 years+/-6) with a biopsy-proven diagnosis of Crohn's disease--Crohn's disease activity index (CDAI)>150 (n=12 patients) or <150 (n=3)--involving the terminal loop of the small bowel (wall thickness>5 mm) were included. In each patient the terminal loop was scanned by contrast-enhanced ultrasound (CEUS) after sulfur hexafluoride-filled microbubble injection before and after 6-month anti-inflammatory treatment. The vascularity of the terminal loop was quantified in gray-scale levels (0-255) by a manually drawn ROI encompassing the thickened bowel wall and it was correlated with CDAI. Before the beginning of the specific treatment all patients revealed diffuse transparietal contrast enhancement after microbubble injection, except for 3 patients who revealed contrast enhancement limited to the submucosa. In 13 patients the slope of the first ascending tract and the area under the enhancement curve were significantly lower after anti-inflammatory treatment (P<0.05; Wilcoxon test) with a significant correlation with the CDAI score (rho=0.85, P<0.05). In 2 patients no significant vascularity changes were found even though a mild reduction of CDAI score was identified (from 200 to 150 gray-scale levels). CEUS is a useful method to assess the therapeutic effectiveness of specific medical anti-inflammatory treatment in patients with Crohn's disease.

  7. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis.

    PubMed

    Lakhan, Shaheen E; Kirchgessner, Annette

    2011-08-02

    Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.

  8. Disease-Regulated Gene Therapy with Anti-Inflammatory Interleukin-10 Under the Control of the CXCL10 Promoter for the Treatment of Rheumatoid Arthritis.

    PubMed

    Broeren, Mathijs G A; de Vries, Marieke; Bennink, Miranda B; Arntz, Onno J; Blom, Arjen B; Koenders, Marije I; van Lent, Peter L E M; van der Kraan, Peter M; van den Berg, Wim B; van de Loo, Fons A J

    2016-03-01

    Disease-inducible promoters for the treatment of rheumatoid arthritis (RA) have the potential to provide regulated expression of therapeutic proteins in arthritic joints. In this study, we set out to identify promoters of human genes that are upregulated during RA and are suitable to drive the expression of relevant amounts of anti-inflammatory interleukin (IL)-10. Microarray analysis of RA synovial biopsies compared with healthy controls yielded a list of 22 genes upregulated during RA. Of these genes, CXCL10 showed the highest induction in lipopolysaccharide-stimulated synovial cells. The CXCL10 promoter was obtained from human cDNA and cloned into a lentiviral vector carrying firefly luciferase to determine the promoter inducibility in primary synovial cells and in THP-1 cells. The promoter activation was strongest 8-12 hr after stimulation with the proinflammatory cytokine tumor necrosis factor (TNF)-α and was reinducible after 96 hr. In addition, the CXCL10 promoter showed a significant response to RA patient serum, compared with sera from healthy individuals. The luciferase gene was replaced with IL-10 to determine the therapeutic properties of the CXCL10p-IL10 lentiviral vector. Primary synovial cells transduced with CXCL10p-IL10 showed a great increase in IL-10 production after stimulation, which reduced the release of proinflammatory cytokines TNF-α and IL-1β. We conclude that the selected proximal promoter of the CXCL10 gene responds to inflammatory mediators present in the serum of patients with RA and that transduction with the lentiviral CXCL10p-IL10 vector reduces inflammatory cytokine production by primary synovial cells from patients with RA. CXCL10 promoter-regulated IL-10 overexpression can thus provide disease-inducible local gene therapy suitable for RA.

  9. Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial.

    PubMed

    Llor, Carl; Moragas, Ana; Bayona, Carolina; Morros, Rosa; Pera, Helena; Plana-Ripoll, Oleguer; Cots, Josep M; Miravitlles, Marc

    2013-10-04

    To evaluate the efficacy of oral anti-inflammatory or antibiotic treatment compared with placebo in the resolution of cough in patients with uncomplicated acute bronchitis and discoloured sputum. Multicentre, parallel, single blinded placebo controlled, randomised clinical trial. Nine primary care centres in Spain. Adults aged 18 to 70 presenting symptoms associated with respiratory tract infection of less than one week's duration, with cough as the predominant symptom, the presence of discoloured sputum, and at least one other symptom of lower respiratory tract infection (dyspnoea, wheezing, chest discomfort, or chest pain). Patients were randomised to receive either ibuprofen 600 mg three times daily, amoxicillin-clavulanic acid 500 mg/125 mg three times daily, or placebo three times daily for 10 days. The duration of symptoms was measured with a diary card. Number of days with frequent cough after the randomisation visit. 416 participants were randomised (136 to ibuprofen, 137 to antibiotic, and 143 to placebo) and 390 returned their symptom diaries fully completed. The median number of days with frequent cough was slightly lower among patients assigned to ibuprofen (9 days, 95% confidence interval 8 to 10 days) compared with those receiving amoxicillin-clavulanic acid (11 days, 10 to 12 days) or placebo (11 days, 8 to 14 days), albeit without statistically significant differences. Neither amoxicillin-clavulanic acid nor ibuprofen increased the probability of cough resolution (hazard ratio 1.03, 95% confidence interval 0.78 to 1.35 and 1.23, 0.93 to 1.61, respectively) compared with placebo. Adverse events were observed in 27 patients, and were more common in the antibiotic arm (12%) than ibuprofen or placebo arms (5% and 3%, respectively; P<0.01). No significant differences were observed in the number of days with cough between patients with uncomplicated acute bronchitis and discoloured sputum treated with ibuprofen, amoxicillin-clavulanic acid, or placebo

  10. Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

    PubMed Central

    Oses, Carolina; Olivares, Belén; Ezquer, Marcelo; Acosta, Cristian; Bosch, Paul; Donoso, Macarena; Léniz, Patricio

    2017-01-01

    Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when

  11. Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy.

    PubMed

    Oses, Carolina; Olivares, Belén; Ezquer, Marcelo; Acosta, Cristian; Bosch, Paul; Donoso, Macarena; Léniz, Patricio; Ezquer, Fernando

    2017-01-01

    Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when

  12. The role of chronic inflammation in the development of gastrointestinal cancers: reviewing cancer prevention with natural anti-inflammatory intervention.

    PubMed

    Lee, Ho-Jae; Park, Jong-Min; Han, Young Min; Gil, Hong Kwon; Kim, Jinhyung; Chang, Ji Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-01-01

    Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

  13. Clinical particularities and response to the anti-inflammatory effect of antiviral treatment in patients with Chronic Hepatitis C and Rheumatoid Syndrome

    PubMed Central

    Lilea, GC; Streba, CT; Baloseanu, CL; Vere, CC; Rogoveanu, I

    2012-01-01

    Hepatitis C virus (HCV) is an important cause for the development of serious hepatic disease such as chronic hepatitis and liver cirrhosis. Though the pathological mechanisms are poorly understood, it is well established that CHC plays an important role in several immune mediated conditions, including rheumatoid arthritis. We focused on the clinical particularities of patients with CHC and associated RS and we specifically investigated the anti-inflammatory role of IFN-alpha concerning the rheumatic symptoms. PMID:23346247

  14. Erdosteine: antitussive and anti-inflammatory effects.

    PubMed

    Dal Negro, Roberto W

    2008-01-01

    lipoperoxidation (8-isoprostane) proved discriminant between treatments, with antioxidant and anti-inflammatory effects the main determinants of the erdosteine multifactorial properties. In addition, antitussive effects may be regarded as related to its anti-inflammatory properties via the improvement of mucociliary clearance and the reduction of chemokines from epithelial cells. Finally, a sort of "sensitization" of 2-adrenoceptors can also be speculated due to the same mechanisms of action; if confirmed by further controlled studies, this particular property would suggest a novel therapeutic role of erdosteine in COPD.

  15. Extended nitric oxide analysis may improve personalized anti-inflammatory treatment in asthmatic children with intermediate F(E)NO50.

    PubMed

    Thornadtsson, A; Neerincx, A H; Högman, M; Hugen, C; Sintnicolaas, C; Harren, F J M; Merkus, P J F M; Cristescu, S M

    2015-12-15

    Exhaled nitric oxide (F(E)NO) is elevated in asthma, and a clinical practice guideline has been published with recommendations for anti-inflammatory treatment. It summarizes that a F(E)NO at an expiratory flow rate of 50 ml s(-1) (F(E)NO50) above 35 ppb in children indicates eosinophilic inflammation, and the most likely response is to use inhaled corticosteroids. Intermediate F(E)NO50 between 20-35 ppb should be interpreted cautiously. The aim of the study was to investigate this guideline in a small group of asthmatic children. Thirty-seven asthmatic children; 23 boys and 14 girls, visited the outpatient clinic, and provided exhaled breath samples for offline NO measurement. These samples were analysed with chemiluminescence techniques. Three flow rates, namely 16, 90 and 230 ml s(-1) were used for the extended NO analysis (Högman-Meriläinen algorithm, HMA) to estimate the alveolar concentration (C(A)NO), diffusion rate of the airway wall (D(aw)NO) and airway wall content (C(aw)NO). For accuracy of the HMA, the estimated value of F(E)NO at 50 ml s(-1) (F(E)NO50) was compared with measured F(E)NO50. In nine children the difference was more than 5 ppb and the data were therefore excluded. Five children with F(E)NO50 <20 ppb had no known allergy and their F(E)NO50 geometrical mean (25th; 75th percentile) was 11 (10;14) and CawNO was 32 (20;43) ppb. Ten children with F(E)NO50  >  35 ppb had an allergy and had F(E)NO50 of 56 (47;60) ppb and C(aw)NO of 140 (121;172) ppb. Thirteen children with allergies, with intermediate F(E)NO50, had F(E)NO50 of 27 (25;30) ppb with a wide range of C(aw)NO. In five of these children, values were comparable to healthy children, 44 (43;50) ppb while eight children had elevated C(aw)NO values of 108 (95;129) ppb. Our data indicate the clinical potential use of extended NO analysis to determine the personal target value of F(E)NO50 for monitoring the treatment outcome. Furthermore, for children with intermediate F(E)NO50

  16. Barriers to anti-inflammatory medication use in childhood asthma.

    PubMed

    Yoos, H Lorrie; Kitzman, Harriet; McMullen, Ann

    2003-01-01

    To identify parental barriers to anti-inflammatory medication use and to develop an instrument for use in research and health care settings to identify at-risk populations. Instrument development consisted of 4 phases: 1) gaining the professional perspective (N = 8 experts in asthma management), 2) gaining the perspective of parents of children with asthma (qualitative interviews with 21 parents), 3) instrument pretesting and refinement (N = 133 parents), and 4) determining the instrument's psychometric properties. Study participants were diverse in race, socioeconomic status, and the child's illness severity. The final instrument consisted of 51 questions in 5 domains (nature of disease, cause, ideas about medications, treatment expectations, and health care provider relationship). The final instrument exhibited strong reliability (Cronbach alpha =.87) and validity. Significant barriers to appropriate anti-inflammatory medication use were parents' diminished treatment expectations and fears about anti-inflammatory medications. Minority families were more likely than white families to view asthma as unpredictable and uncontrollable (P =.01) and to have negative attitudes toward anti-inflammatory medications (P =.004). Eight questions were significantly correlated with a suboptimal medication regimen and may serve as a "quick screen" for potential nonadherence in clinical settings. Diminished treatment expectations and negative attitudes toward anti-inflammatories may be powerful predictors of nonadherence to medications.

  17. Synthesis, antinociceptive and anti-inflammatory effects of porphyrins.

    PubMed

    Alonso-Castro, Angel Josabad; Zapata-Morales, Juan Ramón; Hernández-Munive, Abigail; Campos-Xolalpa, Nimsi; Pérez-Gutiérrez, Salud; Pérez-González, Cuauhtémoc

    2015-05-15

    Porphyrins are natural compounds with several biological activities. We report the synthesis and the evaluation of the anti-inflammatory and antinociceptive effects of 4 porphyrins: 5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetra(4'-fluorophenyl)porphyrin (TpFPP), 5,10,15,20-tetra(4'-chlorophenyl)porphyrin (TpClPP), and 5,10,15,20-tetra(4'-bromophenyl)porphyrin (TpBrPP). The in vitro anti-inflammatory effects were evaluated on heat-induced hemolysis. The antinociceptive effects were evaluated using the hot plate and formalin tests. The in vivo anti-inflammatory assays were tested on the acute and chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema. The anti-arthritic effects were evaluated using carrageenan kaolin induced arthritis (CKIA). All porphyrins inhibited hemolysis with similar potency than naproxen (NPX). In the antinociceptive tests, all porphyrins tested at 200mg/kg showed similar effects compared to 100mg/kg NPX. In the in vivo anti-inflammatory acute assay, only three porphyrins (TPP, TpFPP and TpBrPP) decreased inflammation with similar activity than 2mg/ear indomethacin (IND). Further anti-inflammatory experiments were carried out with TPP, TpFPP and TpBrPP. In the in vivo anti-inflammatory chronic assay, porphyrins decreased inflammation with similar activity than 8mg/kg IND. Porphyrins tested at 200mg/kg showed anti-arthritic effects. The antinociceptive, anti-inflammatory and arthritic activities of porphyrins suggest that these compounds might be a good alternative for the treatment of inflammatory diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial

    PubMed Central

    Moragas, Ana; Bayona, Carolina; Morros, Rosa; Pera, Helena; Plana-Ripoll, Oleguer; Cots, Josep M; Miravitlles, Marc

    2013-01-01

    Objective To evaluate the efficacy of oral anti-inflammatory or antibiotic treatment compared with placebo in the resolution of cough in patients with uncomplicated acute bronchitis and discoloured sputum. Design Multicentre, parallel, single blinded placebo controlled, randomised clinical trial. Setting Nine primary care centres in Spain. Participants Adults aged 18 to 70 presenting symptoms associated with respiratory tract infection of less than one week’s duration, with cough as the predominant symptom, the presence of discoloured sputum, and at least one other symptom of lower respiratory tract infection (dyspnoea, wheezing, chest discomfort, or chest pain). Interventions Patients were randomised to receive either ibuprofen 600 mg three times daily, amoxicillin-clavulanic acid 500 mg/125 mg three times daily, or placebo three times daily for 10 days. The duration of symptoms was measured with a diary card. Main outcome measure Number of days with frequent cough after the randomisation visit. Results 416 participants were randomised (136 to ibuprofen, 137 to antibiotic, and 143 to placebo) and 390 returned their symptom diaries fully completed. The median number of days with frequent cough was slightly lower among patients assigned to ibuprofen (9 days, 95% confidence interval 8 to 10 days) compared with those receiving amoxicillin-clavulanic acid (11 days, 10 to 12 days) or placebo (11 days, 8 to 14 days), albeit without statistically significant differences. Neither amoxicillin-clavulanic acid nor ibuprofen increased the probability of cough resolution (hazard ratio 1.03, 95% confidence interval 0.78 to 1.35 and 1.23, 0.93 to 1.61, respectively) compared with placebo. Adverse events were observed in 27 patients, and were more common in the antibiotic arm (12%) than ibuprofen or placebo arms (5% and 3%, respectively; P<0.01). Conclusion No significant differences were observed in the number of days with cough between patients with uncomplicated acute

  19. IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines

    PubMed Central

    Li, Xinyuan; Mai, Jietang; Virtue, Anthony; Yin, Ying; Gong, Ren; Sha, Xiaojin; Gutchigian, Stefanie; Frisch, Andrew; Hodge, Imani; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies. PMID:22438968

  20. Targeting Fatty Acid Binding Protein (FABP) Anandamide Transporters – A Novel Strategy for Development of Anti-Inflammatory and Anti-Nociceptive Drugs

    PubMed Central

    Sun, Jing; Balius, Trent E.; Rizzo, Robert C.; Haj-Dahmane, Samir; Ojima, Iwao; Deutsch, Dale G.

    2012-01-01

    Fatty acid binding proteins (FABPs), in particular FABP5 and FABP7, have recently been identified by us as intracellular transporters for the endocannabinoid anandamide (AEA). Furthermore, animal studies by others have shown that elevated levels of endocannabinoids resulted in beneficial pharmacological effects on stress, pain and inflammation and also ameliorate the effects of drug withdrawal. Based on these observations, we hypothesized that FABP5 and FABP7 would provide excellent pharmacological targets. Thus, we performed a virtual screening of over one million compounds using DOCK and employed a novel footprint similarity scoring function to identify lead compounds with binding profiles similar to oleic acid, a natural FABP substrate. Forty-eight compounds were purchased based on their footprint similarity scores (FPS) and assayed for biological activity against purified human FABP5 employing a fluorescent displacement-binding assay. Four compounds were found to exhibit approximately 50% inhibition or greater at 10 µM, as good as or better inhibitors of FABP5 than BMS309403, a commercially available inhibitor. The most potent inhibitor, γ-truxillic acid 1-naphthyl ester (ChemDiv 8009-2334), was determined to have Ki value of 1.19±0.01 µM. Accordingly a novel α-truxillic acid 1-naphthyl mono-ester (SB-FI-26) was synthesized and assayed for its inhibitory activity against FABP5, wherein SB-FI-26 exhibited strong binding (Ki 0.93±0.08 µM). Additionally, we found SB-FI-26 to act as a potent anti-nociceptive agent with mild anti-inflammatory activity in mice, which strongly supports our hypothesis that the inhibition of FABPs and subsequent elevation of anandamide is a promising new approach to drug discovery. Truxillic acids and their derivatives were also shown by others to have anti-inflammatory and anti-nociceptive effects in mice and to be the active component of Chinese a herbal medicine (Incarvillea sinensis) used to treat rheumatism and pain in

  1. Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.

    PubMed

    Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

    2013-03-01

    Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action.

  2. Review of Anti-Inflammatory Herbal Medicines

    PubMed Central

    Ghasemian, Mona; Owlia, Sina; Owlia, Mohammad Bagher

    2016-01-01

    Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle. PMID:27247570

  3. Anti-HMG-CoA Reductase, Antioxidant, and Anti-Inflammatory Activities of Amaranthus viridis Leaf Extract as a Potential Treatment for Hypercholesterolemia

    PubMed Central

    Salvamani, Shamala; Gunasekaran, Baskaran; Shukor, Mohd Yunus; Shaharuddin, Noor Azmi; Sabullah, Mohd Khalizan

    2016-01-01

    Inflammation and oxidative stress are believed to contribute to the pathology of several chronic diseases including hypercholesterolemia (elevated levels of cholesterol in blood) and atherosclerosis. HMG-CoA reductase inhibitors of plant origin are needed as synthetic drugs, such as statins, which are known to cause adverse effects on the liver and muscles. Amaranthus viridis (A. viridis) has been used from ancient times for its supposedly medically beneficial properties. In the current study, different parts of A. viridis (leaf, stem, and seed) were evaluated for potential anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities. The putative HMG-CoA reductase inhibitory activity of A. viridis extracts at different concentrations was determined spectrophotometrically by NADPH oxidation, using HMG-CoA as substrate. A. viridis leaf extract revealed the highest HMG-CoA reductase inhibitory effect at about 71%, with noncompetitive inhibition in Lineweaver-Burk plot analysis. The leaf extract showed good inhibition of hydroperoxides, 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and ferric ion radicals in various concentrations. A. viridis leaf extract was proven to be an effective inhibitor of hyaluronidase, lipoxygenase, and xanthine oxidase enzymes. The experimental data suggest that A. viridis leaf extract is a source of potent antioxidant and anti-inflammatory agent and may modulate cholesterol metabolism by inhibition of HMG-CoA reductase. PMID:27051453

  4. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

    PubMed Central

    Perretti, Mauro; Chiang, Nan; La, Mylinh; Fierro, Iolanda M.; Marullo, Stefano; Getting, Stephen J; Solito, Egle; Serhan, Charles N.

    2009-01-01

    Aspirin (ASA) and dexamethasone (DEX) are widely used anti-inflammatory agents yet their mechanism(s) for blocking polymorphonuclear neutrophil (PMN) accumulation at sites of inflammation remains unclear. Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A4 receptor (ALXR/FPRL1) to halt PMN diapedesis. These structurally diverse ligands specifically interact directly with recombinant human ALXR demonstrated by specific radioligand binding and function as well as immunoprecipitation of PMN receptors. In addition, the combination of both ATL and ANXA1-derived peptides limited PMN infiltration and reduced production of inflammatory mediators (that is, prostaglandins and chemokines) in vivo. Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci. PMID:12368905

  5. Anti-HMG-CoA Reductase, Antioxidant, and Anti-Inflammatory Activities of Amaranthus viridis Leaf Extract as a Potential Treatment for Hypercholesterolemia.

    PubMed

    Salvamani, Shamala; Gunasekaran, Baskaran; Shukor, Mohd Yunus; Shaharuddin, Noor Azmi; Sabullah, Mohd Khalizan; Ahmad, Siti Aqlima

    2016-01-01

    Inflammation and oxidative stress are believed to contribute to the pathology of several chronic diseases including hypercholesterolemia (elevated levels of cholesterol in blood) and atherosclerosis. HMG-CoA reductase inhibitors of plant origin are needed as synthetic drugs, such as statins, which are known to cause adverse effects on the liver and muscles. Amaranthus viridis (A. viridis) has been used from ancient times for its supposedly medically beneficial properties. In the current study, different parts of A. viridis (leaf, stem, and seed) were evaluated for potential anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities. The putative HMG-CoA reductase inhibitory activity of A. viridis extracts at different concentrations was determined spectrophotometrically by NADPH oxidation, using HMG-CoA as substrate. A. viridis leaf extract revealed the highest HMG-CoA reductase inhibitory effect at about 71%, with noncompetitive inhibition in Lineweaver-Burk plot analysis. The leaf extract showed good inhibition of hydroperoxides, 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and ferric ion radicals in various concentrations. A. viridis leaf extract was proven to be an effective inhibitor of hyaluronidase, lipoxygenase, and xanthine oxidase enzymes. The experimental data suggest that A. viridis leaf extract is a source of potent antioxidant and anti-inflammatory agent and may modulate cholesterol metabolism by inhibition of HMG-CoA reductase.

  6. Animal Models as Tools to Investigate Antidiabetic and Anti-Inflammatory Plants

    PubMed Central

    Eddouks, Mohamed; Chattopadhyay, Debprasad; Zeggwagh, Naoufel Ali

    2012-01-01

    Plants have been historically used for diabetes treatment and related anti-inflammatory activity throughout the world; few of them have been validated by scientific criteria. Recently, a large diversity of animal models has been developed for better understanding the pathogenesis of diabetes mellitus and its underlying inflammatory mechanism and new drugs have been introduced in the market to treat this disease. The aim of this work is to review the available animal models of diabetes and anti-inflammatory activity along with some in vitro models which have been used as tools to investigate the mechanism of action of drugs with potential antidiabetic properties and related anti-inflammatory mechanism. At present, the rigorous procedures for evaluation of conventional antidiabetic medicines have rarely been applied to test raw plant materials used as traditional treatments for diabetes; and natural products, mainly derived from plants, have been tested in chemically induced diabetes model. This paper contributes to design new strategies for the development of novel antidiabetic drugs and its related inflammatory activity in order to treat this serious condition which represents a global public health problem. PMID:22899950

  7. Naturally derived anti-inflammatory compounds from Chinese medicinal plants.

    PubMed

    Wang, Qiuhong; Kuang, Haixue; Su, Yang; Sun, Yanping; Feng, Jian; Guo, Rui; Chan, Kelvin

    2013-03-07

    Though inflammatory response is beneficial to body damage repair, if it is out of control, it can produce adverse effects on the body. Although purely western anti-inflammatory drugs, orthodox medicines, can control inflammation occurrence and development, it is not enough. The clinical efficacy of anti-inflammation therapies is unsatisfactory, thus the search for new anti-inflammation continues. Chinese Material Medica (CMM) remains a promising source of new therapeutic agents. CMM and herbal formulae from Traditional Chinese Medicine (TCM), unorthodox medicines, play an improtant anti-inflammatory role in multi-targets, multi-levels, and multi-ways in treating inflammation diseases in a long history in China, based on their multi-active ingredient characteristics. Due to these reasons, recently, CMM has been commercialized as an anti-inflammation agent which has become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated vast amount of data associated with CMM in anti-inflammtion aspect. Therefore, a systematic introduction of CMM anti-inflammatory research progress is of great importance and necessity. This paper strives to describe the progress of CMM in the treatment of inflammatory diseases from different aspects, and provide the essential theoretical support and scientific evidence for the further development and utilization of CMM resources as a potential anti-inflammation drug through a variety of databases. Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries. This review mainly introduced the current research on the anti-inflammatory active ingredient, anti-inflammatory effects of CMM, their mechanism, anti-inflammatory drug development of CMM, and toxicological information. CMM is used clinically to treat

  8. Pharmacological treatment of spondyloarthritis: exploring the effectiveness of nonsteroidal anti-inflammatory drugs, traditional disease-modifying antirheumatic drugs and biological therapies

    PubMed Central

    Caso, Francesco; Costa, Luisa; Del Puente, Antonio; Di Minno, Matteo Nicola Dario; Lupoli, Gelsy; Scarpa, Raffaele; Peluso, Rosario

    2015-01-01

    Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. The therapy target of spondyloarthritis relies mainly in improving patients’ quality of life, controlling articular inflammation, preventing the structural joints damage and preserving the functional abilities, autonomy and social participation of patients. Among these, traditional disease-modifying antirheumatic drugs have been demonstrated to be effective in the management of peripheral arthritis; moreover, in the last decade, biological therapies have improved the approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α inhibitors are currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs has failed. The aim of this review is to summarize the current experience and evidence about the pharmacological approach in spondyloarthritis patients. PMID:26568809

  9. Analysis of effect of non-steroidal anti-inflammatory drugs on teeth and oral tissues during orthodontic treatment. Report based on literature review.

    PubMed

    Krasny, Marta; Zadurska, Małgorzata; Cessak, Grzegorz; Fiedor, Piotr

    2013-01-01

    In view of high availability and diversity of non-steroidal anti-inflammatory drugs (NSAIDs) on Polish market it is important for orthodontists to be aware of NSAID effect on the range of orthodontic tooth movement as well as the risk of root resorption in the moved teeth and other adverse effects, which might occur within oral cavity. The disadvantages of NSAID non-selective inhibition of COX include common oral inflammatory conditions, gingival bleeding, and disturbances of salivary secretion. Both, the selective and non-selective COX inhibitors, meloxicam excluded, used to alleviate the pain of orthodontic tooth movement, impede the movement of teeth. Paracetamol, explicitly indicated by most authors as the safest NSAID, seems to be the drug of choice in view of no influence on the range of tooth movement, the risk of root resorption or other adverse effects within oral cavity.

  10. [Risk of fatal/non-fatal events in patients with previous coronary heart disease/acute myocardial infarction and treatment with non-steroidal anti-inflammatory drugs].

    PubMed

    Muñoz Olmo, L; Juan Armas, J; Gomariz García, J J

    2017-09-04

    Primary Care is the fundamental axis of our health system and obliges us to be consistent with our prescriptions. The non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk and increased risk of all causes of death, as well as acute myocardial infarction (AMI) in patients with a previous myocardial infarction. Pain and cardiac patient management are 2 basic pillars in our daily activity, and we must know the limitations of NSAIDs in patients with established cardiovascular risk. We present a review of the scientific literature with primary interest in the role of NSAIDs and cardiovascular risk. The objective is to determine the relationship between the consumption of different NSAIDs and the fatal and non-fatal events among patients with known coronary disease. This is a review of the scientific literature with primary interest in the role of NSAIDs and cardiovascular risk. The literature review was conducted in PubMed search engines like Tripdatabase and with certain keywords. Of the 15 original papers found, 9 did not correspond completely to the central focus, so the approach was decided from 6 original articles from the past 5 years, which address the central focus of increased cardiovascular risk found (fatal and non-fatal events) in patients with prior cardiovascular disease or AMI being prescribed NSAIDs for any reason. The risk of fatal/non-fatal events in each of the studies is expressed by the odds ratio (OR)/hazard ratio (HR), defined as the probability of an event occurring. A moderate risk was observed for ibuprofen. It increases the risk of acute coronary syndrome after 5 years of cardiovascular event, especially in the 2nd year (OR 1.63; 95% CI 1.42-1.87). It also increases the risk of stroke (HR 1.23; 95% IC 1.10-1.38). Cyclo-oxygenase-2 inhibitors were the third risk group, after nabumetone and diclofenac. Celecoxib increases risk from the 14th day of treatment (HR 2.3; 95% CI 1.79-3.02), having an OR

  11. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng

    PubMed Central

    Ravikumar, V.R.; Dhanamani, M.; Sudhamani, T.

    2009-01-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium. PMID:22557324

  12. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng.

    PubMed

    Ravikumar, V R; Dhanamani, M; Sudhamani, T

    2009-04-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium.

  13. Anti-inflammatory activities of Ganoderma lucidum (Lingzhi) and San-Miao-San supplements in MRL/lpr mice for the treatment of systemic lupus erythematosus.

    PubMed

    Cai, Zhe; Wong, Chun Kwok; Dong, Jie; Jiao, Delong; Chu, Man; Leung, Ping Chung; Lau, Clara Bik San; Lau, Ching Po; Tam, Lai Shan; Lam, Christopher Wai Kei

    2016-01-01

    Ganoderma lucidum (Lingzhi; LZ) and San-Miao-San (SMS) are Chinese medicines (CMs) used to treat inflammatory ailments and numbing syndrome/arthralgia syndrome (Bi Zheng), respectively. Given that the main symptoms of systemic lupus erythematosus (SLE) include inflammation of the joints, joint pain, edema and palpitations of the heart because of problems associated with Bi Zheng, it was envisaged that LZ and SMS could be used as potential treatments for this autoimmune disease. This study aims to investigate the anti-inflammatory activity of a combination formulation containing LZ and SMS (LZ-SMS) in SLE mice. Female adult Balb/c mice of 20-24 weeks of age were used as normal mice (n = 10), whereas female MRL/lpr mice of 12-24 weeks of age were divided into three groups (n = 10 in each group), including mild, moderate and severe SLE mice groups. The clinical characteristics of the SLE and Babl/c mice (i.e., body weight, joint thickness, lupus flare, proteinuria, leukocyturia and lymphadenopathy) were assessed. The plasma concentrations of anti-nuclear antibody (ANA) and anti-double stranded DNA antibody (anti-ds-DNA) were analyzed by an enzyme-linked immunosorbent assay, whereas the concentration of several key cytokines (IFN-γ, TNF-α, IL-6, IL-10, IL-2, IL-27, IL-12P70, IL-17A and IL-21) were analyzed by a Luminex multiplex assay. The gene expression profiles for differentiation of the T helper (Th) lymphocytes in splenic CD4(+) Th cells were assessed by RT-qPCR. Flow cytometry was used to measure the percentages of CD4(+)CD25(+)Foxp3(+) Treg cells and CD19(+)CD5(+)CD1d(+)IL-10(+) regulatory B (Breg) cells (IL-10(+) Bregs). Concentrations of anti-ds-DNA in the plasma samples collected from the LZ-SMS-treated (500 mg/kg/day oral administration for 7 days followed with 50 mg/kg/day intraperitoneal administration for 7 days), moderate and severe SLE mice decreased significantly compared with the PBS treated mice (P < 0.05). The gene expression levels

  14. Molecular basis of the anti-inflammatory effects of terpenoids.

    PubMed

    de las Heras, B; Hortelano, Sonsoles

    2009-03-01

    Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Among them, terpenoids (also referred to as terpenes), are the largest and most widespread class of secondary metabolites. They are found in higher plants, mosses, liverworts, algae and lichens, and also in insects, microbes or marine organisms. Some terpenoids have been used for therapeutic purposes for centuries as antibacterial, anti-inflammatory, antitumoral agents, and in recent decades research activity into the clinical potential of this class of compounds has increased continuously as a source of pharmacologically interesting agents. In the present review, molecular basis of the anti-inflammatory action of diterpenoids is presented with special emphasis on their ability to modulate critical cell signaling pathways involved in the inflammatory response of the body such as nuclear transcription factor-kappaB (NF-kappaB) activation. NF-kappaB plays an important role in the regulation of immune and inflammatory responses. Indeed, deregulated NF-kappaB expression is a characteristic phenomenon in several inflammatory diseases and NF-kappaB has become a major target in drug discovery. Hence, this article also introduces our recently elucidated findings about the potential of labdane diterpenoids as anti-inflammatory agents due to their ability to inhibit NF-kappaB. The future development of this class of compounds as anti-inflammatory drugs requires the introduction of novel molecular targets of therapeutic relevance in addition to biotechnological approaches for the production of these molecules.

  15. Antioxidant and anti-inflammatory activity of Potentilla reptans L.

    PubMed

    Tomovic, Marina T; Cupara, Snezana M; Popovic-Milenkovic, Marija T; Ljujic, Biljana T; Kostic, Marina J; Jankovic, Slobodan M

    2015-01-01

    Potentilla species have been used in traditional medicine in the treatment of different ailment, disease or malady. Potentilla reptans (P. reptans) has been scarcely studied. The aim of this study was to test antioxidant and anti-inflammatory activity of P. reptans aerial part and rhizome. DPPH assay was used to measure antioxidant activity of aqueous plant extracts. Anti-inflammatory effect was evaluated by experimental animal model of phenol-in-acetone induced mice ear edema. DPPH radical-scavenging activity of both tested extracts was concentration dependent with IC50 values 12.11 μg/mL (aerial part) and 2.57 μg/mL (rhizome). Maximum anti-inflammatory effect (61.37%) was observed after administration of 10 mg/ear of the rhizome extract and it was 89.24% of effect induced by dexamethasone as a standard. In conclusion, P. reptans rhizome aqueous extract possesses anti-inflammatory effect and higher antioxidant activity than aerial part.

  16. Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives.

    PubMed

    Huang, Mei-Yan; Lin, Jing; Lu, Kuo; Xu, Hong-Gui; Geng, Zhi-Zhong; Sun, Ping-Hua; Chen, Wei-Min

    2016-04-13

    Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti-inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-α and IL-6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARγ mRNA and protein induced by LPS stimulation. Our results identified the promising anti-inflammatory effects of CSA and its derivatives, which may serve as valuable anti-inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-κB and MAPK pathways, relying partly on resisting the LPS-induced decrease of PPARγ through improving its expression.

  17. Treatment strategies for endometriosis.

    PubMed

    Rodgers, Allison K; Falcone, Tommaso

    2008-02-01

    Endometriosis is a common chronic disease that causes symptoms of pain and infertility. The pain syndrome can be quite incapacitating. The pain symptoms usually originate in the reproductive organs but can also involve the urinary or intestinal tracts if endometriosis implantation has occurred there. The presentation and physical appearance of endometriosis is extremely variable and can be characterized by a chronic intraperitoneal inflammatory process and adhesions. The only definitive diagnostic technique is laparoscopy. To review current literature on the treatment strategies for endometriosis. Review of Pubmed, Cochrane database and Medline for current review articles and studies regarding the current treatment strategies for endometriosis. Initial treatment is surgical or medical. Medical therapy is often used as a first-line therapy and can also be used in conjunction with those patients who undergo surgical therapy for pain. No medical therapy has proven effective for infertility. Medical therapy consists mostly of hormonal suppressive therapy in which the medication causes a downregulation of the hypothalamus-pituitary-ovarian pathway. Non-steroidal anti-inflammatory drugs and oral contraceptives are often used as an initial approach even without a definitive diagnosis. Progestins, such as oral norethindrone and depot medroxyprogesterone, are effective while using them but have a high recurrence rate. The norgestrol intrauterine device is also quite effective at relieving pain associated with endometriosis, especially pain arising during menses as well as from lesions in the rectovaginal tissue. Gonadotropin-releasing hormone agonists induce a pseudomenopausal state and have significant side effects, such as hot flashes and genital atrophy. 'Add-back' therapy with a progestin has been shown to relieve most of these drug related symptoms. Gonadotropin-releasing hormone agonists are also very effective at relieving symptoms of pain during treatment but are

  18. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.

    PubMed

    Marjoribanks, Jane; Proctor, Michelle; Farquhar, Cindy; Derks, Roos S

    2010-01-20

    Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. The purpose of this review is to compare nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea versus placebo, versus paracetamol and versus each other, to evaluate their effectiveness and safety. We searched the following databases to May 2009: Cochrane Menstrual Disorders and Subfertility Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Web of Science. The National Research Register and the Clinical Trials Register were also searched. Abstracts of major scientific meetings and the reference lists of relevant articles were checked. All randomised controlled comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea. Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). Inverse variance methods were used to combine data. Seventy-three randomised controlled trials were included. Among women with primary dysmenorrhoea, NSAIDs were significantly more effective for pain relief than placebo (OR 4.50, 95% CI: 3.85, 5.27). There was substantial heterogeneity for this finding (I(2) statistic =53%): exclusion of two outlying studies with no or negligible placebo effect reduced heterogeneity, resulting in an odds ratio of 4.14 (95% CI: 3.52, 4.86, I(2)=40%). NSAIDs were also significantly more effective for pain relief than paracetamol (OR 1.90, 95% CI:1.05 to 3.44). However

  19. Anti-inflammatory effects of Zea mays L. husk extracts.

    PubMed

    Roh, Kyung-Baeg; Kim, Hyoyoung; Shin, Seungwoo; Kim, Young-Soo; Lee, Jung-A; Kim, Mi Ok; Jung, Eunsun; Lee, Jongsung; Park, Deokhoon

    2016-08-19

    Zea mays L. (Z. mays) has been used for human consumption in the various forms of meal, cooking oil, thickener in sauces and puddings, sweetener in processed food and beverage products, bio-disel. However, especially, in case of husk extract of Z. mays, little is known about its anti-inflammatory effects. Therefore, in this study, the anti-inflammatory effects of Z. mays husk extract (ZMHE) and its mechanisms of action were investigated. The husks of Z. Mays were harvested in kangwondo, Korea. To assess the anti-inflammatory activities of ZMHE, we examined effects of ZMHE on nitric oxide (NO) production, and release of soluble intercellular adhesion molecule-1 (sICAM-1) and eotaxin-1. The expression level of inducible nitric oxide synthase (iNOS) gene was also determined by Western blot and luciferase reporter assays. To determine its mechanisms of action, a luciferase reporter assay for nuclear factor kappa B (NF-kB) and activator protein-1 (AP-1) was introduced. ZMHE inhibited lipopolysaccharide (LPS)-induced production of NO in RAW264.7 cells. In addition, expression of iNOS gene was reduced, as confirmed by Western blot and luciferase reporter assays. Effects of ZMHE on the AP-1 and NF-kB promoters were examined to elucidate the mechanism of its anti-inflammatory activity. Activation of AP-1 and NF-kB promoters induced by LPS was significantly reduced by ZMHE treatment. In addition, LPS-induced production of sICAM-1 and IL-4-induced production of eotaxin-1 were all reduced by ZMHE. Our results indicate that ZMHE has anti-inflammatory effects by downregulating the expression of iNOS gene and its downregulation is mediated by inhibiting NF-kB and AP-1 signaling.

  20. Chronic Rhinosinusitis: Therapeutic Efficacy of Anti-Inflammatory and Antibiotic Approaches

    PubMed Central

    Kariyawasam, Harsha H

    2011-01-01

    Despite the high prevalence of chronic rhinosinusitis (CRS) worldwide, the exact pathogenesis of the disease remains unknown. Even with therapeutic intervention, treatment response is often only partial and frequently ineffective. The inability to define exact disease phenotypes in relation to specific disease mechanisms has led to a broad based approach with both anti-inflammatory and anti-microbial intervention. The clinical efficacy of such current therapeutic strategies is highlighted and the urgent need for further robust therapeutic intervention studies in CRS is discussed in this article. PMID:21966602

  1. Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug

    PubMed Central

    Zimmermann, Grant R; Avery, William; Finelli, Alyce L; Farwell, Melissa; Fraser, Christopher C; Borisy, Alexis A

    2009-01-01

    Introduction Glucocorticoids are a mainstay of anti-inflammatory therapy, but significant adverse effects ultimately limit their utility. Previous efforts to design glucocorticoid structures with an increased therapeutic window have focused on dissociating anti-inflammatory transcriptional repression from adverse effects primarily driven by transcriptional activation. An alternative to this medicinal chemistry approach is a systems biology based strategy that seeks to amplify selectively the anti-inflammatory activity of very low dose glucocorticoid in immune cells without modulating alternative cellular networks that mediate glucocorticoid toxicity. Methods The combination of prednisolone and the antithrombotic drug dipyridamole was profiled using in vitro and in vivo models of anti-inflammatory activity and glucocorticoid-induced adverse effects to demonstrate a dissociated activity profile. Results The combination synergistically suppresses release of proinflammatory mediators, including tumour necrosis factor-α, IL-6, chemokine (C-C motif) ligand 5 (RANTES), matrix metalloproteinase-9, and others, from human peripheral blood mononuclear cells and mouse macrophages. In rat models of acute lipopolysaccharide-induced endotoxemia and delayed-type hypersensitivity, and in chronic models of collagen-induced and adjuvant-induced arthritis, the combination produced anti-inflammatory activity that required only a subtherapeutic dose of prednisolone. The immune-specific amplification of prednisolone anti-inflammatory activity by dipyridamole did not extend to glucocorticoid-mediated adverse effects, including corticosterone suppression or increased expression of tyrosine aminotransferase, in vivo after repeat dosing in rats. After 8 weeks of oral dosing in mice, treatment with the combination did not alter prednisolone-induced reduction in osteocalcin and mid-femur bone density, which are markers of steroid-induced osteoporosis. Additionally, amplification was not

  2. An efficient total synthesis of a potent anti-inflammatory agent, benzocamphorin F, and its anti-inflammatory activity.

    PubMed

    Liao, Yu-Ren; Kuo, Ping-Chung; Liang, Jun-Weil; Shen, Yuh-Chiang; Wu, Tian-Shung

    2012-01-01

    A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is valuable for further biological studies. The present study is the first total synthesis of benzocamphorin F and the developed strategy described is a more efficient procedure that allowe the large-scale production of benzocamphorin F for further research of the biological activity both in vitro and in vivo.

  3. An Efficient Total Synthesis of a Potent Anti-Inflammatory Agent, Benzocamphorin F, and Its Anti-Inflammatory Activity

    PubMed Central

    Liao, Yu-Ren; Kuo, Ping-Chung; Liang, Jun-Weil; Shen, Yuh-Chiang; Wu, Tian-Shung

    2012-01-01

    A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is valuable for further biological studies. The present study is the first total synthesis of benzocamphorin F and the developed strategy described is a more efficient procedure that allowe the large-scale production of benzocamphorin F for further research of the biological activity both in vitro and in vivo. PMID:22949872

  4. Chondroprotective and anti-inflammatory effects of sesamin.

    PubMed

    Phitak, Thanyaluck; Pothacharoen, Peraphan; Settakorn, Jongkolnee; Poompimol, Wilart; Caterson, Bruce; Kongtawelert, Prachya

    2012-08-01

    Osteoarthritis (OA) is a major disability of elderly people. Sesamin is the main compound in Sesamun indicum Linn., and it has an anti-inflammatory effect by specifically inhibiting Δ5-desaturase in polyunsaturated fatty acid biosynthesis. The chondroprotective effects of sesamin were thus studied in a porcine cartilage explant induced with interleukin-1beta (IL-1β) and in a papain-induced osteoarthritis rat model. With the porcine cartilage explant, IL-1β induced release of sulfated-glycosaminoglycan (s-GAG) and hydroxyproline release, and this induction was significantly inhibited by sesamin. This ability to inhibit these processes might be due to its ability to decrease expression of MMP-1, -3 and -13, which can degrade both PGs and type II collagen, both at the mRNA and protein levels. Interestingly, activation of MMP-3 might also be inhibited by sesamin. Moreover, in human articular chondrocytes (HACs), some pathways of IL-1β signal transduction were inhibited by sesamin: p38 and JNK. In the papain-induced OA rat model, sesamin treatment reversed the following pathological changes in OA cartilage: reduced disorganization of chondrocytes in cartilage, increased cartilage thickness, and decreased type II collagen and PGs loss. Sesamin alone might increase formation of type II collagen and PGs in the cartilage tissue of control rats. These results demonstrate that sesamin efficiently suppressed the pathological processes in an OA model. Thus, sesamin could be a potential therapeutic strategy for treatment of OA.

  5. Anti-inflammatory activity of Taraxacum officinale.

    PubMed

    Jeon, Hye-Jin; Kang, Hyun-Jung; Jung, Hyun-Joo; Kang, Young-Sook; Lim, Chang-Jin; Kim, Young-Myeong; Park, Eun-Hee

    2008-01-04

    Taraxacum officinale has been widely used as a folkloric medicine for the treatment of diverse diseases. The dried plant was extracted with 70% ethanol to generate its ethanol extract (TEE). For some experiments, ethyl acetate (EA), n-butanol (BuOH) and aqueous (Aq) fractions were prepared in succession from TEE. TEE showed a scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, a diminishing effect on intracellular reactive oxygen species (ROS) level, and an anti-angiogenic activity in the chicken chorioallantoic (CAM) assay. In the carrageenan-induced air pouch model, TEE inhibited production of exudate, and significantly diminished nitric oxide (NO) and leukocyte levels in the exudate. It also possessed an inhibitory effect on acetic acid-induced vascular permeability and caused a dose-dependent inhibition on acetic acid-induced abdominal writhing in mice. Suppressive effects of TEE on the production of NO and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Among the fractions, the n-butanol fraction (BuOH) was identified to be most effective in the CAM assay. Collectively, Taraxacum officinale contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities through its inhibition of NO production and COX-2 expression and/or its antioxidative activity.

  6. Anti-inflammatory activity of Elsholtzia splendens.

    PubMed

    Kim, Dong Wook; Son, Kun Ho; Chang, Hyeun Wook; Bae, KiHwan; Kang, Sam Sik; Kim, Hyun Pyo

    2003-03-01

    Elsholtzia splendens Nakai has been used in North-East Asia as an ingredient of folk medicines for treating cough, headache and inflammation. The present investigation was carried out to establish its in vivo anti-inflammatory activity using several animal models of inflammation and pain. The 75% ethanol extract of the aerial part of E. splendens significantly inhibited mouse croton oil-induced, as well as arachidonic acid-induced, ear edema by oral administration (44.6% inhibition of croton oil-induced edema at 400 mg/kg). This plant material also showed significant inhibitory activity against the mouse ear edema induced by multiple treatment of phorbol ester for 3 days, which is an animal model of subchronic inflammation. In addition, E. splendens exhibited significant analgesic activity against mouse acetic acid-induced writhing (50% inhibition at 400 mg/kg), while indomethacin (5 mg/kg) demonstrated 95% inhibition. E. splendens (5-100 microg/mL) significantly inhibited PGE2 production by pre-induced cyclooxygenase-2 of lipopolysaccharide-treated RAW 264.7 cells, suggesting that cyclooxygenase-2 inhibition might be one of the cellular mechanisms of anti-inflammation.

  7. Anti-inflammatory activity of Sedum kamtschaticum.

    PubMed

    Kim, Dong Wook; Son, Kun Ho; Chang, Hyeun Wook; Bae, KiHwan; Kang, Sam Sik; Kim, Hyun Pyo

    2004-02-01

    Sedum kamtschaticum Fischer (Crassulaceae) has been used as a folk medicine in North-East Asia for treating inflammatory disorders. The present investigation was carried out to establish in vivo anti-inflammatory activity and cyclooxygenase-2 modulating activity of this plant material. The methanol extract of Sedum kamtschaticum significantly inhibited mouse croton oil-induced ear edema (24-47% inhibition at 50-400 mg/kg) and rat paw edema (24-30% inhibition at 400-800 mg/kg) by oral administration. Prednisolone (10 mg/kg) showed 54 and 36% inhibition in the same animal models, respectively. Sedum kamtschaticum also showed significant inhibitory activity against mouse ear edema induced by multiple treatment of phorbol ester for 3 days. In addition, Sedum kamtschaticum exhibited potent analgesic activity against mouse acetic acid-induced writhing (IC50=125 mg/kg), while aspirin (200 mg/kg) showed 57% inhibition. Using lipopolysaccharide-treated RAW 264.7 cells, down-regulation of cyclooxygenase-2 expression was found to be one of the cellular action mechanisms of anti-inflammation by Sedum kamtschaticum.

  8. Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: A review.

    PubMed

    Zhu, Fengmei; Du, Bin; Xu, Baojun

    2017-06-12

    Inflammation is the first biological response of the immune system to infection, injury or irritation. Evidence suggests that the anti-inflammatory effect is mediated through the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ as well as noncytokine mediator, prostaglandin E2. Fruits, vegetables, and food legumes contain high levels of phytochemicals that show anti-inflammatory effect, but their mechanisms of actions have not been completely identified. The aim of this paper was to summarize the recent investigations and findings regarding in vitro and animal model studies on the anti-inflammatory effects of fruits, vegetables, and food legumes. Specific cytokines released for specific type of physiological event might shed some light on the specific use of each source of phytochemicals that can benefit to counter the inflammatory response. As natural modulators of proinflammatory gene expressions, phytochemical from fruits, vegetables, and food legumes could be incorporated into novel bioactive anti-inflammatory formulations of various nutraceuticals and pharmaceuticals. Finally, these phytochemicals are discussed as the natural promotion strategy for the improvement of human health status. The phenolics and triterpenoids in fruits and vegetables showed higher anti-inflammatory activity than other compounds. In food legumes, lectins and peptides had anti-inflammatory activity in most cases. However, there are lack of human study data on the anti-inflammatory activity of phytochemicals from fruits, vegetables, and food legumes.

  9. Anti-Inflammatory Activity of Natural Products.

    PubMed

    Azab, Abdullatif; Nassar, Ahmad; Azab, Abed N

    2016-10-01

    This article presents highlights of the published literature regarding the anti-inflammatory activities of natural products. Many review articles were published in this regard, however, most of them have presented this important issue from a regional, limited perspective. This paper summarizes the vast range of review and research articles that have reported on the anti-inflammatory effects of extracts and/or pure compounds derived from natural products. Moreover, this review pinpoints some interesting traditionally used medicinal plants that were not investigated yet.

  10. ANTI-INFLAMMATORY ACTIVITY OF DODONAEA VISCOSE

    PubMed Central

    Mahadevan, N.; Venkatesh, Sama; Suresh, B.

    1998-01-01

    Dodonaea viscose, Linn is a widely grown plant of Nilgiris district of Tamil and is commonly used by the tribals of Nilgiris as a traditional medicine for done fracture and joint sprains. Since it is generally believed tat fractures are accompanied by either some degree of injury or inflammations, it was felt desirable to carry our anti inflammatory activity of Dodonaea viscose. Anti-inflammatory activity of the plant was carried out by carrageenin induced paw edema method in Wister albino rats. PMID:22556883

  11. Nanocarriers for Vascular Delivery of Anti-Inflammatory Agents

    PubMed Central

    Howard, Melissa D.; Hood, Elizabeth D.; Zern, Blaine; Shuvaev, Vladimir V.; Grosser, Tilo; Muzykantov, Vladimir R.

    2017-01-01

    There is a need for improved treatment of acute vascular inflammation in conditions such as ischemia-reperfusion injury, acute lung injury, sepsis, and stroke. The vascular endothelium represents an important therapeutic target in these conditions. Furthermore, some anti-inflammatory agents (AIAs) (e.g., biotherapeutics) require precise delivery into subcellular compartments. In theory, optimized delivery to the desired site of action may improve the effects and enable new mechanisms of action of these AIAs. Diverse nanocarriers (NCs) and strategies for targeting them to endothelial cells have been designed and explored for this purpose. Studies in animal models suggest that delivery of AIAs using NCs may provide potent and specific molecular interventions in inflammatory pathways. However, the industrial development and clinical translation of complex NC-AIA formulations are challenging. Rigorous analysis of therapeutic/side effect and benefit/cost ratios is necessary to identify and optimize the approaches that may find clinical utility in the management of acute inflammation. PMID:24392694

  12. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  13. Anti-inflammatory prostaglandins for the prevention of preterm labour.

    PubMed

    Sykes, Lynne; MacIntyre, David A; Teoh, Tiong Ghee; Bennett, Phillip R

    2014-08-01

    Preterm birth occurs in 10-12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFκB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 (COX2), prostaglandins (PGs) and the oxytocin receptor (OXTR) as well as key inflammatory genes. Targeting the inhibition of NFκB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-Δ(12,14)PGJ2 (15d-PGJ2) exhibits anti-inflammatory properties via the inhibition of NFκB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro. 15d-PGJ2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.

  14. Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology

    PubMed Central

    Pradhan, Swetalina; Madke, Bhushan; Kabra, Poonam; Singh, Adarsh Lata

    2016-01-01

    Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. This study will review anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology. PMID:27688434

  15. ANTI-INFLAMMATORY ACTIVITY OF MIRABILIS JALAPA LINN. LEAVES

    PubMed Central

    Nath, Lekshmi. R.; Manjunath, K. P.; Savadi, R. V.; Akki, K. S.

    2010-01-01

    Mirabilis Jalapa Linn. is a widely used traditional medicine in many parts of the world for the treatment of various diseases viz. virus inhibitory activity, anti tumour activity. It is claimed in traditional medicine that the leaves of the plant are used in the treatment of inflammation. In the present study, the total alcoholic extract and successive petroleum ether fractions of leaves of Mirabilis Jalapa Linn were screened for its anti-inflammatory activity using carageenan induced rat paw edema and cotton pellet induced granuloma models. The total alcoholic extract at the dose of 300 mg/kg p.o and successive petroleum ether fraction at the dose of 200 mg/kg exhibited significant anti-inflammatory activity in carrageenan induced paw edema model (p<0.01). In cotton pellet granuloma model, the total alcoholic extract at the dose of 300 mg/kg and successive petroleum ether fraction at the dose of 200 mg/kg inhibited granuloma formation significantly (p<0.05) indicating that both test samples inhibit the increase in number of fibroblasts and synthesis of collagen and mucopolysaccharides during granuloma tissue formation during the chronic inflammation. These experimental results have established a pharmacological evidence for the folklore claim of the drug to be used as an anti inflammatory agent. PMID:24825972

  16. Anti-inflammatory and anti-itch activity of sertaconazole nitrate.

    PubMed

    Liebel, Frank; Lyte, Peter; Garay, Michelle; Babad, Jeffrey; Southall, Michael D

    2006-09-01

    Cutaneous fungal infections are frequently associated with an inflammatory component including irritated skin, itching and stinging/burning. Therapeutic anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The anti-inflammatory activities of eight anti-fungal agents (butoconazole, ciclopirox olamine, fluconazole, miconazole nitrate, sertaconazole nitrate, terconazole, tioconazole and ketoconazole) were compared in a number of preclinical models of dermal inflammation and pruritus. While butoconazole, ciclopirox olamine, fluconazole, and miconazole nitrate were all found to have anti-inflammatory activity, only sertaconazole nitrate reduced the release of cytokines from activated lymphocytes and mitigated inflammation in animal models of irritant contact dermatitis and neurogenic inflammation. In addition, sertaconazole nitrate inhibited contact hypersensitivity and scratching responses in a murine model of pruritus. Furthermore, the in vitro and in vivo anti-inflammatory activity of sertaconazole nitrate was found to be greater than other topical anti-fungal agents examined. These studies demonstrate that topical administration of clinically relevant concentrations of sertaconazole nitrate resulted in an efficacious anti-inflammatory activity against a broad spectrum of dermal inflammation models and itch. The anti-inflammatory properties of sertaconazole may contribute to the efficacy of the drug in the treatment of cutaneous fungal conditions and provide greater anti-inflammatory activity compared with other anti-fungal agents.

  17. Anti-inflammatory activity and composition of Senecio salignus Kunth.

    PubMed

    González, Cuauhtemoc Pérez; Vega, Roberto Serrano; González-Chávez, Marco; Sánchez, Miguel Angel Zavala; Gutiérrez, Salud Pérez

    2013-01-01

    We investigated the anti-inflammatory activity of Senecio salignus. This medicinal plant is often used in Mexico for the treatment of fever and rheumatism. Chloroform and methanol extracts of the plant were tested on 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced edema in mice ears. The methanol extract of the plant inhibited edema by 36 ± 4.4% compared with the control, while the chloroform extract exhibited an even greater level of inhibition (64.1%). The chloroform extract was then fractionated, and the composition of the active fraction was determined by GC-MS. The anti-inflammatory activity of this fraction was then tested on TPA-induced ear edema in mice, and we found that the active fraction could inhibit edema by 46.9%. The anti-inflammatory effect of the fraction was also tested on carrageenan-induced paw edema in rats at doses of 100 mg/kg; a 58.9 ± 2.8% reduction of the edema was observed 4 h after administration of carrageenan, and the effect was maintained for 5 h.

  18. Anti-inflammatory properties of pterocarpanquinone LQB-118 in mice.

    PubMed

    Riça, Ingred G; Netto, Chaquip D; Rennó, Magdalena N; Abreu, Paula A; Costa, Paulo R R; da Silva, Alcides J M; Cavalcante, Moisés C M

    2016-09-15

    Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic properties and also shows great inhibitory effect on TNF-α release in vitro. Here, its anti-inflammatory activity was evaluated in a lipopolysaccharide (LPS)-induced lung inflammation model in C57BL/6 mice. LPS inhalation induced a marked neutrophil infiltration to the lungs which was reduced by intraperitoneal treatment with (+/-)-LQB-118 in a similar manner to that of dexamethasone and even better than that of acetylsalicylic acid. Moreover, (+/-)-LQB-118 administration resulted in decrease of NF-κB activation and KC level in lungs, with a pronounced inhibitory effect on TNF-α release, measured in bronchoalveolar lavage fluid. Trying to understand the anti-inflammatory mechanism by which (+/-)-LQB-118 acts, we performed a molecular modeling analysis, including docking to estrogen receptors α and β. Results suggested that (+/-)-LQB-118 may bind to both receptors, with a similar orientation to 17-β-estradiol. Together, these results showed that (+/-)-LQB-118 exhibits an anti-inflammatory effect, most likely by inhibiting TNF-α release and NF-κB activation, which may be related to the estrogen receptor binding.

  19. Anti-Inflammatory Activity and Composition of Senecio salignus Kunth

    PubMed Central

    Pérez González, Cuauhtemoc; Serrano Vega, Roberto; González-Chávez, Marco; Zavala Sánchez, Miguel Angel; Pérez Gutiérrez, Salud

    2013-01-01

    We investigated the anti-inflammatory activity of Senecio salignus. This medicinal plant is often used in Mexico for the treatment of fever and rheumatism. Chloroform and methanol extracts of the plant were tested on 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced edema in mice ears. The methanol extract of the plant inhibited edema by 36 ± 4.4% compared with the control, while the chloroform extract exhibited an even greater level of inhibition (64.1%). The chloroform extract was then fractionated, and the composition of the active fraction was determined by GC-MS. The anti-inflammatory activity of this fraction was then tested on TPA-induced ear edema in mice, and we found that the active fraction could inhibit edema by 46.9%. The anti-inflammatory effect of the fraction was also tested on carrageenan-induced paw edema in rats at doses of 100 mg/kg; a 58.9 ± 2.8% reduction of the edema was observed 4 h after administration of carrageenan, and the effect was maintained for 5 h. PMID:23691512

  20. Cannabinoids as novel anti-inflammatory drugs.

    PubMed

    Nagarkatti, Prakash; Pandey, Rupal; Rieder, Sadiye Amcaoglu; Hegde, Venkatesh L; Nagarkatti, Mitzi

    2009-10-01

    Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.

  1. Anti-inflammatory Action of Green Tea.

    PubMed

    Ohishi, Tomokazu; Goto, Shingo; Monira, Pervin; Isemura, Mamoru; Nakamura, Yoriyuki

    2016-01-01

    Green tea has been shown to have beneficial effects against a variety of diseases such as cancer, obesity, diabetes, cardiovascular disease, and neurodegenerative diseases. Through cellular, animal, and human experiments, green tea and its major component, epigallocatechin-3-gallate (EGCG) have been demonstrated to have anti-inflammatory effects. Our previous findings have indicated that green tea and EGCG suppress the gene and/or protein expression of inflammatory cytokines and inflammation-related enzymes. Using bibliographic databases, particularly PubMed (provided by the http://www.ncbi.nlm.nih.gov/pubmed, US National Library of Medicine, National Institutes of Health, United States), we examined the potential usefulness of green tea/EGCG for the prevention and treatment of inflammatory diseases in human clinical and epidemiological studies. We also reviewed results from cellular and animal experiments and proposed action mechanisms. Most of the results from the human studies indicated the beneficial effects of green tea and tea catechins against inflammatory diseases. The cellular and animal studies also provided evidence for the favorable effects of green tea/EGCG. These results are compatible with our previous findings and can be largely explained by a mechanism wherein green tea/EGCG acts as an antioxidant to scavenge reactive oxygen species, leading to attenuation of nuclear factor-κB activity. Since green tea and EGCG have multiple targets and act in a pleiotropic manner, we may consider their usage to improve the quality of life in patients with inflammatory disease. Green tea and EGCG have beneficial health effects and no severe adverse effects; however, care should be taken to avoid overdosage, which may induce deleterious effects including hepatic injury. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Anti-inflammatory glucocorticoids: changing concepts.

    PubMed

    Newton, Robert

    2014-02-05

    Despite being the most effective anti-inflammatory treatment for chronic inflammatory diseases, the mechanisms by which glucocorticoids (corticosteroids) effect repression of inflammatory gene expression remain incompletely understood. Direct interaction of the glucocorticoid receptor (NR3C1) with inflammatory transcription factors to repress transcriptional activity, i.e. transrepression, represents one mechanism of action. However, transcriptional activation, or transactivation, by NR3C1 also represents an important mechanism of glucocorticoid action. Glucocorticoids rapidly and profoundly increase expression of multiple genes, many with properties consistent with the repression of inflammatory gene expression. For example: the dual specificity phosphatase, DUSP1, reduces activation of mitogen-activated protein kinases; glucocorticoid-induced leucine zipper (TSC22D3) represses nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) transcriptional responses; inhibitor of κBα (NFKBIA) inhibits NF-κB; tristraprolin (ZFP36) destabilises and translationally represses inflammatory mRNAs; CDKN1C, a cell cycle regulator, may attenuate JUN N-terminal kinase signalling; and regulator of G-protein signalling 2 (RGS2), by reducing signalling from Gαq-linked G protein-coupled receptors (GPCRs), is bronchoprotective. While glucocorticoid-dependent transrepression can co-exist with transactivation, transactivation may account for the greatest level and most potent repression of inflammatory genes. Equally, NR3C1 transactivation is enhanced by β2-adrenoceptor agonists and may explain the enhanced clinical efficacy of β2-adrenoceptor/glucocorticoid combination therapies in asthma and chronic obstructive pulmonary disease. Finally, NR3C1 transactivation is reduced by inflammatory stimuli, including respiratory syncytial virus and human rhinovirus. This provides an explanation for glucocorticoid resistance. Continuing efforts to understand roles for glucocorticoid

  3. Topical Ivermectin 10 mg/g and Oral Doxycycline 40 mg Modified-Release: Current Evidence on the Complementary Use of Anti-Inflammatory Rosacea Treatments.

    PubMed

    Steinhoff, Martin; Vocanson, Marc; Voegel, Johannes J; Hacini-Rachinel, Feriel; Schäfer, Gregor

    2016-09-01

    Rosacea is a common, chronic inflammatory skin disease that can present with a variety of signs and symptoms. The potentially simultaneous occurrence of different signs and symptoms is due to different underlying inflammatory pathways, emphasizing the need for complementary treatment approaches. Topical ivermectin cream (10 mg/g) and systemic, oral anti-inflammatory doxycycline (40 mg modified-release) are both approved for the treatment of papulopustular rosacea (PPR). Whether or not a combined therapeutic approach may be more beneficial than monotherapy for patients with PPR remains to be tested. Here, we summarize underlying inflammatory pathways implicated in rosacea and clarify the impact of these two agents on selective pathways during inflammation, due to specific characteristics of their individual mechanisms of action (MoA). Based on the complementary MoA of doxycycline modified-release and ivermectin, a scientific rationale for a combined therapy targeting inflammatory lesions in rosacea is given. We propose that topical ivermectin cream is a promising new candidate as first-line treatment to target the inflammatory lesions of rosacea, which can be used in combination with systemic doxycycline modified-release to provide an optimal treatment approach considering all inflammatory pathways involved in PPR. Funding Galderma.

  4. From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer's disease: the role of NSAIDs and cyclooxygenase in beta-amyloidosis and clinical dementia.

    PubMed

    Pasinetti, Giulio Maria

    2002-10-01

    Epidemiological evidence suggests that non-steroidal anti-inflammatory drugs (NSAID) may protect against Alzheimer's disease (AD). However, therapeutic studies with NSAIDs, including cyclooxygenase (COX) inhibitors and steroids have not supported such epidemiological evidence. The apparent inconsistency may be due to the fact that the epidemiological evidence is based on studies examining AD before clinical manifestations are apparent, while therapeutic studies have been carried out on people with illnesses severe enough to exceed the clinical detection threshold. Thus, it is conceivable that therapeutic strategies administered during early AD dementia or moderate dementia may not be optimally effective. Alternatively, the influence of inflammatory activity in the brain for cases at high risk to develop AD, e.g., mild cognitive impairment (MCI) cases, as a potential target of anti-inflammatory drugs in clinical studies maybe more suitable to be studied. The primary action of NSAIDs is inhibition of the COX enzymes. COX enzymes exist in an inducible form COX-2, that has been found to be elevated in the AD brain, and a constitutive form COX-1. Both COX-1 and COX-2 are known to be involved in numerous inflammatory activities as well as normal neuronal functions. In vitro, it has been demonstrated that non-selective inhibitors of COX can preferentially decrease the levels of the highly amyloidogenic amyloid-beta (Abeta)(1-42)peptide. Recent studies testing non-selective NSAIDs in murine models of AD neuropathology indicated that the frequency of Abeta plaque deposits in the brains of these animals can be significantly reduced by treatment with the non-selective COX inhibitor ibuprofen. These studies and epidemiological data strongly support a therapeutic potential for NSAIDs in the treatment of AD. Upon this premise, industry and academia are devoting a tremendous amount of resources to the testing of anti-inflammatory drugs for the treatment of AD. However, given the

  5. Anti-Inflammatory Activity of the Essential Oil Citral in Experimental Infection with Staphylococcus aureus in a Model Air Pouch.

    PubMed

    Martins, Hellen Braga; Selis, Nathan das Neves; Souza, Clarissa Leal Silva E; Nascimento, Flávia S; de Carvalho, Suzi Pacheco; Gusmão, Lorena D'Oliveira; Nascimento, Jannine Dos Santos; Brito, Anne Karoline Pereira; de Souza, Samira Itana; de Oliveira, Marcio Vasconcelos; Timenetsky, Jorge; Yatsuda, Regiane; Uetanabaro, Ana Paula T; Marques, Lucas M

    2017-01-01

    This study proposes to implement an alternative and effective strategy for local treatment of disease provoked by S. aureus. For the analysis of possible anti-inflammatory activity of essential oil, after establishing an air pouch model, 48 male mice of Balb/c were treated, infected, and euthanized at 4 and 8 h. Thus, the total and differential white blood cells were counted in the animal's blood, and cytokines IL-1β, IL-6, and TNF-α were titrated using ELISA in the air pouch lavage. Moreover, TNF-α, IL-1β, and IL-6 gene expression was analyzed through an RT-qPCR array, and S. aureus was quantified using qPCR. Our results, p < 0.05, showed that EOC reduced the quantity of microorganisms. The group of mice treated with essential oil citral showed a significant decrease in TNF-α levels in tests demonstrating anti-inflammatory activity. There is no data about the mutual influence of the air pouch model, essential oil citral, and S. aureus. Thus, considering the interaction of these variables and the anti-inflammatory activity of the essential oil citral, we demonstrated, by alternative local treatment, a new antimicrobial agent that is not an antibiotic.

  6. Anti-Inflammatory Activity of the Essential Oil Citral in Experimental Infection with Staphylococcus aureus in a Model Air Pouch

    PubMed Central

    Martins, Hellen Braga; Selis, Nathan das Neves; Souza, Clarissa Leal Silva e; Nascimento, Flávia S.; de Carvalho, Suzi Pacheco; Gusmão, Lorena D'Oliveira; Nascimento, Jannine dos Santos; Brito, Anne Karoline Pereira; de Souza, Samira Itana; de Oliveira, Marcio Vasconcelos; Timenetsky, Jorge; Yatsuda, Regiane

    2017-01-01

    This study proposes to implement an alternative and effective strategy for local treatment of disease provoked by S. aureus. For the analysis of possible anti-inflammatory activity of essential oil, after establishing an air pouch model, 48 male mice of Balb/c were treated, infected, and euthanized at 4 and 8 h. Thus, the total and differential white blood cells were counted in the animal's blood, and cytokines IL-1β, IL-6, and TNF-α were titrated using ELISA in the air pouch lavage. Moreover, TNF-α, IL-1β, and IL-6 gene expression was analyzed through an RT-qPCR array, and S. aureus was quantified using qPCR. Our results, p < 0.05, showed that EOC reduced the quantity of microorganisms. The group of mice treated with essential oil citral showed a significant decrease in TNF-α levels in tests demonstrating anti-inflammatory activity. There is no data about the mutual influence of the air pouch model, essential oil citral, and S. aureus. Thus, considering the interaction of these variables and the anti-inflammatory activity of the essential oil citral, we demonstrated, by alternative local treatment, a new antimicrobial agent that is not an antibiotic. PMID:28316634

  7. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation.

    PubMed

    Macedo, E M A; Santos, W C; Sousa, B P; Lopes, E M; Piauilino, C A; Cunha, F V M; Sousa, D P; Oliveira, F A; Almeida, F R C

    2016-06-20

    Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.

  8. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

    PubMed Central

    Macedo, E.M.A.; Santos, W.C.; Sousa, B.P.; Lopes, E.M.; Piauilino, C.A.; Cunha, F.V.M.; Sousa, D.P.; Oliveira, F.A.; Almeida, F.R.C.

    2016-01-01

    Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association

  9. Translational failure of anti-inflammatory compounds for myocardial infarction: a meta-analysis of large animal models.

    PubMed

    van Hout, Gerardus P J; Jansen of Lorkeers, Sanne J; Wever, Kimberly E; Sena, Emily S; Kouwenberg, Lisanne H J A; van Solinge, Wouter W; Macleod, Malcolm R; Doevendans, Pieter A; Pasterkamp, Gerard; Chamuleau, Steven A J; Hoefer, Imo E

    2016-02-01

    Numerous anti-inflammatory drugs have been tested in large animal studies of myocardial infarction (MI). Despite positive results, translation of anti-inflammatory strategies into clinical practice has proved to be difficult. Critical disparities between preclinical and clinical study design that influence efficacy may partly be responsible for this translational failure. The aim of the present systematic review was to better understand which factors underlie the failure of transition towards the clinic. Meta-analysis and regression of large animal studies were performed to identify sources that influenced effect size of anti-inflammatory compounds in large animal models of MI. We included 183 studies, containing 3331 large animals. Infarct size (IS) as a ratio of the area at risk (12.7%; 95% confidence interval, CI 11.1-14.4%, P < 0.001) and IS as a ratio of the left ventricle (3.9%; 95% CI 3.1-4.7%, P < 0.001) were reduced in treatment compared with control groups. Effect size was higher when outcome was assessed early after MI (P = 0.013) and where studies included only male animals (P < 0.001). Mortality in treated animals was higher in studies that blinded the investigator during the experiment (P = 0.041) and depended on the type of drug used (P < 0.001). As expected, treatment with anti-inflammatory drugs leads to smaller infarct size in large animal MI models. Timing of outcome assessment, sex, and study quality are significantly associated with outcome and may explain part of the translational failure in clinical settings. Effect size depends on the type of drug used, enabling identification of compounds for future clinical testing. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  10. A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression?

    PubMed

    Walker, Frederick Rohan

    2013-04-01

    The selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed pharmacological treatment for depression. Since their introduction many have considered the primary mechanism by which the SSRIs produced therapeutic improvement in depression is their effect on monoaminergic signalling. In recent years, however, the credibility of the monoamine theory and the therapeutic efficacy of these compounds in the treatment of depression has been extensively criticized. In the current review the legitimacy of these criticisms is critically examined, in many instances the evidence base used to support these criticisms is found to be weak. Nevertheless, the apparent 'failure' of the monoamine theory has been of benefit in motivating research into alternative mechanisms through which the SSRIs may act. Given research demonstrating that depressive symptoms are intimately linked with disturbances in pro-inflammatory signalling, perhaps the most promising discovery has been the realisation that SSRIs posses significant anti-inflammatory properties. These recent findings are discussed and contextualised with respect to the neurogenic, neurotrophic and gluatamatergic effects that these drugs also possess.

  11. Anti-inflammatory actions of acupuncture.

    PubMed Central

    Zijlstra, Freek J; van den Berg-de Lange, Ineke; Huygen, Frank J P M; Klein, Jan

    2003-01-01

    Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of beta-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-alpha and interleukin-10 are discussed. PMID:12775355

  12. Modulation of glioma risk and progression by dietary nutrients and anti-inflammatory agents

    PubMed Central

    Kyritsis, Athanassios P.; Bondy, Melissa L.; Levin, Victor A.

    2011-01-01

    Gliomas are tumors of glial origin formed in the central nervous system and exhibit profound morphological and genetic heterogeneity. The etiology of this heterogeneity involves an interaction between genetic alterations and environmental risk factors. Scientific evidence suggests that certain natural dietary components, such as phytoestrogens, flavonoids, polyunsaturated fatty acids and vitamins may exert a protective effect against gliomas by changing the nature of the interaction between genetics and environment. Similarly, certain anti-inflammatory drugs and dietary modifications, such as methionine restriction and the adoption of low-calorie or ketogenic diets, may take advantage of glioma and normal glial cells’ differential requirements for glucose, methionine, and ketone bodies and may therefore be effective as part of preventive or treatment strategies for gliomas. Treatment trials of glioma patients and chemoprevention trials of individuals with a known genetic predisposition to glioma using the most promising of these agents, such as the anti-inflammatory drugs curcumin and gamma-linolenic acid, are needed to validate or refute these agents’ putative role in gliomas. PMID:21302177

  13. Anti-inflammatory and immunosuppressive drugs and reproduction

    PubMed Central

    Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

    2006-01-01

    Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. PMID:16712713

  14. Anti-inflammatory bioactivities in plant extracts.

    PubMed

    Talhouk, R S; Karam, C; Fostok, S; El-Jouni, W; Barbour, E K

    2007-03-01

    The medical ethnobotanical knowledge propagated over generations in the coastal regions of the Eastern Mediterranean, including Lebanon, is one that has built on several ancient cultures and civilizations of these regions. Recent interest in medical ethnobotany and the use of medicinal herbs in treating or preventing ailments has rejuvenated interest in folk medicine practices, especially those transcendent across generations. According to Eastern Mediterranean folk medicine practices, herbal remedies that treat many inflammation-related ailments were typically based on plant bioactive water extracts or decoctions. Studies have shown that active anti-inflammatory ingredients in water extracts include many natural chemicals such as phenols, alkaloids, glycosides, and carbohydrates. The intent of this manuscript is twofold: first, to review the literature that describes anti-inflammatory bioactivities in plant extracts of different plant genera; and second, to evaluate indigenous folk remedies used by folk doctors to treat inflammatory ailments in this region of the world. For this aim, the reported literature of five plant genera assumed to possess anti-inflammatory bioactivities and typically prescribed by folk doctors to treat inflammation-related ailments is reviewed.

  15. Anti-Inflammatory Effect of Selected Dihydroxyflavones

    PubMed Central

    Sangeetha, K.S.Sridevi

    2015-01-01

    Background The mechanism of inflammation is attributed, to release of reactive oxygen species from activated neutrophils and macrophages. Over production of reactive oxygen species may result in tissue injury by damaging macromolecules. Flavones are the polyphenolic compounds with antioxidant property. This antioxidant property of flavones may have beneficial effect against inflammation. Aim To study the anti-inflammatory effect of selected dihydroxyflavones (DHF) in albino rats. The prime objective of the present study is to identify safe and effective agents to treat inflammation from among the selected DHF group of compounds. Materials and Methods The present study was designed to investigate the anti-inflammatory action of four selected dihydroxyflavone derivatives; 2’,3’- dihydroxyflavone and 2’, 4’ -dihydroxyflavones, 5, 3’- dihydroxyflavone and 7, 3’ dihydroxyflavone. The anti-inflammatory activity of selected DHF was studied in rats by carrageenan induced hind paw oedema method. Results All the selected dihydroxyflavone derivatives showed dose and time dependent inhibition of carrageenan induced paw oedema. PMID:26155493

  16. Anti-inflammatory and analgesic activities of Chaenomeles speciosa fractions in laboratory animals.

    PubMed

    Li, X; Yang, Y-B; Yang, Q; Sun, L-N; Chen, W-S

    2009-10-01

    The prescription of current existing anti-inflammatory drugs is hampered by their adverse effects over time. Botanical extracts are thought to be a potential source of a natural anti-inflammatory property with fewer adverse effects. Chaenomeles speciosa has long been used as an herbal medicine for treatment of various diseases such as rheumatoid arthritis, prosopalgia, and hepatitis. Until now there have been no reports on the specific anti-inflammatory fractions of extract of C. speciosa (ECS). In the present study the anti-inflammatory activities of different fractions of ECS were evaluated using carrageenan-induced paw edema in rats. The 10% ethanol fraction (C3) was found to have stronger anti-inflammatory effects compared with other fractions at the same dose. We also found that chlorogenic acid was one of the active constituents responsible for the anti-inflammatory effect using bioassay-guided fractionation by means of high-performance liquid chromatography. Compared with controls, fraction C3 demonstrated significant anti-inflammatory activity in the xylene-induced ear edema test (P < .01), acetic acid-induced peritoneal capillary permeability test, and the cotton pellet granuloma test in mice or rats (P < .01); it also showed marked analgesic activity in the acetic acid-induced abdominal contraction test and formalin-induced paw licking test in mice and rats (P < .05 or .01). However, fraction C3 showed no significant effect in the hot plate test in mice. These findings justify the use of the C. speciosa for treating pain and inflammation. These results support the proposal of C. speciosa fraction C3 as a potential anti-inflammatory agent.

  17. Rose geranium essential oil as a source of new and safe anti-inflammatory drugs

    PubMed Central

    Boukhatem, Mohamed Nadjib; Kameli, Abdelkrim; Ferhat, Mohamed Amine; Saidi, Fairouz; Mekarnia, Maamar

    2013-01-01

    Background Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. Aims The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). Methods The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. Results RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Conclusion Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile. PMID:24103319

  18. Rose geranium essential oil as a source of new and safe anti-inflammatory drugs.

    PubMed

    Nadjib Boukhatem, Mohamed; Kameli, Abdelkrim; Amine Ferhat, Mohamed; Saidi, Fairouz; Mekarnia, Maamar

    2013-01-01

    Background Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. Aims The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). Methods The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. Results RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Conclusion Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

  19. Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer

    PubMed Central

    Andersson, Marianne; Arvidsson, Annette; Nordgren, Svante; Brevinge, Hans; Lagerstedt, Kristina; Lundholm, Kent

    2008-01-01

    This study evaluates HLA gene expression and tumor infiltration by B-cells, macrophages, dendritic cells, T-helper and cytotoxic T-lymphocytes in response to short-term preoperative treatment with cyclooxygenase inhibitors. Patients with colorectal carcinoma were randomized to receive oral NSAID (indomethacin or celebrex) for three days preoperatively; controls received esomeprazol. Peroperative tumor biopsies and normal colon tissue were analyzed by microarray, quantitative PCR and immunohistochemistry. Efficacy of short-term systemic NSAID treatment was confirmed by measurement of PGE2 production in blood monocytes from healthy volunteers. NSAID treatment upregulated genes at the MHC locus on chromosome 6p21 in tumor tissue, but not in normal colon tissue, from the same patient. 23 of the 100 most upregulated genes belonged to MHC class II. HLA-DM, -DO (peptide loading), HLA-DP, -DQ, -DR (antigen presentation), granzyme B, H, perforin and FCGR3A (CD16) (cytotoxicity) displayed increased expression, as did CD8, a marker of cytotoxic T-lymphocytes, while HLA-A and -C expression were not increased by NSAID treatment. MHC II protein (HLA-DP, -DQ, -DR) levels and infiltration by CD4+ T-helper cells of tumor stroma increased upon NSAID treatment, while CD8+ cytotoxic T-lymphocytes increased in both tumor stroma and epithelium. Molecules associated with immunosuppressive T regulatory cells (FOXP3, IL-10) were significantly decreased in indomethacin-exposed tumors. Standard oral administration of NSAID three days preoperatively was enough to increase tumor infiltration by seemingly activated immune cells. These findings agree with previous information that high prostanoid activities in colorectal cancer increase the risk for reduced disease-specific survival following tumor resection. PMID:18307280

  20. Randomized Comparison of Systemic Anti-inflammatory Therapy Versus Fluocinolone Acetonide Implant for Intermediate, Posterior and Panuveitis: The Multicenter Uveitis Steroid Treatment Trial

    PubMed Central

    Kempen, John H.; Altaweel, Michael M.; Holbrook, Janet T.; Jabs, Douglas A.; Louis, Thomas A.; Sugar, Elizabeth A.; Thorne, Jennifer E.

    2011-01-01

    Objective To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for non-infectious intermediate, posterior or panuveitis (uveitis). Design Randomized controlled parallel superiority trial. Participants Patients with active/recently active uveitis. Methods Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (three countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis. Main Outcome Measures Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life (QoL), ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked. Results Among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), evaluating changes from baseline to 24 months, the implant and systemic therapy groups respectively had +6.0 vs. +3.2 letters' improvement in visual acuity (p=0.16, 95% confidence interval on difference in improvement between groups: −1.2 to +6.7 letters, positive values favoring implant), +11.4 vs. +6.8 units' vision-related QoL improvement (p=0.043), +0.02 vs. −0.02 change in EuroQol-EQ5D health utility (p=0.060), and 12% vs. 29% had active uveitis (p=0.001). Over 24 months, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio (HR) = 3.3, p<0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, p<0.0001), and glaucoma (17%, HR = 4.2, p=0.0008). Systemic-assigned patients had more

  1. [Appropriate prescription, adherence and safety of non-steroidal anti-inflammatory drugs].

    PubMed

    Sostres, Carlos; Lanas, Ángel

    2016-03-18

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most numerous category of drugs sharing the same mechanism of action and therapeutic activities (anti-inflammatory, analgesic and anti-pyretic). Despite having similar efficacy for pain relieve, the different available NSAIDs show variability in its safety profile. The risk of gastrointestinal and cardiovascular complications varies depending on the dose of NSAID and also the presence of different risk factors. It is necessary, therefore, an individualized case assessment before establishing the indication of the best NSAID for each patient, taking account of the best gastroprotection strategy. Improved prescription and enhanced treatment adherence are central objectives to reduce NSAID-related complications. A recent consensus of the Spanish Association of Gastroenterology and the Spanish societies of Cardiology and Rheumatology intends to promote the rational use of NSAIDs according to new recent studies. This review provides additional aspects to facilitate the optimal decision-making process in the routine use of these drugs in clinical practice.

  2. Nanoparticles prolong N-palmitoylethanolamide anti-inflammatory and analgesic effects in vivo.

    PubMed

    Tronino, Diana; Offerta, Alessia; Ostacolo, Carmine; Russo, Roberto; De Caro, Carmen; Calignano, Antonio; Puglia, Carmelo; Blasi, Paolo

    2016-05-01

    N-Palmitoylethanolamide showed great therapeutic potential in the treatment of inflammation and pain but its unfavourable pharmacokinetics properties will hinder its use in the clinical practice. A nanotechnology-based formulation was developed to enhance the probability of N-palmitoylethanolamide therapeutic success, especially in skin disease management. Lipid nanoparticles were produced and characterized to evaluate their mean size, ζ-potential, thermal behaviour, and morphology. The ability of N-palmitoylethanolamide to diffuse across the epidermis as well as anti-inflammatory and analgesic effects were investigated. Particles had a mean size of about 150 nm and a ζ-potential of -40 mV. DSC data confirmed the solid state of the matrix and the embedding of N-palmitoylethanolamide while electron microscopy have evidenced a peculiar internal structure (i.e., low-electrondense spherical objects within the matrix) that can be reliably ascribed to the presence of oil nanocompartments. Lipid nanoparticles increased N-palmitoylethanolamide percutaneous diffusion and prolonged the anti-inflammatory and analgesic effects in vivo. Lipid nanoparticles seem a good nanotechnology-based strategy to bring N-palmitoylethanolamide to clinics.

  3. Nonsteroidal Anti-Inflammatory Drugs, Gastroprotection, and Benefit–Risk

    PubMed Central

    Moore, Robert Andrew; Derry, Sheena; Simon, Lee S; Emery, Paul

    2014-01-01

    Background Gastroprotective agents (GPA) substantially reduce morbidity and mortality with long-term nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin. Objective To evaluate efficacy of NSAIDs, protection against NSAID-induced gastrointestinal harm, and balance of benefit and risk. Methods Free text searches of PubMed (December 2012) supplemented with “related citation” and “cited by” facilities on PubMed and Google Scholar for patient requirements, NSAID effectiveness, pain relief benefits, gastroprotective strategies, adherence to gastroprotection prescribing, and serious harm with NSAIDs and GPA. Results Patients want 50% reduction in pain intensity and improved fatigue, distress, and quality of life. Meta-analyses of NSAID trials in musculoskeletal conditions had bimodal responses with good pain relief or little. Number needed to treat (NNTs) for good pain relief were 3 to 9. Proton pump inhibitors (PPI) and high-dose histamine-2 receptor antagonists (H2RA) provided similar gastroprotection, with no conclusive evidence of greater PPI efficacy compared with high-dose H2RA. Prescriber adherence to guidance on use of GPA with NSAIDS was 49% in studies published since 2005; patient adherence was less than 100%. PPI use at higher doses over longer periods is associated with increased risk of serious adverse events, including fracture; no such evidence was found for H2RA. Patients with chronic conditions are more willing to accept risk of harm for successful treatment than their physicians. Conclusion Guidance on NSAIDs use should ensure that patients have a good level of pain relief and that gastroprotection is guaranteed for the NSAID delivering good pain relief. Fixed-dose combinations of NSAID plus GPA offer one solution. PMID:23941628

  4. The potential clinical impact of probiotic treatment for the prevention and/or anti-inflammatory therapeutic effect against radiation induced intestinal mucositis. A review.

    PubMed

    Maria-Aggeliki, Kalogeridi S; Nikolaos, Kelekis L; Kyrias, George M; Vassilis, Kouloulias E

    2009-11-01

    Although pelvic radiotherapy, either alone or combined with chemotherapy, has proved to be successful in the treatment of patients with rectal, gynecological and urologic cancer, it is not devoid of side effects. Among patients receiving pelvic radiotherapy more than 70% develop acute inflammatory changes causing gastrointestinal symptoms during treatment. The most frequently reported symptom related to radiation-induced intestinal mucositis is diarrhea. Among nutritional interventions used to manage radiation-induced diarrhoea, probiotics has gained popularity. This term describes organisms and substances that improve microbial balance in the intestines. Although encouraging results have been obtained in clinical trials, the potential of oral probiotics to manage gastrointestinal symptoms needs further research. The article also outlines recent patents related to probiotics therapy to reduce radiation induced mocositis.

  5. Evaluation of the Anti-Inflammatory Effect of Locally Delivered Vitamin C in the Treatment of Persistent Gingival Inflammation: Clinical and Histopathological Study

    PubMed Central

    Abdul Aziz, Manar A.; Abdel Rahman, Ahmed R.

    2016-01-01

    Objective. The purpose of this study is to investigate the role and efficiency of the locally injected vitamin C in the treatment of persistent gingival inflammation. Design. Twenty adult patients with persistent chronic gingival inflammation were included in this study. The same dose of sterile vitamin C was injected in gingival tissues after the completion of phase I therapy. Gingival biopsies were taken after total resolution of inflammation. The specimens were examined histologically, using H&E stain. Results. Clinical evaluation revealed great improvement of the injected sites with recall visits. Histopathological results revealed marked decrease in inflammatory cells and epithelial thickness and a higher number of newly formed subbasal capillaries. Conclusions. Vitamin C is an effective adjunctive treatment in reducing various degrees of chronic gingival inflammation. PMID:28050280

  6. Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor.

    PubMed

    Schepetkin, Igor A; Kirpotina, Liliya N; Hammaker, Deepa; Kochetkova, Irina; Khlebnikov, Andrei I; Lyakhov, Sergey A; Firestein, Gary S; Quinn, Mark T

    2015-06-01

    c-Jun N-terminal kinases (JNKs) participate in many physiologic and pathologic processes, including inflammatory diseases. We recently synthesized the sodium salt of IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime) and demonstrated that it is a high-affinity JNK inhibitor and inhibits murine delayed-type hypersensitivity. Here we show that IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH. Molecular docking of the IQ-1S syn isomer into the JNK1 binding site gave the best pose, which corresponded to the position of cocrystallized JNK inhibitor SP600125 (1,9-pyrazoloanthrone). Evaluation of the therapeutic potential of IQ-1S showed that it inhibited matrix metalloproteinase 1 and 3 gene expression induced by interleukin-1β in human fibroblast-like synoviocytes and significantly attenuated development of murine collagen-induced arthritis (CIA). Treatment with IQ-1S either before or after induction of CIA resulted in decreased clinical scores, and joint sections from IQ-1S-treated CIA mice exhibited only mild signs of inflammation and minimal cartilage loss compared with those from control mice. Collagen II-specific antibody responses were also reduced by IQ-1S treatment. By contrast, the inactive ketone derivative 11H-indeno[1,2-b]quinoxalin-11-one had no effect on CIA clinical scores or collagen II-specific antibody titers. IQ-1S treatment also suppressed proinflammatory cytokine and chemokine levels in joints and lymph node cells. Finally, treatment with IQ-1S increased the number of Foxp3(+)CD4(+)CD25(+) regulatory T cells in lymph nodes. Thus, IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis.

  7. Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor

    PubMed Central

    Schepetkin, Igor A.; Kirpotina, Liliya N.; Hammaker, Deepa; Kochetkova, Irina; Khlebnikov, Andrei I.; Lyakhov, Sergey A.; Firestein, Gary S.

    2015-01-01

    c-Jun N-terminal kinases (JNKs) participate in many physiologic and pathologic processes, including inflammatory diseases. We recently synthesized the sodium salt of IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime) and demonstrated that it is a high-affinity JNK inhibitor and inhibits murine delayed-type hypersensitivity. Here we show that IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH. Molecular docking of the IQ-1S syn isomer into the JNK1 binding site gave the best pose, which corresponded to the position of cocrystallized JNK inhibitor SP600125 (1,9-pyrazoloanthrone). Evaluation of the therapeutic potential of IQ-1S showed that it inhibited matrix metalloproteinase 1 and 3 gene expression induced by interleukin-1β in human fibroblast-like synoviocytes and significantly attenuated development of murine collagen-induced arthritis (CIA). Treatment with IQ-1S either before or after induction of CIA resulted in decreased clinical scores, and joint sections from IQ-1S–treated CIA mice exhibited only mild signs of inflammation and minimal cartilage loss compared with those from control mice. Collagen II–specific antibody responses were also reduced by IQ-1S treatment. By contrast, the inactive ketone derivative 11H-indeno[1,2-b]quinoxalin-11-one had no effect on CIA clinical scores or collagen II–specific antibody titers. IQ-1S treatment also suppressed proinflammatory cytokine and chemokine levels in joints and lymph node cells. Finally, treatment with IQ-1S increased the number of Foxp3+CD4+CD25+ regulatory T cells in lymph nodes. Thus, IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis. PMID:25784649

  8. Natural anti-inflammatory agents for pain relief

    PubMed Central

    Maroon, Joseph C.; Bost, Jeffrey W.; Maroon, Adara

    2010-01-01

    The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use. PMID:21206541

  9. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.

    PubMed

    Kempen, John H; Altaweel, Michael M; Holbrook, Janet T; Jabs, Douglas A; Louis, Thomas A; Sugar, Elizabeth A; Thorne, Jennifer E

    2011-10-01

    To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis). Randomized controlled parallel superiority trial. Patients with active or recently active uveitis. Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis. Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life, ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked. On evaluation of changes from baseline to 24 months among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), the implant and systemic therapy groups had an improvement in visual acuity of +6.0 and +3.2 letters (P = 0.16, 95% confidence interval on difference in improvement between groups, -1.2 to +6.7 letters, positive values favoring implant), an improvement in vision-related quality of life of +11.4 and +6.8 units (P = 0.043), a change in EuroQol-EQ5D health utility of +0.02 and -0.02 (P = 0.060), and residual active uveitis in 12% and 29% (P=0.001), respectively. Over the 24 month period, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio [HR] = 3.3, P < 0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001), and glaucoma (17%, HR=4.2, P = 0.0008). Patients assigned to systemic therapy had more

  10. Effects of kinesiotaping versus non-steroidal anti-inflammatory drugs and physical therapy for treatment of pes anserinus tendino-bursitis: A randomized comparative clinical trial.

    PubMed

    Homayouni, Kaynoosh; Foruzi, Shima; Kalhori, Fereshte

    2016-09-01

    Pes anserinus tendino-bursitis is a condition caused by repetitive friction over the bursa or direct trauma to knee joint and it presents with proximal medial tibial pain and swelling. The aim of this study is to determine the effects of kinesiotaping in comparison with naproxen and physical therapy in treatment of pes anserinus tendino-bursitis. In a randomized comparative clinical trial 56 patients with clinical diagnosis of pes anserinus tendino-bursitis were randomly assigned to kinesiotaping and naproxen/physical therapy (28 patients in each group). Kinesiotaping on the tender area in the form of space-correction (lifting) technique was used and repeated for three times with a one-week interval. Another group received naproxen (250mg TID for 10 days) and ten sessions of daily physical therapy. The visual analog scale (VAS) was used for evaluation of pain. The depth of swelling of the area was measured with sonography before and after treatment. Wilcoxon signed ranks test has been used for determining the influence of interventions on pain (VAS) and swelling scores in each group. The ANCOVA (Analysis of covariance) test was applied for comparing the influence of interventions on VAS and swelling scores after adjustment for co-variables. At end of the study, 27 patients remained in the kinesiotaping group and 19 patients in naproxen/physical therapy group. Treatment with kinesiotaping significantly decreased the pain (P=0.0001) and swelling scores (P=0.0001) in comparison with naproxen/physical therapy after adjustment for baseline characteristics. Kinesiotaping was safe without any complications except for a mild local skin irritation in one patient. Kinesiotaping is more effective than naproxen plus physical therapy in reduction of pain and swelling in patients with pes anserinus tendino-bursitis. www.ClinicalTrials.gov identifier is NCT01680263.

  11. Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome.

    PubMed

    Di Renzo, Laura; Noce, Annalisa; De Angelis, Sandro; Miani, Natascia; Di Daniele, Nicola; Tozzo, Carmela; De Lorenzo, Antonino

    2008-02-01

    Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

  12. Anti-inflammatory agents and inducibility of hepatic drug metabolism.

    PubMed

    Pappas, P; Stephanou, P; Vasiliou, V; Marselos, M

    1998-01-01

    Two rat liver cytosolic aldehyde dehydrogenases, ALDH1 and ALDH3c, are of particular interest because they are inducible by different classes of xenobiotics. ALDHI is mainly increased by phenobarbital-type inducers; polycyclic aromatic hydrocarbons (PAHs), such as 3- methylcholanthrene (3MC), increase ALDH3c enzyme activity in all rat species currently tested. In addition, ALDH3c has been found to reflect the subfamily CYPIA of cytochrome P-450, as well as other enzymes functionally related to the aryl hydrocarbon receptor (the "Ah-receptor enzyme battery"), which is activated by the same type of inducers. In the present study we investigated whether the induction of ALDH3c might be connected with a chemically produced aseptic inflammation of the hepatocyte. To answer this question, we examined the relationship between the induction of ALDH3c by 3MC and the arachidonic acid cascade. Different non-steroid anti-inflammatory drugs (NSAIDs) were tested in combination with 3MC and in post-treatment. The 3MC-induced ALDH3c activity was significantly diminished by the co-administered anti-inflammatory agents. Two microsomal enzyme activities (ethoxyresorufin-O-deethylase, EROD; aryl-hydrocarbon-hydroxylase, AHH) were also decreased. Similar results were obtained with NSAIDs administered to animals pre- treated with 3MC, as far as the ALDH3c activity was concerned, but not for the microsomal enzyme activity (EROD and AHH). In conclusion, the induction of ALDH3c, after PAH treatment, may be related to an aseptic inflammation of the hepatocytes. This effect is reduced by commonly used steroid and non-steroid anti- inflammatory drugs, and although the mechanism of inhibition has not yet been elucidated, it appears likely that ALDH3c and CYP1A activities are associated with the "acute phase" response.

  13. Heterotheca inuloides: anti-inflammatory and analgesic effect.

    PubMed

    Gené, R M; Segura, L; Adzet, T; Marin, E; Iglesias, J

    1998-03-01

    Heterotheca inuloides Cass. (Asteraceae) is used in the traditional medicine of Mexico. The aqueous extract obtained from the flowers of H. inuloides was assessed for anti-inflammatory activity by carrageenan-induced edema test. At 100 mg/kg, i.p, it produced 29% inhibition of inflammation. Ethyl ether (HI-1), butanol (HI-2) and aqueous fraction (HI-3) were obtained from the aqueous extract. The biological assay, by carrageenan-induced edema test, gave the following values (% inhibition): HI-1, 19.9; HI-2, 58.0 and HI-3, 30.0. HI-2 was significantly more effective than HI-1 and HI-3. The dose-effect curve of HI-2 was obtained and the calculated ED50 was 29.7 (22.5-39.2) mg/kg. The peritoneal examination after the treatment with HI-2 showed that the anti-inflammatory action of H. inuloides was not due to an irritating effect at the injection site. At 50-100 mg/kg, i.p., HI-2 inhibited inflammation induced by dextran (38.9-68.1% inhibition) and arachidonic acid (0-33.9%). No effect was observed at the same doses for zymosan or C16-paf-induced edema. In addition, HI-2 reduced abdominal constrictions in mice following injection of acetic acid: at 50-100 mg/kg, it gave 73.8-78.2% inhibition. The ulcerogenic assay showed that ulcer indices after HI-2 i.p. treatment were 0.5 +/- 0.5 at 50 mg/kg and 1.2 +/- 0.4 at 100 mg/kg. The results showed related anti-inflammatory activity and the analgesic effect of HI-2.

  14. Nutritional and Anti-Inflammatory Interventions in Chronic Heart Failure

    PubMed Central

    Kalantar-Zadeh, Kamyar; Anker, Stefan D; Horwich, Tamara B; Fonarow, Gregg C

    2017-01-01

    Summary Five million individuals with chronic heart failure (CHF) in the United States have poor clinical outcomes including high death rates. Observational studies have indicated a reverse epidemiology of traditional cardiovascular risk factors in CHF; in contrast to trends seen in the general population, obesity and hypercholesterolemia are associated with improved survival. The temporal discordance between the overnutrition (long-term killer) and undernutrition (short-term killer) not only can explain some of the observed paradoxes but also may indicate a role for malnutrition, inflammation and oxidative stress that result in cachexia contributing to poor survival in CHF. Diminished appetite or anorexia may be both a cause and a consequence of this so-called malnutrition-inflammation-cachexia (MIC) or wasting syndrome in CHF. Neurohumoral activation, insulin resistance, cytokine activation and survival selection resultant genetic polymorphisms may also contribute to the prominent inflammatory and oxidative characteristics of this population. In CHF patients with wasting, nutritional strategies may be a promising therapeutic approach in CHF, especially if the provision of additional protein and energy also includes nutrients with anti-inflammatory and anti-oxidant properties. Regardless of the etiology of anorexia, appetite stimulating agents especially with anti-inflammatory properties such as megesterol acetate or pentoxyphylline may be appropriate adjuncts to dietary supplementation. Understanding the factors that modulate the MIC and wasting and their associations with clinical outcomes in CHF may lead to the development of nutritional strategies that alter the pathophysiology of CHF and improve outcomes PMID:18514634

  15. Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee osteoarthritis in older patients with multiple comorbidities

    PubMed Central

    Katz, Jeffrey N.; Smith, Savannah R.; Collins, Jamie E.; Solomon, Daniel H.; Jordan, Joanne M.; Hunter, David J.; Suter, Lisa G.; Yelin, Edward; Paltiel, A. David; Losina, Elena

    2015-01-01

    Objective To evaluate long-term clinical and economic outcomes of naproxen, ibuprofen, celecoxib or tramadol for OA patients with cardiovascular disease (CVD) and diabetes. Design We used the Osteoarthritis Policy Model to examine treatment with these analgesics after standard of care -- acetaminophen and corticosteroid injections -- failed to control pain. NSAID regimens were evaluated with and without proton pump inhibitors (PPIs). We evaluated over-the-counter (OTC) regimens where available. Estimates of treatment efficacy (pain reduction, occurring in ~ 57% of patients on all regimens) and toxicity (major cardiac or gastrointestinal toxicity or fractures, risk ranging from 1.09% with celecoxib to 5.62% with tramadol) were derived from published literature. Annual costs came from Red Book Online®. Outcomes were discounted at 3%/year and included costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). Key input parameters were varied in sensitivity analyses. Results Adding ibuprofen to standard of care was cost saving, increasing QALYs by 0.07 while decreasing cost by $800. Incorporating OTC naproxen rather than ibuprofen added 0.01 QALYs and increased costs by $300, resulting in an ICER of $54,800/QALY. Using prescription naproxen with OTC PPIs led to an ICER of $76,700/QALY, while use of prescription naproxen with prescription PPIs resulted in an ICER of $252,300/QALY. Regimens including tramadol or celecoxib cost more but added fewer QALYs and thus were dominated by several of the naproxen-containing regimens. Conclusions In patients with multiple comorbidities, naproxen- and ibuprofen-containing regimens are more effective and cost-effective in managing OA pain than opioids, celecoxib or standard of care. PMID:26525846

  16. Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL.

    PubMed

    Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong-Su; Ro, Seonggu; Cho, Joong Myung; Kim, Hwan-Mook; Lee, Sang-Jin; Oh, Seung Hyun

    2015-04-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.

  17. Novel composite efficacy measure to demonstrate the rationale and efficacy of combination antiviral-anti-inflammatory treatment for recurrent herpes simplex labialis.

    PubMed

    Hull, Christopher M; Levin, Myron J; Tyring, Stephen K; Spruance, Spotswood L

    2014-01-01

    Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target. This was evaluated in a randomized study comparing combination topical 5% acyclovir-1% hydrocortisone cream (AHC) with 5% acyclovir alone (AC; in the AHC vehicle) and the vehicle. The efficacy of each topical therapy was evaluated for cumulative lesion size--a novel composite efficacy endpoint incorporating episode duration, lesion area, and proportion of nonulcerative lesions. In that study, cumulative lesion area was significantly decreased with AHC compared with AC (25% decrease; P<0.05) and the vehicle (50% decrease; P<0.0001). As research continues in this arena, cumulative lesion area should be included as a measure of efficacy in clinical trials of recurrent HSL therapies.

  18. Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis

    PubMed Central

    Levin, Myron J.; Tyring, Stephen K.; Spruance, Spotswood L.

    2014-01-01

    Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target. This was evaluated in a randomized study comparing combination topical 5% acyclovir-1% hydrocortisone cream (AHC) with 5% acyclovir alone (AC; in the AHC vehicle) and the vehicle. The efficacy of each topical therapy was evaluated for cumulative lesion size—a novel composite efficacy endpoint incorporating episode duration, lesion area, and proportion of nonulcerative lesions. In that study, cumulative lesion area was significantly decreased with AHC compared with AC (25% decrease; P < 0.05) and the vehicle (50% decrease; P < 0.0001). As research continues in this arena, cumulative lesion area should be included as a measure of efficacy in clinical trials of recurrent HSL therapies. PMID:24342632

  19. Antipyretic, analgesic and anti-inflammatory effects of Kickxia ramosissima.

    PubMed

    Jan, Shumaila; Khan, Muhammad Rashid

    2016-04-22

    Branched cancerwort, Kickxia ramosissima (Wall.) Janchen (Scrophulariaceae) is traditionally used for the treatment of inflammatory disorders such as rheumatism, diabetes, jaundice and for activation of immune system. Local communities also used this plant for the treatment of spleen enlargement, as febrifuge and in dysmenorrhea. In this investigation antipyretic, analgesic and anti-inflammatory effects of K. ramosissima have been evaluated. Dried powder of the whole plant of K. ramosissima was extracted with methanol (KRM) and partitioned with solvents to obtain the n-hexane (KRH), chloroform (KRC), ethyl acetate (KRE), n-butanol (KRB) and the residual aqueous (KRA) fraction. KRM and the derived fractions were analyzed for the phytochemical constituents, yeast induced pyrexia, analgesic and anti-inflammatory activities by using carrageenan and Freunds' complete adjuvant-induced paw edema model in rat. On account of appreciable effects of KRM in the aforesaid models, KRM was subjected to the carrageenan induced air pouch model in rat. The exudate of air pouch was analyzed for the count of neutrophils, monocytes, lymphocytes and WBCs and for the estimation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO) and prostaglandin (PGE2). Phytochemical investigation of KRM indicated the existence of tannins, flavonoids, alkaloids, coumarins, cardiac glycosides, saponins, terpenoids and phlobatannins. Maximum concentration of total phenolic was determined in KRB followed by KRM while reverse was true for total flavonoids contents. KRM (200mg/kg) distinctly decreased the rectal temperature in yeast induced pyrexia comparable to standard, paracetamol. Pain sensation was effectively inhibited at 200mg/kg p.o. of KRM and KRB as manifested by a decrease (P<0.001) in count of writhing induced with acetic acid and increase of latency time in hot plate. Anti-inflammatory effects of KRM were evident and edema formation induced with carrageenan and Freunds

  20. An update on treatment and prevention strategies for Alzheimer's disease.

    PubMed

    Neugroschl, Judith; Sano, Mary

    2009-09-01

    With the aging of the population, the incidence and prevalence of Alzheimer's disease will grow, increasing the burden on individuals and society. While ameliorating symptoms, the currently available treatments approved by the US Food and Drug Administration do not halt progression or cure the illness. This article discusses recent data on treatment strategies targeting amyloid and tau pathology. Novel therapeutic strategies such as inhibitors of receptors for advanced glycation end products (RAGE), potential mitochondrial modification with Dimebon, anti-inflammatory approaches, and cholesterol-lowering agents are also reviewed. An update on results from pharmacologic and nonpharmacologic prevention trials is provided.

  1. Anti-inflammatory profile of paricalcitol in kidney transplant recipients.

    PubMed

    Donate-Correa, Javier; Henríquez-Palop, Fernando; Martín-Núñez, Ernesto; Hernández-Carballo, Carolina; Ferri, Carla; Pérez-Delgado, Nayra; Muros-de-Fuentes, Mercedes; Mora-Fernández, Carmen; Navarro-González, Juan F

    2017-06-13

    Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients. Thirty one kidney transplant recipients with secondary hyperparathyroidism completed 3 months of treatment with oral paricalcitol (1μg/day). Serum concentrations and gene expression levels of inflammatory cytokines in peripheral blood mononuclear cells were analysed at the beginning and end of the study. Paricalcitol significantly decreased parathyroid hormone levels with no changes in calcium and phosphorous. It also reduced serum concentrations of interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) by 29% (P<0.05) and 9.5% (P<0.05) compared to baseline, respectively. Furthermore, gene expression levels of IL-6 and TNF-α in peripheral blood mononuclear cells decreased by 14.1% (P<0.001) and 34.1% (P<0.001), respectively. The ratios between pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10), both regarding serum concentrations and gene expression, also experienced a significant reduction. Paricalcitol administration to kidney transplant recipients has been found to have beneficial effects on inflammation, which may be associated with potential clinical benefits. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Anti-inflammatory activity of Euphorbia aegyptiaca extract in rats

    PubMed Central

    Abo-dola, Marium A.; Lutfi, Mohamed F.

    2016-01-01

    Background There were no studies on the anti-inflammatory activity of Euphorbia aegyptiaca, though it is commonly used by Sudanese herbalists in the treatment of rheumatoid arthritis. Objectives To determine phytochemical constituents of Euphorbia aegyptiaca To investigate the anti-inflammatory activity of Euphorbia aegyptiaca in rats. Methodology Plant material was extracted by ethanol and phytochemical screening was done according to standard methods. The thickness of Albino rats’ paws were measured before injection of 0.1 ml of 1% formalin in the sub planter region and then, 1, 2, 3, 4 and 24 hours after oral dose of ethanolic extract of Euphorbia aegyptiaca at a rate of 400mg/kg, 800mg/kg, indomethacin (5mg/kg) and normal saline (5ml/kg). Edema inhibition percentage (EI%) and mean paw thickness (MPT) were measured in the different groups and compared using appropriate statistical methods. Results The phytochemical screening revealed the presence of saponins, cumarins, flavonoids, tannins, sterols, triterpenes, and absence of alkaloids, anthraquinones glycosides and cyanogenic glycosides. The mean of EI% of rats treated with indomethacin at a dose of 5 mg/kg over different time intervals (64.0%) was significantly lower compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (75.0%, P< 0.001), but higher compared to rats treated at higher dose of 400 mg/kg (57.4%, P< 0.001). In contrast, MPT of rats treated with indomethacin at a dose of 5 mg/kg (6.5±1.1 mm) was significantly higher compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (6.1±.7 mm, P< 0.001) as well as 400 mg/kg (5.9±.5, P< 0.001). Conclusion Euphorbia aegyptiaca ethanolic extract has a sustained dose-dependent anti-inflammatory activity. PMID:27004059

  3. Antinociceptive and anti-inflammatory potential of Rhododendron arboreum bark.

    PubMed

    Nisar, Muhammad; Ali, Sajid; Muhammad, Naveed; Gillani, Syed N; Shah, Muhmmad R; Khan, Haroon; Maione, Francesco

    2016-07-01

    Rhododendron arboreum Smith. (Ericaceae), an evergreen small tree, is one of the 1000 species that belongs to genus Rhododendron distributed worldwide. In folk medicine, as various parts of this plant exhibit medicinal properties, it is used in the treatment of different ailments.The present study was designed to evaluate the potential anti-inflammatory and antinociceptive effects of methanolic extract of R. arboreum bark, followed by activity-guided fractionation of n-hexane, n-butanol, chloroform, ethyl acetate and aqueous fractions.The ethyl acetate fraction (200 mg/kg i.p.) showed the maximum analgesic effect (82%) in acetic acid-induced writhing, followed, to a less extent, by crude extract and chloroform fraction both at a dose of 200 mg/kg i.p. (65.09% and 67.89%, respectively). In carrageenan-induced mouse paw oedema, the crude extract and its related fractions displayed in a dose-dependent manner (50-200 mg/kg i.p.) an anti-inflammatory activity for all time-courses (1-5 hrs). For the active extract/fractions (200 mg/kg i.p.), the maximum effect was observed 5 h after carrageenan injection. These evidences were also supported by in vitro lipoxygenase inhibitory properties. In conclusion, R. arboreum crude methanolic extract and its fractions exhibited anti-inflammatory and antinociceptive effects. For these reasons, this plant could be a promising source of new compounds for the management of pain and inflammatory diseases. © The Author(s) 2014.

  4. Anti-inflammatory flavonoids from Cryptocarya chingii.

    PubMed

    Feng, Rui; Guo, Zhi Kai; Yan, Chun Min; Li, Er Guang; Tan, Ren Xiang; Ge, Hui Ming

    2012-04-01

    Six flavonoids named cryptogiones A-F, and nine known compounds were isolated from an ethanol extract of stems of Cryptocaryachingii. The structures of the compounds were elucidated by interpretation of comprehensive spectroscopic data and X-ray analysis. A majority of these flavonoids contained an acetic acid/lactone moiety, a possible taxonomic marker. Anti-inflammatory effects of the compounds were evaluated using in vitro assays. At 20 μM concentration, three compounds significantly inhibited TNFα-induced NF-кB activation and LPS-induced IL-1β expression.

  5. Lipoxins exert antiangiogenic and anti-inflammatory effects on Kaposi's sarcoma cells.

    PubMed

    Marginean, Alexandru; Sharma-Walia, Neelam

    2015-08-01

    Lipoxin A4 (LXA4) is an endogenously produced host molecule with anti-inflammatory resolution effects. Previous studies demonstrated it to be involved in anti-vascular endothelial growth factor (VEGF)-mediated angiogenesis and in a possible anticancer role via interaction with its receptor, lipoxin A 4 receptor (ALXR). Here, we examined the effects of LXA4 and its epimer 15-epi-LXA4 in inhibiting proinflammatory and angiogenic functions in a human Kaposi's sarcoma tumor-derived cell line (KS-IMM). KS-IMM cells expressed increased levels of inflammatory cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LO) pathway enzymes when compared with human microvascular dermal endothelial cells (HMVEC-d). KS-IMM cells secreted high levels of prostaglandin E2 (PGE2) and chemotactic leukotriene B4 (LTB4). Treatment with LXA4 or 15-epi-LXA4 effectively reduced the levels of COX-2, 5-LO proteins, and secretion of PGE2 and LTB4 in KS-IMM cells. LXA4 or 15-epi-LXA4 treatment also decreased secretion of proinflammatory interleukin 6 (IL-6) and IL-8 cytokines but induced the secretion of anti-inflammatory IL-10. LXA4 treatment reduced the phosphorylation of VEGF receptor (VEGFR) and ephrin family receptor tyrosine kinases. LXA4 treatment effectively induced dephosphorylation of multiple cellular kinases such as Focal Adhesion Kinase, Protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and Extracellular signal-regulated kinases (ERK)1/2, and reduced angiogenic factor VEGF-C secretion in KS cells. LX treatment drastically induced the Src-homology 2 domain-containing phosphatase tyrosine (Y542) phosphatase and reduced VEGFR-2 phosphorylation at sites Y1059, Y1175, and Y1212. Treatment of KS-IMM cells with LXA4 resulted in selective localization of VEGFR-2 in nonlipid raft (non-LR) and ALXR to LR fractions. These results demonstrated that LXA4 or 15-epi-LXA4 induce anti-inflammatory and antiangiogenic effects in KS cells and suggest that treatment with LXs is

  6. Anti-inflammatory activity of natural dietary flavonoids.

    PubMed

    Pan, Min-Hsiung; Lai, Ching-Shu; Ho, Chi-Tang

    2010-10-01

    Over the past few decades, inflammation has been recognized as a major risk factor for various human diseases. Acute inflammation is short-term, self-limiting and it's easy for host defenses to return the body to homeostasis. Chronic inflammatory responses are predispose to a pathological progression of chronic illnesses characterized by infiltration of inflammatory cells, excessive production of cytokines, dysregulation of cellular signaling and loss of barrier function. Targeting reduction of chronic inflammation is a beneficial strategy to combat several human diseases. Flavonoids are widely present in the average diet in such foods as fruits and vegetables, and have been demonstrated to exhibit a broad spectrum of biological activities for human health including an anti-inflammatory property. Numerous studies have proposed that flavonoids act through a variety mechanisms to prevent and attenuate inflammatory responses and serve as possible cardioprotective, neuroprotective and chemopreventive agents. In this review, we summarize current knowledge and underlying mechanisms on anti-inflammatory activities of flavonoids and their implicated effects in the development of various chronic inflammatory diseases.

  7. Pharmacokinetics and dosage regimens of anti-inflammatory drugs.

    PubMed

    Lees, P; May, S A; White, D

    1990-01-01

    The term anti-inflammatory drug, in its broadest sense, encompasses a number of very diverse compounds, ranging from steroids to non-steroidal anti-inflammatory drugs (NSAIDs) and from disease modifying agents (used in the treatment of canine rheumatoid arthritis) to chondroprotective agents (used in the treatment of osteoarthrosis and traumatic arthritis in the horse). For many of these drugs (eg, chondroprotective and disease modifying agents) the mode of action is unknown and even with steroids and NSAIDs there is no universal agreement on mechanism of action. It is therefore in many cases impossible to link pharmacokinetic data to a drug's pharmacodynamics, for example to an effect on a specific biochemical marker. Some agents, including corticosteroids, may have indirect modes of action, so that the pharmacodynamic half-life can be much longer than (and not clearly related to) the pharmacokinetic half-life. In other cases, clinical benefits may only become apparent after several weeks or even months. It can therefore be difficult or impossible to use classical pharmacokinetic approaches to set dosing intervals and dose rates for clinical use. To some extent, the position is more straightforward with NSAIDs. However, even with these drugs simple approaches are not possible and this paper will review briefly some of the studies undertaken in our laboratory which have attempted to utilize NSAID kinetics to set dosage schedules for clinical use.

  8. Anti-inflammatory and antioxidant effect of ginger in tuberculosis.

    PubMed

    Kulkarni, Rashmi Anant; Deshpande, Ajit Ramesh

    2016-06-01

    Tuberculosis (TB) has reemerged to become the world's leading cause of death from a single infectious agent. Inflammatory cytokines play an important role during the course of the disease and may be responsible for tissue damage by lipid peroxidation. The study was aimed to explore the anti-inflammatory and antioxidant effect of ginger in pulmonary TB patients. A total of 69 pulmonary TB patients participated in a randomized and placebo-controlled study. The intervention group received 3 g of ginger extract daily for 1 month and placebo group was supplemented with starch capsule. Participants of both groups were taking standard antitubercular treatment during the study. The concentrations of tumor necrosis factor (TNF) alpha, ferritin and malondialdehyde (MDA) in blood samples were analyzed before and after the intervention by using enzyme-linked immunosorbent assay for TNF alpha and ferritin and spectrophotometry for MDA. Ginger supplementation significantly reduced the levels of TNF alpha, ferritin and MDA in ginger supplemented group in comparison to baseline. Ginger supplementation with antitubercular treatment significantly lowered TNF alpha, ferritin and MDA concentrations in comparison to control group. Ginger was found to be effective as an anti-inflammatory and antioxidant supplement along with anti-TB therapy as it possesses strong free radical scavenging property.

  9. Anti-inflammatory potential of silk sericin.

    PubMed

    Aramwit, Pornanong; Towiwat, Pasarapa; Srichana, Teerapol

    2013-04-01

    Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats' paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats' tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production.

  10. In vivo and In vitro Anti-Inflammatory Activity of Indazole and Its Derivatives

    PubMed Central

    Muniappan, M.

    2016-01-01

    Introduction The inflammatory response is closely intertwined with the process of repair. However in some diseases the inflammatory response may be exaggerated and sustained without apparent benefit and even with severe adverse complications. For decades, we have been primarily relying upon Nonsteroidal (NSAID) and Steroidal Anti-Inflammatory agents for management of various inflammatory conditions. However, adverse effects of these drugs are severe which often leads to patient’s non-compliance with inadequate relief. Therefore, there has been a constant pursuit to develop newer anti - inflammatory treatment with fewer side effects. Aim The study was designed to investigate the possible anti- inflammatory activity of indazole, its derivatives and to further investigate the possible cellular mechanisms underlying the anti-inflammatory effect. Materials and Methods Carrageenan induced hind paw oedema in rats was employed to study the acute anti-inflammatory activity of indazole and its derivatives. Further, the role of cyclooxygenase – 2, pro-inflammatory cytokines like Tumour Necrosis Factor – α, Interleukin – 1β and free radical scavenging activity (LPO, DPPH and NO) in the action of indazole and its derivatives was investigated using in vitro assays. Results SPSS version 16.0 software was used for analyse the anti-inflamatory data. The IC50 values of indazole and its derivatives obtained in in vitro experiments were calculated by linear regression analysis. Indazole and its derivatives significantly, dose dependently and time dependently inhibited carrageenan induced hind paw oedema. In addition, the test compounds inhibited cyclooxygenase–2, pro-inflammatory cytokines and free radicals in a concentration dependent manner. Conclusion The results of the present study revealed the potential anti-inflammatory action of investigated indazoles. The inhibition of cyclooxygenase -2, cytokines and free radicals may contribute to the anti-inflammatory effect of

  11. Evaluation of antinociceptive and anti-inflammatory effects of aqueous extract of Armadillidium vulgare Latreille.

    PubMed

    Guo, Shen-Shen; Ren, Meng-Yue; Song, Shuai; Wei, Ping; Luo, Jia-Bo

    2017-02-01

    To assess the antinociceptive and anti-inflammatory properties of the aqueous extract of Armadillidium vulgare (AV). The antinociceptive effect of AV (400, 600 and 800 mg/kg) was investigated in mice using the acetic acid-induced writhing, formalin-induced nociceptive, and hot plate tests. Phlogogen-induced paw edema using carrageenan, dextran, or compound 48/80 as phlogogen was used as inflammatory models to evaluate AV's anti-inflammatory effect. Additionally, the bioactive substances glucosamine (GLcN) and taurine in AV were determined using high-performance liquid chromatography. Oral treatment of the mice with AV (600 and 800 mg/kg) significantly reduced the number of writhes in the acetic acid-induced writhing test (P<0.01) but not the hot plate test (P>0.05). All doses tested significantly inhibited paw-withdrawal during the second phase of the formalin-induced nociceptive model (P<0.01). AV demonstrated a strong anti-inflammatory effect in all those inflammatory models (P<0.05). AV has antinociceptive and anti-inflammatory effects, providing scientific evidence of the efficacy of its traditional use in pain treatment. Furthermore, GLcN and taurine contribute, at least in part, to the anti-inflammatory activity of AV.

  12. Anti-inflammatory effects of fibrates: an overview.

    PubMed

    Tziomalos, Konstantinos; Athyros, Vasilios G; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2009-01-01

    Inflammation plays an important role in the pathogenesis of atherosclerosis. Several cardiovascular drugs exert anti-inflammatory effects and accumulating data suggest that fibrates also share this property. This review summarizes the mechanisms implicated in the anti-inflammatory actions of fibrates. We also provide an overview of the existing clinical studies addressing the effects of fibrates on markers of inflammation. Several, but not all, studies reported that fibrates exert anti-inflammatory actions. The small number of patients included in some studies, as well as differences in diagnoses and duration of follow up might partly explain this discrepancy. It is also possible that fibrates differ substantially in terms of anti-inflammatory effects. It is not clear whether an anti-inflammatory action of fibrates is clinically relevant. Future studies should assess whether the anti-inflammatory actions of fibrates (or for that matter, other drugs) will translate into a reduced risk of vascular disease.

  13. Anti-inflammatory effects of linagliptin in hemodialysis patients with diabetes.

    PubMed

    Nakamura, Yuya; Tsuji, Mayumi; Hasegawa, Hitomi; Kimura, Kengo; Fujita, Kiichiro; Inoue, Michiyasu; Shimizu, Tatsuo; Gotoh, Hiromichi; Goto, Yoshikazu; Inagaki, Masahiro; Oguchi, Katsuji

    2014-04-01

    Inflammation and glycemic control are important prognosis-related factors for hemodialysis (HD) patients; moreover, inflammation affects insulin secretion. Here, we evaluated the anti-inflammatory effects of monotherapy with linagliptin-a dipeptidase-4 inhibitor-in HD patients with type 2 diabetes. We examined 21 diabetic HD patients who were not receiving oral diabetes drugs or insulin therapy and with poor glycemic control (glycated albumin [GA] level, >20%). Linagliptin (5 mg) was administered to the patients daily. The levels of prostaglandin E2 (PGE2), interleukin-6 (IL-6), high-sensitivity C-reactive protein, GA, blood glucose, and active glucagon-like peptide-1 were determined before and 6 months after treatment. Body weight and serum levels of albumin, hemoglobin, total cholesterol, and low-density lipoprotein cholesterol were also recorded before and after treatment. The levels of PGE2 and GA were significantly decreased 1 month after starting linagliptin therapy, whereas the IL-6 levels were significantly decreased 6 months after starting linagliptin therapy. After 6 months of treatment, the PGE2 levels decreased from 188 ± 50 ng/mL to 26 ± 5 ng/mL; IL-6 levels, from 1.5 ± 0.4 pg/mL to 0.6 ± 0.1 pg/mL; and GA levels, from 21.3% ± 0.6% to 18.0% ± 0.6%. Glucagon-like peptide-1 levels increased 2.5-fold during the treatment. Over the 6-month treatment period, body weight and levels of high-sensitivity C-reactive protein, blood glucose, albumin, hemoglobin, and cholesterol did not change; none of the patients exhibited hypoglycemia. The anti-inflammatory effects of linagliptin monotherapy indicate that it may serve as a useful glucose control strategy for HD patients with diabetes.

  14. Anti-inflammatory and antinociceptive activity of Urera aurantiaca.

    PubMed

    Riedel, R; Marrassini, C; Anesini, C; Gorzalczany, S

    2015-01-01

    Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti-inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti-inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan-induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose-dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis 3-ethylbenzothiazoline 6-sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50 : 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity.

  15. Oncostatin M in the anti-inflammatory response

    PubMed Central

    Wahl, A; Wallace, P

    2001-01-01

    Oncostatin M (OM) is a pleiotropic cytokine of the interleukin 6 family, whose in vivo properties and physiological function remain in dispute and poorly defined. These in vivo studies strongly suggest that OM is anabolic, promoting wound healing and bone formation, and anti-inflammatory. In models of inflammation OM is produced late in the cytokine response and protects from lipopolysaccharide (LPS)-induced toxicities, promoting the re-establishment of homoeostasis by cooperating with proinflammatory cytokines and acute phase molecules to alter and attenuate the inflammatory response. Administration of OM inhibited bacterial LPS-induced production of tumour necrosis factor α and septic lethality in a dose dependent manner. Consistent with these findings, in animal models of chronic inflammatory disease OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and antibody production were not impaired by OM treatment. Taken together, these data indicate that the activities of this cytokine in vivo are anti-inflammatory without concordant immunosuppression.

 PMID:11890661

  16. Topical anti-inflammatory activity of Solanum corymbiflorum leaves.

    PubMed

    Piana, Mariana; Camponogara, Camila; Boligon, Aline Augusti; Machado, Michel Mansur; de Brum, Thiele Faccim; Oliveira, Sara Marchesan; de Freitas Bauermann, Liliane

    2016-02-17

    Solanum corymbiflorum is popularly known as "baga-de-veado" and its leaves are applied on inflamed legs, scabies, tick bite, boils, mastitis, low back pain and otitis. The aim of this study was evaluate anti-inflammatory in vivo activity and relate this activity with antioxidant compounds present in the extract of S. corymbiflorum leaves. The extract from S. corymbiflorum leaves topically applied was able to reduce the croton oil-induced ear edema and myeloperoxidase (MPO) activity with maximum inhibition of 87±3% and 45±7%, rescpectively in the dose of 1mg/ear. Similar results were found for positive control dexamethasone, which presented inhibitions of ear edema and MPO activity of 89±3% and 50±3%, respectively in a dose of 0.1mg/ear. These findings are due, at least in part, the presence of polyphenols (195.28mg GAE/g) and flavonoids, as chlorogenic acid (59.27mg/g), rutin (12.72mg/g), rosmarinic acid, caffeic acid and gallic acid found by high performance liquid chromatography (HPLC) analysis. This species showed potencial antioxidant by 1,1-diphenyl-2-picrylhydrazyl (DPPH), and carbonyl groups in proteins methods which may be related with the presence of this compounds. This species possess anti-inflammatory activity confirming their popular use for the local treatment of skin inflammatory disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  18. Anti-inflammatory therapy for obstructive sleep apnea in children

    PubMed Central

    Friedman, Bat-Chen; Goldman, Ran D.

    2011-01-01

    Abstract Question A 4-year-old child was diagnosed by polysomnography as experiencing mild obstructive sleep apnea (OSA). Despite the child being inattentive and distracted during the day at school, his parents prefer to avoid surgical treatment (adenotonsillectomy). Are there any non-surgical treatments for mild OSA in young children? Answer Obstructive sleep apnea in children is caused mainly by adenotonsillar hypertrophy and can lead to considerable morbidities, including neurocognitive and behavioural disturbances. Surgical removal of the tonsils and adenoids is the treatment of choice. In recent years, however, a new understanding of the inflammatory components of OSA has led to the assumption that anti-inflammatory treatment can reduce adenotonsillar size and improve OSA symptoms. Evidence from a few studies suggests that intranasal steroids and oral leukotriene receptor antagonists have beneficial effects, but data from randomized controlled trials are still lacking. PMID:21841108

  19. Review of anti-inflammatory, immune-modulatory and wound healing properties of molluscs.

    PubMed

    Ahmad, Tarek B; Liu, Lei; Kotiw, Michael; Benkendorff, Kirsten

    2017-08-19

    This review focuses on traditional and contemporary anti-inflammatory uses of mollusc-derived products summarising all the in vitro, in vivo and human clinical trials that have tested the anti-inflammatory activity of molluscan natural products. Inflammatory conditions, burns and wounds have been an ongoing concern for human health since the early era of civilisation. Many texts from ancient medicine have recorded the symptoms, signs and treatments for these conditions. Natural treatments are well-documented in traditional European medicine, Traditional Chinese Medicine (TCM), Siddha and ancient Mediterranean and African traditional medicine and include a surprisingly large number of molluscan species. An extensive review of the Materia Medica and scientific literature was undertaken using key word searches for "mollusc" and "anti-inflammatory" or "immunomodulatory" or "wound healing". Molluscs have been used in ethnomedicine by many traditional cultures to treat different aspects of inflammatory conditions. We found 104 different anti-inflammatory preparations from a variety of molluscan species, of which 70 were from the well-documented Traditional Chinese Medicine (TCM). This traditional use of molluscs has driven the testing for inflammatory activity in extracts from some species in the phylum Mollusca, with 20 in vitro studies, 40 in vivo animal studies and 14 human clinical trials performed to substantiate the anti-inflammatory and wound healing activity of molluscs. Some of these studies have led to the approval of mollusc-derived products to be used as over-the-counter (OTC) nutraceuticals, like Lyprinol® and Biolane™ from the New Zealand green lipped mussel Perna canaliculus. Natural products provide important leads for the development of pharmaceuticals, including anti-inflammatory agents. Only a small proportion of the molluscan traditional medicines have been tested to confirm their anti-inflammatory activity and most screening studies have tested

  20. Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center, randomized, open-label, non-inferiority trial.

    PubMed

    Ishijima, Muneaki; Nakamura, Toshitaka; Shimizu, Katsuji; Hayashi, Kunihiko; Kikuchi, Hiraku; Soen, Satoshi; Omori, Go; Yamashita, Toshihiko; Uchio, Yuji; Chiba, Junji; Ideno, Yuki; Kubota, Mitsuaki; Kurosawa, Hisashi; Kaneko, Kazuo

    2014-01-21

    While many of the commonly used conservative treatments for knee osteoarthritis (OA) have been recognized to be effective, there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA. However, frequent and serious adverse effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and improve joint function. However, there has been no qualified direct comparison study of the efficacy and safety between IA-HA and NSAIDs for patients with knee OA. The aim of this study was to clarify the efficacy and safety of early-phase IA-HA in comparison to those of NSAIDs for patients with knee OA. This multicenter, randomized, open-label, parallel-group, non-inferiority comparison study with an oral NSAID involved a total of 200 patients with knee OA. An independent, computer-generated randomization sequence was used to randomly assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n = 100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned regarding any adverse events during treatment. The full analysis set (FAS) was used for analysis. The margin of non-inferiority was 10%. The analyses of primary endpoint included 98 patients in the IA-HA group and 86 patients in the NSAID group. The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2% (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were significantly lower than those in the

  1. Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center, randomized, open-label, non-inferiority trial

    PubMed Central

    2014-01-01

    Introduction While many of the commonly used conservative treatments for knee osteoarthritis (OA) have been recognized to be effective, there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA. However, frequent and serious adverse effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and improve joint function. However, there has been no qualified direct comparison study of the efficacy and safety between IA-HA and NSAIDs for patients with knee OA. The aim of this study was to clarify the efficacy and safety of early-phase IA-HA in comparison to those of NSAIDs for patients with knee OA. Methods This multicenter, randomized, open-label, parallel-group, non-inferiority comparison study with an oral NSAID involved a total of 200 patients with knee OA. An independent, computer-generated randomization sequence was used to randomly assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n = 100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned regarding any adverse events during treatment. The full analysis set (FAS) was used for analysis. The margin of non-inferiority was 10%. Results The analyses of primary endpoint included 98 patients in the IA-HA group and 86 patients in the NSAID group. The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2% (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were

  2. Simvastatin attenuates intestinal fibrosis independent of the anti-inflammatory effect by promoting fibroblast/myofibroblast apoptosis in the regeneration/healing process from TNBS-induced colitis.

    PubMed

    Abe, Yosuke; Murano, Mitsuyuki; Murano, Naoko; Morita, Eijiro; Inoue, Takuya; Kawakami, Ken; Ishida, Kumi; Kuramoto, Takanori; Kakimoto, Kazuki; Okada, Toshihiko; Narabayashi, Ken; Umegaki, Eiji; Higuchi, Kazuhide

    2012-02-01

    Intestinal deformity and stenosis are induced by fibrosis during the process healing of intestinal chronic inflammation in inflammatory bowel disease (IBD). Potent anti-inflammatory treatment of patients with Crohn's disease (CD) may induce fibrous stenosis, and this is often difficult to treat in clinical practice. Therefore, it is necessary to develop a treatment strategy that concomitantly exhibits repair/regenerative and anti-fibrotic effects, in addition to the current anti-inflammatory effect, for the treatment of inflammatory bowel diseases. However, the relationship between the course of inflammatory activity and the healing process and fibrogenesis has not been elucidated; although the complex involvement of various factors in the mechanism of biological fibrosis has been investigated. Simvastatin (SIMV), an HMG-CoA reductase inhibitor, exhibits anti-inflammatory and anti-fibrotic effects. The current study established a model of the regeneration/healing process from TNBS-induced colitis and investigated the anti-inflammatory and anti-fibrotic effects of SIMV. Four groups of TNBS-induced colitis model were prepared using male SJL/J mice: A: Normal control group, B: control group, and C and D: treatment groups. The mucosal healing process was classified into three phases (an early phase: inflammation period, a mid-phase: regeneration promoting period, and a late phase: regeneration-converging period), and inflammation, the expression of fibrosis-related growth factors, and induction of apoptosis of fibrosis-related cells were compared in each period. (1) The clinical findings showed that SIMV showed anti-inflammatory effects with body weight gain and improvement of epithelial injury in the late phase. Histological (macroscopic/microscopic) improvement was noted in the mid- and late phases. The inflammatory cytokine (TNF-α) level significantly decreased in the mid- and late phases in the high-dose treatment group. (2) SIMV also had anti-fibrotic effects

  3. Anti-inflammatory activity of Vismia guianensis (Aubl.) Pers. extracts and antifungal activity against Sporothrix schenckii.

    PubMed

    Oliveira, A H; de Oliveira, G G; Carnevale Neto, F; Portuondo, D F; Batista-Duharte, A; Carlos, I Z

    2017-01-04

    Vismia guianensis (Aubl.) Pers. is traditionally used in North and Northeast of Brazil for the treatment of dermatomycoses. Since the strategy associating immunomodulators with antifungal drugs seems to be promissory to improve the treatment efficacy in fungal infections, we aimed to investigate the antifungal activity of V. guianensis ethanolic extract of leaves (VGL) and bark (VGB) against Sporothrix schenckii ATCC 16345 and their antinflammatory activities. The extracts were analyzed by HPLC-DAD-IT MS/MS for in situ identification of major compounds. Antifungal activity was evaluated in vitro (microdilution test) and in vivo using a murine model of S. schenckii infection. The production of TNF-α, IFN-γ, IL-4, IL-10 and IL-12 by measured by ELISA, as well as measured the production and inhibition of the NO after treatment with the plant extracts or itraconazole (ITR). Two O-glucosyl-flavonoids and 16 prenylated benzophenone derivatives already described for Vismia were detected. Both VGL and VGB showed significant antifungal activity either in in vitro assay of microdilution (MIC=3.9µg/mL) and in vivo model of infection with reduction of S. schenckii load in spleen. It was also observed a predominance of reduction in the production of NO and the proinflammatory cytokines evaluated except TNFα, but with stimulation of IL-10, as evidence of a potential anti-inflammatory effect associated. The results showed that both VGL and VGB have a significant antifungal against S. schenckii and an anti-inflammatory activity. These results can support the use of these extracts for alternative treatment of sporotrichosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Evaluating ancient Egyptian prescriptions today: Anti-inflammatory activity of Ziziphus spina-christi.

    PubMed

    Kadioglu, Onat; Jacob, Stefan; Bohnert, Stefan; Naß, Janine; Saeed, Mohamed E M; Khalid, Hassan; Merfort, Irmgard; Thines, Eckhard; Pommerening, Tanja; Efferth, Thomas

    2016-03-15

    Ziziphus spina-christi (L.) Desf. (Christ's Thorn Jujube) is a wild tree today found in Jordan, Israel, Egypt, and some parts of Africa, which was already in use as a medicinal plant in Ancient Egypt. In ancient Egyptian prescriptions, it was used in remedies against swellings, pain, and heat, and thus should have anti-inflammatory effects. Nowadays, Z. spina-christi, is used in Egypt (by Bedouins, and Nubians), the Arabian Peninsula, Jordan, Iraq, and Morocco against a wide range of illnesses, most of them associated with inflammation. Pharmacological research undertaken to date suggests that it possesses anti-inflammatory, hypoglycemic, hypotensive and anti-microbial effects. The transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is critical in inflammation, proliferation and involved in various types of cancer. Identification of new anti-inflammatory compounds might be an effective strategy to target inflammatory disorders and cancer. Therefore, extracts from Z. spina-christi are investigated in terms of their anti-inflammatory effects. Our intention is to evaluate the effects of Z. spina-christi described in ancient Egyptian papyri, and to show whether the effects can be proven with modern pharmacological methods. Furthermore, we determine the active ingredients in crude extracts for their inhibitory activity toward NF-κB pathway. To determine the active ingredients of Z. spina-christi, we fractionated the extracts for bioassays and identified the active compounds. Epigallocatechin, gallocatechin, spinosin, 6''' feruloylspinosin and 6''' sinapoylspinosin and crude extracts of seed, leaf, root or stem were analyzed for their effect on NF-κB DNA binding by electromobility shift assay (EMSA) and nuclear translocation of NF-κB-p65 by Western blot analysis. The binding mode of the compounds to NF-κB pathway proteins was compared with the known inhibitor, MG-132, by in silico molecular docking calculations. Log10IC50

  5. Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation.

    PubMed

    Abdul, Latif; Abdul, Razique; Sukul, R R; Nazish, Siddiqui

    2010-01-01

    The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.

  6. Structure–activity relationship of terpenes with anti-inflammatory profile – a systematic review.

    PubMed

    Souza, Marilia Trindade de Santana; Almeida, Jackson Roberto Guedes da Silva; Araujo, Adriano Antunes de Souza; Duarte, Marcelo Cavalcante; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca; dos Santos, Marcio Roberto Viana; Quintans-Júnior, Lucindo José

    2014-09-01

    Inflammation is a complex biological response that in spite of having available treatments, their side effects limit their usefulness. Because of this, natural products have been the subject of incessant studies, among which the class of terpenes stands out. They have been the source of study for the development of anti-inflammatory drugs, once their chemical diversity is well suited to provide skeleton for future anti-inflammatory drugs. This systematic review reports the studies present in the literature that evaluate the anti-inflammatory activity of terpenes suffering any change in their structures, assessing whether these changes also brought changes in their effects. The search terms anti-inflammatory agents, terpenes, and structure–activity relationship were used to retrieve English language articles in SCOPUS, PUBMED and EMBASE published between January 2002 and August 2013. Twenty-seven papers were found concerning the structural modification of terpenes with the evaluation of antiinflammatory activity. The data reviewed here suggest that modified terpenes are an interesting tool for the development of new anti-inflammatory drugs.

  7. Systems Pharmacology Dissection of the Anti-Inflammatory Mechanism for the Medicinal Herb Folium Eriobotryae

    PubMed Central

    Zhang, Jingxiao; Li, Yan; Chen, Su-Shing; Zhang, Lilei; Wang, Jinghui; Yang, Yinfeng; Zhang, Shuwei; Pan, Yanqiu; Wang, Yonghua; Yang, Ling

    2015-01-01

    Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations. PMID:25636035

  8. Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation

    PubMed Central

    Abdul, Latif; Abdul, Razique; Sukul, R.R.; Nazish, Siddiqui

    2010-01-01

    The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities. PMID:23861612

  9. Evaluation of anti-inflammatory activity of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae) fruit extract in rats.

    PubMed

    Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

    2013-01-01

    Several species of the family Bromeliaceae are characterized by the production of proteases in unusual amounts, especially in fruits. Bromelain, an extract rich in cysteine endopeptidases obtained from Ananas comosus L., and a few other proteases have been used as anti-inflammatory agents for some years, but bromelain is still mainly being used as alternative and/or complementary therapy to the treatment with glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. In this study, the anti-inflammatory action of a partially purified extract from Pseudananas macrodontes (Morr.) Harms fruits (PPE(Pm)) is presented, whose main components are cysteine endopeptidases. The effect of PPE(Pm) was assessed in carrageenan-induced and serotonin-induced rat paw edema, as well as in the cotton pellet granuloma model. Doses with equal proteolytic activity of PPE(Pm) and bromelain produced significantly similar anti-inflammatory responses in the acute inflammatory models assayed, supporting the hypothesis that proteolytic activity could be responsible for the anti-inflammatory action. On the contrary, comparable anti-inflammatory effects of PPE(Pm) and bromelain in the chronic inflammatory assay required a much lower proteolytic activity content of PPE(Pm), which could be due to a differential affinity for the protein target involved in this process.

  10. Potential anti-inflammatory effect of Leea macrophylla Roxb. leaves: a wild edible plant.

    PubMed

    Dewanjee, Saikat; Dua, Tarun K; Sahu, Ranabir

    2013-09-01

    Leea macrophylla (Leeaceae) is a wild edible plant with ethomedicinal importance as anti-inflammatory agent. However, no systematic studies on its anti-inflammatory activity and mechanisms have been reported. Present study was undertaken to evaluate anti-inflammatory activity of methanol extract of L. macrophylla leaves. Phytochemical investigation revealed presence of sterols, triterpenoids and ascorbic acid in extract. Methanol extract inhibited lipopolysaccharide stimulated production of inflammatory mediators viz. prostaglandin E2, tumor necrotic factor-α, interleukin-6 and interleukin-1β in vitro in mouse peritoneal macrophages. Additionally, the in vivo anti-inflammatory activity of this extract was evaluated by using carrageenan induced paw edema and cotton pellet granuloma assays in experimental rats. Oral administration of extract (100 and 200 mg/kg) exhibited dose dependant inhibition of carrageenan induced inflammation (p<0.05) and the reduction of the granuloma tissue formation (p<0.05-0.01). The extract (100 and 200 mg/kg, orally) exhibited significant central and peripheral analgesic activity in hot-plate test (p<0.01) and acetic acid induced writhing test (p<0.05-0.01) respectively in experimental mice. Treatment with extract (100 and 200 mg/kg, orally) significantly reduced the yeast provoked elevated body temperature (p<0.05-0.01) in experimental rats. These results confirmed the traditional anti-inflammatory indication of L. macrophylla leaves. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Adiponectin as an anti-inflammatory factor

    PubMed Central

    Ouchi, Noriyuki; Walsh, Kenneth

    2009-01-01

    Obesity is characterized by low-grade systemic inflammation. Adiponectin is an adipose tissue-derived hormone, which is downregulated in obesity. Adiponectin displays protective actions on the development of various obesity-linked diseases. Several clinical studies demonstrate the inverse relationship between plasma adiponectin levels and several inflammatory markers including C-reactive protein. Adiponectin attenuates inflammatory responses to multiple stimuli by modulating signaling pathways in a variety of cell types. The anti-inflammatory properties of adiponectin may be a major component of its beneficial effects on cardiovascular and metabolic disorders including atherosclerosis and insulin resistance. In this reviews, we focus on the role of adiponectin in regulation of inflammatory response and discuss its potential as an antiinflammatory marker. PMID:17343838

  12. Corneal reepithelialization and anti-inflammatory agents.

    PubMed Central

    Srinivasan, B D

    1982-01-01

    These studies have demonstrated that nonsteroidal anti-inflammatory agents (cyclooxygenase and lipoxygenase inhibitors) can inhibit PMN arrival in the tear fluid following corneal injury but do not inhibit the reepithelialization either by corneal epithelial cells or by conjunctival epithelial cells. Therefore, they can be used safely in ocular inflammatory conditions even when corneal epithelial defects are present. Corticosteroids, on the other hand, inhibit reepithelialization by conjunctival epithelial cells and not by corneal epithelial cells in the doses tested. This inhibition does not occur with pretreatment prior to injury, suggesting that corticosteroids can be used clinically in conditions that have intact corneal epithelium without fear of slowing down wound healing should epithelial defects occur when not on steroid therapy. Furthermore, the steroid inhibition is temporary since there is a breakthrough in steroid inhibition with time, and occurs only if the steroids have been used shortly after deepithelialization. The steroid inhibition can be reversed by specific steroid antagonist, indicating that the steroid effect is mediated through specific receptors. An exciting and new hypothesis proposes that corticosteroids induce the formation of an inhibitory protein that inhibits the phospholipase enzyme to cause a block in arachidonic acid release from cell membranes. This mechanism of action may also be prevalent in the steroid effect on corneal reepithelialization, and experiments are under way to isolate this inhibitory protein from steroid-treated conjunctival epithelium. This isolation and pharmacologic characterization of this inhibitory protein is of obvious advantage to the field of ophthalmic therapeutics since this protein may have the anti-inflammatory potential of the steroids without their steroid sideeffects. Images FIGURE 3 a FIGURE 3 b PMID:6763806

  13. Flavonoids as anti-inflammatory agents.

    PubMed

    Serafini, Mauro; Peluso, Ilaria; Raguzzini, Anna

    2010-08-01

    Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases. However, the mechanism of action and the components involved in this effect have not been identified clearly. In recent years, the scientific community has agreed to focus its attention on a class of secondary metabolites extensively present in a wide range of plant foods: the flavonoids, suggested as having different biological roles. The anti-inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different pro-inflammatory mediators such as eicosanoids, cytokines, adhesion molecules and C-reactive protein. Molecular activities of flavonoids include inhibition of transcription factors such as NF-kappaB and activating protein-1 (AP-1), as well as activation of nuclear factor-erythroid 2-related factor 2 (Nrf2). However, the in vitro evidence might be somehow of limited impact due to the non-physiological concentrations utilized and to the fact that in vivo flavonoids are extensively metabolized to molecules with different chemical structures and activities compared with the ones originally present in the food. Human studies investigating the effect of flavonoids on markers of inflammation are insufficient, and are mainly focused on flavonoid-rich foods but not on pure molecules. Most of the studies lack assessment of flavonoid absorption or fail to associate an effect on inflammation with a change in circulating levels of flavonoids. Human trials with appropriate placebo and pure flavonoid molecules are needed to clarify if flavonoids represent ancillary ingredients or key molecules involved in the anti-inflammatory properties of plant foods.

  14. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.

    PubMed

    Marjoribanks, Jane; Ayeleke, Reuben Olugbenga; Farquhar, Cindy; Proctor, Michelle

    2015-07-30

    Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs that act by blocking prostaglandin production. They inhibit the action of cyclooxygenase (COX), an enzyme responsible for the formation of prostaglandins. The COX enzyme exists in two forms, COX-1 and COX-2. Traditional NSAIDs are considered 'non-selective' because they inhibit both COX-1 and COX-2 enzymes. More selective NSAIDs that solely target COX-2 enzymes (COX-2-specific inhibitors) were launched in 1999 with the aim of reducing side effects commonly reported in association with NSAIDs, such as indigestion, headaches and drowsiness. To determine the effectiveness and safety of NSAIDs in the treatment of primary dysmenorrhoea. We searched the following databases in January 2015: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, November 2014 issue), MEDLINE, EMBASE and Web of Science. We also searched clinical trials registers (ClinicalTrials.gov and ICTRP). We checked the abstracts of major scientific meetings and the reference lists of relevant articles. All randomised controlled trial (RCT) comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea. Two review authors independently selected the studies, assessed their risk of bias and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). We used inverse variance methods to combine data. We assessed the overall quality of the evidence using GRADE methods. We included 80 randomised controlled trials (5820

  15. Anti-Inflammatory and Anti-Nociceptive Activities of Native and Modified Hen Egg White Lysozyme.

    PubMed

    Carrillo, Wilman; Spindola, Humberto; Ramos, Mercedes; Recio, Isidra; Carvalho, Joao Ernesto

    2016-09-28

    Persistent inflammatory conditions can have severe pathological consequences. Although the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is effective, it has side effects, particularly at the gastrointestinal level. There is then a high interest to identify natural anti-inflammatory compounds with no side effects. The anti-inflammatory and anti-nociceptive activities of hen egg lysozyme (LZ), both in its native form and modified by heat treatment, chemically or by enzymatic digestion have been tested in this study. The carrageenan-induced model in mice using native LZ or modified LZ has been applied. It was observed that LZ denatured by heat treatment at pH 6.0 presented 39.47% of inhibition of paw edema when administered at 30 mg/kg. LZ denatured with DL-dithiothreitol (DTT) presented a significant result of 42.10% inhibition of paw edema when administered at 30 mg/kg of animal weight. Modified LZ showed anti-inflammatory capacity comparable with the activity of the positive control dexamethasone. A classical model of acetic acid-induced abdominal writhing tests in mice was used to assess anti-nociceptive activity of native LZ and denatured heat treatment LZ and denatured chemical agent LZ. Finally, hydrolyzed native LZ presented 48% of inhibition of abdominal writhing in mice. Modified LZ with heat, chemical, and hydrolysis presented anti-inflammatory and anti-nociceptive activities independently of their natural enzymatic activity. These novel data point out the potential use of denatured and digested LZ as therapeutic agents and offer alternatives to the use of NSAIDs. LZ can be a natural source of anti-inflammatory and anti-nociceptive agents.

  16. Developing anti-inflammatory therapeutics for patients with osteoarthritis.

    PubMed

    Philp, Ashleigh M; Davis, Edward T; Jones, Simon W

    2016-08-07

    OA is the most common joint disorder in the world, but there are no approved therapeutics to prevent disease progression. Historically, OA has been considered a wear-and-tear joint disease, and efforts to identify and develop disease-modifying therapeutics have predominantly focused on direct inhibition of cartilage degeneration. However, there is now increasing evidence that inflammation is a key mediator of OA joint pathology, and also that the link between obesity and OA is not solely due to excessive load-bearing, suggesting therefore that targeting inflammation in OA could be a rewarding therapeutic strategy. In this review we therefore re-evaluate historical clinical trial data on anti-inflammatory therapeutics in OA patients, highlight some of the more promising emerging therapeutic targets and discuss the implications for future clinical trial design.

  17. A Polysaccharide Virulence Factor from Aspergillus fumigatus Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist

    PubMed Central

    Gresnigt, Mark S.; Bozza, Silvia; Becker, Katharina L.; Joosten, Leo A. B.; Abdollahi-Roodsaz, Shahla; van der Berg, Wim B.; Dinarello, Charles A.; Netea, Mihai G.; Fontaine, Thierry; De Luca, Antonella; Moretti, Silvia; Romani, Luigina; Latge, Jean-Paul; van de Veerdonk, Frank L.

    2014-01-01

    The galactosaminogalactan (GAG) is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated. In the present study we used in vitro PBMC stimulation assays to demonstrate, that GAG inhibits proinflammatory T-helper (Th)1 and Th17 cytokine production in human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra), a potent anti-inflammatory cytokine that blocks IL-1 signalling. GAG cannot suppress human T-helper cytokine production in the presence of neutralizing antibodies against IL-1Ra. In a mouse model of invasive aspergillosis, GAG induces IL-1Ra in vivo, and the increased susceptibility to invasive aspergillosis in the presence of GAG in wild type mice is not observed in mice deficient for IL-1Ra. Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model. In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis. This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. However, the observation that GAG can also protect mice from allergy and colitis makes GAG or a derivative structure of GAG a potential treatment compound for IL-1 driven inflammatory diseases. PMID:24603878

  18. Self-assembling polymeric nanoparticles for enhanced intra-articular anti-inflammatory protein delivery

    NASA Astrophysics Data System (ADS)

    Whitmire, Rachel Elisabeth

    Osteoarthritis (OA) affects 26 million Americans, or approximately 14% of the adult population. The incidence of OA is predicted to dramatically increase in the next 20 years as the US grows older and the rate of obesity continues to increase. There are currently no clinical interventions that cure OA. Current biomaterial delivery systems exhibit several limitations. First, most drug-delivery particles are hydrophobic, which is not optimal for hydrophilic protein encapsulation. Second, hydrophobic particles, such as PLGA, could cause wear damage to the already-fragile OA cartilage structure. Additionally, these particles usually suffer from non-specific protein adsorption, which causes increased phagocytosis and can lead to increased inflammation. New therapies that increase the effectiveness of OA treatments or reverse OA disease progression will greatly decrease the economic costs and individual pain associated with this disease. The goal of this thesis was to develop a new drug-delivering material to deliver anti-inflammatory protein for treating OA. Our central hypothesis for this work is that a controlled release/presentation system will more effectively deliver anti-inflammatory protein therapies to the OA joint. The primary goal of this work was to synthesize a block copolymer that could self-assemble into injectable, sub-micron-scale particles and would allow an anti-inflammatory protein, IL-1ra, to be tethered to its surface for efficient protein delivery. The block copolymer incorporated an oligo-ethylene monomer for tissue compatibility and non-fouling behavior, a 4-nitrophenol group for efficient protein tethering, and cyclohexyl methacrylate, a hydrophobic monomer, for particle stability. We engineered the copolymer and tested it in both in vitro culture experiments and an in vivo model to evaluate protein retention in the knee joint. The rationale for this project was that the rational design and synthesis of a new drug- and protein

  19. Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil.

    PubMed

    Intahphuak, S; Khonsung, P; Panthong, A

    2010-02-01

    This study investigated some pharmacological properties of virgin coconut oil (VCO), the natural pure oil from coconut [Cocos nucifera Linn (Palmae)] milk, which was prepared without using chemical or high-heat treatment. The anti-inflammatory, analgesic, and antipyretic effects of VCO were assessed. In acute inflammatory models, VCO showed moderate anti-inflammatory effects on ethyl phenylpropiolate-induced ear edema in rats, and carrageenin- and arachidonic acid-induced paw edema. VCO exhibited an inhibitory effect on chronic inflammation by reducing the transudative weight, granuloma formation, and serum alkaline phosphatase activity. VCO also showed a moderate analgesic effect on the acetic acid-induced writhing response as well as an antipyretic effect in yeast-induced hyperthermia. The results obtained suggest anti-inflammatory, analgesic, and antipyretic properties of VCO.

  20. Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

    PubMed Central

    Steel, Helen C.; Theron, Annette J.; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

    2012-01-01

    Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance. PMID:22778497

  1. Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.

    PubMed Central

    Kim, Wan-Su; Choi, Woo Jin; Lee, Sunwoo; Kim, Woo Joong; Lee, Dong Chae; Sohn, Uy Dong; Shin, Hyoung-Shik

    2015-01-01

    The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin E2 (PGE2), and proinflammatory cytokine (IL-1β , IL-6, and IL-10) production. Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, (91.0±3.2%), similar to α-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases. PMID:25605993

  2. Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

    PubMed Central

    Lee, Young-Sun; Jun, Hee-Sook

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion. GLP-1 has beneficial effects for glucose homeostasis by stimulating insulin secretion from pancreatic beta-cells, delaying gastric emptying, decreasing plasma glucagon, reducing food intake, and stimulating glucose disposal. Therefore, GLP-1-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4, which is a GLP-1 inactivating enzyme, have been developed for treatment of type 2 diabetes. In addition to glucose-lowering effects, emerging data suggests that GLP-1-based therapies also show anti-inflammatory effects in chronic inflammatory diseases including type 1 and 2 diabetes, atherosclerosis, neurodegenerative disorders, nonalcoholic steatohepatitis, diabetic nephropathy, asthma, and psoriasis. This review outlines the anti-inflammatory actions of GLP-1-based therapies on diseases associated with chronic inflammation in vivo and in vitro, and their molecular mechanisms of anti-inflammatory action. PMID:27110066

  3. Comparison of beneficial actions of non-steroidal anti-inflammatory drugs to flavonoids.

    PubMed

    Conti, P; Varvara, G; Murmura, G; Tete, S; Sabatino, G; Saggini, A; Rosati, M; Toniato, E; Caraffa, A; Antinolfi, P; Pandolfi, F; Potalivo, G; Galzio, R; Theoharides, T C

    2013-01-01

    Inflammation is involved in increasing number of diseases necessitating the development of new, effective and safe treatments. Non steroidal anti-inflammatory drugs (NSAIDs) have been helpful in many instances, but they only inhibit cyclooxygenase (COX), but not the generation or actions of cytokines. Instead, some natural flavonoids have multiple anti-inflammatory effects, including COX inhibition, and a much safer profile. Increasing evidence indicates that inflammation plays a critical role in the pathogenesis of many diseases that also involve mast cells. Consequently, the need for new, effective and safe anti-inflammatory drugs is all the more urgent. Corticosteroids are quite potent, but have many adverse effects such as increased risk of infections, osteoporosis, glaucoma and depression. Biological agents such anti-TNF are useful in certain conditions, such as rheumatoid arthritis and psoriasis, but has been associated with increased risk of infection and leukemia.

  4. Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden).

    PubMed

    Toker, Gülnur; Küpeli, Esra; Memisoğlu, Merve; Yesilada, Erdem

    2004-12-01

    Silver linden, Tilia argentea Desf. ex DC (Tiliaceae) leaves are used in the treatment of common cold and bronchitis. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the two main flavonoid glycosides: kaempferol-3,7-O-alpha-dirhamnoside and quercetin-3,7-O-alpha-dirhamnoside isolated from the leaves, were investigated. For the antinociceptive activity, p-benzoquinone-induced writhing test and for the anti-inflammatory activity, carrageenan-induced hind paw edema model in mice were used. Both compounds were shown to possess potent antinociceptive and anti-inflammatory activity at 50 mg/kg dose, per os, without inducing any apparent acute toxicity as well as gastric damage.

  5. A structure-activity relationship of non-peptide macrocyclic histone deacetylase inhibitors and their anti-proliferative and anti-inflammatory activities.

    PubMed

    Tapadar, Subhasish; Fathi, Shaghayegh; Raji, Idris; Omesiete, Wilson; Kornacki, James R; Mwakwari, Sandra C; Miyata, Masanori; Mitsutake, Kazunori; Li, Jian-Dong; Mrksich, Milan; Oyelere, Adegboyega K

    2015-12-15

    Inhibition of the enzymatic activity of histone deacetylase (HDAC) is a promising therapeutic strategy for cancer treatment and several distinct small molecule histone deacetylase inhibitors (HDACi) have been reported. We have previously identified a new class of non-peptide macrocyclic HDACi derived from 14- and 15-membered macrolide skeletons. In these HDACi, the macrocyclic ring is linked to the zinc chelating hydroxamate moiety through a para-substituted aryl-triazole cap group. To further delineate the depth of the SAR of this class of HDACi, we have synthesized series of analogous compounds and investigated the influence of various substitution patterns on their HDAC inhibitory, anti-proliferative and anti-inflammatory activities. We identified compounds 25b and 38f with robust anti-proliferative activities and compound 26f (IC50 47.2 nM) with superior anti-inflammatory (IC50 88 nM) activity relative to SAHA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Anti-inflammatory and antifibrotic effects of methyl palmitate

    SciTech Connect

    El-Demerdash, Ebtehal

    2011-08-01

    Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5 mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was a significant decrease in TNF-{alpha} and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (I{kappa}B{alpha}) protein was significantly decreased in RAW cells treated with 0.5 mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-{kappa}B, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. - Research Highlights: >Methyl palmitate is a universal macrophage inhibitor. >It could be a promising nucleus of anti-inflammatory and antifibrotic drugs. >The underlying mechanism of these effects could be through NF-kB inhibition.

  7. A review of anti-inflammatory agents for symptoms of schizophrenia.

    PubMed

    Keller, William R; Kum, Lionel M; Wehring, Heidi J; Koola, Maju Mathew; Buchanan, Robert W; Kelly, Deanna L

    2013-04-01

    Schizophrenia is a chronic debilitating mental disorder that affects about 1% of the US population. The pathophysiology and etiology remain unknown, thus new treatment targets have been challenging and few novel treatments with new mechanisms of action have come to market in the past few decades. Increasing attention has been paid to the role of inflammation in schizophrenia and new data suggests that decreasing inflammation and inflammatory biomarkers may play some role in schizophrenia treatment. This review summarizes the clinical trial literature regarding medications that possess anti-inflammatory properties that have been tested for schizophrenia symptoms and covers such medications as non-steroidal anti-inflammatory agents, such as the cyclo-oxygenase-2 (COX-2) inhibitors and aspirin, omega-3 fatty acids, neurosteroids and minocycline. Overall, there is accumulating evidence, albeit mostly adjunctive treatments, that agents working on inflammatory pathways have some benefits in people with schizophrenia. In the next few years the field will begin to see data on many treatments with anti-inflammatory properties that are currently under study. Hopefully advancements in understanding inflammation and effective treatments having anti-inflammatory properties may help revolutionize our understanding and provide new targets for prevention and treatment in schizophrenia.

  8. Anti-cancer small molecule JP-8g exhibits potent in vivo anti-inflammatory activity

    PubMed Central

    Sun, Yulong; Liu, Jia; Sun, Tao; Zhang, Xiaoyuan; Yao, Jia; Kai, Ming; Jiang, Xianxing; Wang, Rui

    2014-01-01

    Spirooxindoles are a class of compounds with diverse biological activity. Previously, we identified a series of spirooxindole-pyranopyrimidine compounds that exhibited broad-spectrum anti-cancer activity. In this study, we evaluated one of these compounds, JP-8g, on mouse models and found that it showed potent in vivo anti-inflammatory activity. Further investigation suggested that JP-8g may execute its anti-inflammatory activity through nitric oxide synthase signaling pathways. Our results suggest that these spirooxindole-pyranopyrimidine class compounds have potential for not only cancer treatment but also inflammation therapy. PMID:24626153

  9. Treating tendinopathy: perspective on anti-inflammatory intervention and therapeutic exercise.

    PubMed

    Joseph, Michael F; Denegar, Craig R

    2015-04-01

    Tendinopathy is a common and complex disorder. Once viewed as an inflammatory condition labeled tendinitis, it is now viewed along a continuum that can lead to tissue necrosis and risk of tendon rupture. Anti-inflammatory medications can alter symptoms but may also promote tissue degeneration. Loading of the tendon through exercise, especially exercise involving eccentric muscle contraction, has been shown to promote symptom resolution and functional recovery in many patients. This article reviews the pathoetiology of tendinopathy and the role anti-inflammatory interventions and therapeutic exercise in treatment of active patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Antimicrobial, Anti-inflammatory and Antioxidant Activities of Jatropha multifida L. (Euphorbiaceae)

    PubMed Central

    Anani, Kokou; Adjrah, Yao; Améyapoh, Yaovi; Karou, Simplice Damintoti; Agbonon, Amegnona; de Souza, Comlan; Gbeassor, Messanvi

    2016-01-01

    Background: Jatropha multifida is used in Togolease folk medicine for the healing of chronic wounds. Objective: This study aims to investigate antibacterial, anti-inflammatory and antioxidant activities of the leaves ethanolic extract. Materials and Methods: The antimicrobial activity was assayed by National Committee for Clinical Laboratory Standards broth microdilution method on strains of Staphylococcus aureus and Pseudomoas aeruginosa isolated from wounds, whereas the anti-inflammatory activity was performed by carrageenan and histamine induced paw edema method in rat modele. The 2, 2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) were used for the antioxidant activity. Results: The antibacterial assay showed an in vitro growth inhibition of P. aeruginosa and S. aureus in dose-dependent manner, with minimum inhibitory concentration values ranging from 2.5 to 3.12 mg/mL for S. aureus and from 6.25 to 12.5 mg/mL for P. aeruginosa. The maximum paw anti-inflammatory effect occurred after 3 and 5 h administration of histamine and carrageenan, respectively. The DPPH radical scavenging and the FRAP assays yielded weak antioxidant activity. Conclusion: J. multifida possesses antibacterial and anti-inflammatory activities that could justify the use of the plant for the treatment of wounds in the folk medicine. SUMMARY Antibacterial on germs isolated from wound, anti-inflammatory and antioxidant activities of Jatropha multifida were assayed by NCCLS broth method, carrageenan and histamine, DPPH and FRAP respectively. The results indicated that Jatropha multifida possesses antibacterial and anti-inflammatory and weak antioxidant activities that could justify its use for the treatment of wounds in the folk medicine. PMID:27034606

  11. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status

    PubMed Central

    Cameron, Amy R.; Morrison, Vicky L.; Levin, Daniel; Mohan, Mohapradeep; Forteath, Calum; Beall, Craig; McNeilly, Alison D.; Balfour, David J.K.; Savinko, Terhi; Wong, Aaron K.F.; Viollet, Benoit; Sakamoto, Kei; Fagerholm, Susanna C.; Foretz, Marc

    2016-01-01

    Rationale: The diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood. Objective: Here, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties. Methods and Results: In primary hepatocytes from healthy animals, metformin and the IKKβ (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α–dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1β, and CXCL1/2 (C-X-C motif ligand 1/2). Metformin suppressed IKKα/β activation, an effect that could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production, and AMP-activated protein kinase activation. Equally AMP-activated protein kinase was not required either for mitochondrial suppression of IκB degradation. Consistent with discrete anti-inflammatory actions, in macrophages, metformin specifically blunted secretion of proinflammatory cytokines, without inhibiting M1/M2 differentiation or activation. In a large treatment naive diabetes mellitus population cohort, we observed differences in the systemic inflammation marker, neutrophil to lymphocyte ratio, after incident treatment with either metformin or sulfonylurea monotherapy. Compared with sulfonylurea exposure, metformin reduced the mean log-transformed neutrophil to lymphocyte ratio after 8 to 16 months by 0.09 U (95% confidence interval, 0.02–0.17; P=0.013) and increased the likelihood that neutrophil to lymphocyte ratio would be lower than baseline after 8 to 16 months (odds ratio, 1.83; 95% confidence interval, 1.22–2.75; P=0.00364). Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging

  12. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    SciTech Connect

    Nagib, Marwa M.; Tadros, Mariane G.; ELSayed, Moushira I.; Khalifa, Amani E.

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  13. Potential anti-inflammatory natural products from marine algae.

    PubMed

    Fernando, I P Shanura; Nah, Jae-Woon; Jeon, You-Jin

    2016-12-01

    Inflammatory diseases have become one of the leading causes of health issue throughout the world, having a considerable influence on healthcare costs. With the emerging developments in natural product, synthetic and combinatorial chemistry, a notable success has been achieved in discovering natural products and their synthetic structural analogs with anti-inflammatory activity. However, many of these therapeutics have indicated detrimental side effects upon prolonged usage. Marine algae have been identified as an underexplored reservoir of unique anti-inflammatory compounds. These include polyphenols, sulfated polysaccharides, terpenes, fatty acids, proteins and several other bioactives. Consumption of these marine algae could provide defense against the pathophysiology of many chronic inflammatory diseases. With further investigation, algal anti-inflammatory phytochemicals have the potential to be used as therapeutics or in the synthesis of structural analogs with profound anti-inflammatory activity with reduced side effects. The current review summarizes the latest knowledge about the potential anti-inflammatory compounds discovered from marine algae.

  14. Anti-inflammatory activity of polysaccharide from Schizophyllum commune as affected by ultrasonication.

    PubMed

    Du, Bin; Zeng, Huansong; Yang, Yuedong; Bian, Zhaoxiang; Xu, Baojun

    2016-10-01

    Ultrasound treatment was applied to modify the physicochemical properties of an exopolysaccharide from mycelial culture of Schizophyllum commune. Molecular weight (MW) degradation, viscosity and anti-inflammatory property of ultrasonic treated polysaccharide were optimized with response surface methodology. The best ultrasonic parameters were obtained with a three-variable-three-level Box-Behnken design. The optimized conditions for efficient anti-inflammatory activity are initial concentration at 0.4%, ultrasonic power at 600W, and duration of ultrasonic irradiation for 9min. Under these conditions, the nitric oxide inhibition rate was 95±0.03% which agreed closely with the predicted value (96%). Average MW of polysaccharide decreased after ultrasonic treatments. The viscosity of degraded polysaccharide dropped compared with native polysaccharide. The anti-inflammatory activity was improved by ultrasound treatment. The results suggested that ultrasound treatment is an effective approach to decrease the MW of polysaccharide with high anti-inflammatory activity. Ultrasonic treatment is a viable modification technology for high MW polymer materials. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Pharmacological interactions of anti-inflammatory-analgesics in odontology.

    PubMed

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-02-01

    In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments prescribed daily in odontology for moderate pain treatment and inflammation in the oral cavity. Paracetamol can interact with warfarin and therefore care should be taken with chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently are capable of reducing the efficacy of medicaments used for treating arterial hypertension, which act via a renal mechanism. Especial attention should be taken considering the risk of interaction between the antagonists of AT1 receptors of angiostensin II (ARAII) and the NSAIs.

  16. [Anti-inflammatory effects of tea-flavonoids].

    PubMed

    Hoensch, H; Oertel, R

    2012-12-01

    Tea flavonoids belong to the large group of polyphenols and display antioxidative, anti-inflammatory and anti-neoplastic activities. These phytochemicals are xenobiotics and are synthesized by tea plants such as Camellia sinensis and Camomilla recucita. These botanicals exhibit in vivo activities similar to that of biologicals which are widely used for chronic inflammatory diseases (rheumatoid arthritis, chronic inflammatory bowel disease). Epigallocathechin gallate and apigenin from these plants inhibit cytokines, chemokines and activated immune cells in vivo and in vitro. Clinical disorders with induced inflammatory pathways could benefit from flavonoid treatment. Dietary supplementation with specific tea-flavonoids could be used for Crohn's disease, ulcerative colitis and irritable bowel syndrome. Suppression of cytokine production could ultimately lead to inhibition of carcinogenesis. This mechanism could explain why flavonoids are effective in the prevention of intestinal neoplasia. This innovative new form of therapy should be tested in controlled, randomized clinical studies.

  17. Atomic force microscopy based investigations of anti-inflammatory effects in lipopolysaccharide-stimulated macrophages.

    PubMed

    Pi, Jiang; Cai, Huaihong; Yang, Fen; Jin, Hua; Liu, Jianxin; Yang, Peihui; Cai, Jiye

    2016-01-01

    A new method based on atomic force microscopy (AFM) was developed to investigate the anti-inflammatory effects of drugs on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The LPS-stimulated RAW264.7 macrophage cell line is a widely used in vitro cell model for the screening of anti-inflammatory drugs or the study of anti-inflammatory mechanisms. In this work, the inhibitory effects of dexamethasone and quercetin on LPS-CD14 receptor binding in RAW264.7 macrophages was probed by LPS-functionalized tips for the first time. Both dexamethasone and quercetin were found to inhibit LPS-induced NO production, iNOS expression, IκBα phosphorylation, and IKKα/β phosphorylation in RAW264.7 macrophages. The morphology and ultrastructure of RAW264.7 macrophages were determined by AFM, which indicated that dexamethasone and quercetin could inhibit LPS-induced cell surface particle size and roughness increase in RAW264.7 macrophages. The binding of LPS and its receptor in RAW264.7 macrophages was determined by LPS-functionalized AFM tips, which demonstrated that the binding force and binding probability between LPS and CD14 receptor on the surface of RAW264.7 macrophages were also inhibited by dexamethasone or quercetin treatment. The obtained results imply that AFM, which is very useful for the investigation of potential targets for anti-inflammatory drugs on native macrophages and the enhancement of our understanding of the anti-inflammatory effects of drugs, is expected to be developed into a promising tool for the study of anti-inflammatory drugs.

  18. Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities.

    PubMed

    Del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G; LeBlanc, Jean Guy

    2014-02-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti-inflammatory

  19. Genetically Engineered Immunomodulatory Streptococcus thermophilus Strains Producing Antioxidant Enzymes Exhibit Enhanced Anti-Inflammatory Activities

    PubMed Central

    del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2014-01-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti-inflammatory

  20. Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium

    PubMed Central

    Lin, Wang-Ching; Deng, Jeng-Shyan; Huang, Shyh-Shyun; Wu, Sheng-Hua; Chen, Chin-Chu; Lin, Wan-Rong; Lin, Hui-Yi; Huang, Guan-Jhong

    2017-01-01

    Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with lipopolysaccharides (LPS)-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit myeloperoxidase (MPO) activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit high mobility group box-1 protein 1 (HNGB1) activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes Heme oxygenase 1 (HO-1) and Thioredoxin-1 (Trx-1) in the lung tissue and regulate signal transduction in the KRAB-associated protein-1 (KAP1)/nuclear factor erythroid-2-related factor Nrf2/Kelch Like ECH associated Protein 1 (Keap1) pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced ALI in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases. PMID:28178212

  1. Non-steroidal anti-inflammatory drug gastropathy: clinical results with antacids and sucralfate.

    PubMed

    Lazzaroni, M; Sainaghi, M; Bianchi Porro, G

    1999-01-01

    The efficacy of antacids in the short- and long-term treatment of peptic ulcers, has suggested a possible use in the prevention and in the treatment of non-steroidal anti-inflammatory drug related gastroduodenal lesions. In short-term prevention studies, significant protection against ASA-related lesions was observed when antacids at high-dose were given before the administration of the offending drug. To the contrary, antacids at low dose did not prevent ASA-induced lesions of gastric and duodenal mucosa. As for long-term prophylaxis, no clinical effect was observed. In the treatment of non-steroidal anti-inflammatory drug-related mucosal lesions in patients who were able to discontinue the offending drugs, antacids proved of some use, when compared with placebo, but were significantly less effective than H2 blockers, as cimetidine. Sucralfate is an effective antiulcer drug thought to provide cytoprotective action. Although initial studies utilizing sucralfate for protection against short-term aspirin administration were encouraging, longer term studies (more than 7 days) were generally disappointing. A comparative study with misoprostol demonstrated that the PGE1 analogue was far superior for the prevention of non-steroidal anti-inflammatory drugs ulcers, and that ulceration rates in the sucralfate group were equivalent to rates in the placebo group. As far as the treatment of non-steroidal anti-inflammatory drug-related mucosal lesions is concerned, sucralfate proved superior to placebo, similar to ranitidine, but significantly less effective than omeprazole.

  2. A Systematic Review of Anti-malarial Properties, Immunosuppressive Properties, Anti-inflammatory Properties, and Anti-cancer Properties of Artemisia Annua.

    PubMed

    Alesaeidi, Samira; Miraj, Sepide

    2016-10-01

    Artemisia annua belongs to the asteraceae family, indigenous to the mild climate of Asia. The aim of this study was to overview its anti-malarial properties, immunosuppressive properties, anti-inflammatory properties and anti-cancer properties. This systematic review was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified approximately ninety eight references. In this study, forty six studies were accepted for further screening and met all of our inclusion. The search terms were "Artemisia annua", "therapeutic properties", "and pharmacological effects". Artemisia annua is commonly used for its anti-malarial, immunosuppressive anti-inflammatory properties. Artemisia annua contributes to the treatment of various diseases such as diabetes, heart diseases, arthritis and eczema and possesses various effects such as antibacterial, antioxidant, anticoccidial, and antiviral effects. Furthermore, it was said to be good for cancer treatment. In this study, anti-malarial, immunosuppressive, anti-inflammatory properties of this plant are presented using published articles in scientific sites.

  3. A Systematic Review of Anti-malarial Properties, Immunosuppressive Properties, Anti-inflammatory Properties, and Anti-cancer Properties of Artemisia Annua

    PubMed Central

    Alesaeidi, Samira; Miraj, Sepide

    2016-01-01

    Artemisia annua belongs to the asteraceae family, indigenous to the mild climate of Asia. The aim of this study was to overview its anti-malarial properties, immunosuppressive properties, anti-inflammatory properties and anti-cancer properties. This systematic review was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified approximately ninety eight references. In this study, forty six studies were accepted for further screening and met all of our inclusion. The search terms were “Artemisia annua”, “therapeutic properties”, “and pharmacological effects”. Artemisia annua is commonly used for its anti-malarial, immunosuppressive anti-inflammatory properties. Artemisia annua contributes to the treatment of various diseases such as diabetes, heart diseases, arthritis and eczema and possesses various effects such as antibacterial, antioxidant, anticoccidial, and antiviral effects. Furthermore, it was said to be good for cancer treatment. In this study, anti-malarial, immunosuppressive, anti-inflammatory properties of this plant are presented using published articles in scientific sites. PMID:27957318

  4. Anti-inflammatory constituents of Sappan Lignum.

    PubMed

    Washiyama, Makiko; Sasaki, Yohei; Hosokawa, Tomokazu; Nagumo, Seiji

    2009-05-01

    We performed an in vitro assay for seven compounds from methanolic extract of Sappan Lignum (CSE) that inhibit the chemical mediators of inflammation using the J774.1 cell line: brazilin (1), sappanchalcone (2), protosappanin A (3), protosappanin B (4), protosappanin C (5), protosappanin D (6), and protosappanin E (7). Those compounds were evaluated for their inhibitory effects on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production and their suppressive effects on tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA expression. As a result, we clarified that 1 inhibited NO production, and almost no inhibition in PGE(2). On the contrary, 2, 6, and 7 inhibited both NO and PGE(2) production and suppressed TNF-alpha, IL-6, COX-2, and iNOS mRNA expression. An examination of carrageenin-induced mouse paw edema suggested that the CSE contained active compounds other than 1, the main constituent in CSE. It was thus revealed that several compounds and mechanisms contributed to the anti-inflammatory effect of CSE.

  5. Anti-Inflammatory Constituents from Bidens frondosa.

    PubMed

    Le, Jiamei; Lu, Wenquan; Xiong, Xiaojuan; Wu, Zhijun; Chen, Wansheng

    2015-10-09

    A new polyacetylene glucoside (3E,5E,11E)-tridecatriene-7,9-diyne-1,2,13-triol-2-O-β-D-glucopyranoside (1), a new phenylpropanoid glucoside 2'-butoxyethylconiferin (2), and a new flavonoid glycoside 8,3',4'-trihydroxyflavone-7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (3), have been isolated from Bidens frondosa together with fifty-three known compounds 4-56. The structures of these compounds were established by spectroscopic methods. mainly ESIMS, 1D- and 2D-NMR spectroscopic data. and comparison with literature data. Compounds 1-34, 36, 39, 43, 47, 51, and 52 were tested for inhibition of nuclear factor kappa B (NF-κB) in 293-NF-κB-luciferase report cell line induced by lipopolysaccharide (LPS), and compounds 1, 2, 3, 9, 15, 21, 24 and 51 were tested for the production of TNF-α, IL-1β, IL-6, IL-10 in RAW 264.7 macrophages induced by LPS. In conclusion, the isolated compounds 1, 2, 3, 9, 15, 21, 24 and 51 exhibited significant activity in anti-inflammatory activity assays.

  6. Anti-inflammatory activity of low molecular weight polysialic acid on human macrophages

    PubMed Central

    Shahraz, Anahita; Kopatz, Jens; Mathy, Rene; Kappler, Joachim; Winter, Dominic; Kapoor, Shoba; Schütza, Vlad; Scheper, Thomas; Gieselmann, Volkmar; Neumann, Harald

    2015-01-01

    Oligosialic and polysialic acid (oligoSia and polySia) of the glycocalyx of neural and immune cells are linear chains, in which the sialic acid monomers are α2.8-glycosidically linked. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a primate-lineage specific receptor of human tissue macrophages and microglia that binds to α2.8-linked oligoSia. Here, we show that soluble low molecular weight polySia with an average degree of polymerization 20 (avDP20) interacts with SIGLEC-11 and acts anti-inflammatory on human THP1 macrophages involving the SIGLEC-11 receptor. Soluble polySia avDP20 inhibited the lipopolysaccharide (LPS)-induced gene transcription and protein expression of tumor necrosis factor-α (Tumor Necrosis Factor Superfamily Member 2, TNFSF2). In addition, polySia avDP20 neutralized the LPS-triggered increase in macrophage phagocytosis, but did not affect basal phagocytosis or endocytosis. Moreover, polySia avDP20 prevented the oxidative burst of human macrophages triggered by neural debris or fibrillary amyloid-β1–42. In a human macrophage-neuron co-culture system, polySia avDP20 also reduced loss of neurites triggered by fibrillary amyloid-β1–42. Thus, treatment with polySia avDP20 might be a new anti-inflammatory therapeutic strategy that also prevents the oxidative burst of macrophages. PMID:26582367

  7. Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy

    PubMed Central

    2011-01-01

    Background The effectiveness of ginseng in preventing and treating various central nervous system (CNS) diseases has been widely confirmed. However, ginsenosides, the principal components of ginseng, are characterized by poor accessibility to the brain, and this pharmacokinetic-pharmacological paradox remains poorly explained. Anti-inflammatory approaches are becoming promising therapeutic strategies for depression and other CNS diseases; however, previous studies have focused largely on anti-inflammatory therapies directed at the central nervous system. It is thus of interest to determine whether ginsenosides, characterized by poor brain distribution, are also effective in treating lipopolysaccharide- (LPS) induced depression-like behavior and neuroinflammation. Methods In an LPS-induced depression-like behavior model, the antidepressant effects of ginseng total saponins (GTS) were assessed using a forced swimming test, a tail suspension test, and a sucrose preference test. The anti-inflammatory efficacies of GTS in brain, plasma, and LPS-challenged RAW264.7 cells were validated using ELISA and quantitative real-time PCR. Moreover, indoleamine 2,3-dioxygenase (IDO) activity in the periphery and brain were also determined by measuring levels of kynurenine/tryptophan. Results GTS significantly attenuated LPS-induced depression-like behavior. Moreover, LPS-induced increases in 5-HT and tryptophane turnover in the brain were significantly reduced by GTS. IDO activities in brain and periphery were also suppressed after pretreatment with GTS. Furthermore, GTS-associated recovery from LPS-induced depression-like behavior was paralleled with reduced mRNA levels for IL-1β, IL-6, TNF-α, and IDO in hippocampus. Poor brain distribution of ginsenosides was confirmed in LPS-challenged mice. GTS treatment significantly decreased production of various proinflammatory cytokines in both LPS-challenged mice and RAW264.7 cells. Conclusion This study suggests that the anti

  8. Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: Comparison with ethyl pyruvate.

    PubMed

    Algieri, F; Rodriguez-Nogales, A; Garrido-Mesa, J; Camuesco, D; Vezza, T; Garrido-Mesa, N; Utrilla, P; Rodriguez-Cabezas, M E; Pischel, I; Galvez, J

    2016-03-01

    Pyruvate is a key intermediate of the carbohydrate metabolism with endogenous scavenger properties. However, it cannot be used in clinics due to its instability. Ethyl pyruvate (EP) has shown better stability as well as an antioxidant and anti-inflammatory activity. Calcium pyruvate monohydrate (CPM) is another stable pyruvate derivative that could also provide the benefits from calcium, fundamental for bone health. Considering everything, we propose CPM as a therapeutic strategy to treat diseases with an immune component in which there is also a significant dysregulation of the skeletal homeostasis. This could be applicable to inflammatory bowel disease, which is characterized by over-production of pro-inflammatory mediators, including cytokines and reactive oxygen and nitrogen metabolites that induces intestinal mucosal damage and chronic inflammation, and extra-intestinal symptoms like osteopenia and osteoporosis. The effects of CPM and EP (20, 40 and 100mg/kg) were evaluated on the trinitrobenzenesulfonic acid (TNBS) model of colitis in rats, after a 7-day oral treatment, with main focus on colonic histology and inflammatory mediators. Both pyruvates showed intestinal anti-inflammatory effects in the TNBS-induced colitis. They were evident both histologically, with a recovery of the mucosal cytoarchitecture and a reduction of the neutrophil infiltration, and through the profile of inflammatory mediators (IL-1, IL-6, IL-17, IL-23, iNOS). However, CPM appeared to be more effective than ethyl pyruvate. In conclusion, CPM exerts intestinal anti-inflammatory effect on the TNBS-induced colitis in rats, although further experiments are needed to explore its beneficial effects on bone health and osteoporosis.

  9. Optimization and biological evaluation of aminopyrimidine-based IκB kinase β inhibitors with potent anti-inflammatory effects.

    PubMed

    Shin, Yongje; Lim, Sang Min; Yan, Hong Hua; Jung, Sungwoo; Fang, Zhenghuan; Jung, Kyung Hee; Hong, Soon-Sun; Hong, Sungwoo

    2016-11-10

    Targeting IκB kinase β (IKKβ) can be a promising strategy in the development of a therapeutic treatment of inflammatory diseases because IKKβ is well-recognized as a key mediator of the NF-κB signaling pathway. In this study, we have successfully developed a structure-activity relationship (SAR) profile of the aminopyrimidine-based IKKβ inhibitors through the structure-based design strategy to improve the physicochemical properties and cellular activity in terms of the anti-inflammatory effects. Representative compounds exhibited desirable activity in nitric oxide (NO) reduction by inhibiting the synthesis of inducible nitric oxide synthase (iNOS), and strongly inhibited the expression of pro-inflammatory cytokines (IL-1α, IL-6, and TNF-α). The inhibitory effects of 8e on the phosphorylation in the NF-κB pathway further supported that the suppression of the NF-κB signaling pathway induced the anti-inflammatory effect in LPS-stimulated Raw 264.7 cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Flavone deglycosylation increases their anti-inflammatory activity and absorption

    PubMed Central

    Hostetler, Gregory; Riedl, Ken; Cardenas, Horacio; Diosa-Toro, Mayra; Arango, Daniel; Schwartz, Steven; Doseff, Andrea I.

    2014-01-01

    Scope Flavones have reported anti-inflammatory activities, but the ability of flavone-rich foods to reduce inflammation is unclear. Here, we report the effect of flavone glycosylation in the regulation of inflammatory mediators in vitro and the absorption of dietary flavones in vivo. Methods and results The anti-inflammatory activities of celery extracts, some rich in flavone aglycones and others rich in flavone glycosides, were tested on the inflammatory mediators tumor necrosis factor α (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lipopolysaccharide-stimulated macrophages. Pure flavone aglycones and aglycone-rich extracts effectively reduced TNF-α production and inhibited the transcriptional activity of NF-κB, while glycoside-rich extracts showed no significant effects. Deglycosylation of flavones increased cellular uptake and cytoplasmic localization as shown by high-performance liquid chromatography (HPLC) and microscopy using the flavonoid fluorescent dye diphenyl-boric acid 2-aminoethyl ester (DPBA). Celery diets with different glycoside or aglycone contents were formulated and absorption was evaluated in mice fed with 5 or 10% celery diets. Relative absorption in vivo was significantly higher in mice fed with aglycone-rich diets as determined by HPLC-MS/MS (where MS/MS is tandem mass spectrometry). Conclusion These results demonstrate that deglycosylation increases absorption of dietary flavones in vivo and modulates inflammation by reducing TNF-α and NF-κB, suggesting the potential use of functional foods rich in flavones for the treatment and prevention of inflammatory diseases. PMID:22351119

  11. Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

    PubMed

    Polak, David; Martin, Conchita; Sanz-Sánchez, Ignacio; Beyth, Nurit; Shapira, Lior

    2015-04-01

    Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Antioxidant, Anti-inflammatory, and Genomic Stability Enhancement Effects of Zinc l-carnosine: A Potential Cancer Chemopreventive Agent?

    PubMed

    Ooi, Theng Choon; Chan, Kok Meng; Sharif, Razinah

    2017-01-01

    Cancer is one of the major causes of death worldwide, and the incidence and mortality rates of cancer are expected to rise tremendously in the near future. Despite a better understanding of cancer biology and advancement in cancer management, current strategies in cancer treatment remain costly and ineffective. Hence, instead of putting more efforts to search for new cancer cures, attention has now been shifted to the development of cancer chemopreventive agents as a preventive measure for cancer formation. It is well known that neoplastic transformation of cells is multifactorial, and the occurrence of oxidative stress, chronic inflammation, and genomic instability events has been implicated in the carcinogenesis of cells. Zinc l-carnosine (ZnC), which is clinically used as gastric ulcer treatment in Japan, has been suggested to have the potential in preventing cancer development. Multiple studies have revealed that ZnC possesses potent antioxidant, anti-inflammatory, and genomic stability enhancement effects. Thus, this review provides some mechanistic insight into the antioxidant, anti-inflammatory, and genomic stability enhancement effects of ZnC in relevance to its chemopreventive potential.

  13. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

    PubMed Central

    Piazza, Gary A.

    2015-01-01

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  14. The anti-inflammatory activity of dillapiole and some semisynthetic analogues.

    PubMed

    Parise-Filho, Roberto; Pastrello, Michelli; Pereira Camerlingo, Carla Emygdio; Silva, Gisele Juni; Agostinho, Leonardo Aguiar; de Souza, Thaís; Motter Magri, Fátima Maria; Ribeiro, Roberto Rodrigues; Brandt, Carlos Alberto; Polli, Michelle Carneiro

    2011-11-01

    Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

  15. Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

    PubMed Central

    Theron, Annette J; Steel, Helen C; Tintinger, Gregory R; Feldman, Charles; Anderson, Ronald

    2013-01-01

    Beta2-adrenoreceptor agonists (β2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled β2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of β2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of β2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of β2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3′,5′-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells. PMID:24285920

  16. Anti-inflammatory and antinociceptive action of the dimeric enkephalin peptide biphalin in the mouse model of colitis: new potential treatment of abdominal pain associated with inflammatory bowel diseases.

    PubMed

    Sobczak, Marta; Pilarczyk, Andrzej; Jonakowski, Mateusz; Jarmuż, Agata; Sałaga, Maciej; Lipkowski, Andrzej W; Fichna, Jakub

    2014-10-01

    Biphalin, a mixed MOP/DOP agonist, displays a potent antinociceptive activity in numerous animal models of pain. The aim of the study was to characterize the anti-inflammatory and antinociceptive action of biphalin in the mouse models of colitis. The anti-inflammatory effect of biphalin (5mg/kg, twice daily, i.c. and i.p.) was characterized in a semi-chronic mouse model of colitis, induced by i.c. injection of trinitrobenzenesulfonic acid (TNBS). The antinociceptive action of biphalin (5mg/kg, i.p. and i.c.) in inflamed mice was assessed in mustard oil-induced model of visceral pain and in the hot plate test. In the semi-chronic mouse model of colitis, biphalin i.c. (5mg/kg), but not i.p. improved colitis macroscopic score (2.88±0.19 and 4.99±0.80 units for biphalin and vehicle treated animals, respectively). Biphalin injected i.p. and i.c. (5mg/kg) displayed a potent antinociceptive action in the mustard oil-induced pain test. In the hot plate test, biphalin (5mg/kg, i.p.) produced a potent antinociceptive activity in inflamed mice, suggesting central site of action. Our data suggest that biphalin may become a novel opioid-based analgesic agent in IBD therapy and warrant further investigation of its pharmacological profile.

  17. Repositioning drugs for inflammatory disease – fishing for new anti-inflammatory agents

    PubMed Central

    Hall, Christopher J.; Wicker, Sophie M.; Chien, An-Tzu; Tromp, Alisha; Lawrence, Lisa M.; Sun, Xueying; Krissansen, Geoffrey W.; Crosier, Kathryn E.; Crosier, Philip S.

    2014-01-01

    Inflammation is an important and appropriate host response to infection or injury. However, dysregulation of this response, with resulting persistent or inappropriate inflammation, underlies a broad range of pathological processes, from inflammatory dermatoses to type 2 diabetes and cancer. As such, identifying new drugs to suppress inflammation is an area of intense interest. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat inflammation. Traditional drug discovery, including structure-based drug design, have largely fallen short of satisfying this unmet need. With faster development times and reduced safety and pharmacokinetic uncertainty, drug repositioning – the process of finding new uses for existing drugs – is emerging as an alternative strategy to traditional drug design that promises an improved risk-reward trade-off. Using a zebrafish in vivo neutrophil migration assay, we undertook a drug repositioning screen to identify unknown anti-inflammatory activities for known drugs. By interrogating a library of 1280 approved drugs for their ability to suppress the recruitment of neutrophils to tail fin injury, we identified a number of drugs with significant anti-inflammatory activity that have not previously been characterized as general anti-inflammatories. Importantly, we reveal that the ten most potent repositioned drugs from our zebrafish screen displayed conserved anti-inflammatory activity in a mouse model of skin inflammation (atopic dermatitis). This study provides compelling evidence that exploiting the zebrafish as an in vivo drug repositioning platform holds promise as a strategy to reveal new anti-inflammatory activities for existing drugs. PMID:25038060

  18. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease.

    PubMed

    García-Lafuente, Ana; Guillamón, Eva; Villares, Ana; Rostagno, Mauricio A; Martínez, José Alfredo

    2009-09-01

    Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease.

  19. The anti-inflammatory effects of methane.

    PubMed

    Boros, Mihály; Ghyczy, Miklós; Érces, Dániel; Varga, Gabriella; Tőkés, Tünde; Kupai, Krisztina; Torday, Csilla; Kaszaki, József

    2012-04-01

    Gastrointestinal methane generation has been demonstrated in various stress conditions, but it is not known whether nonasphyxiating amounts have any impact on the mammalian pathophysiology. We set out to characterize the effects of exogenous methane administration on the process of inflammatory events arising after reoxygenation in a large animal model of ischemia-reperfusion. A randomized, controlled in vivo animal study. A university research laboratory. Inbred beagle dogs (12.7 6 2 kg). Sodium pentobarbital-anesthetized animals were randomly assigned to sham-operated or ischemia-reperfusion groups, where superior mesenteric artery occlusion was maintained for 1 hr and the subsequent reperfusion was monitored for 3 hrs. For 5 mins before reperfusion, the animals were mechanically ventilated with normoxic artificial air with or without 2.5% methane. Biological responses to methane-oxygen respirations were defined in pilot rat studies and assay systems were used with xanthine oxidase and activated canine granulocytes to test the in vitro bioactivity potential of different gas concentrations. The macrohemodynamics and small intestinal pCO(2) gap changes were recorded and peripheral blood samples were taken for plasma nitrite/nitrate and myeloperoxidase analyses. Tissue superoxide and nitrotyrosine levels and myeloperoxidase activity changes were determined in intestinal biopsy samples; structural mucosal damage was measured by hematoxylin and eosin staining. Methane inhalation did not influence the macrohemodynamics but significantly reduced the magnitude of the tissue damage and the intestinal pCO(2) gap changes after reperfusion. Furthermore, the plasma and mucosal myeloperoxidase activity and the intestinal superoxide and nitrotyrosine levels were reduced, whereas the plasma nitrite/nitrate concentrations were increased. Additionally, methane effectively and specifically inhibited leukocyte activation in vitro. These data demonstrate the anti-inflammatory profile

  20. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis.

    PubMed

    Lands, Larry C; Stanojevic, Sanja

    2016-04-07

    Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. To assess the effectiveness of treatment with non-steroidal anti-inflammatory drugs in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs.Latest search of the Group's Trials Register: 04 February 2016. Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis. Two authors independently assessed trials for inclusion the review and their potential risk of bias. The searches identified 10 trials; four are included (287 participants aged five to 39 years; maximum follow up of four years) and one is currently awaiting classification pending publication of the full trial report. Three trials compared ibuprofen to placebo (two from the same centre with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a significantly lower annual rate of decline for lung function, percent predicted forced expiratory volume in one second mean difference 1.32 (95% confidence interval 0.21 to 2.42); forced vital capacity mean difference 1.27 (95% confidence interval 0.26 to 2.28); forced expiratory

  1. Anti-inflammatory effects of short chain fatty acids in IFN-gamma-stimulated RAW 264.7 murine macrophage cells: involvement of NF-kappaB and ERK signaling pathways.

    PubMed

    Park, Jin-Sun; Lee, Eun-Jung; Lee, Jae-Chul; Kim, Won-Ki; Kim, Hee-Sun

    2007-01-01

    The overactivation of macrophages causes abnormal cell death and chronic inflammatory diseases. Therefore, the modulation of macrophage-mediated cytotoxicity is expected to become a new therapeutic strategy for various inflammatory diseases. In this study, three types of short chain fatty acids (sodium butyrate (NaB), sodium phenylbutyrate (NaPB), sodium phenylacetate (NaPA)) were found to have anti-inflammatory effects in IFN-gamma-stimulated RAW 264.7 cells. They inhibited the expression of iNOS, TNF-alpha, and IL-6 induced by IFN-gamma, while they enhanced the expression of the anti-inflammatory cytokine, IL-10. Their potency as anti-inflammatory agents was in the order of NaB>NaPB>NaPA. Further mechanistic studies revealed these three agents to repress the DNA binding and transcriptional activities of NF-kappaB, which is an important modulator of inflammation. In addition, these agents repressed the IFN-gamma-induced ERK1/2 phosphorylation without affecting the Jak/STAT activities. The potency of NF-kappaB and ERK inhibition was also in the order of NaB>NaPB>NaPA. The results suggest that the NF-kappaB and ERK signaling pathways are at least in part involved in the anti-inflammatory activities of these SCFAs. Considering that SCFAs are normally present in the body and have few side effects, they might be promising agents for the prevention and/or treatment of various inflammatory diseases.

  2. In vivo anti-inflammatory and antiarthritic activities of aqueous extracts from Thymelaea hirsuta

    PubMed Central

    Azza, Zora; Oudghiri, Mounia

    2015-01-01

    Background: The aerial parts of Thymelaea hirsuta (TH) are used as a decoction in the treatment of different pathologies in folk medicine in Morocco. Objective: The aqueous extracts were evaluated for its anti-inflammatory activity and in inhibition of adjuvant induction arthritis in male Wistar rats. Materials and Methods: The anti-inflammatory activity was carried out using carrageenan-induced rat paw edema model, and the antiarthritic activity was carried out using complete Freund's adjuvant-induced arthritis model. Results: The plant extract (500 mg/kg body weight) exhibited significant activity in acute inflammation produced 60% of inhibition after 4 h as compared with that of the standard anti-inflammatory drug, the diclofenac (100 mg/kg) which showed 40% of inhibition. In arthritis model, the extract produced 85% inhibition after 18 days when compared with the diclofenac (10 mg/kg; 72%). Conclusion: These results indicate that the aqueous extract of TH had an anti-inflammatory activity and inhibited the induction of adjuvant arthritis in male Wistar rats. PMID:25829798

  3. Enhanced acute anti-inflammatory effects of CORM-2-loaded nanoparticles via sustained carbon monoxide delivery.

    PubMed

    Qureshi, Omer Salman; Zeb, Alam; Akram, Muhammad; Kim, Myung-Sic; Kang, Jong-Ho; Kim, Hoo-Seong; Majid, Arshad; Han, Inbo; Chang, Sun-Young; Bae, Ok-Nam; Kim, Jin-Ki

    2016-11-01

    The aim of this study was to enhance the anti-inflammatory effects of carbon monoxide (CO) via sustained release of CO from carbon monoxide-releasing molecule-2-loaded lipid nanoparticles (CORM-2-NPs). CORM-2-NPs were prepared by hot high pressure homogenization method using trilaurin as a solid lipid core and Tween 20/Span 20/Myrj S40 as surfactant mixture. The physicochemical properties of CORM-2-NPs were characterized and CO release from CORM-2-NPs was assessed by myoglobin assay. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. In vivo anti-inflammatory activity was investigated by measuring paw volumes and histological examination in carrageenan-induced rat paw edema. Spherical CORM-2-NPs were around 100nm with narrow particle size distribution. The sustained CO release from CORM-2-NPs was observed and the half-life of CO release increased up to 10 times compared with CORM-2 solution. CORM-2-NPs showed enhanced in vitro anti-inflammatory effects by inhibition of nitric oxide production. Edema volume in rat paw was significantly reduced after treatment with CORM-2-NPs. Taken together, CORM-2-NPs have a great potential for CO therapeutics against inflammation via sustained release of CO. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Antioxidant and anti-inflammatory activities of polyphenolics from Southeastern U.S. range blackberry cultivars.

    PubMed

    Srivastava, Anita; Greenspan, Phillip; Hartle, Diane K; Hargrove, James L; Amarowicz, Ryszard; Pegg, Ronald B

    2010-05-26

    The antioxidant and topical anti-inflammatory activities of low and high molecular weight phenolic fractions (LMPF and HMPF, respectively) isolated from three blackberry cultivars (i.e., Navaho, Kiowa, and Ouachita), bred to tolerate the warm and humid climatic conditions of the southeastern United States, were investigated by the in vitro ferric reducing antioxidant power (FRAP) assay and an in vivo mouse ear edema model. Seventy percent (v/v) acidified acetone was employed to extract phenolics from the Georgia-grown blackberry cultivars, which were subsequently cleaned up on an Amberlite XAD-16 column and then further fractionated with Sephadex LH-20 to LMPF and HMPF. The anti-inflammatory response from topical application of solutions of the LMPF and HMPF as well as indomethacin, a potent nonsteroidal anti-inflammatory drug, was assessed in the TPA mouse ear model. All treatments significantly (P < 0.05) reduced TPA-induced irritation injury. Furthermore, mouse ear myeloperoxidase (MPO) activity, an indicator of polymorphonuclear leukocyte infiltration, was assessed and found to be significantly (P < 0.05) reduced after topical application of indomethacin and all blackberry preparations. Correlation coefficients of 0.925 and 0.923 (P < 0.01) were determined when the anti-inflammatory activities of the blackberry fractions were compared to their total phenolics contents and antioxidant activities (i.e., FRAP values), respectively.

  5. Design and In Vivo Anti-Inflammatory Effect of Ketoprofen Delayed Delivery Systems.

    PubMed

    Cerciello, Andrea; Auriemma, Giulia; Morello, Silvana; Pinto, Aldo; Del Gaudio, Pasquale; Russo, Paola; Aquino, Rita P

    2015-10-01

    For the treatment of inflammatory-based diseases affected by circadian rhythms, the development of once-daily dosage forms is required to target early morning symptoms. In this study, Zn-alginate beads containing ketoprofen (K) were developed by a tandem technique prilling/ionotropic gelation. The effect of main critical variables on particles micromeritics, inner structure as well as on drug loading and in vitro drug release was studied. The in vivo anti-inflammatory efficacy was evaluated using a modified protocol of carrageenan-induced edema in rat paw administering beads to rats by oral gavage at 0, 3, or 5 h before edema induction. Good drug loading and desired particle size and morphology were obtained for the optimized formulation F20. In vitro dissolution studies showed that F20 had a gastroresistant behavior and delayed release of the drug in simulated intestinal fluid. The in vitro delayed release pattern was clearly reflected in the prolonged anti-inflammatory effect in vivo of F20, compared to pure ketoprofen; F20, administered 3 h before edema induction, showed a significant anti-inflammatory activity, reducing maximum paw volume in response to carrageenan injection, whereas no response was observed for ketoprofen. The designed beads appear a promising platform suitable for a delayed release of anti-inflammatory drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3451-3458, 2015.

  6. Wound healing and anti-inflammatory properties of Ranunculus pedatus and Ranunculus constantinapolitanus: a comparative study.

    PubMed

    Akkol, Esra Küpeli; Süntar, Ipek; Erdoğan, Tuğçe Fafal; Keleş, Hikmet; Gonenç, Tuba Mert; Kıvçak, Bijen

    2012-01-31

    In Turkish folk medicine Ranunculus species are used for wound healing and for the treatment of rheumatism. The present study was conducted to evaluate in vivo wound healing and anti-inflammatory properties of Ranunculus pedatus and Ranunculus constantinapolitanus. In vivo wound healing activity of the extracts prepared from Ranunculus pedatus and Ranunculus constantinapolitanus was evaluated by linear incision and circular excision wound models. Hydroxyproline content of the treated tissues was also assessed. We also studied the anti-inflammatory activity using Whittle method with some modifications. Methanolic extract of Ranunculus pedatus showed significant wound healing effect both in incision (31.4%) and excision (55.74%) wound models. Methanolic extract of both Ranunculus pedatus and Ranunculus constantinapolitanus demonstrated anti-inflammatory activity with the inhibition value of 26.2% and 23.3% respectively, at the dose of 100 mg/kg. Hydroxyproline content of the tissues treated with the methanolic and aqueous extracts of Ranunculus pedatus and methanolic extract of Ranunculus constantinapolitanus were found to be significantly higher than that of the other extracts. The experimental data revealed that Ranunculus pedatus showed significant wound healing and anti-inflammatory effect. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Feijoa sellowiana Berg fruit juice: anti-inflammatory effect and activity on superoxide anion generation.

    PubMed

    Monforte, Maria T; Fimiani, Vincenzo; Lanuzza, Francesco; Naccari, Clara; Restuccia, Salvatore; Galati, Enza M

    2014-04-01

    Feijoa sellowiana Berg var. coolidge fruit juice was studied in vivo for the anti-inflammatory activity by carrageenin-induced paw edema test and in vitro for the effects on superoxide anion release from neutrophils in human whole blood. The fruit juice was analyzed by the high-performance liquid chromatography method, and quercetin, ellagic acid, catechin, rutin, eriodictyol, gallic acid, pyrocatechol, syringic acid, and eriocitrin were identified. The results showed a significant anti-inflammatory activity of F. sellowiana fruit juice, sustained also by an effective antioxidant activity observed in preliminary studies on 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. In particular, the anti-inflammatory activity edema inhibition is significant since the first hour (44.11%) and persists until the fifth hour (44.12%) of the treatment. The effect on superoxide anion release was studied in human whole blood, in the presence of activators affecting neutrophils by different mechanisms. The juice showed an inhibiting response on neutrophils basal activity in all experimental conditions. In stimulated neutrophils, the higher inhibition of superoxide anion generation was observed at concentration of 10(-4) and 10(-2) mg/mL in whole blood stimulate with phorbol-myristate-13-acetate (PMA; 20% and 40%) and with N-formyl-methionyl-leucyl-phenylalanine (FMLP; 15% and 48%). The significant reduction of edema and the inhibition of O2(-) production, occurring mainly through interaction with protein-kinase C pathway, confirm the anti-inflammatory effect of F. sellowiana fruit juice.

  8. Anti-inflammatory and antinociceptive activities of Solenostemon monostachyus aerial part extract in mice

    PubMed Central

    Okokon, Jude Fiom; Davis, Koofreh; Nwidu, Lucky Legbosi

    2016-01-01

    Objective: Solenostemon monostachyus is used in traditional medicine for the treatment of various ailments such as ulcer, hypertension, pains and inflammatory diseases. Evaluation of anti-inflammatory and analgesic activities of S. monostachyus aerial parts was carried out to ascertain its uses in traditional medicine. Materials and Methods: The aerial parts of S. monostachyus was cold extracted by soaking the dried powdered material in ethanol. The aerial parts crude extract (75 –225 mg/kg) of S. monostachyus was investigated for analgesic and anti-inflammatory activities using various experimental models; acetic acid, formalin and thermal- induced pains models for analgesic study and carrageenin, egg albumin and xylene – induced edema models for anti-inflammatory investigation. Results: The extract caused a significant (p<0.05 – 0.001) dose-dependent reduction of inflammation and pains induced by different phlogistic agents used. These effects were comparable to those of the standard drug, (ASA, 100 mg/kg) used in some models. Conclusion: The anti-inflammatory and analgesic effects of this plant may in part be mediated through the chemical constituents of the plant and the results of the analgesic action suggest central and peripheral mechanisms. The findings of this work confirm the ethno medical use of this plant to treat inflammatory conditions. PMID:27462551

  9. Analgesic and Anti-Inflammatory Activities of Resveratrol through Classic Models in Mice and Rats

    PubMed Central

    Wang, Guangxi; Hu, Zhiqiang; Song, Xu; Cui, Qiankun; Fu, Qiuting; Jia, Renyong; Zou, Yuanfeng; Li, Lixia

    2017-01-01

    Background. Inflammation and pain are closely related to humans' and animals' health. Resveratrol (RSV) is a natural compound with various biological activities. The current study is aimed to evaluate the analgesic and anti-inflammatory activities of RSV in vivo. Materials and Methods. The analgesic effects were assessed by the acetic acid-induced writhing and hot plate tests. The anti-inflammatory effects were determined using the xylene-induced mouse ear oedema, the acetic acid-induced rat pleurisy, and carrageenan-induced rat synovitis tests, respectively. Results. The analgesic results showed that RSV could significantly inhibit the number of writhes and improve the time and pain threshold of mice standing on hot plate. The anti-inflammatory results showed that RSV could inhibit the ear oedema of mice. In acetic acid-induced pleurisy test, RSV could significantly inhibit the WBC and pleurisy exudates, could decrease the production of NO, and elevate the activity of SOD in serum. In carrageenan-induced synovitis test, RSV could reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA. Conclusion. Shortly, these results indicated that RSV had potent analgesic and anti-inflammatory activities and could be a potential new drug candidate for the treatment of inflammation and pain. PMID:28386290

  10. Improvement of bioavailability and anti-inflammatory potential of curcumin in combination with emu oil.

    PubMed

    Jeengar, Manish Kumar; Shrivastava, Shweta; Nair, Kala; Singareddy, Sreenivasa Reddy; Putcha, Uday Kumar; Talluri, M V N Kumar; Naidu, V G M; Sistla, Ramakrishna

    2014-12-01

    The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.

  11. Brine Shrimp Cytotoxicity, Anti-inflammatory and Analgesic Properties of Woodfordia fruticosa Kurz Flowers

    PubMed Central

    Baravalia, Yogesh; Vaghasiya, Yogeshkumar; Chanda, Sumitra

    2012-01-01

    The present study was designed to assess the cytotoxicity, anti-inflammatory and analgesic properties of methanol extract of Woodfordia fruticosa flowers. Cytotoxic activity of methanol extract of Woodfordia fruticosa flowers was tested using Artemia salina (Brine shrimp) bioassay. Two doses (400 and 600 mg/Kg) were evaluated for the anti-inflammatory activity against the carrageenan, histamine, dextran, serotonin and formaldehyde-induced rat paw edema, cotton pellet-induced granuloma and formaldehyde-induced analgesia in rats. In cytotoxicity study, extract caused 73% mortality of Brine shrimp larvae after 24 h at a concentration of 1000 μg/mL. The results of the anti-inflammatory study showed that the extract produced significant (p < 0.05) decrease in paw volume in different models of paw edema. The extract also inhibited the formation of granuloma in cotton pellet-induced granuloma and reduced the frequency of formaldehyde-induced paw licking. These results showed that the methanol extract of Woodfordia fruticosa flowers have weak cytotoxic and potent anti-inflammatory compounds and justifies the traditional uses for the treatment of inflammatory conditions. PMID:24250512

  12. Molecular weight and helix conformation determine intestinal anti-inflammatory effects of exopolysaccharide from Schizophyllum commune.

    PubMed

    Du, Bin; Yang, Yuedong; Bian, Zhaoxiang; Xu, Baojun

    2017-09-15

    Intestinal anti-inflammatory activities of exopolysaccharide from S. commune were assessed using dextran sulfate sodium (DSS)-induced colitis in mice model. The changes of molecular weight (MW), atomic force microscope morphology, X-ray diffraction, particle size distribution, and viscosity were recorded after sonication treatment. The results indicated that the triple helical structure of exopolysaccharide was dissociated into single helical structure and random coiled structure by ultrasonication via breaking of inter- and intramolecular hydrogen bonds. The medium (936kDa) and high MW (1437kDa) exopolysaccharide had the mixture of triple helix and single helix conformation, while the low MW (197kDa) exopolysaccharide exhibit random coiled conformation. The intestinal anti-inflammatory activity study showed that oral administration of medium and high MW (1437kDa) exopolysaccharide significantly recovered DSS-induced colitis in inflamed tissues and reduced inflammation induced infiltration of macrophages. These results showed that medium (936kDa) and high MW (1437kDa) exopolysaccharide had intestinal anti-inflammatory activity. The intestinal anti-inflammatory activity of exopolysaccharide was related to helical structure and molecular weight. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil.

    PubMed

    Silva, Gabriela L da; Luft, Carolina; Lunardelli, Adroaldo; Amaral, Robson H; Melo, Denizar A da Silva; Donadio, Márcio V F; Nunes, Fernanda B; de Azambuja, Marcos S; Santana, João C; Moraes, Cristina M B; Mello, Ricardo O; Cassel, Eduardo; Pereira, Marcos Aurélio de Almeida; de Oliveira, Jarbas R

    2015-08-01

    Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO), however to date, there is still lack of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo) the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.

  14. Anti-inflammatory and analgesic activities of Melanthera scandens

    PubMed Central

    Okokon, Jude E; Udoh, Anwanga E; Frank, Samuel G; Amazu, Louis U

    2012-01-01

    Objective To evaluate the anti-inflammatory and analgesic activities of leaf extract of Melanthera scandens (M. scandens). Methods The crude leaf extract (39–111 mg/kg) of M. scandens was investigated for anti-inflammatory and analgesic activities using various experimental models. The anti-inflammatory activity was investigated using carragenin, egg-albumin induced oedema models, while acetic acid, formalin-induced paw licking and thermal-induced pain models were used to evaluate the antinociceptive property. Results The extract caused a significant (P<0.05 – 0.001) dose-dependent reduction of inflammation and pains induced by different agents used. Conclusions The leaf extract possesses anti-inflammatory and analgesic effects which may be mediated through the phytochemical constituents of the plant. PMID:23569885

  15. Anti-inflammatory evaluation of Ionidium suffruticosam Ging. in rats.

    PubMed

    Boominathan, R; Parimaladevi, B; Mandal, S C; Ghoshal, S K

    2004-04-01

    The anti-inflammatory activity of Ionidium suffruticosam (Violaceae) methanol extract was evaluated on carrageenin, histamine and serotonin-induced rat hind paw oedema acute models. The extract at doses of 200 and 400 mg/kg has been found to possess significant anti-inflammatory activity on the tested experimental models. The extract at the dose level of 400 mg/kg exhibited maximum anti-inflammatory activity in all the animal models. In a chronic test, the extract (400 mg/kg) showed 42.78% reduction in granuloma weight. The effect produced by the extract was comparable to that of phenylbutazone, a proto type of a non-steroidal anti-inflammatory agent.

  16. [Non steroidal anti-inflammatory drugs and rheumatic diseases].

    PubMed

    Cossermelli, W; Pastor, E H

    1995-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

  17. Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins.

    PubMed

    Tubaro, Aurelia; Giangaspero, Anna; Sosa, Silvio; Negri, Roberto; Grassi, Gianpaolo; Casano, Salvatore; Della Loggia, Roberto; Appendino, Giovanni

    2010-10-01

    A selection of seven phytocannabinoids representative of the major structural types of classic cannabinoids and their corresponding cannabivarins was investigated for in vivo topical anti-inflammatory activity in the Croton oil mouse ear dermatitis assay. Differences in the terpenoid moiety were far more important for anti-inflammatory activity than those at the C-3 alkyl residue, suggesting the involvement not only of cannabinoid receptors, but also of other inflammatory end-points targeted by phytocannabinoids.

  18. Anti-inflammatory drugs and risk of Parkinson disease

    PubMed Central

    Gagne, Joshua J.; Power, Melinda C.

    2010-01-01

    Background/Objective: Anti-inflammatory drugs may prevent Parkinson disease (PD) by inhibiting a putative underlying neuroinflammatory process. We tested the hypothesis that anti-inflammatory drugs reduce PD incidence and that there are differential effects by type of anti-inflammatory, duration of use, or intensity of use. Methods: MEDLINE and EMBASE were searched for studies that reported risk of PD associated with anti-inflammatory medications. Random-effects meta-analyses were used to pool results across studies for each type of anti-inflammatory drug. Stratified meta-analyses were used to assess duration- and intensity-response. Results: Seven studies were identified that met the inclusion criteria, all of which reported associations between nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and PD, 6 of which reported on aspirin, and 2 of which reported on acetaminophen. Overall, a 15% reduction in PD incidence was observed among users of nonaspirin NSAIDS (relative risk [RR] 0.85, 95% confidence interval [CI] 0.77–0.94), with a similar effect observed for ibuprofen use. The protective effect of nonaspirin NSAIDs was more pronounced among regular users (RR 0.71, 95% CI 0.58–0.89) and long-term users (RR 0.79, 95% CI 0.59–1.07). No protective effect was observed for aspirin (RR 1.08, 95% CI 0.92–1.27) or acetaminophen (RR 1.06, 95% CI 0.87–1.30). Sensitivity analyses found results to be robust. Conclusions: There may be a protective effect of nonaspirin nonsteroidal anti-inflammatory drug use on risk of Parkinson disease (PD) consistent with a possible neuroinflammatory pathway in PD pathogenesis. GLOSSARY CI = confidence interval; COX = cyclooxygenase; NOS = Newcastle-Ottawa Scale; NSAID = nonsteroidal anti-inflammatory drug; OTC = over-the-counter; PD = Parkinson disease; RR = relative risk. PMID:20308684

  19. Analgesic, anti-inflammatory and anti-pyretic activities of Caesalpinia decapetala

    PubMed Central

    Parveen, Amna; Sajid Hamid Akash, Muhammad; Rehman, Kanwal; Mahmood, Qaisar; Qadir, Muhammad Imran

    2014-01-01

    Introduction: In many pathological conditions, pain, inflammation and fever are interdependent to each other. Due to the use of synthetic drugs, many unwanted effects usually appear. Various studies have been conducted on Caesalpinia decapetala (C. decapetala) to evaluate its effects in the treatment of various diseases but no sufficient scientific literature is available online to prove its analgesic, anti-inflammatory and anti-pyretic activities. Methods: The analgesic, anti-inflammatory and anti-pyretic activities of 70% aqueous methanolic and n-hexane extracts of C. decapetala was evaluated using Swiss albino mice (20-30 g). Results: The results showed that aqueous methanolic extract of C. decapetala at the dose of 100 mg/kg exhibited significant (p< 0.05) activities in various pain models including acetic acid-induced writhing (18.4 ± 0.53), formalin-induced licking (275 ± 4.18) and hot plate method (2.3 ± 0.0328); whereas,  n-hexane extract showed its effects in acetic acid-induced writhing (20 ± 0.31), formalin-induced licking (293 ± 1.20) and hot plate method (2.224 ± 0.029) compared to the effects observed in control group animals. Similarly, the aqueous methanolic extract of C. decapetala after 2 h of treatment exhibited more significant anti-inflammatory (0.66 ± 0.06) and anti-pyretic (38.81 ± 0.05) activities compared to the control group animals. Conclusion: From the findings of our present study, we concluded that the aqueous methanolic extract of C. decapetala has stronger analgesic, anti-inflammatory and anti-pyretic effects than its n-hexane extract. Further studies are required to investigate the active constituents of C. decapetala that exhibit analgesic, anti-inflammatory and anti-pyretic activities. PMID:24790898

  20. Right Cervical Vagotomy Aggravates Viral Myocarditis in Mice Via the Cholinergic Anti-inflammatory Pathway

    PubMed Central

    Li-Sha, Ge; Xing-Xing, Chen; Lian-Pin, Wu; De-Pu, Zhou; Xiao-Wei, Li; Jia-Feng, Lin; Yue-Chun, Li

    2017-01-01

    The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a ‘cholinergic anti-inflammatory pathway’ dependent on the α7-nicotinic acetylcholine receptor (α7nAChR). Although the role of β-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied. Therefore, in the present study, we investigated the effects of cervical vagotomy in a murine model of viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of right cervical vagotomy and nAChR agonist nicotine on echocardiography, myocardial histopathology, viral RNA, and proinflammatory cytokine levels were studied. We found that right cervical vagotomy inhibited the cholinergic anti-inflammatory pathway, aggravated myocardial lesions, up-regulated the expression of TNF-α, IL-1β, and IL-6, and worsened the impaired left ventricular function in murine viral myocarditis, and these changes were reversed by co-treatment with nicotine by activating the cholinergic anti-inflammatory pathway. These results indicate that vagal nerve plays an important role in mediating the anti-inflammatory effect in viral myocarditis, and that cholinergic stimulation with nicotine also plays its peripheral anti-inflammatory role relying on α7nAChR, without requirement for the integrity of vagal nerve in the model. The findings suggest that vagus nerve stimulation mediated inhibition of the inflammatory processes likely provide important benefits in myocarditis treatment. PMID:28197102

  1. Molecular mechanisms of the anti-inflammatory functions of interferons

    PubMed Central

    Kovarik, Pavel; Sauer, Ines; Schaljo, Barbara

    2014-01-01

    Interferons are pleiotropic cytokines with important proinflammatory functions required in defence against infections with bacteria, viruses and multicellular parasites. In recent years, fundamental functions of interferons in other processes such as cancer immunosurveillance, immune homeostasis and immunosuppression have been established. In addition, anti-inflammatory roles of interferons are well-documented in several inflammatory disease models in the mouse, most importantly in experimental autoimmune encephalomyelitis that resembles multiple sclerosis in humans. While the beneficial effects of interferons in such disease models are known, the molecular mechanisms remain poorly understood. Only recently a few molecular principles for the anti-inflammatory properties of interferons at the cellular level have been revealed. They include the ability of interferons to reduce the expression of the receptors for the inflammation-related cytokines IL-1 and IL-4, or to increase the expression of the potent anti-inflammatory genes tristetraprolin and Twist. However, the individual contribution of these anti-inflammatory responses to the overall beneficial effects of interferons in inflammatory diseases is still an open question. Also, the reason for the apparently limited number of tissues that are susceptible to the anti-inflammatory functions of interferons remains enigmatic. This review summarizes the present knowledge of the anti-inflammatory effects of interferons, and describes the currently known molecular mechanisms that may help explain the benefits of interferon signalling in several inflammatory diseases. PMID:18086388

  2. Topical nonsteroidal anti-inflammatory drugs for osteoarthritis.

    PubMed

    Barthel, H Richard; Axford-Gatley, Robert A

    2010-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays of the treatment of osteoarthritis (OA) but have dose- and age-related risks of gastrointestinal, cardiovascular, and renal adverse events (AEs). As a result, US and international guidelines recommend caution when prescribing oral NSAIDs, particularly in older patients and those with significant comorbidities. For OA of the hands and knees, topical NSAIDs provide efficacy similar to oral NSAIDs, with far less systemic distribution. Treatment-related cardiovascular, renal, and other serious AEs with topical NSAIDs have not been reported. At present, only 2 topical NSAIDs are approved in the United States for the treatment of OA: diclofenac sodium 1% gel for hand or knee OA and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution for knee OA. Clinical trial data for these products have demonstrated efficacy superior to placebo or similar to oral diclofenac with AE profiles similar to placebo, except for application site reactions. In large double-blind trials, gastrointestinal AEs were infrequent and did not include ulcers, perforations, or bleeding. The purpose of this brief review is to examine the data from controlled double-blind trials evaluating the use of topical NSAIDs in patients with OA. Articles included were identified via a search of PubMed covering the period from January 1, 2005 through March 31, 2010. Reference lists from OA treatment guidelines and meta-analyses were reviewed for additional citations of importance.

  3. Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?

    PubMed

    Ferlazzo, Nadia; Cirmi, Santa; Calapai, Gioacchino; Ventura-Spagnolo, Elvira; Gangemi, Sebastiano; Navarra, Michele

    2016-09-23

    Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative and/or complementary medicine to treat several pathologies, including inflammation. During the last decades, the biological properties of Citrus bergamia (bergamot) derivatives have obtained important scientific achievements, and it has been suggested their use in a context of a multitarget pharmacological strategy. Here, we present an overview of the anti-inflammatory properties of bergamot extracts that could represent the scientific basis for develop novel and alternative strategies to improve health status and attenuate inflammatory conditions.

  4. Anti-inflammatory sesquiterpene lactones from Lychnophora trichocarpha Spreng. (Brazilian Arnica).

    PubMed

    Ferrari, Fernanda C; Ferreira, Leidiane C; Souza, Maíra R; Grabe-Guimarães, Andrea; Paula, Carmen A; Rezende, Simone A; Saúde-Guimarães, Dênia A

    2013-03-01

    The aerial parts of Lychnophora trichocarpha Spreng. (Asteraceae) are used macerated in water or ethanol to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. In this study, anti-inflammatory activity of ethanol extract from aerial parts of L. trichocarpha and its ethyl acetate fraction was investigated. Sesquiterpene lactones, lychnopholide (Lyc) and eremantholide C (EreC), isolated of ethyl acetate fraction, were also assayed for in vitro and in vivo anti-inflammatory activity. Topical treatment with ointments containing ethanol extract, its ethyl acetate fraction and sesquiterpene lactones significantly reduced carrageenan-induced mice paw oedema. In vitro assays demonstrated that Lyc inhibited interferon -γ/lipopolysaccharide -stimulated nitric oxide (NO) production in J774A.1 macrophages and increased production of IL-10 anti-inflammatory cytokine. The reduction of tumor necrosis factor-α (TNF-α) production by EreC was accompanied by an increased production of IL-10 in a concentration-dependent manner in J774A.1 macrophages. The anti-inflammatory effect of Lyc seems to involve the inhibition of production of NO and increased production of IL-10. The mechanism of the effect of EreC on the reduction of carrageenan-induced paw oedema may be attributed to inhibition of production of TNF-α and stimulation of IL-10 production. The results corroborate the use of ethanol extract from Lychnophora trichocarpha in folk medicine for anti-inflammatory action and indicate that the topical route is suitable for use.

  5. Topical antiedematogenic and anti-inflammatory effect of Scutia buxifolia Reissek gel and stability study.

    PubMed

    Boligon, Aline Augusti; da Rosa Moreira, Laís; Piana, Mariana; de Campos, Marli Matiko Anraku; Oliveira, Sara Marchesan

    2017-02-01

    Scutia buxifolia Reissek (Rhamnaceae), popularly known in Brazil as "coronilha", is a plant species used in folk medicine for several disorders, including inflammation. However, no studies have been done with this species to confirm its topical anti-inflammatory action. In this study we evaluate the topical antiedematogenic and anti-inflammatory effects of the gel containing crude extract (CE) and the gel containing ethyl acetate (EtOAc) fraction of S. buxifolia on croton oil or UVB radiation-induced ear edema in mice, and perform gel stability study. Antiedematogenic and anti-inflammatory effects were evaluated through ear edema induced by irritant agent croton oil, UVB irradiation-induced skin injury model and neutrophil infiltration. The gel stability study was performed by analyzing organoleptical aspects, pH, viscosity, and quantification of quercetin and rutin by HPLC. The topical treatment with S. buxifolia gel reduced the ear edema and myeloperoxidase activity. Antiedematogenic and anti-inflammatory effects of S. buxifolia were obtained with concentrations of 0.3, 1 and 3%, with maximal inhibition in the concentration of 1% for gel containing CE (inhibitions of 100, 73±0.05 and 97±0.08% for croton oil- or UVB irradiation-induced ear edema and myeloperoxidase activity, respectively) and EtOAc fraction (inhibitions of 79±0.05, 73±0.05 and 89±0.04% for croton oil- or UVB irradiation-induced ear edema and myeloperoxidase activity, respectively). Such effects may be attributed, at least in part, to rutin and quercetin, as well as other compounds found in this species. No important changes were detected in the stability study, in all aspects analyzed in temperature below 25°C. Our results demonstrate that topically applied S. buxifolia gel presented anti-inflammatory effects, provided that it was maintained at a temperature below 25°C.

  6. Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

    PubMed Central

    Khajah, Maitham A.; Fateel, Maryam M.; Ananthalakshmi, Kethireddy V.; Luqmani, Yunus A.

    2016-01-01

    Background There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. Methods The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. Results Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. Conclusion Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression. PMID:26963721

  7. Nonsteroidal anti-inflammatory drugs may affect cytokine response and benefit healing of combat-related extremity wounds.

    PubMed

    Lisboa, Felipe A; Bradley, Matthew J; Hueman, Matthew T; Schobel, Seth A; Gaucher, Beverly J; Styrmisdottir, Edda L; Potter, Benjamin K; Forsberg, Jonathan A; Elster, Eric A

    2017-04-01

    After adequate operative debridement and antimicrobial therapies, combat-related extremity wounds that either heal or fail are both associated with a distinct inflammatory response. Short-term use of nonsteroidal anti-inflammatory drugs in postoperative pain management may affect this response and, by consequence, the healing potential of these wounds. We investigated whether patients treated with nonsteroidal anti-inflammatory drugs had a distinct inflammatory response; different rates of critical colonization, defined as >10(5) colony forming units on quantitative bacteriology; and healing potential. We retrospectively reviewed the records of 73 patients with combat-related extremity wounds. Patients were separated into 2 groups: those who received nonsteroidal anti-inflammatory drugs during the debridement period (nonsteroidal anti-inflammatory drugs group, N = 17) and those who did not (control group; N = 56). Serum and wound tissue samples collected during each operative debridement were measured for 32 known cytokines and tested for quantitative bacteriology, respectively. We compared cytokine concentrations between groups and then designed a logistic regression model to identify variables associated with successful wound healing, while controlling for known confounders. Despite similar demographics and wound characteristics, the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. On multivariate analysis, nonsteroidal anti-inflammatory drug treatment emerged as a predictor of successful wound healing after controlling for known confounders such as wound size, tobacco use, Acute Physiology and Chronic Health Evaluation II score, and critical colonization. Treatment with nonsteroidal anti-inflammatory drugs for postoperative pain management after major combat-related extremity trauma is associated with lesser

  8. Anti-inflammatory effects of flavonoids in neurodegenerative disorders.

    PubMed

    Spagnuolo, Carmela; Moccia, Stefania; Russo, Gian Luigi

    2017-09-07

    Neuroinflammation is one of the main mechanisms involved in the progression of several neurodegenerative diseases, such as Parkinson, Alzheimer, multiple sclerosis, amyotrophic lateral sclerosis and others. The activation of microglia is the main feature of neuroinflammation, promoting the release of pro-inflammatory cytokines and resulting in the progressive neuronal cell death. Natural compounds, such as flavonoids, possess neuroprotective potential probably related to their ability to modulate the inflammatory responses involved in neurodegenerative diseases. In fact, pure flavonoids (e.g., quercetin, genistein, hesperetin, epigallocatechin-3-gallate) or enriched-extracts, can reduce the expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2), down-regulate inflammatory markers and prevent neural damage. This anti-inflammatory activity is primarily related to the regulation of microglial cells, mediated by their effects on MAPKs and NF-κB signalling pathways, as demonstrated by in vivo and in vitro data. The present work reviews the role of inflammation in neurodegenerative diseases, highlighting the potential therapeutic effects of flavonoids as a promising approach to develop innovative neuroprotective strategy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Invited review: The anti-inflammatory properties of dairy lipids.

    PubMed

    Lordan, R; Zabetakis, I

    2017-03-22

    Dairy product consumption is often associated with negative effects because of its naturally high levels of saturated fatty acids. However, recent research has shown that dairy lipids possess putative bioactivity against chronic inflammation. Inflammation triggers the onset of several chronic diseases, including cardiovascular disease, type 2 diabetes mellitus, obesity, and cancer. This review discusses the anti-inflammatory properties of dairy lipids found in milk, yogurt, and cheese, and it examines them in relation to their implications for human health: their protective effects and their role in pathology. We also consider the effect of lipid profile alteration in dairy products-by using ruminant dietary strategies to enrich the milk, or by lipid fortification in the products. We critically review the in vivo, in vitro, ex vivo, and epidemiological studies associated with these dairy lipids and their role in various inflammatory conditions. Finally, we discuss some suggestions for future research in the study of bioactive lipids and dairy products, with reference to the novel field of metabolomics and epidemiological studies.

  10. Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis.

    PubMed

    Kanashiro, Alexandre; Sônego, Fabiane; Ferreira, Raphael G; Castanheira, Fernanda V S; Leite, Caio A; Borges, Vanessa F; Nascimento, Daniele C; Cólon, David F; Alves-Filho, José Carlos; Ulloa, Luis; Cunha, Fernando Q

    2017-03-01

    Sepsis is one of the main causes of mortality in hospitalized patients. Despite the recent technical advances and the development of novel generation of antibiotics, severe sepsis remains a major clinical and scientific challenge in modern medicine. Unsuccessful efforts have been dedicated to the search of therapeutic options to treat the deleterious inflammatory components of sepsis. Recent findings on neuronal networks controlling immunity raised expectations for novel therapeutic strategies to promote the regulation of sterile inflammation, such as autoimmune diseases. Interesting studies have dissected the anatomical constituents of the so-called "cholinergic anti-inflammatory pathway", suggesting that electrical vagus nerve stimulation and pharmacological activation of beta-2 adrenergic and alpha-7 nicotinic receptors could be alternative strategies for improving inflammatory conditions. However, the literature on infectious diseases, such as sepsis, is still controversial and, therefore, the real therapeutic potential of this neuroimmune pathway is not well defined. In this review, we will discuss the beneficial and detrimental effects of neural manipulation in sepsis, which depend on the multiple variables of the immune system and the nature of the infection. These observations suggest future critical studies to validate the clinical implications of vagal parasympathetic signaling in sepsis treatment.

  11. Anti-inflammatory effect of geranium nanoemulsion macrophages induced with soluble protein of Candida albicans.

    PubMed

    Giongo, Janice Luehring; de Almeida Vaucher, Rodrigo; Sagrillo, Michele Rorato; Vianna Santos, Roberto Christ; Duarte, Marta M M F; Rech, Vírginia Cielo; Soares Lopes, Leonardo Quintana; Beatriz da Cruz, Ivana; Tatsch, Etiane; Moresco, Rafael Noal; Gomes, Patricia; Luchese, Cristiane; Steppe, Martin

    2017-09-01

    Pelargonium graveolens is a member of the Geraniaceae family and has been used in folk medicine in many countries because of its anti-inflammatory activity. No studies have yet been reported to evaluate the anti-inflammatory activity of a nanoemulsion containing geranium oil (GO) model in macrophages. In this study the anti-inflammatory effect of Geranium nanoemulsion (NEG) macrophages induced with soluble proteins of Candida albicans was investigated. GO presented citronellol (17.74%) and geraniol (14.43%) as main constituents. The characterization in NEG was demonstrated, showing the particle size of 164 ± 3.5 nm, PDI of 0.12 ± 0.006 and zeta potential -10 mV ± 1.7. The MIC obtained for NEG and GO were 3.64 μg ml(-1) and 1.82 μg ml(-1), respectively. The viability of the macrophages treated with NEG and GO concentrations (1/2 x, 1x and 2x MIC) was evaluated. There was a significant reduction of viability and the MTT assay was not confirmed after the LDH assay. Anti-inflammatory activity was evaluated by determining nitric oxide (NO), cytokines (interleukin IL-1, IL-6 and IL-10), tumor necrosis factor-α (TNF) and the expression levels gene of interleukin (IL-2), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The apoptosis inhibition capacity was assessed by determination of INFγ, caspase 3 and caspase 8. The results indicated that there was a significant increase of NO in the levels after treatment with NEG and significantly reduced levels after treatment with GO. The cytokines (IL-1, IL-6, IL-10, and TNF) were evaluated and NEG (½ x, 1x MIC) decreased IL-1 levels by 1.25-1.37 times, respectively. The NEG did not decrease IL-6 levels and a significant increase was observed for IL-10. GO significantly decreased IL-6 and IL-10 levels. There was a significant decrease in IL-2 and COX-2 levels and increased levels of iNOs. The levels of IFNγ and caspase-3 after treatment with NEG decreased indicating an anti-inflammatory

  12. Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.

    PubMed Central

    Kaushik, Dhirender; Kumar, Ajay; Kaushik, Pawan; Rana, A. C.

    2012-01-01

    The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models. PMID:22761611

  13. Anti-inflammatory role of obestatin in autoimmune myocarditis.

    PubMed

    Pamukcu, Ozge; Baykan, Ali; Bayram, Latife Cakir; Narin, Figen; Cetin, Nazmi; Narin, Nazmi; Argun, Mustafa; Ozyurt, Abdullah; Uzum, Kazim

    2016-01-01

    Obestatin is a popular endogeneous peptide, known to have an autoimmune regulatory effect on energy metabolism and the gastrointestinal system. Studies regarding the anti-inflammatory effects of obestatin are scarce. The aim of this study was to show the anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis in rats. Experimental autoimmune myocarditis was induced in Lewis rats by immunization with subcutaneous administration of porcine cardiac myosin, twice at 7-day intervals. Intraperitoneal pretreatment with obestatin (50 μg/kg) was started before the induction of myocarditis and continued for 3 weeks. The severity of myocarditis was evidenced by clinical, echocardiographic and histological findings. In addition, by-products of neutrophil activation, lipid peroxidation, inflammatory and anti-inflammatory cytokines were measured in serum. Obestatin significantly ameliorated the clinical and histopathological severity of autoimmune myocarditis. Therapeutic effects of obestatin in myocarditis were associated with reduced lipid peroxidation, suppression of polymorphonuclear leukocyte infiltration and enhancement of glutathione synthesis, inhibition of serum inflammatory and activation of anti-inflammatory cytokines. Histopathologically, the left ventricle was significantly dilated, and its wall thickened, along with widespread lymphocytic and histocytic infiltration. The myocardium was severely infiltrated with relatively large mononuclear cells. These histopathological changes were observed in lesser degrees in obestatin-treated rats. This study demonstrated a novel anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis. Consequently, obestatin administration may represent a promising therapeutic approach for myocarditis and dilated cardiomyopathy in the future.

  14. Anti-inflammatory activity of selected plants from Saudi Arabia.

    PubMed

    Abdallah, Hossam M; Abdel-Naim, Ashraf B; Ashour, Osama M; Shehata, Ibrahim A; Abdel-Sattar, Essam A

    2014-01-01

    Thirteen selected Saudi Arabian plants, belonging to seven different families, were tested for possible anti-inflammatory activity using the carrageenin-induced paw edema model in rats. The methanolic extracts of Vernonia schimperi, Trichodesma trichodesmoides var. tomentosum, and Anabasis articulata exhibited the highest anti-inflammatory activity. The active extracts were further subjected to fractionation with chloroform, ethyl acetate, and n-butanol and tested together with their mother liquor for their anti-inflammatory activity in the same rat model. The most potent fractions were the n-butanol fractions of Anabasis articulata and Vernonia shimperi and the aqueous mother liquor of Trichodesma trichodesmoides. Nevertheless, the three potent methanolic extracts showed higher anti-inflammatory activities than their individual fractions. The antioxidant properties were assessed by their in vitro 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activities. It was concluded that the anti-inflammatory activity is dependent, at least in part, on the reduction of prostaglandin (PGE2) and tumour necrosis factor-alpha (TNF-alpha) levels and cyclooxygenase-2 (COX-2) activity.

  15. Anti arthritic and anti inflammatory activity of a cytotoxic protein NN-32 from Indian spectacle cobra (Naja naja) venom in male albino rats.

    PubMed

    Gomes, Antony; Datta, Poulami; Das, Tanaya; Biswas, Ajoy Kumar; Gomes, Aparna

    2014-11-01

    The anti arthritic and anti inflammatory activity of NN-32, a cytotoxic protein from Indian spectacle cobra snake (Naja naja) venom has been studied in Freund's complete adjuvant (FCA) induced arthritis and carrageenan induced anti inflammatory model. NN-32 treatment showed significant decrease in physical and urinary parameters, serum enzymes, serum cytokines levels as compared to arthritic control group of rats. NN-32 treatment recovered carrageenan induced inflammation as compared to control group of rats. The findings showed that the cytotoxic protein NN-32 shares anti arthritic and anti inflammatory activity and thus NN-32 may target complex pathophysiological processes like cancer- arthritis-inflammation.

  16. [Meloxicam: the golden mean of nonsteroidal anti-inflammatory drugs].

    PubMed

    Karateev, A E

    2014-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used to treat acute and chronic pain in locomotor system (LMS) diseases. However, their administration may be accompanied by the development of dangerous complications as organic and functional disorders of the cardiovascular system (CVS) and gastrointestinal tract (GIT). Physicians have currently a wide range of NSAIDs at their disposal; but none of the representatives of this group can be considered the best. Thus, highly selective cyclooxygenase-2 inhibitors (Coxibs) are substantially safer for GIT; however, their use is clearly associated with the increased risk of severe cardiovascular events. Nonselective NSAIDs, such as naproxen or ketoprofen, are safer for CVS, but more frequently cause significant GIT organic and functional disorders. Moderately selective NSAIDs, such as meloxicam (movalis), conceivably could be the most acceptable choice for treating the majority of patients in this situation. This drug has been long and extensively used in global clinical practice and has gained the confidence of physicians and patients. The major benefits of meloxicam are its proven efficacy, convenient treatment regimen, relatively low risk of complications as organic and functional disorders of the GIT and CVD and good compatibility with low-dose aspirin.

  17. Immunomodulatory and anti-inflammatory effects of chondroitin sulphate

    PubMed Central

    du Souich, Patrick; García, Antonio G; Vergés, Josep; Montell, Eulàlia

    2009-01-01

    Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1–3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 p (IL-1p)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-KB (NF-kB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1 p and TNF-a, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2). The mechanism of action of CS explains its beneficial effect on the cartilage, synovial membrane and subchondral bone. On the other hand, in vivo, CS given orally prevents hepatic NF-κB nuclear translocation, suggesting that systemic CS may elicit an anti-inflammatory effect in many tissues besides the articulation. There is preliminary evidence showing that in human beings, CS may be of benefit in other diseases where inflammation is an essential marker, such as psoriasis and atherosclerosis. The review of the literature suggest that CS might also be of interest for the treatment of other diseases with an inflammatory and/or autoimmune character, such as inflammatory bowel disease, degenerative diseases of the central nervous system and stroke, multiple sclerosis and other autoimmune diseases. PMID:19522843

  18. Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

    PubMed

    Hodkinson, Duncan J; Khawaja, Nadine; OʼDaly, Owen; Thacker, Michael A; Zelaya, Fernando O; Wooldridge, Caroline L; Renton, Tara F; Williams, Steven C R; Howard, Matthew A

    2015-07-01

    Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction, and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow under pain-free conditions (presurgery). However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.

  19. Anti-Inflammatory Effect of Ethanolic Extract of Sargassum serratifolium in Lipopolysaccharide-Stimulated BV2 Microglial Cells.

    PubMed

    Oh, Sun-Ji; Joung, Eun-Ji; Kwon, Mi-Sung; Lee, Bonggi; Utsuki, Tadanobu; Oh, Chul-Woong; Kim, Hyeung-Rak

    2016-11-01

    Sargassum serratifolium was found to contain high concentrations of meroterpenoids, having strong antioxidant, anti-inflammatory, and neuroprotective activities. This study aims to investigate the anti-inflammatory mechanisms of an ethanolic extract of S. serratifolium (ESS) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and to identify the anti-inflammatory components in ESS. The level of proinflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of inflammation-related proteins and mRNA was evaluated by Western blot and reverse transcription-polymerase chain reaction analysis, respectively. Anti-inflammatory activities of isolated components from ESS were analyzed in LPS-stimulated BV2 cells. ESS inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 and the expression of inducible NO synthase and cyclooxygenase-2. ESS also decreased the release of proinflammatory cytokines in a dose-dependent manner. LPS-induced nuclear factor-kappa B (κB) transcriptional activity and translocation into the nucleus were remarkably suppressed by ESS through the prevention of inhibitor κB-α degradation. The main anti-inflammatory components in ESS were identified as sargahydroquinoic acid, sargachromenol, and sargaquinoic acid based on the inhibition of NO production using LPS-stimulated BV2 cells. Furthermore, treatment with ESS significantly reduced levels of tumor necrosis factor-α and interleukin-1β stimulated with LPS in mouse hippocampus. Our results indicate that ESS can be used as a functional food or therapeutic agent for the treatment of neuroinflammatory diseases.

  20. Antimetastatic and Anti-Inflammatory Potentials of Essential Oil from Edible Ocimum sanctum Leaves

    PubMed Central

    Thirugnanasampandan, Ramaraj; Jayakumar, Rajarajeswaran; Ramya, Gunasekar; Ramnath, Gogul

    2014-01-01

    Antimetastatic and anti-inflammatory activities of Ocimum sanctum essential oil (OSEO) have been assessed in this study. OSEO at the concentration of 250 μg/mL and above showed a significant (*P < 0.05) decrease in the number of migrated cancer cells. In addition, OSEO at concentration of 250 μg/mL and above suppressed MMP-9 activity in lipopolysaccharide (LPS) induced inflammatory cells. A dose-dependent downregulation of MMP-9 expression was observed with the treatment of OSEO compared to the control. Our findings indicate that OSEO has both antimetastatic and anti-inflammatory potentials, advocating further investigation for clinical applications in the treatment of inflammation associated cancer. PMID:25431779

  1. Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review.

    PubMed

    Dua, Kamal; Sheshala, Ravi; Ling, Teck Ying; Hui Ling, Shiau; Gorajana, Adinarayana

    2013-01-01

    At present, approximately 25%of drugs in modern pharmacopoeia are derived from plant sources (phytomedicines) that can be developed for the treatment of diseases and disorders. Many other drugs are synthetic analogues built on the prototype compounds isolated from plants. Cocos nucifera Linn. (Arecaceae), which is commonly known as coconut, is a plant possessing a lot of potential as an ingredient in traditional medicines for the treatment of metabolic disorders and particularly as an anti-inflammatory, antimicrobial and analgesic agent. This review emphasizes on the recent literature and research findings that highlight the significant biological activities of C. nucifera Linn. such as its anti-inflammatory, antimicrobial and analgesic properties. This review can help researchers keen on exploiting the therapeutic potential of C. nucifera Linn. which may motivate them to further explore their commercial viability.

  2. Antioxidant and anti-inflammatory activities of aqueous extract of Centipeda minima.

    PubMed

    Huang, Shyh-Shyun; Chiu, Chuan-Sung; Lin, Tsung-Hui; Lee, Min-Min; Lee, Chao-Ying; Chang, Shu-Jen; Hou, Wen-Chi; Huang, Guan-Jhong; Deng, Jeng-Shyan

    2013-05-20

    Centipeda minima (L.) is traditionally used in Chinese folk medicine for the treatments of rhinitis, sinusitis, relieving pain, reducing swelling, and treating cancer for a long history in Taiwan. However, there is no scientific evidence which supports the use in the literature. The aim of this study was to evaluate the antioxidant and anti-inflammatory activities of the aqueous extract of Centipeda minima (ACM). The following activities were investigated: antioxidant activities [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), DPPH (1,1-diphenyl-2-picrylhydrazyl)], and anti-inflammatory [lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 macrophages and paw-edema induced by λ-carrageenan (Carr)]. We also investigated the anti-inflammatory mechanism of ACM via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the edema paw. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were also measured in vivo. In HPLC analysis, the fingerprint chromatogram of ACM was established. ACM showed the highest TEAC and DPPH radical scavenging activities, respectively. ACM also had highest contents of polyphenol and flavonoid contents. We evaluated that ACM and the reference compound of protocatechualdehyde and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Administration of ACM showed a concentration dependent inhibition on paw edema development after Carr treatment in mice. The anti-inflammatory effects of ACM could be via NO, TNF-α, and IL-1β suppressions and associated with the increase in the activities of antioxidant enzymes. Western blotting revealed that ACM decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. Anti-inflammatory mechanisms of ACM might be correlated to the decrease in the level of Malondialdehyde (MDA), iNOS, and COX-2 via

  3. Antioxidant, analgesic, and anti-inflammatory activities of the ethanolic extracts of Taxillus liquidambaricola.

    PubMed

    Deng, Jeng-Shyan; Chi, Chuan-Sung; Huang, Shyh-Shyun; Shie, Pei-Hsin; Lin, Tsung-Hui; Huang, Guan-Jhong

    2011-10-11

    [corrected] The Taxillus liquidambaricola has been used to treat rheumatic arthralgia, threatened abortion and hypertension in the Chinese traditional medicine. However, there is no scientific evidence which supports the use in the literature. This study aimed to determine the antioxidant, and analgesic activities and the mechanism of anti-inflammatory activities of the ethanolic extracts of Taxillus liquidambaricola (ETL) in cell and animal models. The following activities were investigated: free radical scavenging and antioxidant activities [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and DPPH (1, 1-diphenyl-2-picrylhydrazyl)], analgesic (writhing and formalin test), and anti-inflammatory [lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 macrophages and paw-edema induced by λ-carrageenan (Carr)]. We also investigate the anti-inflammatory mechanism of ETL via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the edema paw. Serum NO and tumor necrosis factor α (TNF-α) were also measured in vivo. ETL showed the highest TEAC and DPPH radical scavenging activities, respectively. ETL also had highest contents of polyphenol and flavonoid contents. We evaluated that ETL and the reference compound of quercetin decreased the LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. Treatment of male ICR mice with ETL significantly inhibited the numbers of acetic acid-induced writhing response and the formalin-induced pain in the late phase. Administration of ETL showed a concentration dependent inhibition on paw edema development after Carr treatment in mice. The anti-inflammatory effects of ETL could be via NO and TNF-α suppression and associated with the increase in the activities of antioxidant enzymes. Western blotting revealed that ETL decreased Carr-induced inducible nitric oxide synthase (iNOS) and

  4. Anti-inflammatory and immunological effects of Centaurea cyanus flower-heads.

    PubMed

    Garbacki, N; Gloaguen, V; Damas, J; Bodart, P; Tits, M; Angenot, L

    1999-12-15

    Centaurea cyanus flower-heads are used in European phytotherapy for the treatment of minor ocular inflammations. Different pharmacological experiments (inhibition of carrageenan, zymosan and croton oil-induced oedemas, inhibition of plasma haemolytic activity, induction of anaphylatoxin activity) showed that polysaccharides extracted from C. cyanus flower-heads had anti-inflammatory properties and interfered with complement. Moreover, these polysaccharides were found to be mainly composed of galacturonic acid, arabinose, glucose, rhamnose and galactose.

  5. Studies on anti-inflammatory and analgesic properties of Lactobacillus rhamnosus in experimental animal models.

    PubMed

    Amdekar, Sarika; Singh, Vinod

    2016-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for the treatment of inflammatory diseases. However, constant use of NSAID may lead to some side effects like gastrointestinal ulcers, bleeding and renal disorders. This study evaluates analgesic and anti-inflammatory activities of Lactobacillus rhamnosus in female Wistar rats. Diclofenac sodium was used as a standard drug for comparison. L. rhamnosus, drugs and vehicle were administered orally. Acetic acid-induced writhing test and carrageenan-induced paw edema model were used for evaluation. Paw edema and number of writhes were measured subsequently. Pro-inflammatory (interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines were estimated in serum after 24 h. Results showed that L. rhamnosus significantly decreased the paw thickness at t=24 h by 28.66 % while drug decreased by 19.33 %. Also, L. rhamnosus treatment and standard drug showed a protection of 66.66 % and 41.66 %, respectively. L. rhamnosus and diclofenac sodium treatment significantly down-regulated pro-inflammatory and up-regulated anti-inflammatory cytokines at p<0.0001. Overall, protection provided by L. rhamnosus was more pronounced in comparison to diclofenac sodium. The present study clearly suggests that L. rhamnosus suppressed carrageenan-induced paw edema after second phase and decreased the acetic acid-induced writhings. It ameliorated the inflammatory pathways by down-regulating pro-inflammatory cytokines. However, additional clinical investigations are needed to prove the efficacy of L. rhamnosus in treatment/management of inflammatory joint diseases.

  6. Aloe vera and gibberellin. Anti-inflammatory activity in diabetes.

    PubMed

    Davis, R H; Maro, N P

    1989-01-01

    Aloe vera inhibits inflammation and adjuvant-induced arthritis. The authors' laboratory has shown that A. vera improves wound healing, which suggests that it does not act like an adrenal steroid. Diabetic animals were used in this study because of their poor wound healing and anti-inflammatory capabilities. The anti-inflammatory activity of A. vera and gibberellin was measured in streptozotocin-induced diabetic mice by measuring the inhibition of polymorphonuclear leukocyte infiltration into a site of gelatin-induced inflammation over a dose range of 2 to 100 mg/kg. Both Aloe and gibberellin similarly inhibited inflammation in a dose-response manner. These data tend to suggest that gibberellin or a gibberellin-like substance is an active anti-inflammatory component in A. vera.

  7. Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors.

    PubMed

    Smith, Christina E; Soti, Subada; Jones, Torey A; Nakagawa, Akihisa; Xue, Ding; Yin, Hang

    2017-02-15

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo. We characterize caspase activity in both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design.

  8. Anti-inflammatory Flavonoids Isolated from Passiflora foetida.

    PubMed

    Nguyen, Thi Yen; To, Dao Cuong; Tran, Manh Hung; Lee, Joo Sang; Lee, Jeong Hyung; Kim, Jeong Ah; Woo, Mi Hee; Min, Byung Sun

    2015-06-01

    In this study, we evaluated the anti-inflammatory activity of the soluble ethyl acetate fraction and chemical components of the stem bark of Passiflora foetida (Passifloraceae). Ten flavonoids (1-10) were isolated by various chromatographic techniques, and their structures were determined based on spectroscopic analyses by using nuclear magnetic resonance (NMR). Luteolin (2) and chrysoeriol (3) showed the most potent inhibition of nitric oxide (NO) production in macrophage cell line, RAW264.7, with half maximal inhibitor concentration (IC50) values of 1.2 and 3.1 μM, respectively. These compounds suppressed lipopolysaccharide (LPS)-induced inducible NO synthase (iNOS) expression at the transcription level. Our research indicates that the stem bark of P. foetida has significant anti-inflammatory properties, suggesting that its flavonoids may have anti-inflammatory benefits.

  9. The use of polymeric microcarriers loaded with anti-inflammatory substances in the therapy of experimental skin wounds.

    PubMed

    Murueva, A V; Shershneva, A M; Shishatskaya, E I; Volova, T G

    2014-09-01

    We studied the effects of anti-inflammatory substances incorporated in polymeric microparticles made of degradable natural polyhydroxyalkanoate polyesters on experimental skin wounds caused by chemical burns in laboratory animals. Treatment with encapsulated forms of anti-inflammatory substances (applied in gel) accelerated wound healing in comparison with routine therapy (estimated by area of burn wound, wound healing activity, number of acanthotic cells, and number of hair and sebaceous follicles). The results showed the perspectives of usage of developed form of substances (degradable polymeric microparticles) for treatment of skin defects.

  10. Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances

    PubMed Central

    Mahdizadeh, Shahla; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2015-01-01

    Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain. PMID:26101752

  11. Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.

    PubMed

    Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Garrido-Mesa, Jose; Garrido-Mesa, Natividad; Utrilla, M Pilar; González-Tejero, M Reyes; Casares-Porcel, Manuel; Molero-Mesa, Joaquin; Del Mar Contreras, Maria; Segura-Carretero, Antonio; Pérez-Palacio, José; Diaz, Caridad; Vergara, Noemí; Vicente, Francisca; Rodriguez-Cabezas, M Elena; Galvez, Julio

    2016-08-22

    effect, confirming their potential use as herbal remedies in gastrointestinal disorders. In addition, their anti-inflammatory effect was also observed in other locations, thus suggesting a possible use for the treatment of the extra-intestinal symptoms of IBD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Evaluation of anti-inflammatory and antinociceptive effects of D-002 (beeswax alcohols).

    PubMed

    Ravelo, Yazmin; Molina, Vivian; Carbajal, Daisy; Fernández, Lilia; Fernández, Julio C; Arruzazabala, María L; Más, Rosa

    2011-04-01

    D-002, a mixture of six higher aliphatic alcohols purified from beeswax, displayed anti-inflammatory effects in carrageenan-induced pleurisy and cotton pellet granuloma in rats. The aim of the present study was to confirm the anti-inflammatory properties of D-002 and to explore its potential analgesic effects. Xylene-induced mouse ear oedema was used to assess the anti-inflammatory effect, acetic acid-induced writhing and hot plate responses for the analgesic activity, and the open field and horizontal rotarod tests for motor performance. For anti-inflammatory tests, mice were randomised into a negative vehicle control and five xylene-treated groups: the vehicle, D-002 (25, 50 and 200 mg/kg) and indomethacin 1 mg/kg (reference drug). Treatments were given for 15 days. Effects on oedema formation and myeloperoxidase (MPO) activity were tested. For analgesia and motor performance tests, mice were randomised into a vehicle control and D-002-treated groups (25, 50 and 200 mg/kg). Two sets of experiments were done, which included acute and repeat (15 days) dosing. D-002 (25, 50 and 200 mg/kg) significantly decreased xylene-induced ear oedema (44.7, 60.8 and 76.4%, respectively) and the increase of MPO activity induced by xylene (38.0, 47.0 and 57.0%, respectively), while indomethacin significantly inhibited xylene-induced oedema (59.9%) and MPO activity (57.5%). Single and repeat doses of D-002 (25, 50 and 200 mg/kg) decreased the acetic acid-induced writhing responses by 21.2, 28.2 and 40.1%, for the single doses; 25.2, 35.1 and 43.2%, respectively, for the repeat doses, but did not affect the hot plate, open field and rotarod behaviours. Aspirin 100 mg/kg significantly decreased acetic acid-induced abdominal constrictions and morphine (5 mg/kg) significantly increased the latency of the hot plate response. This study confirmed the anti-inflammatory effects of D-002 and demonstrated its analgesic effects on the acetic acid-induced writhing, but not on the hot plate

  13. Anti-inflammatory phenylpropanoids and phenolics from Ficus hirta Vahl.

    PubMed

    Cheng, Jun; Yi, Xiaomin; Chen, Haiying; Wang, Yihai; He, Xiangjiu

    2017-09-01

    Four new phenylpropanoids (1-4) along with ten known phenolics were isolated and purified from the roots of hairy fig (Ficus hirta Vahl.). Their structures were elucidated by the extensive spectroscopic analysis and chemical degradation. The anti-inflammatory activities of the purified compounds were evaluated. Results indicated that the extracts and some purified compounds exhibited pronounced inhibitory effects on the lipopolysaccharides (LPS) induced nitric oxide (NO) production in murine macrophage RAW 264.7 compared to indomethacin, which suggested that hairy fig could be served as an anti-inflammatory agent for health products. Copyright © 2017. Published by Elsevier B.V.

  14. Anti-inflammatory new coumarin from the Ammi majus L

    PubMed Central

    2012-01-01

    Investigation of the aerial parts of the Egyptian medicinal plant Ammi majus L. led to isolation of new coumarin, 6-hydroxy-7-methoxy-4 methyl coumarin (2) and 6-hydroxy-7-methoxy coumarin (3); this is the first time they have been isolated from this plant. The structures of the compounds (2 &3) were elucidated by spectroscopic data interpretation and showed anti-inflammatory and anti-viral activity. Graphical abstract An efficient, one-new coumarin (2) was isolated from the aerial parts of the A. Majus L. was evaluated for their anti-viral and anti-inflammatory activities. PMID:22373472

  15. Nonsteroidal anti-inflammatory drugs in cats: a review.

    PubMed

    Lascelles, B Duncan X; Court, Michael H; Hardie, Elizabeth M; Robertson, Sheilah A

    2007-07-01

    To review the evidence regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in cats. PubMed, CAB abstracts. Nonsteroidal anti-inflammatory drugs should be used with caution in cats because of their low capacity for hepatic glucuronidation, which is the major mechanism of metabolism and excretion for this category of drugs. However, the evidence presented supports the short-term use of carprofen, flunixin, ketoprofen, meloxicam and tolfenamic acid as analgesics in cats. There were no data to support the safe chronic use of NSAIDs in cats.

  16. Dietary flavonoids: molecular mechanisms of action as anti- inflammatory agents.

    PubMed

    Marzocchella, Laura; Fantini, Massimo; Benvenuto, Monica; Masuelli, Laura; Tresoldi, Ilaria; Modesti, Andrea; Bei, Roberto

    2011-09-01

    Flavonoids are a large group of polyphenolic compounds, which are ubiquitously expressed in plants. They are grouped according to their chemical structure and function into flavonols, flavones, flavan-3-ols, anthocyanins, flavanones and isoflavones. Many of flavonoids are found in fruits, vegetables and beverages. Flavonoids have been demonstrated to have advantageous effects on human health because their anti-allergic, anti-inflammatory, anti-platelet aggregation, anti-tumor and anti-oxidant behavior. This report reviews the current knowledge on the molecular mechanisms of action of flavonoids as anti-inflammatory agents and also discusses the relevant patents.

  17. Kalanchosine dimalate, an anti-inflammatory salt from Kalanchoe brasiliensis.

    PubMed

    Costa, Sônia Soares; de Souza, Maria de Lourdes Mendes; Ibrahim, Tereza; de Melo, Giany Oliveira; de Almeida, Ana Paula; Guette, Catherine; Férézou, Jean-Pierre; Koatz, Vera Lucia G

    2006-05-01

    This report describes the isolation and characterization of kalanchosine dimalate (KMC), an anti-inflammatory salt from the fresh juice of the aerial parts of Kalanchoe brasiliensis. KMC comprises the new metabolite kalanchosine (1) and malic acid (2) in a 1:2 stoichiometric ratio. Kalanchosine (1), 3,6-diamino-4,5-dihydroxyoctanedioic acid, is the first naturally occurring dimeric bis(gamma-hydroxy-beta-amino acid) and is at least partially responsible for the anti-inflammatory properties of K. brasiliensis.

  18. Isoflavones: Anti-Inflammatory Benefit and Possible Caveats.

    PubMed

    Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

    2016-06-10

    Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks.

  19. New anti-inflammatory flavonoids from Cadaba glandulosa Forssk.

    PubMed

    Mohamed, Gamal A; Ibrahim, Sabrin R M; Al-Musayeib, Nawal M; Ross, Samir A

    2014-04-01

    Three new flavonoids; kaempferol-4'-phenoxy-3,3',5'-trimethylether (3), rhamnocitrin-4'-(4-hydroxy-3-methoxy)phenoxy-3-methyl ether (4), and rhamnocitrin-3-O-neohesperoside-4'-O-rhamnoside (6), along with three known compounds; 4-methoxy-benzyldehyde (1), kaempferol-3-methylether (2), and stachydrine (5) were isolated from the aerial parts of Cadaba glandulosa Forssk. Their chemical structures were established by physical, chemical, and spectral methods, as well as comparison with literature data. The antioxidant and anti-inflammatory activities of the isolated compounds were determined. Compounds 2-4, and 6 exhibited potent anti-inflammatory activity comparable with indomethacin and moderate antioxidant activity.

  20. Nonsteroidal Anti-inflammatory Drug Use in Horses.

    PubMed

    Knych, Heather K

    2017-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic agents and are arguably the most commonly used class of drugs in equine medicine. This article provides a brief review of the mechanism of action, therapeutic uses, pharmacokinetics, and adverse effects associated with their use in horses. The use of COX-2 selective NSAIDs in veterinary medicine has increased over the past several years and special emphasis is given to the use of these drugs in horses. A brief discussion of the use of NSAIDs in performance horses is also included.

  1. Anti-inflammatory and analgesic activities of Tunisian Citrullus colocynthis Schrad. immature fruit and seed organic extracts.

    PubMed

    Marzouk, B; Marzouk, Z; Fenina, N; Bouraoui, A; Aouni, M

    2011-06-01

    Inflammations and immune-related diseases including rheumatoid arthritis are widespread in the entire globe. The treatment of these illnesses is mainly based on the use of synthetic and biotechnological drugs, in recent years. Tunisian traditional medicine is a potential source of new remedies namely Citrullus colocynthis Schrad. (Cucurbitaceae): endemic in southern Tunisia and used in folk medicine to treat many inflammation disorders. Our goal was to assess the in vivo analgesic and anti-inflammatory activities of Tunisian Citrullus colocynthis immature fruit and seed organic extracts (petroleum ether, chloroform, ethyl acetate, acetone and finely methanol extract). Yields of prepared organic extracts are gravimetrically determined. For the analgesic and anti-inflammatory activities, we have used respectively, the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats. All extracts displayed an important analgesic and anti-inflammatory activities at different doses without inducing any side effects. This study has demonstrated the analgesic and anti-inflammatory activities of Citrullus colocynthis immature fruit and seed extracts. Experiment results provide scientific insight into the ancient practice of utilizing Citrullus colocynthis Schrad. as analgesic and as anti-inflammatory agents.

  2. TUDCA: An Agonist of the Bile Acid Receptor GPBAR1/TGR5 With Anti-Inflammatory Effects in Microglial Cells.

    PubMed

    Yanguas-Casás, Natalia; Barreda-Manso, M Asunción; Nieto-Sampedro, Manuel; Romero-Ramírez, Lorenzo

    2017-08-01

    Bile acids are steroid acids found in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of stroke and neurological diseases. We have previously shown that TUDCA has anti-inflammatory effects on glial cell cultures and in a mouse model of acute neuroinflammation. We show now that microglial cells (central nervous system resident macrophages) express the G protein-coupled bile acid receptor 1/Takeda G protein-coupled receptor 5 (GPBAR1/TGR5) in vivo and in vitro. TUDCA binding to GPBAR1/TGR5 caused an increase in intracellular cAMP levels in microglia that induced anti-inflammatory markers, while reducing pro-inflammatory ones. This anti-inflammatory effect of TUDCA was inhibited by small interference RNA for GPBAR1/TGR5 receptor, as well as by treatment with a protein kinase A (PKA) inhibitor. In the mouse model of acute neuroinflammation, treating the animals with TUDCA was clearly anti-inflammatory. TUDCA biased the microglial phenotype in vivo and in vitro toward the anti-inflammatory. The bile acid receptor GPBAR1/TGR5 could be a new therapeutic target for pathologies coursing with neuroinflammation and microglia activation, such as traumatic brain injuries, stroke, or neurodegenerative diseases. TUDCA and other GPBAR1/TGR5 agonists need to be further investigated, to determine their potential in attenuating the neuropathologies associated with microglia activation. J. Cell. Physiol. 232: 2231-2245, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Anti-inflammatory and antinociceptive effects of hydroalcoholic extract from Pseudobombax marginatum inner bark from caatinga potiguar.

    PubMed

    Paiva, Dayane Carla Costa; dos Santos, Cliomar Alves; Diniz, Jaécio Carlos; Viana, Francisco Arnaldo; Thomazzi, Sara Maria; Falcão, Dayseanne Araujo

    2013-09-16

    The Pseudobombax marginatum (St Hil) Rob., Malvaceae, is mentioned in ethnobotanical studies. It is used as anti-inflammatory, for ulcers and gastritis, and back pain. To evaluate anti-inflammatory and antinociceptive activities a hydroalcoholic extract (HE) from inner bark was prepared. For the anti-inflammatory activity, carrageenan-induced paw edema and peritonitis models, and also myeloperoxidase assay were used. For the antinociceptiva activity acetic acid-induced writhing, hot plate and formalin tests were employed. The HE extract exhibited an intense inhibition in carrageenan-induced edema model and also in myeloperoxidase activity at the doses of 100 and 300 mg/kg. The leukocyte migration into the peritoneal cavity was also inhibited at the doses of 30, 100 and 300 mg/kg. A similar profile was observed against acid-induced abdominal contortions and in formalin second phase test at the doses of 30 and 100 mg/kg, but this treatment did not affect the behavior of animals in the hot plate test. The experimental data of the HE from Pseudobombax marginatum show anti-inflammatory and antinociceptiva activities, confirming the indication from traditional medicine; however further studies are required to define and isolate the active anti-inflammatory and antinociceptiva components from this active specie. © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation.

    PubMed

    Vandevyver, Sofie; Dejager, Lien; Tuckermann, Jan; Libert, Claude

    2013-03-01

    Glucocorticoids are anti-inflammatory drugs that are widely used for the treatment of numerous (autoimmune) inflammatory diseases. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor family of transcription factors. Upon ligand binding, the GR translocates to the nucleus, where it acts either as a homodimeric transcription factor that binds glucocorticoid response elements (GREs) in promoter regions of glucocorticoid (GC)-inducible genes, or as a monomeric protein that cooperates with other transcription factors to affect transcription. For decades, it has generally been believed that the undesirable side effects of GC therapy are induced by dimer-mediated transactivation, whereas its beneficial anti-inflammatory effects are mainly due to the monomer-mediated transrepressive actions of GR. Therefore, current research is focused on the development of dissociated compounds that exert only the GR monomer-dependent actions. However, many recent reports undermine this dogma by clearly showing that GR dimer-dependent transactivation is essential in the anti-inflammatory activities of GR. Many of these studies used GR(dim/dim) mutant mice, which show reduced GR dimerization and hence cannot control inflammation in several disease models. Here, we review the importance of GR dimers in the anti-inflammatory actions of GCs/GR, and hence we question the central dogma. We summarize the contribution of various GR dimer-inducible anti-inflammatory genes and question the use of selective GR agonists as therapeutic agents.

  5. Adverse effects of conventional non-steroidal anti-inflammatory drugs on the upper gastrointestinal tract.

    PubMed

    Langman, Michael J S

    2003-08-01

    This article reviews the clinical and epidemiological features of conventional non-steroidal anti-inflammatory drug (NSAID) related peptic ulcer complications, and the associated risk factors. The degree of gastrointestinal toxicity varies widely between the available drugs and with dose of each. The risk of ulcer complications can however be reduced, and perhaps completely removed, by using the lowest dose of the least toxic member of the class. Enteric coating and other delayed release formulations have not been shown to reduce risk. Estimates of the imposed disease burden have varied widely, in part through assuming that risks in selected patient groups will necessarily translate to the general population. Nevertheless, the imposed disease burden is one of the largest associated with current drug treatment. Associated risk factors such as prior ulcer, corticosteroid use and concurrent aspirin as well as general cardiovascular disease will raise the likelihood of an ulcer complication in NSAID takers and non-takers. Therefore, strategies dependent on substituting COX-selective drugs will then be only partially successful.

  6. Prevention of Renal Complications Induced by Non- Steroidal Anti-Inflammatory Drugs.

    PubMed

    Ković, Sonja Vuč; Vujović, Katarina Savić; Srebro, Dragana; Medić, Branislava; Ilic-Mostic, Tatjana

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain, inflamation and fever. They are usually well tolerated in healthy persons, but in patients with risk factors (advanced age, renal impairment, heart failure, liver disease, concurrent medications with antihypertensive drugs), NSAIDs can induce serious renal adverse effects. They include sodium and water retention with edema, worsening of heart failure, hypertension, hyponatremia, hyperkalemia, acute kidney injury, chronic kidney disease, renal papillary necrosis and acute interstitial nephritis. The majority of these adverse effects are due to the inhibition of prostaglandins synthesis and they are dose and duration-dependent. Acute forms of kidney injuries are transient and often reversible upon drug withdrawal. Chronic use of NSAIDs in some patients may result in chronic kidney disease. It is recommended that patients at risk should have preventative strategies in place, including the use of the "lowest effective dose" of NSAID for the "shortest possible time" and monitoring renal function, fluid retention and electrolyte abnormalities. Patients who are taking antihypertensive medications should be monitored for high blood pressure and the doses of antihypertensive medications should be adjusted if needed. In general, the combination of NSAIDs and angiotensin inhibitors should be avoided. Some other preventive measures are dietary salt restriction, use of topical NSAIDs/non-pharmacological therapies and use of calcium channel blockers for treating hypertension.

  7. Management of gastroduodenal ulcers caused by non-steroidal anti-inflammatory drugs.

    PubMed

    Hawkey, C J

    2000-02-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are a major cause of morbidity and mortality, probably resulting in the death of 1200 patients per annum in the UK. The main mechanism of toxicity involves an inhibition of prostaglandin synthesis that results in mucosal erosion as a result of the abrogation of defence mechanisms. However, acid peptic attack can deepen this initial injury. Thus, logical treatments include prostaglandin analogues as 'replacement therapy', acid suppression, enteric coating to avoid topical effects and the use of safer NSAIDs, including those that have little or no effect on gastric mucosal prostaglandin synthesis. There is less logic to the strategy of Helicobacter pylori (H. pylori) eradication, and the status of this approach is controversial. Overall, proton pump inhibitors have the best profile of efficacy and side-effects for the healing and prevention of NSAID-associated ulcers. Misoprostol is also effective and appears to be superior to proton pump inhibitors for superficial erosive injury. Early indications are that selective inhibitors of the inducible cyclooxygenase-2 enzyme have little or no effect in causing ulcers. Growing experience with these agents will probably revolutionize the management of patients with arthritic conditions. However, the increasing use of low-dose aspirin for cardiovascular prophylaxis means that gastroenterologists will have to continue to grapple with the problems of NSAID-associated ulcers for some time to come.

  8. Therapeutic window for cyclooxygenase-2 related anti-inflammatory therapy after status epilepticus

    PubMed Central

    Jiang, Jianxiong; Yang, Myung-Soon; Quan, Yi; Gueorguieva, Paoula; Ganesh, Thota; Dingledine, Raymond

    2015-01-01

    As a prominent inflammatory effector of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) mediates brain inflammation and injury in many chronic central nervous system (CNS) conditions including seizures and epilepsy, largely through its receptor subtype EP2. However, EP2 receptor activation might also be neuroprotective in models of excitotoxicity and ischemia. These seemingly incongruent observations expose the delicacy of immune and inflammatory signaling in the brain, thus the therapeutic window for quelling neuroinflammation might vary with injury type and target molecule. Here, we identify a therapeutic window for EP2 antagonism to reduce delayed mortality and functional morbidity after status epilepticus (SE) in mice. Importantly, treatment must be delayed relative to SE onset to be effective, a finding that could be explained by the time-course of COX-2 induction after SE and compound pharmacokinetics. A large number of inflammatory mediators were upregulated in hippocampus after SE with COX-2 and IL-1β temporally leading many others. Thus, EP2 antagonism represents a novel anti-inflammatory strategy to treat SE with a tightly-regulated therapeutic window. PMID:25600211

  9. Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity.

    PubMed

    Danilov, Anton; Shaposhnikov, Mikhail; Shevchenko, Oksana; Zemskaya, Nadezhda; Zhavoronkov, Alex; Moskalev, Alexey

    2015-08-14

    Most age-related diseases and aging itself are associated with chronic inflammation. Thus pharmacological inhibition of inflammatory processes may be effective antiaging strategy. In this study we demonstrated that treatment of Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs: CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age-dependent decline of locomotor activity and increases stress resistance. The effect of the lifespan increase was associated with decrease of fecundity. Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant properties in Drosophila tissues. However, we failed to identify clear correlation between antioxidant properties of NSAIDs and their pro-longevity effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, and licofelone were more pronounced in males, valdecoxib and aspirin - in females. We demonstrated that lifespan extension effect of NSAIDs was abolished in flies with defective genes involved in Pkh2-ypk1-lem3-tat2 pathway.

  10. Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities.

    PubMed

    Mathema, Vivek Bhakta; Koh, Young-Sang; Thakuri, Balkrishna Chand; Sillanpää, Mika

    2012-04-01

    Parthenolide, a naturally occurring sesquiterpene lactone derived from feverfew (Tanacetum parthenium), exhibits exceptional anti-cancer and anti-inflammatory properties, making it a prominent candidate for further studies and drug development. In this review, we briefly investigate molecular events and cell-specific activities of this chemical in relation to cytochrome c, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), signal transduction and activation of transcription (STAT), reactive oxygen species (ROS), TCP, HDACs, microtubules, and inflammasomes. This paper reports that parthenolide shows strong NF-κB- and STAT-inhibition-mediated transcriptional suppression of pro-apoptotic genes. This compound acts both at the transcriptional level and by direct inhibition of associated kinases (IKK-β). Similarly, this review discusses parthenolide-induced ROS-mediated apoptosis of tumor cells via the intrinsic apoptotic signaling pathway. The unique ability of this compound to not harm normal cells but at the same time induce sensitization to extrinsic as well as intrinsic apoptosis signaling in cancer cells provides an important, novel therapeutic strategy for treatment of cancer and inflammation-related disorders.

  11. Novel anti-inflammatory interleukin-35 as an emerging target for antiatherosclerotic therapy.

    PubMed

    Bobryshev, Yuri V; Sobenin, Igor A; Orekhov, Alexander N; Chistiakov, Dimitry A

    2015-01-01

    Atherosclerosis has been widely recognized as a slow progressing inflammatory disease of the aorta and other large caliber arterial vessels. Accumulating evidence suggest that interleukin (IL)-35 can represent an attractive target for future anti-atherosclerotic therapy due to several atheroprotective properties. First, immunosuppressive and anti-inflammatory activity of this cytokine could be beneficial against vascular inflammation. Second, IL-35 can suppress a variety of T cells including proinflammatory Th1 and Th17 cells and probably dendritic cells. Third, IL-35 supports proliferation of regulatory T cells (Tregs), increases their inhibitory function, and induces a new set of Tregs called inducible IL-35-producing Tregs (iTr35 cells). Fourth, this cytokine promotes production of antiinflammatory cytokines such as IL-10 and down-regulates expression of proinflammatory cytokines such as IL-17. Finally, IL-35 is inducible. The fact that IL-35 could be induced by simple compounds such as chemical chaperons may provide advances in developing new efficient strategies for treatment of atherosclerosis. However, it is necessary to test IL-35-inducing factors in order to understand mechanisms of induction and then select the most optimal one. Probably, constructing of humanized antibodies that mimic IL-35 function may provide benefits for advanced atheroprotective therapy.

  12. Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity

    PubMed Central

    Danilov, Anton; Shaposhnikov, Mikhail; Shevchenko, Oksana; Zemskaya, Nadezhda; Zhavoronkov, Alex; Moskalev, Alexey

    2015-01-01

    Most age-related diseases and aging itself are associated with chronic inflammation. Thus pharmacological inhibition of inflammatory processes may be effective antiaging strategy. In this study we demonstrated that treatment of Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs: CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age-dependent decline of locomotor activity and increases stress resistance. The effect of the lifespan increase was associated with decrease of fecundity. Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant properties in Drosophila tissues. However, we failed to identify clear correlation between antioxidant properties of NSAIDs and their pro-longevity effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, and licofelone were more pronounced in males, valdecoxib and aspirin - in females. We demonstrated that lifespan extension effect of NSAIDs was abolished in flies with defective genes involved in Pkh2-ypk1-lem3-tat2 pathway. PMID:26305987

  13. Increased temperature and entropy production in cancer: the role of anti-inflammatory drugs.

    PubMed

    Pitt, Michael A

    2015-02-01

    Some cancers have been shown to have a higher temperature than surrounding normal tissue. This higher temperature is due to heat generated internally in the cancer. The higher temperature of cancer (compared to surrounding tissue) enables a thermodynamic analysis to be carried out. Here I show that there is increased entropy production in cancer compared with surrounding tissue. This is termed excess entropy production. The excess entropy production is expressed in terms of heat flow from the cancer to surrounding tissue and enzymic reactions in the cancer and surrounding tissue. The excess entropy production in cancer drives it away from the stationary state that is characterised by minimum entropy production. Treatments that reduce inflammation (and therefore temperature) should drive a cancer towards the stationary state. Anti-inflammatory agents, such as aspirin, other non-steroidal anti-inflammatory drugs, corticosteroids and also thyroxine analogues have been shown (using various criteria) to reduce the progress of cancer.

  14. In vivo anti-inflammatory and in vitro antioxidant activities of Mediterranean dietary plants.

    PubMed

    Conforti, Filomena; Sosa, Silvio; Marrelli, Mariangela; Menichini, Federica; Statti, Giancarlo A; Uzunov, Dimitar; Tubaro, Aurelia; Menichini, Francesco; Loggia, Roberto Della

    2008-02-28

    Five hydroalcoholic extracts of edible plants from Calabria region (Italy) used in local traditional medicine for the treatment of inflammatory diseases were evaluated for their in vivo topical anti-inflammatory activity (inhibition of croton oil-induced ear oedema in mice) and in vitro antioxidant and antiradical properties (inhibition of linoleic acid oxidation and bovine brain liposomes peroxidation, DPPH radical scavenging). All the extracts showed an anti-inflammatory effect: 300 microg/cm(2) provoked oedema reductions ranging from 21 to 27%. All the extracts exerted also radical scavenging and/or antioxidant properties, the most active plant being Mentha aquatica L. (Lamiaceae) which contained the highest amount of phenolics (337 mg/g) and of flavonoids (15.75 mg/g). Moreover, the content and the composition of sterols were assessed by GC-MS in the examined plants Borago officinalis L. (Boraginaceae) contained the highest number of sterols.

  15. In vivo anti-inflammatory and in vitro antioxidant activities of Moroccan medicinal plants.

    PubMed

    Moussaid, Mina; Elamrani, Abd Elaziz; Bourhim, Nourdinne; Benaissa, Mohamed

    2011-10-01

    Five ethanol extracts of wild plants from the Casablanca region (Morocco) used in local traditional medicine for the treatment of inflammatory diseases were evaluated for their in vivo topical anti-inflammatory activity (inhibition of carrageenan-induced ear edema in mice) and in vitro antioxidant and antiradical properties (inhibition of linoleic acid oxidation, DPPH radical scavenging). All the extracts showed an anti-inflammatory effect: 300 microg/cm2 provoked edema reductions ranging from 22 to 28%. All the extracts also exerted radical scavenging and/or antioxidant properties, the most active plant being Mentha pulegium L. (Lamiaceae), which contained the highest amount of phenolics (339 mg/g), and flavonoids (16.7 mg/g).

  16. Analgesic and anti-inflammatory effects of Ligularia fischeri leaves in experimental animals.

    PubMed

    Lee, Kyung-Hee; Choi, Eun-Mi

    2008-10-30

    The ethanol extract (LF) of Ligularia fischeri var. spiciformis (leaf) has been evaluated for antinociceptive and anti-inflammatory activities in mice. Analgesic and anti-inflammatory activities were studied by measuring nociception induced by formalin, acetic acid and hot-plate, and inflammation induced by carrageenan, formalin, and arachidonic acid. The acute treatment of mice with LF at doses of 100 and 200mg/kg, by oral administration, produced a significant antinociceptive effect in the acetic acid-induced writhing, formalin-induced pain licking and hot-plate-induced pain. Also, the LF significantly inhibited both carrageenan- and formalin-induced inflammation as well as arachidonic acid-induced ear edema in mice. These inhibitions were statistically significant (P<0.05). Thus, our investigation suggests a potential benefit of Ligularia fischeri in treating conditions associated with inflammatory pain.

  17. The effect of nonsteroidal anti-inflammatory drugs on the equine intestine.

    PubMed

    Marshall, J F; Blikslager, A T

    2011-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the management of pain and endotoxaemia associated with colic in the horse. While NSAIDs effectively treat the symptoms of colic, there is evidence to suggest that their administration is associated with adverse gastrointestinal effects including right dorsal colitis and inhibition of mucosal barrier healing. Several studies have examined the pathophysiology of NSAID associated effects on the large and small intestine in an effort to avoid these complications and identify effective alternative medications. Differences in the response of the large and small intestines to injury and NSAID treatment have been identified. Flunixin meglumine has been shown in the small intestine to inhibit barrier function recovery and increase permeability to lipopolysaccharide (LPS). A range of NSAIDs has been examined in the small intestine and experimental evidence suggests that those NSAIDs with cyclooxygenase independent anti-inflammatory effects or a COX-2 selective mode of action may offer significant advantages over traditional NSAIDs.

  18. Anti-inflammatory effect of Lonicera japonica in proteinase-activated receptor 2-mediated paw edema.

    PubMed

    Tae, Jin; Han, Seung-Woo; Yoo, Jae-Young; Kim, Jin-A; Kang, Ok-Hwa; Baek, Ok-Seon; Lim, Jong-Pil; Kim, Dae-Ki; Kim, Young-Ho; Bae, Ki-Hwan; Lee, Young-Mi

    2003-04-01

    Lonicera japonica (Caprifoliaceae) has long been used for treatment of infectious diseases. In the present study, the anti-inflammatory effects of L. japonica water extract (AELJ) were investigated in proteinase-activated receptor 2 (PAR2)-mediated mouse paw edema. Paw edema was induced by injection of trypsin or trans-cinnamoyl-LIGRLO-NH(2) (tc-NH(2)) into hindpaw of mice. AELJ (10, 50, 100, and 200 mg/kg) was orally administered 1 h before induction of inflammation. At doses of 50, 100 and 200 mg/kg, the AELJ showed significant inhibition of both change in paw thickness and vascular permeability. The AELJ (100 mg/kg) also significantly inhibited PAR2 agonists-induced myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-alpha expression in paw tissue. The present study demonstrated that AELJ has an anti-inflammatory action for PAR2-mediated paw edema.

  19. Mediators, Receptors, and Signalling Pathways in the Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture

    PubMed Central

    McDonald, John L.; Cripps, Allan W.; Smith, Peter K.

    2015-01-01

    Acupuncture has been used for millennia to treat allergic diseases including both intermittent rhinitis and persistent rhinitis. Besides the research on the efficacy and safety of acupuncture treatment for allergic rhinitis, research has also investigated how acupuncture might modulate immune function to exert anti-inflammatory effects. A proposed model has previously hypothesized that acupuncture might downregulate proinflammatory neuropeptides, proinflammatory cytokines, and neurotrophins, modulating transient receptor potential vallinoid (TRPV1), a G-protein coupled receptor which plays a central role in allergic rhinitis. Recent research has been largely supportive of this model. New advances in research include the discovery of a novel cholinergic anti-inflammatory pathway activated by acupuncture. A chemokine-mediated proliferation of opioid-containing macrophages in inflamed tissues, in response to acupuncture, has also been demonstrated for the first time. Further research on the complex cross talk between receptors during inflammation is also helping to elucidate the mediators and signalling pathways activated by acupuncture. PMID:26339274

  20. Prediction of Anti-inflammatory Plants and Discovery of Their Biomarkers by Machine Learning Algorithms and Metabolomic Studies.

    PubMed

    Chagas-Paula, Daniela Aparecida; Oliveira, Tiago Branquinho; Zhang, Tong; Edrada-Ebel, RuAngelie; Da Costa, Fernando Batista

    2015-04-01

    Nonsteroidal anti-inflammatory drugs are the most used anti-inflammatory medicines in the world. Side effects still occur, however, and some inflammatory pathologies lack efficient treatment. Cyclooxygenase and lipoxygenase pathways are of utmost importance in inflammatory processes; therefore, novel inhibitors are currently needed for both of them. Dual inhibitors of cyclooxygenase-1 and 5-lipoxygenase are anti-inflammatory drugs with high efficacy and low side effects. In this work, 57 leaf extracts (EtOH-H2O 7 : 3, v/v) from Asteraceae species with in vitro dual inhibition of cyclooxygenase-1 and 5-lipoxygenase were analyzed by high-performance liquid chromatography-high-resolution-ORBITRAP-mass spectrometry analysis and subjected to in silico studies using machine learning algorithms. The data from all samples were processed by employing differential expression analysis software coupled to the Dictionary of Natural Products for dereplication studies. The 6052 chromatographic peaks (ESI positive and negative modes) of the extracts were selected by a genetic algorithm according to their respective anti-inflammatory properties; after this procedure, 1241 of them remained. A study using a decision tree classifier was carried out, and 11 compounds were determined to be biomarkers due to their anti-inflammatory potential. Finally, a model to predict new biologically active extracts from Asteraceae species using liquid chromatography-mass spectrometry information with no prior knowledge of their biological data was built using a multilayer perceptron (artificial neural networks) with the back-propagation algorithm using the biomarker data. As a result, a new and robust artificial neural network model for predicting the anti-inflammatory activity of natural compounds was obtained, resulting in a high percentage of correct predictions (81 %), high precision (100 %) for dual inhibition, and low error values (mean absolute error = 0.3), as also shown in the

  1. Optimization and Pharmacological Validation of a Leukocyte Migration Assay in Zebrafish Larvae for the Rapid In Vivo Bioactivity Analysis of Anti-Inflammatory Secondary Metabolites

    PubMed Central

    Vicet-Muro, Liliana; Wilches-Arizábala, Isabel María; Esguerra, Camila V.; de Witte, Peter A. M.; Crawford, Alexander D.

    2013-01-01

    Over the past decade, zebrafish (Danio rerio) have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs) and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf) zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS), resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO) staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM). Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs). Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts. PMID:24124487

  2. Antibacterials as anti-inflammatory agents: dual action agents for oral health.

    PubMed

    Sreenivasan, Prem K; Gaffar, Abdul

    2008-03-01

    Inflammatory processes with a range of specialized cells and biochemical mediators form a complex network of inter-related signal transducing pathways that relay information to preserve normal functions. Advances in molecular analyses of the information relay pathways for their constituents and principal ligands along with mechanisms utilized by the host for microbial recognition have stimulated interest in therapeutic agents with dual functionalities i.e. antibacterial and anti-inflammatory effects. This review examines clinically tested agents for oral health applications with both antimicrobial and anti-inflammatory effects to include antibiotics, antimicrobials and phenolics. Bis-phenols such as triclosan, representing a unique dual functional therapeutic for routine oral hygiene, with its demonstrated clinical effects on inhibiting the dental plaque biofilm, reducing inflammation (gingivitis) and subsequent periodontitis is described. Cyclines, comprising another class of approved anti-inflammatory agents used at the patient level for oral health is discussed. Dual active agents in current clinical practice for systemic conditions are highlighted to summarize the clinical validity of dual function agents as an emerging therapeutic strategy. Clinical studies demonstrate therapeutic benefits of agents with dual functionality with their effects on microorganisms and the concomitant host inflammatory response. Advances in microbial pathogenesis and resultant inflammation will facilitate progress in this emerging area poised to be a significant milestone for dental therapeutics.

  3. The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis

    PubMed Central

    Poniatowski, Łukasz A.

    2014-01-01

    Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1β, TNFα, IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed. PMID:24876674

  4. No Beneficial Effect of General and Specific Anti-Inflammatory Therapies on Aortic Dilatation in Marfan Mice

    PubMed Central

    den Hartog, Alexander W.; Radonic, Teodora; de Vries, Carlie J. M.; Zwinderman, Aeilko H.; Groenink, Maarten; Mulder, Barbara J. M.; de Waard, Vivian

    2014-01-01

    Aims Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. In the FBN1C1039G/+ Marfan mouse model, losartan decreases aortic root dilatation. We recently confirmed this beneficial effect of losartan in adult patients with Marfan syndrome. The straightforward translation of this mouse model to man is reassuring to test novel treatment strategies. A number of studies have shown signs of inflammation in aortic tissue of Marfan patients. This study examined the efficacy of anti-inflammatory therapies in attenuating aortic root dilation in Marfan syndrome and compared effects to the main preventative agent, losartan. Methods and Results To inhibit inflammation in FBN1C1039G/+ Marfan mice, we treated the mice with losartan (angiotensin II receptor type 1 inhibitor), methylprednisolone (corticosteroid) or abatacept (T-cell-specific inhibitor). Treatment was initiated in adult Marfan mice with already existing aortic root dilatation, and applied for eight weeks. Methylprednisolone- or abatacept-treated mice did not reveal a reduction in aortic root dilatation. In this short time frame, losartan was the only treatment that significantly reduced aorta inflammation, transforming growth factor-beta (TGF-β) signaling and aortic root dilatation rate in these adult Marfan mice. Moreover, the methylprednisolone-treated mice had significantly more aortic alcian blue staining as a marker for aortic damage. Conclusion Anti-inflammatory agents do not reduce the aortic dilatation rate in Marfan mice, but possibly increase aortic damage. Currently, the most promising therapeutic drug in Marfan syndrome is losartan, by blocking the angiotensin II receptor type 1 and thereby inhibiting pSmad2 signaling. PMID:25238161

  5. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

    PubMed Central

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin’ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD. PMID:27621596

  6. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

    SciTech Connect

    Gross, N.J.; Holloway, N.O.; Narine, K.R. )

    1991-09-01

    Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.

  7. Brazilian Green Propolis: Anti-Inflammatory Property by an Immunomodulatory Activity

    PubMed Central

    Machado, Joleen Lopes; da Silva, Mayara Cristina Pinto; dos Reis, Aramys Silva; Costa, Graciomar Conceição; Arruda, Diêgo de Sousa; Rocha, Bruno Alves; Vaz, Mirela Mara de Oliveira Lima Leite; Paes, Antonio Marcus de Andrade; Guerra, Rosane Nassar Meireles; Berretta, Andresa Aparecida; do Nascimento, Flávia Raquel Fernandes

    2012-01-01

    The immunomodulatory and anti-inflammatory activities of green propolis extracts from Apis mellifera were investigated using acute and chronic inflammation models. Swiss mice were anesthetized and a cotton pellet granuloma was implanted in subcutaneous tissue. Then the mice were divided into six groups and received apyrogenic water or different propolis extracts by oral route (5 mg/kg). According to the treatment the groups were designated as E1A, E1B, E10, E11, and E12. The control group received apyrogenic water. The treatment was performed by six days when the mice were killed. The blood and the bronchoalveolar lavage (BAL) were collected to measure the leukocyte recruitment. In acute pulmonary inflammation, Balb/c mice received lipopolysaccharide (LPS) of Escherichia coli by intranasal route for three days. Concomitantly the mice received by oral route apyrogenic water (control) or E10 and E11 propolis extracts. BAL was performed to assess the inflammatory infiltrate and cytokine quantification. The results showed that the E11 extract has anti-inflammatory property in both models by the inhibition of proinflammatory cytokines and increase of anti-inflammatory cytokines suggesting an immunomodulatory activity. PMID:23320022

  8. Anti-Inflammatory Properties of NAP in Acute Toxoplasma Gondii-Induced Ileitis in Mice.

    PubMed

    Heimesaat, Markus M; Fischer, André; Kühl, Anja A; Göbel, Ulf B; Gozes, Illana; Bereswill, Stefan

    2015-09-01

    The octapeptide NAP has been shown to exert neuroprotective properties. Here, we investigated potential anti-inflammatory effects of NAP in an acute ileitis model. To address this, C57BL/6j mice were perorally infected with Toxoplasma gondii (day 0). Within 1 week postinfection (p.i.), placebo (PLC)-treated mice developed acute ileitis due to Th1-type immune responses. Mice that were subjected to intraperitoneal NAP treatment from day 1 until day 6 p.i., however, developed less distinct macroscopic and microscopic disease as indicated by less body weight loss, less distinct histopathological ileal changes, and lower ileal apoptotic, but higher proliferating cell numbers, less abundance of neutrophils, macrophages, monocytes, and T lymphocytes, but higher numbers of regulatory T cells in the ileal mucosa and lamina propria, and lower concentrations of pro-inflammatory mediators in the ilea as compared to PLC controls at day 7 p.i. Remarkably, NAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments including liver and spleen. Strikingly, lower MCP-1, TNF, and IL-12p70 serum concentrations in NAP as compared to PLC-treated mice at day 7 p.i. indicate a pronounced systemic anti-inflammatory effect of NAP in acute ileitis. These findings provide first evidence for NAP as a potential novel treatment option in intestinal inflammation.

  9. Mechanisms of Action of Ig Preparations: Immunomodulatory and Anti-Inflammatory Effects

    PubMed Central

    Matucci, Andrea; Maggi, Enrico; Vultaggio, Alessandra

    2015-01-01

    Primary immunodeficiency (PID) disorders that predispose patients to recurrent infections require immunoglobulin (Ig) replacement therapy. Ig replacement therapy has been stated as beneficial, although the optimal IgG trough level to be maintained over time in order to minimize infectious risk has not been established. The most common route of administration of Ig has been intravenously, although there are different options, one of them being the subcutaneous route. Ig replacement therapy has been a life-saving treatment for patients suffering from primary and secondary antibody immunodeficiency. The key role of regular Ig replacement in patients with antibody deficiencies is related to the ability to provide specific antibodies that could not be produced by these patients as demonstrated by the reduction of severe infections such as meningitis and pneumonia. The therapeutic benefits of Ig may also be due to an active role in various anti-inflammatory and immunomodulatory activities, which may complicate the clinical picture of PID. Anti-inflammatory activities are seen more generally when intravenous Ig is administered at high dose. The immunomodulatory and anti-inflammatory activities are important not only in the treatment of autoimmune diseases but also in patients suffering from immunodeficiency. PMID:25628625

  10. Anticancer and anti-inflammatory activities of shallot (Allium ascalonicum) extract

    PubMed Central

    Mohammadi-Motlagh, Hamid-Reza; Mostafaie, Ali; Mansouri, Kamran

    2011-01-01

    Introduction Alliumplants are an important part of the diet of many populations and there is a long-held belief in their health-enhancing properties such as cancer prevention. In this study, the anticancer and anti-inflammatory activities of the aqueous extract of the Allium ascalonicum bulbs have been studied. Material and methods The antiproliferative and anti-growth activity of the aqueous extract of A. ascalonicum was examined in vitro on different tumor cell lines. Furthermore, the acetic acid-induced vascular permeability as an in vivo assay was used for studying anti-inflammatory activity of the extract. Results The aqueous extract of A. ascalonicum had the most anti-growth activity on the cancer cell lines; Jurkat and K562 against Wehi 164 with lower cytotoxic preference. The extract also showed much less cytotoxicity against the normal cell (HUVEC) line and significant anti-inflammatory activity in vivo. Conclusions It is of interest that the extract of this plant has shown much less cytotoxicity against the normal cell line, and, if this also occurs in vivo, the use of this plant clinically for the treatment of cancer patients would have some scientific support. The results of these assays indicated that A. ascalonicum can be a candidate for prevention and treatment of many diseases related to inflammation and malignancy. PMID:22291731

  11. Anticancer and anti-inflammatory activities of shallot (Allium ascalonicum) extract.

    PubMed

    Mohammadi-Motlagh, Hamid-Reza; Mostafaie, Ali; Mansouri, Kamran

    2011-02-01

    Alliumplants are an important part of the diet of many populations and there is a long-held belief in their health-enhancing properties such as cancer prevention. In this study, the anticancer and anti-inflammatory activities of the aqueous extract of the Allium ascalonicum bulbs have been studied. The antiproliferative and anti-growth activity of the aqueous extract of A. ascalonicum was examined in vitro on different tumor cell lines. Furthermore, the acetic acid-induced vascular permeability as an in vivo assay was used for studying anti-inflammatory activity of the extract. The aqueous extract of A. ascalonicum had the most anti-growth activity on the cancer cell lines; Jurkat and K562 against Wehi 164 with lower cytotoxic preference. The extract also showed much less cytotoxicity against the normal cell (HUVEC) line and significant anti-inflammatory activity in vivo. It is of interest that the extract of this plant has shown much less cytotoxicity against the normal cell line, and, if this also occurs in vivo, the use of this plant clinically for the treatment of cancer patients would have some scientific support. The results of these assays indicated that A. ascalonicum can be a candidate for prevention and treatment of many diseases related to inflammation and malignancy.

  12. Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation.

    PubMed

    Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender; Raj, Arun

    2016-11-01

    Picrorhiza kurroa is an important medicinal plant in the Ayurvedic system of medicine. The root and rhizome of this plant are used for the treatment of various liver and inflammatory conditions. In the present study, we sought to investigate the anti-inflammatory activity of P. kurroa rhizome extract against carrageenan-induced paw edema and cotton pellet implantation-induced granuloma formation in rats. In addition, its immunomodulatory activity was evaluated in Complete Freund's Adjuvant-induced stimulation of a peritoneal macrophage model and lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Pretreatment with P. kurroa rhizome extract inhibited carrageenan-induced paw edema and cotton pellet-induced granuloma formation in a dose-dependent manner. This was associated with reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) accompanied with increased anti-inflammatory cytokine (IL-10) in the serum and peritoneal macrophages. Additionally, P. kurroa rhizome extract inhibited inflammatory TNF-receptor 1 and cyclooxygenase-2 in Complete Freund's Adjuvant-induced activated peritoneal macrophages. Furthermore, P. kurroa rhizome extract treatment significantly inhibited iNOS and suppressed the activation of NF-κB through inhibition of its phosphorylation and by blocking the activation of IκB kinase alpha in lipopolysaccharide-stimulated RAW264.7 macrophages. Taken together, these results suggest that P. kurroa has anti-inflammatory activity that is mediated through the suppression of macrophage-derived cytokine and mediators via suppression of NF-κB signaling.

  13. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

    PubMed Central

    van der Velden, V H

    1998-01-01

    GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized. PMID:9792333

  14. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

    PubMed

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

  15. Anti-inflammatory activity studies on the stems and roots of Jasminum lanceolarium Roxb.

    PubMed

    Yan, Wen-xia; Zhang, Jian-hua; Zhang, Yi; Meng, Da-li; Yan, Dan

    2015-08-02

    Jasminum lanceolarium Roxb is an important traditional Chinese medicine. Its stems and roots have been used for the treatment of rheumatism and fever while the leaves are used as an anti-inflammatory agent to relieve pain. In order to support its traditional Chinese medicinal uses, five animal models were designed and the anti-inflammatory and analgesic properties of the 70% EtOH-H2O extracts of J. lanceolarium (EJL) were investigated. Meanwhile, biochemical parameters such as cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) in blood serum of rats exposed to acute (carrageenan) inflammation model were evaluated. At doses of 400 mg/kg, EJL exhibited higher anti-inflammation effect than that of indomethacin and better analgesic activity than that of aspirin (P<0.001). Furthermore, eleven isolated compounds including six lignanoids (1, 2, 6, 7, 8, and 11) and five iridoids (3, 4, 5, 9, and 10) were isolated from the active extracts and showed significant anti-inflammatory activities with the IC50 values of 1.76-5.22 mg/mL, respectively, when testing their inhibitory effects on phospholipase A2 in vitro. The results demonstrated that the possible anti-inflammatory mechanisms might be attributed to inhibit the hydrolysis of membrane phospholipids, production on both COX-2 and 5-LOX, and then finally inhibit the release of prostaglandins (PGs), which suggested that EJL had a non-selective inhibitory effect on the release or actions of these mediators, and might be a dual LOX-COX inhibitor for the treatment of inflammation from the natural resource. The studies on the animals and the inflammatory mediators, along with the bioactive compounds presumed that the existences of iridoids and lignanoids could be response for their bioactivities of the whole plants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Anti-inflammatory and antiarthritic activity of UNIM-301 (a polyherbal unani formulation) in Wistar rats

    PubMed Central

    Singh, Surender; Kumar, Rohit; Jain, Hitesh; Gupta, Y. K.

    2015-01-01

    Background: UNIM-301 is a polyherbal formulation used in the Unani system of medicine for the treatment of joint pain and rheumatoid arthritis (RA). Objective: The objective was to evaluate the anti-inflammatory and antiarthritic activity of UNIM-301 in carrageenan-induced paw edema and complete Freund's Adjuvant (CFA) induced arthritis. Materials and Methods: The anti-inflammatory and antiarthritic activity of UNIM-301 was evaluated using carrageenan-induced paw edema and CFA induced animal arthritis models, respectively, in doses of 250, 500, and 1000 mg/kg body weight. Anti-inflammatory activity of UNIM-301 was evaluated using carrageenan-induced paw edema model using a digital plethysmometer. Anti-arthritic activity was evaluated using CFA induced arthritis, and joint sizes were measured at regular intervals using a micrometer screw gauge. Serum was collected and subjected to estimation of pro-inflammatory cytokine. Indomethacin 3 mg/kg body weight) was used as a standard drug in both the models. The acute and chronic toxicity study was carried out to evaluate the safety of the test drug. Results: UNIM-301 treatment produced a dose-dependent reduction in paw edema and paw thickness in carrageenan-induced paw edema and CFA-induced arthritis, respectively, as compared to control. UNIM 301 also reduced the expression of pro-inflammatory mediator in a dose-dependent manner as compared to control. Conclusion: The result of the present study suggests that anti-inflammatory and anti-arthritic activity of UNIM-301, which might be accredited to inhibitory activity on pro-inflammatory cytokines to its various individual constituents. PMID:25829793

  17. Anti-inflammatory effects of 4-methylcyclopentadecanone on edema models in mice.

    PubMed

    Ma, Yukui; Li, Yue; Li, Xiufeng; Wu, Yingliang

    2013-12-09

    The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE2 and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD50 value of 4-MCPC in rats is greater than 5000 mg/kg. The ED50 of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE2 and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE2 and MPO in inflamed paws.

  18. Antioxidant, anti-inflammatory activities and acute toxicity of the polyherbal formulation: Romix®.

    PubMed

    Ince, Iskender; Kayalar, Husniye; Elgin, Gozde; Koksal, Cinel; Yavasoglu, N Ulku Karabay

    2012-06-01

    Polyherbal formulations containing different plants are used for the treatment of various diseases. Romix® powder is a polyherbal formulation consisting of 14 traditionally used herbs and is used as a food supplement. There is no information about pharmaceutical activities of Romix®. This study determined the total phenolic and total flavonoid content, and investigated the antioxidant and anti-inflammatory activities and acute toxicity of Romix®. The total phenolics in the extracts were determined colorimetrically by using the Folin-Ciocalteu reagent. The total flavonoid content of the extracts was evaluated by a spectrophotometric method. The quercetin content of the extract was analyzed using the high-performance liquid chromatography (HPLC) method. Antioxidant activity of the extracts was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assays. The anti-inflammatory activity was evaluated by the carrageenan-induced paw edema test in the rat. The flavonoid and phenolics contents of Romix® were 50.58 and 265.83 mg/g in ethanol extract and 18.60 and 222.50 mg/g in water extract, respectively. Total quercetin content of Romix® was determined as 2.857 mg/g. Antioxidant activity results showed that ethanol extract in 1 mg/mL concentration (4.49775 µg/mL) had moderate antioxidant activity than water extract in the same concentration (4.28191 µg/mL). Intraperitoneal administration of 25 mg/kg Romix® extract exhibited anti-inflammatory activity and inhibited paw swelling at 1, 2, 3, 4, 5 and 6 h in rats with no acute toxicity. These findings suggest that Romix® due to its antioxidant and anti-inflammatory activities may be useful in the prevention or treatment of aging-related and inflammatory diseases.

  19. Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs.

    PubMed

    Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

    2014-01-01

    Volatile oils obtained from lemon grass [Cymbopogon citratus (DC.) Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. In the present study, lemon grass essential oil (LGEO) was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. The chemical profile of LGEO as determined by gas chromatography-mass spectrometry analysis revealed two major components: geranial (42.2%), and neral (31.5%). The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs) (35-90 mm). IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally) significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg), which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. RESULTS of the present study indicate that LGEO has a noteworthy potential for the development of drugs for the treatment of fungal infections and skin inflammation that

  20. Antinociceptive and anti-inflammatory effects of Memora nodosa and allantoin in mice.

    PubMed

    Florentino, Iziara F; Silva, Daiany P B; Galdino, Pablinny M; Lino, Roberta C; Martins, José L R; Silva, Dayane M; de Paula, José R; Tresvenzol, Leonice M F; Costa, Elson A

    2016-06-20

    The leaves and stems bark of Memora nodosa (Silva Manso) Miers (Bignoniaceae) are used in Brazilian traditional medicine in the treatment of external ulcers and wounds; its roots are used to treat abdominal pain and scabies. Our aim was to evaluate the antinociceptive and anti-inflammatory activities of Memora nodosa roots ethanolic extract (EMN) and allantoin, a secondary metabolite isolated from this plant. The EMN and allantoin antinociceptive activity were evaluated in mice using both chemical and heat-induced pain models such as acetic acid-induced writhing, formalin and tail-flick tests. In the formalin test, a pre-treatment with naloxone was used to verify an involvement of opioid receptor in the antinociceptive effect of EMN and allantoin. Pre-treatment with glibenclemide was used to verity an involvement of ATP-sensitive K(+)channel in the allantoin antinociceptive effect. EMN and allantoin anti-inflammatory activity were assessed by carrageenan-induced paw edema and pleurisy tests. The treatment with EMN (250, 500 and 1000mg/kg, p.o.) inhibit the acetic acid and formalin (both phases)-induced nociception. However, just at doses 500 and 1000mg/kg increased the latency time in tail-flick test. These results suggest the involvement of both peripheral and central antinociceptive mechanisms. The treatment with allantoin (40, 60 and 80mg/kg p.o.) produced a dose-dependent antinociceptive effect in both phases of formalin-induced nociception test; allantoin (60mg/kg) was not able to increase the latency time in tail flick-test. The pre-treatment with naloxone completely reversed the EMN (1000mg/kg) and allantoin (60mg/kg) effect in the first phase of formalin test; and glibenclamide reversed the allantoin effect. The administration of EMN (250, 500 and 1000mg/kg) and allantoin (60mg/kg) showed significant anti-inflammatory activity in the whole carrageenan-induced paw edema. Furthermore, EMN and allantoin reduced the leukocytes migration and pleural exudate to

  1. Oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults.

    PubMed

    Derry, Sheena; Wiffen, Philip J; Häuser, Winfried; Mücke, Martin; Tölle, Thomas Rudolf; Bell, Rae F; Moore, R Andrew

    2017-03-27

    Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain in fibromyalgia, despite being considered not to be effective. To assess the analgesic efficacy, tolerability (drop-out due to adverse events), and safety (serious adverse events) of oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults. We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from inception to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. We included randomised, double-blind trials of two weeks' duration or longer, comparing any oral NSAID with placebo or another active treatment for relief of pain in fibromyalgia, with subjective pain assessment by the participant. Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)) or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC), serious adverse events, and withdrawals due to adverse events; secondary outcomes were adverse events, withdrawals due to lack of efficacy, and outcomes relating to sleep, fatigue, and quality of life. Where pooled analysis was possible, we used dichotomous data to calculate risk difference (RD) and number needed to treat for an additional beneficial outcome (NNT), using standard methods. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. Our searches identified six randomised, double-blind studies involving 292 participants in suitably characterised fibromyalgia. The mean age of participants was between 39 and 50 years, and 89% to 100% were women. The initial pain intensity was around 7/10 on a 0 to 10 pain scale, indicating severe pain. NSAIDs tested were etoricoxib 90 mg

  2. Development and characterization of targeted poly(NIPAm) nanoparticles for delivery of anti-inflammatory peptides in peripheral artery disease and osteoarthritis

    NASA Astrophysics Data System (ADS)

    McMasters, James F.

    Inflammation is the underlying cause of several severe diseases including cardiovascular disease and osteoarthritis. Peripheral artery disease (PAD) is characterized by atherosclerotic occlusions within the peripheral vasculature. Current treatment for severe PAD involves mechanical widening of the artery via percutaneous transluminal angioplasty. Unfortunately, deployment of the balloon damages the endothelial layer, exposing the underlying collagenous matrix. Circulating platelets can bind to this collagen and become activated, releasing proinflammatory cytokines that promote proliferation of local smooth muscle cells. These proliferating cells eventually reocclude the vessel, resulting in restenosis and necessitating the need for a second procedure to reopen the vessel. Current treatments for moderate osteoarthritis include local injection of anti-inflammatory compounds such as glucocorticoids. Unfortunately, prolonged treatment carries with it significant side effects including osteoporosis, and cardiovascular complications. Our lab has developed an anti-inflammatory cell-penetrating peptide that inhibits mitogen-activated protein kinase activated protein kinase 2 (MK2). MK2 is implicated in the inflammatory cascade of atherosclerosis and osteoarthritis, making it a potentially effective strategy for reducing inflammation in both disease states. Unfortunately, these peptides are untargeted and quickly degraded in the presence of serum proteases, making the development of an effective delivery system of paramount importance. The overall goal of the research presented here is to detail the development of a poly(N-isopropylacrylamide) nanoparticle that is able to effectively load and release anti-inflammatory peptides for the treatment of these inflammatory diseases. In this dissertation, I will discuss the development of a collagen-binding nanoparticle that is able to inhibit platelet binding following angioplasty, thereby halting the initial inflammatory cascade

  3. Discovery of anti-inflammatory role of prostaglandin D2

    PubMed Central

    MURATA, Takahisa; MAEHARA, Toko

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin are one of the most frequently used classes of drug worldwide and inhibit prostaglandin (PG) production by inhibiting cyclooxygenase activity. Although NSAIDs are broadly used against inflammatory diseases, they have side effects including alimentary canal disorders, kidney damage, infection and cardiovascular disorders. Thus, it is necessary to elucidate the pathophysiological role of each PG in various diseases to develop better therapies with fewer and milder side effects. PGD2 is a PG that was identified in 1973 by Hamberg and is produced by the activities of cyclooxygenase and either hematopoietic or lipocalin-type PGD synthase. PGD2 exerts its physiological effects by stimulating two distinct G protein-coupled receptors, namely D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). The physiological role of PGD2 remains controversial. Some studies have reported that PGD2 has bronchoconstrictory and pro-inflammatory effects inducing immune cell accumulation. In contrast, other groups have reported that PGD2 has anti-inflammatory effects by inhibiting the recruitment of dendritic cells and neutrophils. We have investigated the pathophysiological role of PGD2 using various disease models and reported on its anti-inflammatory actions. Here, we review the anti-inflammatory roles of PGD2 and the underlying mechanisms. PMID:27498997

  4. The Use of Nonsteroidal Anti-Inflammatory Drugs in Sports.

    ERIC Educational Resources Information Center

    Calabrese, Leonard H.; Rooney, Theodore W.

    1986-01-01

    Recent advances in the understanding of the mechanism of action and clinical pharmacology of the new nonsteroidal anti-inflammatory drugs (NSAIDs) can help practitioners decide which to use and how to administer them. Indications for and effects of NSAIDs are described. (MT)

  5. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  6. Evaluation of labdane derivatives as potential anti-inflammatory agents.

    PubMed

    Girón, Natalia; Pérez-Sacau, Elisa; López-Fontal, Raquel; Amaro-Luis, Juan M; Hortelano, Sonsoles; Estevez-Braun, Ana; de Las Heras, Beatriz

    2010-07-01

    In the present study, a series of labdane derivatives (2-9) were prepared from labdanediol (1) and their potential as anti-inflammatory agents were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. All compounds were able to inhibit LPS-induced nitric oxide (NO), although compounds 1, 2, 5, 8 and 9 exhibited the most potent effects with a range of IC(50) values of 5-15 microM. Similarly to the inhibitory effects on NO release, these labdane derivatives also inhibited prostaglandin E(2) (PGE(2)) production. However, analysis of cell viability demonstrated that effects on NO release and (PGE(2)) production of compounds 1, 8 and 9 were due to citotoxicity, whereas compound 2 and 5 did not show any effect in the survival of RAW 264.7 macrophages. In addition to these in vitro data, compound 5 also showed anti-inflammatory activity in vivo, when tested in mice. They prevented the extent of swelling in the TPA-induced ear edema model and inhibited MPO activity, showing similar potency to that of the widely used anti-inflammatory drug indomethacin. These results indicate that compound 2 and in particular compound 5 might be used for the design of new anti-inflammatory agents. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  7. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules.

  8. Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate

    PubMed Central

    Yena, Maryna S.; Kotlyar, Iryna P.; Ogloblya, Olexandr V.; Rybalchenko, Volodymyr K.

    2016-01-01

    In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes. PMID:28101521

  9. Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate.

    PubMed

    Kuznietsova, Halyna M; Yena, Maryna S; Kotlyar, Iryna P; Ogloblya, Olexandr V; Rybalchenko, Volodymyr K

    2016-01-01

    In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes.

  10. Anti-inflammatory effects of novel sinomenine derivatives.

    PubMed

    Zhao, Zijian; Xiao, Jing; Wang, Jiancheng; Dong, Wanrong; Peng, Zhihong; An, Delie

    2015-12-01

    Sinomenine is an isoquinoline-type alkaloid found in Sinomenium acutum (Thunb.) Rehd. et Wils and S. acutum (Thunb.) Rehd. et Wils var. cinereum Rehd. et Wils. When used as a medicine, this compound exhibits anti-inflammatory properties; however, sinomenine's use as a medication is limited by side effects, a short half-life, and low efficacy. Owing to these limits, attempts have been made to synthesize sinomenine derivatives with enhanced efficacy. In this study, the anti-inflammatory effects of novel sinomenine derivatives (S1a-S1f) were examined on the basis of lipopolysaccharide-induced inflammatory factor expression in Raw264.7 cells, dimethylbenzene-induced ear oedema, and Evan's blue leakage in mice, and carrageenan-induced paw oedema in rats. Compared with sinomenine, the derivatives significantly inhibited the expression of the inflammatory factors IL-1β and IL-6 at the transcriptional and translational levels. Topical application of 3.250mg/kg of the derivatives also alleviated ear oedema. Compared with the vehicle, the derivatives significantly inhibited carrageenan-induced rat paw oedema after 6h. Among the derivatives, S1a exhibited the most potent anti-inflammatory activity. S1a also significantly increased the sinomenine-induced inhibition of Evan's blue leakage. Thus, S1a may elicit the strongest anti-inflammatory effects of the tested compounds. Based on these results, further development of this compound may be warranted.

  11. [Helicobacter pylori, nonsteroidal anti-inflammatory agents and gastroduodenal changes].

    PubMed

    Teixeira, A V

    1995-09-01

    The author discusses the possible interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (Hp) which may play an important role in the unleashing of gastroduodenal lesions. To our knowledge, AINEs have no influence on the prevalence of infection by Hp and the latter does not seem to influence the development and intensity of the lesions caused by NSAIDs.

  12. Analgesic and anti-inflammatory activities of Passiflora foetida L.

    PubMed

    Sasikala, V; Saravanan, S; Parimelazhagan, T

    2011-08-01

    To investigate the analgesic and anti-inflammatory activities of ethanol extract of Passiflora foetida (P. foetida) leaves. Ethanol extract of P. foetida leaf was evaluated for analgesic action by acetic acid-induced writhing and hot plate method in albino mice. The anti-inflammatory property of ethanolic leaf extract was tested by carrageenan induced acute paw edema and histamine induced acute paw edema in rats. The dose 200 mg/kg of P. foetida leaf extract exhibited highest significant analgesic activity [(13.50±0.43) min] at a reaction time of 20 min in hot plate method in mice. The ethanol extract of leaf dose 100 mg/kg produced a highly significant anti inflammatory effect [(1.302±0.079) mL] in rats. It is very clear that P. foetida also has analgesic and anti-inflammatory activities for the pharmaceuticals. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  13. Mouse lung slices: An ex vivo model for the evaluation of antiviral and anti-inflammatory agents against influenza viruses.

    PubMed

    Liu, Rui; An, Liwei; Liu, Ge; Li, Xiaoyu; Tang, Wei; Chen, Xulin

    2015-08-01

    The influenza A virus is notoriously known for its ability to cause recurrent epidemics and global pandemics. Antiviral therapy is effective when treatment is initiated within 48h of symptom onset, and delaying treatment beyond this time frame is associated with decreased efficacy. Research on anti-inflammatory therapy to ameliorate influenza-induced inflammation is currently underway and seems important to the impact on the clinical outcome. Both antiviral and anti-inflammatory drugs with novel mechanisms of action are urgently needed. Current methods for evaluating the efficacy of anti-influenza drugs rely mostly on transformed cells and animals. Transformed cell models are distantly related to physiological and pathological conditions. Although animals are the best choices for preclinical drug testing, they are not time- or cost-efficient. In this study, we established an ex vivo model using mouse lung slices to evaluate both antiviral and anti-inflammatory agents against influenza virus infection. Both influenza virus PR8 (H1N1) and A/Human/Hubei/3/2005 (H3N2) can replicate efficiently in mouse lung slices and trigger significant cytokine and chemokine responses. The induction of selected cytokines and chemokines were found to have a positive correlation between ex vivo and in vivo experiments, suggesting that the ex vivo cultured lung slices may closely resemble the lung functionally in an in vivo configuration when challenged by influenza virus. Furthermore, a set of agents with known antiviral and/or anti-inflammatory activities were tested to validate the ex vivo model. Our results suggested that mouse lung slices provide a robust, convenient and cost-efficient model for the assessment of both antiviral and anti-inflammatory agents against influenza virus infection in one assay. This ex vivo model may predict the efficacy of drug candidates' antiviral and anti-inflammatory activities in vivo.

  14. Topical anti-inflammatory activity of semisolid containing standardized Aleurites moluccana L. Willd (Euphorbiaceae) leaves extract.

    PubMed

    Mendes Hoepers, Silmara; Tolentino de Souza, Hugo Guilherme Martins; Meira Quintão, Nara Lins; Roberto Santin, José; Cechinel Filho, Valdir; Silva, Ruth Meri Lucinda; Garcia Couto, Angelica; Simão da Silva, Kathryn Ana Bortolini

    2015-09-15

    Aleurites moluccana is a medicinal plant popularly used to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general. Recently, pre-clinical studies have demonstrated that the dry extract obtained from A. moluccana leaves was effective as analgesic, anti-inflammatory and wound healing. The present study has aimed to evaluate the mechanisms involved in the topical anti-inflammatory effects of the semisolid containing 10mg/g of A. moluccana dried extract. Ear edema induced by croton oil (2.5%) in mice was used throughout the study. The level of cytokines tumour necrosis factor (TNF) and interleukine-1β (IL-1β) and chemokine keratinocyte chemoattractant (CXCL1/KC), and neutrophil migration were quantified. The histological analysis has also been performed. The topical treatment with the semisolid was able to significantly inhibite the ear edema (35.77±7.35%). This effect was accompanied by the reduction of leukocyte migration, as well as TNF (53.75±12.96%), IL-1β (38.36±5.92%), and CXCL1/KC (62.29±11.65%) decreased levels. This study demonstrated for the first time the mechanisms involved in the topical anti-inflammatory effect presented by the semisolid containing A. moluccana dried extract pointing as the main mechanism is the reduction in the leukocyte migration and consequently resulting in diminished levels of cytokins and chemokines, indicating this herbal product as a promissor anti-inflammatory phytomedicine to treat skin inflammatory diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark.

    PubMed

    Eo, Hyun Ji; Park, Jae Ho; Park, Gwang Hun; Lee, Man Hyo; Lee, Jeong Rak; Koo, Jin Suk; Jeong, Jin Boo

    2014-06-25

    Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity.

  16. Antipyretic, analgesic and anti-inflammatory activity of Viola betonicifolia whole plant

    PubMed Central

    2012-01-01

    Background Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME). Methods VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300mg/kg body weight intra peritoneally (i.p). Results In yeast induced pyrexia, VBME demonstrated dose dependently (78.23%) protection at 300mg/kg, similar to standard drug, paracetamol (90%) at 150mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300mg/kg. Conclusions It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant. PMID:22551220

  17. Anti-inflammatory and wound healing potential of cashew apple juice (Anacardium occidentale L.) in mice

    PubMed Central

    da Silveira Vasconcelos, Mirele; Gomes-Rochette, Neuza F; de Oliveira, Maria Liduína M; Nunes-Pinheiro, Diana Célia S; Tomé, Adriana R; Maia de Sousa, Francisco Yuri; Pinheiro, Francisco Geraldo M; Moura, Carlos Farley H; Miranda, Maria Raquel A; Mota, Erika Freitas

    2015-01-01

    Cashew apple is a tropical pseudofruit consumed as juice due to its excellent nutritional and sensory properties. In spite of being well known for its important antioxidant properties, the cashew apple has not been thoroughly investigated for its therapeutic potential. Thereby, this study evaluated the antioxidant capacity, anti-inflammatory, and wound-healing activities of cashew apple juice. Juices from ripe and immature cashew apples were analyzed for antioxidant, anti-inflammatory, and wound-healing properties. Those were evaluated in murine models of xylene-induced ear edema and wound excision. Swiss mice were treated with cashew juice by gavage. Edema thickness was measured and skin lesions were analyzed by planimetry and histology. Both antioxidant content and total antioxidant activity were higher in ripe cashew apple juice (RCAJ) than in unripe cashew apple juice (UNCAJ). The UNCAJ presented the main anti-inflammatory activity by a significant inhibition of ear edema (66.5%) when compared to RCAJ (10%). Moreover, UNCAJ also showed the best result for wound contraction (86.31%) compared to RCAJ (67.54%). Despite of higher antioxidant capacity, RCAJ did not promote better anti-inflammatory, and healing responses, which may be explained by the fact that treatment increased antioxidants level leading to a redox “imbalance” turning down the inflammatory response modulation exerted by reactive oxygen species (ROS). The results suggest that UNCAJ presents a greater therapeutic activity due to a synergistic effect of its phytochemical components, which improve the immunological mechanisms as well as an optimal balance between ROS and antioxidants leading to a better wound healing process. PMID:25819683

  18. Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents.

    PubMed

    Costa, Gustavo; Ferreira, João Pinto; Vitorino, Carla; Pina, Maria Eugénia; Sousa, João José; Figueiredo, Isabel Vitória; Batista, Maria Teresa

    2016-02-03

    A variety of plant polyphenols have been reported to have anti-inflammatory, frequently associated with erythema, edema, hyperplasia, skin photoaging and photocarcinogenesis. Cymbopogon citratus (DC). Stapf (Poaceae) is a worldwide known medicinal plant, used in traditional medicine in inflammation-related conditions. In this work, the anti-inflammatory potential of C. citratus infusion (CcI) and its polyphenols as topical agents was evaluated in vivo. The plant extract was prepared and its fractioning led two polyphenol-rich fractions: flavonoids fraction (CcF) and tannins fraction (CcT). An oil/water emulsion was developed with each active (CcI, CcF+CcT and diclofenac), pH and texture having been evaluated. Release tests were further performed using static Franz diffusion cells and all collected samples were monitored by HPLC-PDA. In vivo topical anti-inflammatory activity evaluation was performed by the carrageenan-induced rat paw edema model. The texture analysis revealed statistically significant differences for all tested parameters to CcF+CcT, supporting its topical application. Release experiments lead to the detection of the phenolic compounds from each sample in the receptor medium and the six major flavonoids were quantified, by HPLC-PDA: carlinoside, isoorientin, cynaroside, luteolin 7-O-neohesperidoside, kurilesin A and cassiaoccidentalin B. The CcF+CcT formulation prompted to the higher release rate for all these flavonoids. CcI4%, CcI1% and CcF+CcT exhibited an edema reduction of 43.18, 29.55 and 59.09%, respectively. Our findings highlight that CcI, containing luteolin 7-O-neohesperidoside, cassiaoccidentalin B, carlinoside, cynaroside and tannins have a potential anti-inflammatory topical activity, suggesting their promising application in the treatment of skin inflammatory pathologies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity

    PubMed Central

    Akhtar, Most A.; Raju, Ritesh; Beattie, Karren D.; Bodkin, Frances

    2016-01-01

    Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson's and Alzheimer's disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50  5.57 ± 1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL. PMID:28115968

  20. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

    PubMed Central

    2014-01-01

    Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. Results In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. Conclusions These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity. PMID:24962785

  1. Anti-inflammatory activity of two classical formulations of Laghupanchamula in rats

    PubMed Central

    Ghildiyal, Shivani; Gautam, Manish K.; Joshi, Vinod K.; Goel, Raj K.

    2013-01-01

    Background: Laghupanchamula denotes combinations of roots of five herbs. However, in Ayurvedic classics besides four common herbs viz. Kantakari, Brihati, Shaliparni, and Prinshniparni, the fifth one is either Gokshura (Laghupanchamula with Gokshura LPG) or Eranda (Laghupanchamula with Eranda LPE), and both formulations have been documented to have shothahara (anti-inflammatory) action. Objectives: The present study was undertaken to compare the anti-inflammatory activity of 50% ethanolic extract of LPG (LPGE) and LPE (LPEE) in rats and safety in mice. Materials and Methods: LPGE and LPEE were given orally, administered either just before or 60 min before experiment on mice and for 7 days to rats. Paw edema was induced by carrageenan (acute) and formalin (sub-acute), whereas granuloma pouch (sub-acute) was induced by turpentine in rats. Results: Both LPGE and LPEE (1.0 g/kg) at 3 h after their administration showed inhibition of formalin-induced paw edema by 46.2% and 44.3% (P < 0.001) and carrageenan-induced paw edema by 53.9% and 60.4% (P < 0.001), respectively. After 7 days of treatment, both LPGE and LPEE showed 26.3% (P < 0.01) and 32.5% (P < 0.05) inhibition, respectively, against formalin-induced paw edema, and reduced weight of turpentine-induced granuloma pouch by 42.8% and 36.1% (P < 0.001), and volume of exudates by 31.2% and 36.2% (P < 0.001), respectively. No acute toxicity was observed in mice even with a 10.0-g/kg dose of both extracts. Conclusion: LPGE and LPEE significantly reduced acute and sub-acute inflammation, and showed effective and similar anti-inflammatory activity. They seemed to be safe, and use of both formulations in the Laghupanchamula for their anti-inflammatory activity is, thus, authenticated. PMID:23741158

  2. Antioxidant, antinociceptive, and anti-inflammatory activities of Xanthii Fructus extract.

    PubMed

    Huang, Ming-Hsing; Wang, Bor-Sen; Chiu, Chuan-Sung; Amagaya, Sakae; Hsieh, Wen-Tsong; Huang, Shyh-Shyun; Shie, Pei-Hsin; Huang, Guan-Jhong

    2011-05-17

    Xanthii seeds commonly called Cang-Erzi were used as a traditional Chinese medicine for treating sinusitis, headache due to rheumatism and skin pruritus. In order to evaluate the actions of this plant, studies were performed on antioxidant, antinociceptive, and anti-inflammatory activities. The aqueous extract of Xanthii Fructus (AXF) was evaluated in mice for anti-inflammatory activity using carrageenan-induced hind paw edema model. The antinociceptive activity of AXF was evaluated by writhing and formalin tests. Antioxidant properties were assayed in terms of antioxidant activity by scavenging abilities on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS), reducing activity and liposome protection. In addition, the total phenolic content was determined with spectrophotometric method. AXF exhibited significant radical scavenging and reducing activity. And oral treatment with AXF elicited inhibitory activity on acetic acid effect and reduced the formalin effect at the late-phase. In the anti-inflammatory test, AXF inhibited the development of paw edema induced by λ-carrageenan (Carr). AXF decreased the paw edema at the fifth hour after Carr administration, and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue and decreased the malondialdehyde (MDA) level in the edema paw. AXF decreased the level of serum nitric oxide (NO) and tumor necrosis factor (TNF)-α after Carr injection and AXF decreased the levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in paw edema at the fifth hour. AXF shows antioxidant, antinociceptive, and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Anti-nociceptive and anti-inflammatory effects of the methanolic extract of Opuntia humifusa stem

    PubMed Central

    Sharma, Bhesh Raj; Park, Chul Min; Choi, Jong Won; Rhyu, Dong Young

    2017-01-01

    Objective: Opuntia humifusa (O. humifusa) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). Materials and Methods: The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular permeability and carrageenan and serotonin-induced paw edema tests in rats. Furthermore, anti-inflammatory effect was also measured using macrophage-like LPS-induced RAW 264.7 cells. Results: OHS extract inhibited acetic acid-induced writhing (p<0.0001), and delayed the reaction time of mice to the hot plate-induced thermal stimulation (p<0.0001) and tail flick tests (p<0.05). OHS extract attenuated the carrageenan and serotonin-induced paw edema in rats (p<0.001). Similarly, OHS extract significantly decreased Evans blue concentration in acetic acid induced vascular permeability test (p<0.0001), revealing its strong anti-inflammatory effect. Finally, among four different fractions of OHS extract, n-butanol fraction strongly decreased NO production (p<0.0001) and iNOS expression in LPS-induced RAW 264.7 cells. Conclusion: Our results suggest that the methanolic extract of O. humifusa stem can be used to develop a therapeutic or supportive drug and/or functional food against pain and inflammation related diseases. PMID:28884086

  4. Anti-nociceptive and anti-inflammatory effects of the methanolic extract of Opuntia humifusa stem.

    PubMed

    Sharma, Bhesh Raj; Park, Chul Min; Choi, Jong Won; Rhyu, Dong Young

    2017-01-01

    Opuntia humifusa (O. humifusa) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular permeability and carrageenan and serotonin-induced paw edema tests in rats. Furthermore, anti-inflammatory effect was also measured using macrophage-like LPS-induced RAW 264.7 cells. OHS extract inhibited acetic acid-induced writhing (p<0.0001), and delayed the reaction time of mice to the hot plate-induced thermal stimulation (p<0.0001) and tail flick tests (p<0.05). OHS extract attenuated the carrageenan and serotonin-induced paw edema in rats (p<0.001). Similarly, OHS extract significantly decreased Evans blue concentration in acetic acid induced vascular permeability test (p<0.0001), revealing its strong anti-inflammatory effect. Finally, among four different fractions of OHS extract, n-butanol fraction strongly decreased NO production (p<0.0001) and iNOS expression in LPS-induced RAW 264.7 cells. Our results suggest that the methanolic extract of O. humifusa stem can be used to develop a therapeutic or supportive drug and/or functional food against pain and inflammation related diseases.

  5. Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity.

    PubMed

    Akhtar, Most A; Raju, Ritesh; Beattie, Karren D; Bodkin, Frances; Münch, Gerald

    2016-01-01

    Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson's and Alzheimer's disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50  5.57 ± 1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL.

  6. Antipyretic, analgesic and anti-inflammatory activity of Viola betonicifolia whole plant.

    PubMed

    Muhammad, Naveed; Saeed, Muhammad; Khan, Haroon

    2012-05-02

    Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME). VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300 mg/kg body weight intra peritoneally (i.p). In yeast induced pyrexia, VBME demonstrated dose dependently (78.23%) protection at 300 mg/kg, similar to standard drug, paracetamol (90%) at 150 mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300 mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300 mg/kg. It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant.

  7. Evaluation of the antinociceptive and anti-inflammatory effect of Caralluma dalzielii.

    PubMed

    Ugwah-Oguejiofor, Chinenye J; Abubakar, Kabiru; Ugwah, Michael O; Njan, Anoka A

    2013-12-12

    Caralluma dalzielii has been used for treating several ailments including convulsion, leprosy, snake bites, otitis (ear pain), fungal diseases and rheumatoid arthritis in Northern Nigeria. However there is no scientific evidence to support its use in literature. To evaluate the antinociceptive and anti-inflammatory properties of the aqueous extract of Caralluma dalzielii in animal models. The antinociceptive and anti-inflammatory properties were assessed using acetic acid induced writhing test in mice, sub plantar formalin induced nociception, the tail-flick test and formalin induced oedema in rats. Three doses of the extract (25, 50, 100 mg/kg) were used for the assessment. Caralluma dalzielii extract demonstrated strong dose-dependent antinociceptive and anti-inflammatory activities in all the models employed. All doses (25, 50, 100 mg/kg) produced a significant percentage inhibition (41.77, 77.11, and 90.76% in the early phase and 52.02, 85.35, 93.93% in the late phase) in the acetic acid writhing test and (42.85, 55.71, 86.43% in the early phase and 23.26, 37.98, 72.87 in the late phase) in the formalin induced nociception test, respectively. The tail-flick test showed a significant increase in the antinociceptive effect of the extract in both early and late phases when compared with the control. The inhibition of oedema in the formalin test was significant when compared to the control. The results indicated that Caralluma dalzielii showed excellent antinociceptive and anti-inflammatory properties suggesting that its traditional use in the treatment of pains and inflammatory diseases may be valid. © 2013 Published by Elsevier Ireland Ltd.