Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

PubMed Central

Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

2016-01-01

Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

Anti-inflammatory effect of simvastatin in an experimental model of spinal cord trauma: involvement of PPAR-α

PubMed Central

2012-01-01

Background Statins such as simvastatin are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase used in the prevention of cardiovascular disease. In addition to their cholesterol-lowering activities, statins exert pleiotropic anti-inflammatory effects, which might contribute to their beneficial effects on lipid-unrelated inflammatory diseases. Recently it has been demonstrated that the peroxisome proliferator-activated receptor (PPAR)-α mediates anti-inflammatory effects of simvastatin in vivo models of acute inflammation. Moreover, previous results suggest that PPAR-α plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI). Methods With the aim to characterize the role of PPAR-α in simvastatin activity, we tested the efficacy of simvastatin (10 mg/kg dissolved in saline i.p. 1 h and 6 h after the trauma) in an experimental model of SCI induced in mice by extradural compression of the spinal cord (T6-T7 level) using an aneurysm clip with a closing force of 24 g via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-α KO) with wild type (WT) mice. In order to elucidate whether the effects of simvastatin are due to activation of the PPAR-α, we also investigated the effect of a PPAR-α antagonist, GW6471 (1 mg/kg administered i.p. 30 min prior treatment with simvastatin) on the protective effects of on simvastatin. Results Results indicate that simvastatin activity is weakened in PPAR-α KO mice, as compared to WT controls. In particular, simvastatin was less effective in PPAR-α KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation, neutrophil infiltration, nitrotyrosine formation, pro-inflammmatory cytokine expression, nuclear factor (NF)-κB activation, inducible nitric-oxide synthase (iNOS) expression, and apoptosis. In addition we demonstrated that GW6471 significantly antagonized the effect of the statin and thus abolished the protective effect. Conclusions This study indicates that PPAR-α can contribute to the anti-inflammatory activity of simvastatin in SCI. PMID:22537532

Inhibition of retinoic acid catabolism by minocycline: evidence for a novel mode of action?

PubMed

Regen, Francesca; Hildebrand, Martin; Le Bret, Nathalie; Herzog, Irmelin; Heuser, Isabella; Hellmann-Regen, Julian

2015-06-01

Retinoic acid (RA) represents an essential and highly potent endogenous retinoid with pronounced anti-inflammatory properties and potent anti-acne activity, and has recently been suggested to share a common anti-inflammatory mode of action with tetracycline antibiotics. We hypothesized that tetracyclines may directly interfere with RA homeostasis via inhibition of its local cytochrome P450 (CYP450)-mediated degradation, an essential component of tightly regulated skin RA homeostasis. To test this hypothesis, we performed controlled in vitro RA metabolism assays using rat skin microsomes and measured RA levels in a RA-synthesizing human keratinocyte cell line, both in the presence and in the absence of minocycline, a tetracycline popular in acne treatment. Interestingly, minocycline potently blocked RA degradation in rat skin microsomes, and strikingly enhanced RA levels in RA-synthesizing cell cultures, in a dose-dependent manner. These findings indicate a potential role for CYP-450-mediated RA metabolism in minocycline's pleiotropic mode of action and anti-acne efficacy and could account for the overlap between minocycline and RA-induced effects at the level of their molecular mode of action, but also clinically at the level of the rare side effect of pseudotumor cerebri, which is observed for both, RA and minocycline treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pleiotropic effects of interleukin-6 in a "two-hit" murine model of acute respiratory distress syndrome.

PubMed

Goldman, Julia L; Sammani, Saad; Kempf, Carrie; Saadat, Laleh; Letsiou, Eleftheria; Wang, Ting; Moreno-Vinasco, Liliana; Rizzo, Alicia N; Fortman, Jeffrey D; Garcia, Joe G N

2014-06-01

Patients with acute respiratory distress syndrome (ARDS) exhibit elevated levels of interleukin-6 (IL-6), which correlate with increased morbidity and mortality. The exact role of IL-6 in ARDS has proven difficult to study because it exhibits either pro- or anti-inflammatory actions in mouse models of lung injury, depending on the model utilized. In order to improve understanding of the role of this complex cytokine in ARDS, we evaluated IL-6 using the clinically relevant combination of lipopolysaccharide (LPS) and ventilator-induced lung injury (VILI) in IL-6(-/-) mice. Bronchoalveolar lavage fluid (BAL), whole-lung tissue, and histology were evaluated for inflammatory markers of injury. Transendothelial electrical resistance was used to evaluate the action of IL-6 on endothelial cells in vitro. In wild-type mice, the combination model showed a significant increase in lung injury compared to either LPS or VILI alone. IL-6(-/-) mice exhibited a statistically significant decrease in BAL cellular inflammation as well as lower histologic scores for lung injury, changes observed only in the combination model. A paradoxical increase in BAL total protein was observed in IL-6(-/-) mice exposed to LPS, suggesting that IL-6 provides protection from vascular leakage. However, in vitro data showed that IL-6, when combined with its soluble receptor, actually caused a significant increase in endothelial cell permeability, suggesting that the protection seen in vivo was likely due to complex interactions of IL-6 and other inflammatory mediators rather than to direct effects of IL-6. These studies suggest that a dual-injury model exhibits utility in evaluating the pleiotropic effects of IL-6 in ARDS on inflammatory cells and lung endothelium.

Exploring novel pharmacotherapeutic applications and repurposing potential of sodium glucose CoTransporter 2 (SGLT2) inhibitors.

PubMed

Madaan, Tushar; Husain, Ibraheem; Akhtar, Mohamad; Najmi, Abul Kalam

2018-05-11

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of anti-hyperglycemic drugs with a distinctive mechanism of action focusing on renal absorption ofglucose. Apart from its anti-hyperglycemic effects, a multitude of research studies on this classhave revealed that these drugs have far more versatile and comprehensive pharmacologicaleffects than previously believed. Approximately 30% of FDA approved drugs are repurposedand used for indications other than those they were initially intended for. Repurposing alreadyapproved drugs leads to significant reduction in pre-clinical and clinical R&D costs as well as minimizes the burden with respect to obtaining regulatory approval. SGLT2 inhibitors have been found to exhibit cardioprotective, renoprotective, anti-hyperlipidemic, anti-atherosclerotic, anti- obesity, anti-neoplastic, hepatoprotective, and renoprotective effects in in vitro, pre-clinical, and clinical studies. The pleiotropic effects of this class have been attributed to a variety of itspharmacodynamic actions such as natriuresis, hemoconcentration, deactivation of RAAS, ketone body formation, alterations in energy homeostasis, glycosuria, lipolysis, anti-inflammatory, andanti-oxidative actions. These favorable observations encourage further research on this multifaceted class in order to effectively explore and harness its full potential and consequently lead to clinical outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Monocarbonyl Curcumin Analogs: Heterocyclic Pleiotropic Kinase Inhibitors that Mediate Anti-Cancer Properties

PubMed Central

Brown, Andrew; Shi, Qi; Moore, Terry W.; Yoon, Younghyoun; Prussia, Andrew; Maddox, Clinton; Liotta, Dennis C.; Shim*, Hyunsuk; Snyder*, James P.

2014-01-01

Curcumin is a biologically active component of curry powder. A structurally-related class of mimetics possesses similar anti-inflammatory and anticancer properties. Mechanism has been examined by exploring kinase inhibition trends. In a screen of 50 kinases relevant to many forms of cancer, one member of the series (4, EF31) showed ≥85% inhibition for ten of the enzymes at 5 μM, while twenty-two of the proteins were blocked at ≥40%. IC50’s for an expanded set of curcumin analogs established a rank order of potencies, and analyses of IKKβ and AKT2 enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition dominating. Our curcumin mimetics are generally selective for Ser/Thr kinases. Both selectivity and potency trends are compatible with protein sequence comparisons, while modeled kinase binding site geometries deliver a reasonable correlation with mixed inhibition. Overall, these analogs are shown to be pleiotropic inhibitors that operate at multiple points along cell signaling pathways. PMID:23550937

Exercise training reduces inflammatory mediators in the intestinal tract of healthy older adult mice.

PubMed

Packer, Nicholas; Hoffman-Goetz, Laurie

2012-06-01

Aging is associated with increased intestinal inflammation and elevated risk of chronic diseases including inflammatory bowel diseases and colon cancer; many epidemiologic studies show that regular exercise reduces risk. This study examined the effects of long-term voluntary exercise on inflammatory mediators expressed in the intestine of older (15-16 months), healthy C57BL/6 mice. Animals were assigned to four months of freewheel running (WR; n = 20) or to a "sedentary" no wheel running (NWR; n = 20) control group. Intestinal lymphocytes were harvested and analysed for expression of (1) pro-inflammatory (TNF-α, IL-1β) and pleiotropic (IL-6) cytokines, and (2) pro-(caspase-3/-7) and anti-(Bcl-2) apoptotic proteins. Training was confirmed by skeletal muscle enzyme activity; stress was assessed by plasma 8-iso-PGF(2α) and corticosterone. The WR mice had a lower expression of TNF-α, caspase-7, and 8-isoprostanes (p < .05) compared to sedentary controls, suggesting that long-term exercise may "protect" the bowel by reducing inflammatory cytokine and apoptotic protein expression.

VIP impairs acquisition of the macrophage proinflammatory polarization profile.

PubMed

Carrión, Mar; Pérez-García, Selene; Martínez, Carmen; Juarranz, Yasmina; Estrada-Capetillo, Lizbeth; Puig-Kröger, Amaya; Gomariz, Rosa P; Gutiérrez-Cañas, Irene

2016-12-01

This study tested the hypothesis that vasoactive intestinal peptide (VIP) is able to modify the macrophage inflammatory profile, thus supporting its therapeutic role in autoimmune diseases. Macrophages are innate immune cells that display a variety of functions and inflammatory profiles in response to the environment that critically controls their polarization. Deregulation between the pro- and anti-inflammatory phenotypes has been involved in different pathologies. Rheumatoid arthritis (RA) is an autoimmune disease, in which macrophages are considered central effectors of synovial inflammation, displaying a proinflammatory profile. VIP is a pleiotropic neuropeptide with proven anti-inflammatory actions. As modulation of the macrophage phenotype has been implicated in the resolution of inflammatory diseases, we evaluated whether VIP is able to modulate human macrophage polarization. In vitro-polarized macrophages by GM-CSF (GM-MØ), with a proinflammatory profile, expressed higher levels of VIP receptors, vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2, respectively), than macrophages polarized by M-CSF (M-MØ) with anti-inflammatory activities. RA synovial macrophages, according to their GM-CSF-like polarization state, expressed both VPAC1 and VPAC2. In vitro-generated GM-MØ exposed to VIP exhibited an up-regulation of M-MØ gene marker expression, whereas their proinflammatory cytokine profile was reduced in favor of an anti-inflammatory function. Likewise, in GM-MØ, generated in the presence of VIP, VIP somehow changes the macrophages physiology profile to a less-damaging phenotype. Therefore, these results add new value to VIP as an immunomodulatory agent on inflammatory diseases. © Society for Leukocyte Biology.

Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer’s Disease

PubMed Central

Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

2018-01-01

Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer’s disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD. PMID:29636677

Prospects for the therapeutic application of sulfated polysaccharides of brown algae in diseases of the cardiovascular system: review.

PubMed

Zaporozhets, Tatyana; Besednova, Natalia

2016-12-01

Fucoidans are water-soluble, highly sulfated, branched homo- and hetero-polysaccharides derived from the fibrillar cell walls and intercellular spaces of brown seaweeds of the class Phaeophyceae. Fucoidans possess mimetic properties of the natural ligands of protein receptors and regulate functions of biological systems via key signaling molecules. The aim of this review was to collect and combine all available scientific literature about the potential use of the fucoidans for diseases of cardiovascular system. The review has been compiled using references from major databases such as Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to September 2015). After obtaining all reports from database (a total number is about 580), the papers were carefully analyzed in order to find data related to the topic of this review (129 references). An exhaustive survey of literature revealed that fucoidans possess a broad spectrum of biological activity, including anti-coagulant, hypolipidemic, anti-thrombotic, anti-inflammatory, immunomodulatory, anti-tumor, anti-adhesive and anti-hypertensive properties. Numerous investigations of fucoidans in diseases of the cardiovascular system mainly focus on pleiotropic anti-inflammatory effects. Fucoidans also possess pro-angiogenic and pro-vasculogenic properties. A great number of investigations in the past years have demonstrated that fucoidans has great potential for in-depth investigation of their effects on cardiovascular system. Through this review, the authors hope to attract the attention of researchers to use fucoidan as mimetic of natural ligand receptor protein with the view of developing new formulations with an improved therapeutic value.

Diabetes as a negative risk factor for abdominal aortic aneurysm - does the disease aetiology or the treatment provide the mechanism of protection?

PubMed

Torsney, Evelyn; Pirianov, Grisha; Cockerill, Gillian W

2013-05-01

There is strong epidemiological evidence that patients with diabetes have a lower incidence of abdominal aortic aneurysm. The precise mechanism of this negative association is unknown. Whilst a number of studies have supported the hypothesis that protection is a function of diabetes-mediated changes in the vascular extracellular matrix biology, there is also support for the idea that the treatment regimens used in diabetes may afford protection against AAA. In particular the pleiotropic drug family, the thiazolidinediones have been examined as candidates to ameliorate aneurysm formation. Both the thiazolidinediones, and the structurally related family, fibrates, have been shown to have anti-inflammatory and antioxidative effects, in addition to ability to modulatate glucose and lipid homeostasis. In this brief review we present the current data exploring the use of thiazolidinediones in experimental aneurysm development. Despite the fact that both thiazolidinediones Rosiglitazone and Pioglitazone are no longer prescribed in Europe and the US, they have provided important insights into the mechanism of action, and the application of other pleiotropic drugs in the treatment of AAA. One such pleiotropic drug is high-density lipoproteins (HDLs), which have been shown to have a broad spectrum of effects, including activation of PPARs, which may favour their use as a new drug target for protection against AAA development.

Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury

PubMed Central

Endesfelder, Stefanie; Weichelt, Ulrike; Strauß, Evelyn; Schlör, Anja; Sifringer, Marco; Scheuer, Till; Bührer, Christoph; Schmitz, Thomas

2017-01-01

Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. PMID:28106777

Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury.

PubMed

Endesfelder, Stefanie; Weichelt, Ulrike; Strauß, Evelyn; Schlör, Anja; Sifringer, Marco; Scheuer, Till; Bührer, Christoph; Schmitz, Thomas

2017-01-18

Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28-32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

PubMed Central

Kawanami, Daiji; Matoba, Keiichiro; Sango, Kazunori; Utsunomiya, Kazunori

2016-01-01

An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications. PMID:27483245

Vitamin D Axis in Inflammatory Bowel Diseases: Role, Current Uses and Future Perspectives

PubMed Central

Del Pinto, Rita; Ferri, Claudio; Cominelli, Fabio

2017-01-01

Increasing evidence supports the concept that the vitamin D axis possesses immunoregulatory functions, with vitamin D receptor (VDR) status representing the major determinant of vitamin D’s pleiotropic effects. Vitamin D promotes the production of anti-microbial peptides, including β-defensins and cathelicidins, the shift towards Th2 immune responses, and regulates autophagy and epithelial barrier integrity. Impairment of vitamin D-mediated pathways are associated with chronic inflammatory conditions, including inflammatory bowel diseases (IBD). Interestingly, inhibition of vitamin D pathways results in dysbiosis of the gut microbiome, which has mechanistically been implicated in the development of IBD. Herein, we explore the role of the vitamin D axis in immune-mediated diseases, with particular emphasis on its interplay with the gut microbiome in the pathogenesis of IBD. The potential clinical implications and therapeutic relevance of this interaction will also be discussed, including optimizing VDR function, both with vitamin D analogues and probiotics, which may represent a complementary approach to current IBD treatments. PMID:29112157

Ticagrelor - toward more efficient platelet inhibition and beyond.

PubMed

Kubisa, Michał J; Jezewski, Mateusz P; Gasecka, Aleksandra; Siller-Matula, Jolanta M; Postuła, Marek

2018-01-01

Novel antiplatelet drugs, including ticagrelor, are being successively introduced into the therapy of atherothrombotic conditions due to their superiority over a standard combination of clopidogrel with acetylsalicylic acid in patients with acute coronary syndromes (ACS). A P2Y12 receptor antagonist, ticagrelor, is unique among antiplatelet drugs, because ticagrelor inhibits the platelet P2Y12 receptor in a reversible manner, and because it demonstrates a wide palette of advantageous pleiotropic effects associated with the increased concentration of adenosine. The pleiotropic effects of ticagrelor comprise cardioprotection, restoration of the myocardium after an ischemic event, promotion of the release of anticoagulative factors and, eventually, anti-inflammatory effects. Beyond the advantageous effects, the increased concentration of adenosine is responsible for some of ticagrelor's adverse effects, including dyspnea and bradycardia. Large-scale clinical trials demonstrated that both standard 12-month therapy and long-term use of ticagrelor reduce the risk of cardiovascular events in patients with ACS, but at the expense of a higher risk of major bleeding. Further trials focused on the use of ticagrelor in conditions other than ACS, including ischemic stroke, peripheral artery disease and status after coronary artery bypass grafting. The results of these trials suggest comparable efficacy and safety of ticagrelor and clopidogrel in extra-coronary indications, but firm conclusions are anticipated from currently ongoing studies. Here, we summarize current evidence on the superiority of ticagrelor over other P2Y12 antagonists in ACS, discuss the mechanism underlying the drug-drug interactions and pleiotropic effects of ticagrelor, and present future perspectives of non-coronary indications for ticagrelor.

Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

PubMed

Waghela, Bhargav N; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

Curcumin and its analogues: a potential natural compound against HIV infection and AIDS.

PubMed

Prasad, Sahdeo; Tyagi, Amit K

2015-11-01

No safe and effective cure currently exists for human immunodeficiency virus (HIV). However, antiretroviral therapy can prolong the lives of HIV patients and lowers the secondary infections. Natural compounds, which are considered to be pleiotropic molecules, could be useful against HIV. Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), can be used for the treatment of several diseases including HIV-AIDS because of its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial nature. In this review we have summarized that how curcumin and its analogues inhibit the infection and replication of viral genes and prevent multiplicity of HIV. They are inhibitors of HIV protease and integrase. Curcumin also inhibits Tat transactivation of the HIV1-LTR genome, inflammatory molecules (interleukins, TNF-α, NF-κB, COX-2) and HIV associated various kinases including tyrosine kinase, PAK1, MAPK, PKC, cdk and others. In addition, curcumin enhances the effect of conventional therapeutic drugs and minimizes their side effects.

Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.

PubMed

Liu, Ting Ting; Zeng, Yi; Tang, Kun; Chen, XueMeng; Zhang, Wei; Xu, Xiao Le

2017-07-01

Dihydromyricetin, the most abundant flavonoid in Ampelopsis grossedentata, exerts numerous pharmacological activities, including anti-inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities; however, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of dihydromyricetin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr -/- ) mice. Blood samples were collected for determination of serum lipid profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology, hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation were performed on liver and aorta samples by molecular biology methods. The effects of dihydromyricetin on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation were further studied. (1) Dihydromyricetin ameliorated hyperlipidemia, reduced serum ox-LDL, IL-6 and TNF-α levels in HFD-fed LDLr -/- mice. Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and increased protein expressions of PPARα, LXRα and ABCA1. (3) It inhibited atherosclerotic lesion formation and favoured features of plaque stability. (4) Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the reduced IL-6 and TNF-α mRNA expression; (5) it prevented hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in the liver and suppressing reactive oxygen species generation and NOX2 protein expression in both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation and enhanced cholesterol efflux. These findings suggest that dihydromyricetin could reduce atherosclerosis via its pleiotropic effects, including improvement of endothelial dysfunction, inhibition of macrophage foam cell formation, amelioration of lipid profiles, anti-inflammatory action and anti-oxidative effect. Copyright © 2017 Elsevier B.V. All rights reserved.

Withania somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation.

PubMed

Gupta, Muskan; Kaur, Gurcharan

2018-05-30

Reactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities. In Ayurveda, Ashwagandha (Withania somnifera) is well known for its immunomodulatory properties. The current study is an extension of our previous report on in vitro model system and was aimed to investigate anti-neuroinflammatory potential of water extract from the Ashwagandha leaves (ASH-WEX) against systemic LPS-induced neuroinflammation and associated behavioral impairments using in vivo rat model system. Oral feeding of ASH-WEX for 8 weeks significantly ameliorated the anxiety-like behavior as evident from Elevated plus maze test. Suppression of reactive gliosis, inflammatory cytokines production like TNF-α, IL-1β, IL-6, and expression of nitro-oxidative stress enzymes like iNOS, COX2, NOX2 etc were observed in ASH-WEX-treated animals. NFκB, P38, and JNK MAPKs pathways analysis showed their involvement in inflammation suppression which was further confirmed by inhibitor studies. The current study provides first ever preclinical evidence and scientific validation that ASH-WEX exhibits the anti-neuroinflammatory potential against systemic LPS-induced neuroinflammation and ameliorates associated behavioral abnormalities. Aqueous extract from Ashwagandha leaves and its active phytochemicals may prove to be promising candidates to prevent neuroinflammation associated with various neuropathologies.

Renal synthesis of leukaemia inhibitory factor (LIF), under normal and inflammatory conditions.

PubMed

Morel, D S; Taupin, J L; Potier, M; Deminière, C; Potaux, L; Gualde, N; Moreau, J F

2000-03-01

Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine that is particularly involved in nephrogenesis and repair of the extracellular matrix. Transgenic mice overexpressing LIF have mesangial proliferative glomerulonephritis. Also, during local inflammatory reactions, such as kidney graft rejection or urinary tract infections, urinary LIF excretion is enhanced. The aim of the study therefore was to study LIF production by normal and inflammatory diseased kidneys (glomerulonephritis or graft rejection), maintained in short cultures. To determine the responsibility of the kidney itself in LIF synthesis, we measured LIF secretion into the culture supernatants of human mesangial or renal tubular epithelial cells. Fragments from diseased kidneys, whether grafts or not, released more LIF than normal human kidney fragments, mesangial or renal tubular epithelial cells. However, LIF production was delayed in renal transplants compared to glomerulonephritic samples taken from untreated patients. In every case, LIF production was enhanced by interleukin 1beta (IL-1beta) and inhibited by IL-4 or dexamethasone, except in two severe rejection episodes. So, LIF appeared to respond to pro- and anti-inflammatory stimuli, in vitro and in vivo. Considering its biological effects, LIF could play a role in inflammatory renal diseases. Copyright 2000 Academic Press.

Amelioration of systemic lupus erythematosus by Withangulatin A in MRL/lpr mice.

PubMed

Sun, Lijuan; Zhou, Lin; Chen, Mingcang; Zhong, Renqian; Liu, Jianwen

2011-09-01

We have previously reported the anti-inflammatory potential and the possible underlying mechanisms of Withangulatin A (WA), which is an active component isolated from Physalis angulata L. Here, we demonstrated that WA might improve the life quality, as well as reduced the accumulation of proteinuria symptoms and levels of anti-double-stranded DNA antibodies in MRL/lpr mice. Moreover, WA could improve renal histopathologic characteristics of MRL/lpr mice. Intriguingly, expression of B cell-activating factor (BAFF), BAFF-R and related gene in the spleen were significantly reduced in 10 mg/kg WA-treated mice compared with that in 5 mg/kg WA-treated mice and untreated mice. These findings indicate that WA might have a pleiotropic therapeutic effect through their immunosuppression via inhibiting BAFF signaling, which suggest a potential application of this active constituent in the treatment of SLE. Copyright © 2011 Wiley-Liss, Inc.

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

PubMed Central

Lei, Beilei; Mace, Brian; Dawson, Hana N.; Warner, David S.; Laskowitz, Daniel T.; James, Michael L.

2014-01-01

Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO) and prostaglandin E2 (PGE2), mediated by inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone’s effects on tumor necrosis factor alpha (TNF-α), iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways. LPS (30 ng/ml) upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury. PMID:25080336

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

PubMed Central

Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

Novel tactics for neuroprotection in Parkinson's disease: Role of antibiotics, polyphenols and neuropeptides.

PubMed

Reglodi, Dora; Renaud, Justine; Tamas, Andrea; Tizabi, Yousef; Socías, Sergio B; Del-Bel, Elaine; Raisman-Vozari, Rita

2017-08-01

Parkinson's disease is a progressive neurodegenerative disorder characterized by the degeneration of midbrain nigral dopaminergic neurons. Although its etiology remains unknown, the pathological role of several factors has been highlighted, namely oxidative stress, neuroinflammation, protein misfolding, and mitochondrial dysfunction, in addition to genetic predispositions. The current therapy is mainly symptomatic with l-DOPA aiming to replace dopamine. Novel therapeutic approaches are being investigated with the intention of influencing pathways leading to neuronal death and dysfunction. The present review summarizes three novel approaches, the use of which is promising in pre-clinical studies. Polyphenols have been shown to possess neuroprotective properties on account of their well-established antioxidative and anti-inflammatory actions but also due to their influence on protein misfolding and mitochondrial homeostasis. Within the amazing ancillary effects of antibiotics, their neuroprotective properties against neurodegenerative and neuroinflammatory processes are of great interest for the development of effective therapies against Parkinson's disease. Experimental evidence supports the potential of antibiotics as neuroprotective agents, being useful not only to prevent the formation of toxic α-synuclein oligomers but also to ameliorate mitochondrial dysfunction and neuroinflammation. Neuropeptides offer another approach with their diverse effects in the nervous system. Among them, pituitary adenylate cyclase-activating polypeptide, a member of the secretin/glucagon superfamily, has several advantageous effects in models of neurodegeneration, namely anti-apoptotic, anti-inflammatory and antioxidant actions, the combination of which offers a potent protective effect in dopaminergic neurons. Owing to their pleiotropic modes of action, these novel therapeutic candidates have potential in tackling the multidimensional features of Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

PubMed

Mathew, Geetha; Unnikrishnan, M K

2015-10-01

Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.

PubMed

Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N

2016-08-15

Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

The pleotropic role of statins: Could it be the imminent host modulation agent in periodontics?

PubMed

Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti; Maroo, Niteeka

2013-03-01

Periodontal disease is a chronic inflammatory disease which represents a primarily anaerobic Gram-negative oral infection that results in gingival inflammation, loss of attachment, bone destruction. Bacterial endotoxins in the form of lipopolysaccharides (LPS) that are instrumental in generating a host-mediated tissue destructive immune response by mobilizing their defensive cells and releasing cytokines like Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6), which lead to tissue destruction by stimulating the production of the collagenolytic enzymes: Matrix metalloproteinases (MMPs). Since the host-mediated tissue destruction is to be controlled, various means have been employed for modulating this response. Statins, 3-hydroxy-3-methylglutarylcoenzyme A (HMG CoA) reductase inhibitors, besides having lipid-lowering abilities also have antioxidant, antithrombotic, anti-inflammatory, immunomodulatory and osteomodulatory properties. All of these pleiotropic effects of statins point out to it perhaps becoming the novel host modulation agent in periodontics.

The pleotropic role of statins: Could it be the imminent host modulation agent in periodontics?

PubMed Central

Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti; Maroo, Niteeka

2013-01-01

Periodontal disease is a chronic inflammatory disease which represents a primarily anaerobic Gram-negative oral infection that results in gingival inflammation, loss of attachment, bone destruction. Bacterial endotoxins in the form of lipopolysaccharides (LPS) that are instrumental in generating a host-mediated tissue destructive immune response by mobilizing their defensive cells and releasing cytokines like Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6), which lead to tissue destruction by stimulating the production of the collagenolytic enzymes: Matrix metalloproteinases (MMPs). Since the host-mediated tissue destruction is to be controlled, various means have been employed for modulating this response. Statins, 3-hydroxy-3-methylglutarylcoenzyme A (HMG CoA) reductase inhibitors, besides having lipid-lowering abilities also have antioxidant, antithrombotic, anti-inflammatory, immunomodulatory and osteomodulatory properties. All of these pleiotropic effects of statins point out to it perhaps becoming the novel host modulation agent in periodontics. PMID:23946727

Acetyl-L-carnitine and alpha-lipoic acid: possible neurotherapeutic agents for mood disorders?

PubMed

Soczynska, Joanna K; Kennedy, Sidney H; Chow, Cindy S M; Woldeyohannes, Hanna O; Konarski, Jakub Z; McIntyre, Roger S

2008-06-01

Mood disorders are associated with decrements in cognitive function, which are insufficiently treated with contemporary pharmacotherapies. To evaluate the putative neurotherapeutic effects of the mitochondrial cofactors, L-carnitine, acetyl-L-carnitine, and alpha-lipoic acid; and to provide a rationale for investigating their efficacy in the treatment of neurocognitive deficits associated with mood disorders. A PubMed search of English-language articles published between January 1966 and March 2007 was conducted using the search terms carnitine and lipoic acid. L-carnitine and alpha-lipoic acid may offer neurotherapeutic effects (e.g., neurocognitive enhancement) via disparate mechanisms including antioxidant, anti-inflammatory, and metabolic regulation. Preliminary controlled trials in depressed geriatric populations also suggest an antidepressant effect with acetyl-L-carnitine. L-carnitine and alpha-lipoic acid are pleiotropic agents capable of offering neuroprotective and possibly cognitive-enhancing effects for neuropsychiatric disorders in which cognitive deficits are an integral feature.

HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases

PubMed Central

Montgomery, McKale R.; Leyva, Kathryn J.

2016-01-01

Histone deacetylase (HDAC) inhibitors are powerful epigenetic regulators that have enormous therapeutic potential and have pleiotropic effects at the cellular and systemic levels. To date, HDAC inhibitors are used clinically for a wide variety of disorders ranging from hematopoietic malignancies to psychiatric disorders, are known to have anti-inflammatory properties, and are in clinical trials for several other diseases. In addition to influencing gene expression, HDAC enzymes also function as part of large, multisubunit complexes which have many nonhistone targets, alter signaling at the cellular and systemic levels, and result in divergent and cell-type specific effects. Thus, the effects of HDAC inhibitor treatment are too intricate to completely understand with current knowledge but the ability of HDAC inhibitors to modulate the immune system presents intriguing therapeutic possibilities. This review will explore the complexity of HDAC inhibitor treatment at the cellular and systemic levels and suggest strategies for effective use of HDAC inhibitors in biomedical research, focusing on the ability of HDAC inhibitors to modulate the immune system. The possibility of combining the documented anticancer effects and newly emerging immunomodulatory effects of HDAC inhibitors represents a promising new combinatorial therapeutic approach for HDAC inhibitor treatments. PMID:27556043

Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy.

PubMed

Kaur, Harpreet; Patro, Ishan; Tikoo, Kulbhushan; Sandhir, Rajat

2015-10-01

Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vitro protective effects of two extracts from bergamot peels on human endothelial cells exposed to tumor necrosis factor-alpha (TNF-alpha).

PubMed

Trombetta, Domenico; Cimino, Francesco; Cristani, Mariateresa; Mandalari, Giuseppina; Saija, Antonella; Ginestra, Giovanna; Speciale, Antonio; Chirafisi, Joselita; Bisignano, Giuseppe; Waldron, Keith; Narbad, Arjan; Faulds, Craig B

2010-07-28

Bergamot ( Citrus bergamia Risso) is a less commercialized Citrus fruit, mainly used for its essential oil extracted from the peel. Bergamot peel (BP) represents about 60% of the processed fruits and is regarded as primary waste. However, it contains good amounts of useful compounds, such as pectins and flavonoids. Many of the bioactivities of Citrus flavonoids appear to impact vascular endothelial cells. Herein, we report the protective effect of two flavonoid-rich extracts from BP (endowed with radical-scavenging properties and lacking genotoxic activity) against alterations in cell modifications induced by the pleiotropic inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) on human umbilical vein endothelial cells (HUVECs), as demonstrated by monitoring intracellular levels of malondialdehyde/4-hydroxynonenal, reduced and oxidized glutathione and superoxide dismutase activity, and the activation status of nuclear factor-kappaB (NF-kappaB). Thus, BP appears to be a potential source of natural antioxidant/anti-inflammatory phytocomplexes to be employed as ingredients of nutraceutical products or functional foods.

Pleiotropic benefit of monomeric and oligomeric flavanols on vascular health--a randomized controlled clinical pilot study.

PubMed

Weseler, Antje R; Ruijters, Erik J B; Drittij-Reijnders, Marie-José; Reesink, Koen D; Haenen, Guido R M M; Bast, Aalt

2011-01-01

Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded. In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets. In the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P ≤ 0.05). Our integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans. ClinicalTrials.gov NCT00742287.

Human Uterine Cervical Stromal Stem Cells (hUCESCs): Why and How they Exert their Antitumor Activity

PubMed Central

SCHNEIDER, JOSÉ; EIRÓ, NOEMÍ; PÉREZ-FERNÁNDEZ, ROMÁN; MARTÍNEZ-ORDÓÑEZ, ANXO; VIZOSO, FRANCISCO

2016-01-01

Our research team has recently isolated and characterized a new stromal stem cell line (hUCESCs) obtained from cytological smears, as routinely performed for cervical cancer screening. We have, furthermore, described that both hUCESCs directly, as well as the secretome contained in the conditioned medium used for growing them (hUCESCs-CM) have potent antitumoral, anti-inflammatory, antibiotic, antimycotic and re-epitheliasation-enhancing properties. The scientific explanation our team proposes for these pleiotropic effects are directly related to the site of origin of hUCESCs, the human cervical transition zone, which has unique features that biologically justify the different actions of hUCESCs and hUCESCs-CM. We, herein, expose our working theory for the biological activity of hUCESCs and hUCESCs-CM. PMID:27566652

Histone Deacetylase Inhibition and Dietary Short-Chain Fatty Acids

PubMed Central

Licciardi, Paul V.; Ververis, Katherine; Karagiannis, Tom C.

2011-01-01

Changes in diet can also have dramatic effects on the composition of gut microbiota. Commensal bacteria of the gastrointestinal tract are critical regulators of health and disease by protecting against pathogen encounter whilst also maintaining immune tolerance to certain allergens. Moreover, consumption of fibre and vegetables typical of a non-Western diet generates substantial quantities of short-chain fatty acids (SCFAs) which have potent anti-inflammatory properties. Dietary interventions such as probiotic supplementation have been investigated for their pleiotropic effects on microbiota composition and immune function. Probiotics may restore intestinal dysbiosis and improve clinical disease through elevated SCFA levels in the intestine. Although the precise mechanisms by which such dietary factors mediate these effects, SCFA metabolites such as butyrate also function as histone deacetylase inhibitors (HDACi), that can act on the epigenome through chromatin remodeling changes. The aim of this review is to provide an overview of HDAC enzymes and to discuss the biological effects of HDACi. Further, we discuss the important relationship between diet and the balance between health and disease and how novel dietary interventions such as probiotics could be alternative approach for the prevention and/or treatment of chronic inflammatory disease through modulation of the intestinal microbiome. PMID:23724235

Histone deacetylase inhibition and dietary short-chain Fatty acids.

PubMed

Licciardi, Paul V; Ververis, Katherine; Karagiannis, Tom C

2011-01-01

Changes in diet can also have dramatic effects on the composition of gut microbiota. Commensal bacteria of the gastrointestinal tract are critical regulators of health and disease by protecting against pathogen encounter whilst also maintaining immune tolerance to certain allergens. Moreover, consumption of fibre and vegetables typical of a non-Western diet generates substantial quantities of short-chain fatty acids (SCFAs) which have potent anti-inflammatory properties. Dietary interventions such as probiotic supplementation have been investigated for their pleiotropic effects on microbiota composition and immune function. Probiotics may restore intestinal dysbiosis and improve clinical disease through elevated SCFA levels in the intestine. Although the precise mechanisms by which such dietary factors mediate these effects, SCFA metabolites such as butyrate also function as histone deacetylase inhibitors (HDACi), that can act on the epigenome through chromatin remodeling changes. The aim of this review is to provide an overview of HDAC enzymes and to discuss the biological effects of HDACi. Further, we discuss the important relationship between diet and the balance between health and disease and how novel dietary interventions such as probiotics could be alternative approach for the prevention and/or treatment of chronic inflammatory disease through modulation of the intestinal microbiome.

Omega-3 fatty acid supplementation and cardiovascular disease

PubMed Central

Jump, Donald B.; Depner, Christopher M.; Tripathy, Sasmita

2012-01-01

Epidemiological studies on Greenland Inuits in the 1970s and subsequent human studies have established an inverse relationship between the ingestion of omega-3 fatty acids [C20–22 ω 3 polyunsaturated fatty acids (PUFA)], blood levels of C20–22 ω 3 PUFA, and mortality associated with cardiovascular disease (CVD). C20–22 ω 3 PUFA have pleiotropic effects on cell function and regulate multiple pathways controlling blood lipids, inflammatory factors, and cellular events in cardiomyocytes and vascular endothelial cells. The hypolipemic, anti-inflammatory, anti-arrhythmic properties of these fatty acids confer cardioprotection. Accordingly, national heart associations and government agencies have recommended increased consumption of fatty fish or ω 3 PUFA supplements to prevent CVD. In addition to fatty fish, sources of ω 3 PUFA are available from plants, algae, and yeast. A key question examined in this review is whether nonfish sources of ω 3 PUFA are as effective as fatty fish-derived C20–22 ω 3 PUFA at managing risk factors linked to CVD. We focused on ω 3 PUFA metabolism and the capacity of ω 3 PUFA supplements to regulate key cellular events linked to CVD. The outcome of our analysis reveals that nonfish sources of ω 3 PUFA vary in their capacity to regulate blood levels of C20–22 ω 3 PUFA and CVD risk factors. PMID:22904344

[A new possible strategy for prevention and preventive treatment of age-related macular degeneration resting on recent clinical and pathophysiological observations].

PubMed

Fischer, Tamás

2009-03-15

The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins and third generation beta blockers help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. The angiotensin II receptor blocker telmisartan with its peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist effect inhibits the development of choroidal neovascularisation (CNV) and improves it clinically favourably. The third generation beta adrenergic receptor blocker carvedilol and nebivolol as well as the peroxisome proliferator-activated receptor-gamma agonist pioglitazone elicit their antioxidant vascular protective effects mitochondrially. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into consideration all possible side effects--ACE-inhibitor and/or AR blocker and statin and aspirin treatment, and trimetazidine as adjuvant medicine, and third generation beta adrenergic receptor blockers: 1. those without macular degeneration but being above the age of 50 and having risk factors inducing endothelial dysfunction; 2. those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3. those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory and important to eliminate AMD risk factors (cardiovascular risk factors also) inducing oxidative stress with consecutive endothelial dysfunction.

Prevention & treatment of obstetrical complications in APS: Is hydroxychloroquine the Holy Grail we are looking for?

PubMed

Meroni, Pier Luigi

2016-12-01

Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory. Copyright © 2016. Published by Elsevier Ltd.

Vitamin C promotes wound healing through novel pleiotropic mechanisms.

PubMed

Mohammed, Bassem M; Fisher, Bernard J; Kraskauskas, Donatas; Ward, Susan; Wayne, Jennifer S; Brophy, Donald F; Fowler, Alpha A; Yager, Dorne R; Natarajan, Ramesh

2016-08-01

Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by altering the inflammatory, proliferative and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo(-/-) ) were used in this study. VitC was provided in the water (sufficient), withheld from another group (deficient) and supplemented by daily intra-peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full thickness excisional wounds (6 mm) were created and tissue collected on days 7 and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects of In conclusion, VitC favorably on proliferation. Histological analysis showed improved wound matrix deposition and organisation in sufficient and deficient +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced expression of pro-inflammatory mediators and higher expression of wound healing mediators. Supplementation of HnDF with AscA induced the expression of self-renewal genes and promoted fibroblast proliferation. VitC favourably impacts the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodelling. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Monocarbonyl curcumin analogues: heterocyclic pleiotropic kinase inhibitors that mediate anticancer properties.

PubMed

Brown, Andrew; Shi, Qi; Moore, Terry W; Yoon, Younghyoun; Prussia, Andrew; Maddox, Clinton; Liotta, Dennis C; Shim, Hyunsuk; Snyder, James P

2013-05-09

Curcumin is a biologically active component of curry powder. A structurally related class of mimetics possesses similar anti-inflammatory and anticancer properties. Mechanism has been examined by exploring kinase inhibition trends. In a screen of 50 kinases relevant to many forms of cancer, one member of the series (4, EF31) showed ≥85% inhibition for 10 of the enzymes at 5 μM, while 22 of the proteins were blocked at ≥40%. IC50 values for an expanded set of curcumin analogues established a rank order of potencies, and analyses of IKKβ and AKT2 enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition dominating. Our curcumin mimetics are generally selective for Ser/Thr kinases. Both selectivity and potency trends are compatible with protein sequence comparisons, while modeled kinase binding site geometries deliver a reasonable correlation with mixed inhibition. Overall, these analogues are shown to be pleiotropic inhibitors that operate at multiple points along cell signaling pathways.

Statins Reduce Lipopolysaccharide-Induced Cytokine and Inflammatory Mediator Release in an In Vitro Model of Microglial-Like Cells

PubMed Central

McFarland, A. J.

2017-01-01

The anti-inflammatory effects of statins (HMG-CoA reductase inhibitors) within the cardiovascular system are well-established; however, their neuroinflammatory potential is unclear. It is currently unknown whether statins' neurological effects are lipid-dependent or due to pleiotropic mechanisms. Therefore, the assumption that all statin compounds will have the same effect within the central nervous system is potentially inappropriate, with no studies to date having compared all statins in a single model. Thus, the aim of this study was to compare the effects of the six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) within a single in vitro model of neuroinflammation. To achieve this, PMA-differentiated THP-1 cells were used as surrogate microglial cells, and LPS was used to induce inflammatory conditions. Here, we show that pretreatment with all statins was able to significantly reduce LPS-induced interleukin (IL)-1β and tumour necrosis factor (TNF)-α release, as well as decrease LPS-induced prostaglandin E2 (PGE2). Similarly, global reactive oxygen species (ROS) and nitric oxide (NO) production were decreased following pretreatment with all statins. Based on these findings, it is suggested that more complex cellular models should be considered to further compare individual statin compounds, including translation into in vivo models of acute and/or chronic neuroinflammation. PMID:28546657

The future role of anti-tumour necrosis factor (TNF) products in the treatment of rheumatoid arthritis.

PubMed

Camussi, G; Lupia, E

1998-05-01

Tumour necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potential pathogenic role in the establishment of rheumatoid synovitis, in the formation of pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNF alpha a potential target for anticytokine therapy. Experimental studies have shown that TNF alpha blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis both in collagen-induced arthritis in mice and in transgenic mice overexpressing TNF alpha, which develop a rheumatoid-like destructive arthritis. Clinical studies based on the use of anti-TNF alpha antibodies or soluble receptors have suggested a potential beneficial effect of TNF alpha-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNF alpha therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated with an improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNF alpha therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNF alpha production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNF alpha therapy must be carefully evaluated. In addition, targeting a single mediator may be not sufficient to block the complex inflammatory response in rheumatoid arthritis. For these reasons therapeutic strategies aimed at concomitantly interfering with multiple pathogenic pathways are currently under investigation.

[In vitro study over statins effects on cellular growth curves and its reversibility with mevalonate].

PubMed

Millan Núñez-Cortés, Jesús; Alvarez Rodriguez, Ysmael; Alvarez Novés, Granada; Recarte Garcia-Andrade, Carlos; Alvarez-Sala Walther, Luis

2014-01-01

HMG-CoA-Reductase inhibitors, also known as statins, are currently the most powerful cholesterol-lowering drugs available on the market. Clinical trials and experimental evidence suggest that statins have heavy anti-atherosclerotic effects. These are in part consequence of lipid lowering but also result from pleiotropic actions of the drugs. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL-c reduction or via a direct effect on cellular functions. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. So, although statins typically have similar effects on LDL-c levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects. In this paper we analize the in vitro effects of different statins over different cell lines from cells implicated in atherosclerotic process: endothelial cells, fibroblasts, and vascular muscular cells. In relation with our results we can proof that the effects of different dosis of different statins provides singular effects over growth curves of different cellular lines, a despite of a class-dependent effects. So, pleiotropic effects and its reversibility with mevalonate are different according with the molecule and the dosis. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

Statins in Asthma: Potential Beneficial Effects and Limitations

PubMed Central

Bhattacharjee, Dipanjan

2015-01-01

Asthma's sustenance as a global pandemic, across centuries, can be attributed to the lack of an understanding of its workings and the inability of the existing treatment modalities to provide a long lasting cure without major adverse effects. The discovery of statins boosted by a better comprehension of the pathophysiology of asthma in the past few decades has opened up a potentially alternative line of treatment that promises to be a big boon for the asthmatics globally. However, the initial excellent results from the preclinical and animal studies have not borne the results in clinical trials that the scientific world was hoping for. In light of this, this review analyzes the ways by which statins could benefit in asthma via their pleiotropic anti-inflammatory properties and explain some of the queries raised in the previous studies and provide recommendations for future studies in this field. PMID:26618001

Effects of clopidogrel on inflammatory cytokines and adhesion molecules in human endothelial cells: Role of nitric oxide mediating pleiotropic effects.

PubMed

Cerda, Alvaro; Pavez, Monica; Manriquez, Victor; Luchessi, Andre Ducati; Leal, Pamela; Benavente, Felipe; Fajardo, Cristina Moreno; Salazar, Luis; Hirata, Mario Hiroyuki; Hirata, Rosario Dominguez Crespo

2017-08-01

Clopidogrel is commonly used in prevention and treatment of atherothrombosis. Some previous studies have suggested a pleiotropic effect of clopidogrel; however, when this drug causes platelet-independent effects on endothelial function remains unclear. To evaluate the influence of clopidogrel on inflammatory biomarkers and adhesion molecules in human endothelial cells and the role of nitric oxide (NO) in this process. TNF-α-induced human umbilical vein endothelial cells (HUVEC) were exposed to clopidogrel. Gene expression and protein expression of ICAM-1, P-selectin, IL-8, IL-6, and MCP-1 were evaluated by qPCR, flux cytometry, or milliplex technology. Expression of endothelial nitric oxide synthase (NOS3) and NO release were also evaluated. Influence of clopidogrel was further evaluated in NOS3 downregulated HUVEC by RNAi. Clopidogrel at 20 μmol/L induced NO release in HUVEC after 24-hours treatment. Gene expressions of inflammatory markers IL-8 and MCP1 were reduced after clopidogrel treatment (P<.05); however, only MCP-1 remained reduced at protein level. IL-6 was not modified by clopidogrel treatment. Gene expression and protein expression of ICAM-1 were diminished by 24-hours clopidogrel exposure, whereas P-selectin was not modified. NOS3 downregulated HUVEC model revealed that ICAM-1 modification by clopidogrel is dependent of this via, whereas MCP-1 is modulated in an NO-independent form. Our results support new evidence for pleiotropic effects of clopidogrel on inflammation and endothelial function. Reduction in ICAM-1 and MCP-1 in human endothelium is an important extent of the use of this drug for treatment of cardiovascular diseases, and NO has an important role in this process. © 2017 John Wiley & Sons Ltd.

Antinociception induced by atorvastatin in different pain models.

PubMed

Garcia, G G; Miranda, H F; Noriega, V; Sierralta, F; Olavarría, L; Zepeda, R J; Prieto, J C

2011-11-01

Atorvastatin is a statin that inhibits the 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Several landmark clinical trials have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. It is assumed that the beneficial effects of statin therapy are entirely due to cholesterol reduction. Statins have an additional activity (pleiotropic effect) that has been associated to their anti-inflammatory effects. The aim of the present study was to assess the antinociceptive activity of atorvastatin in five animal pain models. The daily administration of 3-100mg/kg of atorvastatin by oral gavage induced a significant dose-dependent antinociception in the writhing, tail-flick, orofacial formalin and formalin hind paw tests. However, this antinociceptive activity of atorvastatin was detectable only at high concentrations in the hot plate assay. The data obtained in the present study demonstrates the effect of atorvastatin to reduce nociception and inflammation in different animal pain models. Copyright © 2011 Elsevier Inc. All rights reserved.

Proteomic and transcriptomic analyses to explain the pleiotropic effects of Ankaferd blood stopper

PubMed Central

Simsek, Cem; Selek, Sebnem; Koca, Meltem; Haznedaroglu, Ibrahim Celal

2017-01-01

Ankaferd blood stopper is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica and has been used as a topical hemostatic agent and with its clinical application established in randomized controlled trials and case reports. Ankaferd has been successfully used in gastrointestinal endobronchial mucosal and cutaneous bleedings and also in abdominal, thoracic, dental and oropharyngeal, and pelvic surgeries. Ankaferd’s hemostatic action is thought to form a protein complex with coagulation factors that facilitate adhesion of blood components. Besides its hemostatic action, Ankaferd has demonstrated pleiotropic effects, including anti-neoplastic and anti-microbial activities and tissue-healing properties; the underlying mechanisms for these have not been well studied. Ankaferd’s individual components were determined by proteomic and chemical analyses. Ankaferd also augments transcription of some transcription factors which is shown with transcriptomic analysis. The independent effects of these ingredients and augmented transcription factors are not known precisely. Here, we review what is known of Ankaferd blood stopper components from chemical, proteomic, and transcriptomic analyses and propose that individual components can explain some pleiotropic effects of Ankaferd. Certainly more research is needed focusing on individual ingredients of Ankaferd to elucidate their precise and effects. PMID:28839937

Atorvastatin reduces cardiac and adipose tissue inflammation in rats with metabolic syndrome.

PubMed

Yamada, Yuichiro; Takeuchi, Shino; Yoneda, Mamoru; Ito, Shogo; Sano, Yusuke; Nagasawa, Kai; Matsuura, Natsumi; Uchinaka, Ayako; Murohara, Toyoaki; Nagata, Kohzo

2017-08-01

Statins are strong inhibitors of cholesterol biosynthesis and help to prevent cardiovascular disease. They also exert additional pleiotropic effects that include an anti-inflammatory action and are independent of cholesterol, but the molecular mechanisms underlying these additional effects have remained unclear. We have now examined the effects of atorvastatin on cardiac and adipose tissue inflammation in DahlS.Z-Lepr fa /Lepr fa (DS/obese) rats, which we previously established as a model of metabolic syndrome (MetS). DS/obese rats were treated with atorvastatin (6 or 20mgkg -1 day -1 ) from 9 to 13weeks of age. Atorvastatin ameliorated cardiac fibrosis, diastolic dysfunction, oxidative stress, and inflammation as well as adipose tissue inflammation in these animals at both doses. The high dose of atorvastatin reduced adipocyte hypertrophy to a greater extent than did the low dose. Atorvastatin inhibited the up-regulation of peroxisome proliferator-activated receptor γ gene expression in adipose tissue as well as decreased the serum adiponectin concentration in DS/obese rats. It also activated AMP-activated protein kinase (AMPK) as well as inactivated nuclear factor-κB (NF-κB) in the heart of these animals. The down-regulation of AMPK and NF-κB activities in adipose tissue of DS/obese rats was attenuated and further enhanced, respectively, by atorvastatin treatment. The present results suggest that the anti-inflammatory effects of atorvastatin on the heart and adipose tissue are attributable at least partly to increased AMPK activity and decreased NF-κB activity in this rat model of MetS. Copyright © 2017 Elsevier B.V. All rights reserved.

Discovery of Curcumin, a Component of the Golden Spice, and Its Miraculous Biological Activities

PubMed Central

Gupta, Subash C; Patchva, Sridevi; Koh, Wonil; Aggarwal, Bharat B

2012-01-01

SUMMARY 1. Curcumin is the active ingredient of the dietary spice turmeric and has been consumed for medicinal purposes for thousands of years. Modern science has shown that curcumin modulates various signaling molecules, including inflammatory molecules, transcription factors, enzymes, protein kinases, protein reductases, carrier proteins, cell survival proteins, drug resistance proteins, adhesion molecules, growth factors, receptors, cell-cycle regulatory proteins, chemokines, DNA, RNA, and metal ions. 2. Because of this polyphenol's potential to modulate multiple signaling molecules, it has been reported to possess pleiotropic activities. First shown to have anti-bacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, anti-proliferative, wound healing, anti-nociceptive, anti-parasitic, and anti-malarial properties as well. Animal studies have suggested that curcumin may be active against a wide range of human diseases, including diabetes, obesity, neurologic and psychiatric disorders, and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys, and gastrointestinal and cardiovascular systems. 3. Although many clinical trials evaluating curcumin's safety and efficacy against human ailments have already been completed, others are still ongoing. Moreover, curcumin is used as a supplement in several countries, including India, Japan, the United States, Thailand, China, Korea, Turkey, South Africa, Nepal, and Pakistan. Although inexpensive, apparently well tolerated, and potentially active, curcumin has yet not been approved for treatment of any human disease. 4. In this article, we discuss the discovery and key biological activities of curcumin, with a particular emphasis on its activities at the molecular, cellular, animal, and human levels. PMID:22118895

Statins: Do they have potential in the treatment of polycystic ovary syndrome?

PubMed Central

Kodaman, Pinar H.; Duleba, Antoni J.

2010-01-01

Many women of reproductive age are affected by polycystic ovary syndrome (PCOS), a heterogeneous endocrinopathy characterized by androgen excess, chronic oligo-anovulation and/or polycystic ovarian morphology. In addition, PCOS is often associated with insulin resistance, systemic inflammation and oxidative stress which, on one hand, lead to endothelial dysfunction and dyslipidemia with subsequent cardiovascular sequelae and, on the other hand, to hyperplasia of the ovarian theca compartment with resultant hyperandrogenism and anovulation. While traditionally statins have been used to treat dyslipidemia by blocking HMG-CoA reductase, the rate limiting step in cholesterol biosynthesis; in fact, they possess pleiotropic actions, resulting in antioxidant, anti-inflammatory and anti-proliferative effects. Statins offer a novel therapeutic approach to PCOS in that they address the dyslipidemia associated with the syndrome, as well as hyperandrogenism/hyperandrogenemia. These actions may be due to an inhibition of the effects of systemic inflammation and insulin resistance/hyperinsulinemia. Evidence to date, both in vitro and in vivo, suggests that statins have potential in the treatment of PCOS; however, further clinical trials are needed before they can be considered a standard of care in the medical management of this common endocrinopathy. PMID:18181091

The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salles von-Held-Ventura, Juliana; Mázala-de-Oliveira, Thalita; Cândida da Rocha Oliveira, Amanda

Ouabain is a steroid hormone that binds to the enzyme Na{sup +}, K{sup +} – ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α couldmore » be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival. - Highlights: • Pro-inflammatory cytokines regulates the ouabain effect on RGC survival. • Ouabain treatment modulates the intracellular levels of TNF-α and IL-1β. • Ouabain induces the release of TNF-α and IL-1β in retinal cell cultures.« less

Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation.

PubMed

Sessa, Rosa; Di Pietro, Marisa; Filardo, Simone; Bressan, Alessia; Rosa, Luigi; Cutone, Antimo; Frioni, Alessandra; Berlutti, Francesca; Paesano, Rosalba; Valenti, Piera

2017-02-01

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

Human Uterine Cervical Stromal Stem Cells (hUCESCs): Why and How they Exert their Antitumor Activity.

PubMed

Schneider, José; Eiró, Noemí; Pérez-Fernández, Román; Martínez-Ordóñez, Anxo; Vizoso, Francisco

Our research team has recently isolated and characterized a new stromal stem cell line (hUCESCs) obtained from cytological smears, as routinely performed for cervical cancer screening. We have, furthermore, described that both hUCESCs directly, as well as the secretome contained in the conditioned medium used for growing them (hUCESCs-CM) have potent antitumoral, anti-inflammatory, antibiotic, antimycotic and re-epitheliasation-enhancing properties. The scientific explanation our team proposes for these pleiotropic effects are directly related to the site of origin of hUCESCs, the human cervical transition zone, which has unique features that biologically justify the different actions of hUCESCs and hUCESCs-CM. We, herein, expose our working theory for the biological activity of hUCESCs and hUCESCs-CM. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update.

PubMed

Ghosh, Shatadal; Banerjee, Sharmistha; Sil, Parames C

2015-09-01

The concept of using phytochemicals has ushered in a new revolution in pharmaceuticals. Naturally occurring polyphenols (like curcumin, morin, resveratrol, etc.) have gained importance because of their minimal side effects, low cost and abundance. Curcumin (diferuloylmethane) is a component of turmeric isolated from the rhizome of Curcuma longa. Research for more than two decades has revealed the pleiotropic nature of the biological effects of this molecule. More than 7000 published articles have shed light on the various aspects of curcumin including its antioxidant, hypoglycemic, anti-inflammatory and anti-cancer activities. Apart from these well-known activities, this natural polyphenolic compound also exerts its beneficial effects by modulating different signalling molecules including transcription factors, chemokines, cytokines, tumour suppressor genes, adhesion molecules, microRNAs, etc. Oxidative stress and inflammation play a pivotal role in various diseases like diabetes, cancer, arthritis, Alzheimer's disease and cardiovascular diseases. Curcumin, therefore, could be a therapeutic option for the treatment of these diseases, provided limitations in its oral bioavailability can be overcome. The current review provides an updated overview of the metabolism and mechanism of action of curcumin in various organ pathophysiologies. The review also discusses the potential for multifunctional therapeutic application of curcumin and its recent progress in clinical biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Current Insights Into the Biological Action of Squalene.

PubMed

Lou-Bonafonte, José M; Martínez-Beamonte, Roberto; Sanclemente, Teresa; Surra, Joaquín C; Herrera-Marcos, Luis V; Sanchez-Marco, Javier; Arnal, Carmen; Osada, Jesús

2018-06-08

Squalene is a triterpenic compound found in a large number of plants and other sources with a long tradition of research since it was first reported in 1926. Herein we present a systematic review of studies concerning squalene published in the last eight years. These studies have provided further support for its antioxidant, anti-inflammatory and anti-atherosclerotic properties in vivo and in vitro. Moreover, an anti-neoplastic effect in nutrigenetic-type treatments, which depend on the failing metabolic pathway of tumors, has also been reported. The bioavailability of squalene in cell cultures, animal models and in humans has been well established, and further progress has been made as regards the intracellular transport of this lipophilic molecule. Squalene accumulates in the liver and decreases hepatic cholesterol and triglycerides, with these actions being exerted via a complex network of changes in gene expression at both transcriptional and post-transcriptional levels. Its presence in different biological fluids has also been studied. The combination of squalene with other bioactive compounds has been shown to enhance its pleiotropic properties and might lead to the formulation of functional foods and nutraceuticals to control oxidative stress and, therefore, numerous age-related diseases in human and veterinary medicine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Jack of All Trades: Pleiotropy and the application of Chemically Modified Tetracycline -3 in Sepsis and the Acute Respiratory Distress Syndrome (ARDS)

PubMed Central

Roy, Shreyas K.; Kendrick, Daniel; Sadowitz, Benjamin D.; Gatto, Louis; Snyder, Kathleen; Satalin, Joshua M.; Golub, Lorne M.; Nieman, Gary

2011-01-01

Sepsis is a disease process that has humbled the medical profession for centuries with its resistance to therapy, relentless mortality, and pathophysiologic complexity. Despite 30 years of aggressive, concerted, well-resourced efforts the biomedical community has been unable to reduce the mortality of sepsis from 30%, nor the mortality of septic shock from greater than 50%. In the last decade only one new drug for sepsis has been brought to the market, drotrecogin alfa-activated (Xigris™), and the success of this drug has been limited by patient safety issues. Clearly a new agent is desperately needed. The advent of recombinant human immune modulators held promise but the outcomes of clinical trials using biologics that target single immune mediators have been disappointing. The complex pathophysiology of the systemic inflammatory response syndrome (SIRS) is self-amplifying and redundant at multiple levels. In this review we argue that perhaps pharmacologic therapy for sepsis will only be successful if it addresses this pathophysiologic complexity; the drug would have to be pleiotropic, working on many components of the inflammatory cascade at once. In this context, therapy that targets any single inflammatory mediator will not adequately address the complexity of SIRS. We propose that Chemically Modified Tetracycline-3, CMT-3 (or COL-3), a non-antimicrobial modified tetracycline with pleiotropic anti-inflammatory properties, is an excellent agent for the management of sepsis and its associated complication of the Acute Respiratory Distress Syndrome (ARDS). The purpose of this review is threefold: 1) to examine the shortcomings of current approaches to treatment of sepsis and ARDS in light of their pathophysiology, 2) to explore the application of COL-3 in ARDS and sepsis, and finally 3) to elucidate the mechanisms of COL-3 that may have potential therapeutic benefit in ARDS and sepsis. PMID:21767646

Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats

PubMed Central

Chen, Yen-Cheng; Ho, Ching-Chun; Yi, Chih-Hsun; Liu, Xiu-Zhu; Cheng, Tzu-Ting

2017-01-01

Background Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats. Methods and results Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area. Conclusion Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes. PMID:29095895

Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking

PubMed Central

Yang, Qian; Nanayakkara, Gayani K.; Drummer, Charles; Sun, Yu; Johnson, Candice; Cueto, Ramon; Fu, Hangfei; Shao, Ying; Wang, Luqiao; Yang, William Y.; Tang, Peng; Liu, Li-Wen; Ge, Shuping; Zhou, Xiao-Dong; Khan, Mohsin; Wang, Hong; Yang, Xiaofeng

2017-01-01

Background: Low-intensity ultrasound (LIUS) was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders. Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS. Results: Our data revealed following interesting findings: (1) LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2) LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells), MSCs (mesenchymal stem cells), B1-B cells and Treg (regulatory T cells); (3) LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4) LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5) Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6) LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways. Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair. PMID:29109687

Low-dose atorvastatin, losartan, and particularly their combination, provide cardiovascular protection in isolated rat heart and aorta.

PubMed

Lunder, Mojca; Ziberna, Lovro; Janić, Miodrag; Jerin, Aleš; Skitek, Milan; Sabovič, Mišo; Drevenšek, Gorazd

2013-03-01

Statins and angiotensin receptor blockers at therapeutic doses have beneficial cardiovascular effects, which can be applied for cardiovascular protection. We explored whether low doses of atorvastatin, losartan, and particularly their combination, possess important pleiotropic vasodilatory effects. Wistar rats were treated daily with low-dose atorvastatin (2 mg/kg, n = 15), low-dose losartan (5 mg/kg, n = 15), their combination (n = 15), or saline (n = 15). After 4, 6, or 8 weeks the animals were anesthetized, blood samples taken, and their hearts and thoracic aortas isolated. Two kinds of experiments were performed: the measurement of coronary flow rate after ischemia/reperfusion myocardial injury and endothelium-dependent relaxation of thoracic aorta. In both models, maximal vasodilation activity was obtained in rats treated for 6 weeks. In the ischemia/reperfusion myocardial injury model, coronary flow increased (atorvastatin or losartan 1.9-fold, P < 0.01; combination 2.4-fold, P < 0.001) compared with controls. In the thoracic aorta model, endothelium-dependent relaxation significantly increased only in the combination group compared with the control group (up to 1.4-fold; P < 0.01). Simultaneously, we detected increased anti-inflammatory activity and increased nitric oxide concentration, but no changes in lipids and blood pressure. In a rat model we showed important vasodilatory activity of low-dose atorvastatin, losartan, and particularly their combination. The effects of the low-dose combination were accompanied by, and probably at least partly achieved by, anti-inflammatory and nitric oxide pathways. Overall, these results could be valuable for the development of new vascular protective strategies focusing on a low-dose regimen of statins and sartans, and particularly their combination.

[Gamma interferon: basics aspects, clinic significance and terapeutic uses].

PubMed

Mata-Espinosa, Dulce A; Hernández-Pando, Rogelio

2008-01-01

Interferons are a family of pleiotropic cytokines, their name was assigned because of their anti-replicative viral activity. IFNgamma or immune type II interferon does not share receptors with the type I interferon, its structure is different and its gene is located in different chromosome, although its biologic effects are similar. Along of several years of research, it has been found that IFNgamma enhances the transcription of genes involved in immunomodulation, antiviral responses and antitumoral activities. Regarding to the immune system, IFNgamma increases the cytotoxic and phagocytic activity of macrophages and upregulates the expression of major histocompatibility complex (MHC) class I and class II molecules in dendritics cells and other antigen presenting cells. IFNgamma also promotes the development and differentiation of naive CD4+ T lymphocytes to Th1 helper subset. Indeed, this cytokine has a key role in the control of bacterial, micotic, viral and parasitic infections. Depending of the micro-environment, IFNgamma has a dual role as pro or anti inflammatory cytokine. Novel therapeutic strategies are currently being developed with the aim to enhance the immune response or replace IFNgamma gene abnormal expression with beneficial results in humans, being recombinant IFNgamma safe and well tolerated.

The effect of ultraviolet radiation on the anti-inflammatory effect of filters.

PubMed

Couteau, C; Couteau, O; Chauvet, C; Paparis, E; Coiffard, L J M

2013-08-16

A certain number of filters have notable anti-inflammatory properties with percentage inhibition of PMA-induced edema in mice at over 70%. The question arose as to whether this effect was likely to continue after UV irradiation. It can be noted that 7 filters retain an equivalent anti-inflammatory effect before and after 2h of irradiation in a Suntest device (650 W/m(2)). For 9 filters, the anti-inflammatory effect decreases and for 5 filters, the anti-inflammatory effect increases. Various behaviors should be noted. 3 groups of substances can be distinguished: such as phenylbenzimidazole sulfonic acid which loses its anti-inflammatory character after irradiation (the percentage inhibition falls from 80 to 44%), oxybenzone which retains a constant anti-inflammatory character (89% inhibition before and after irradiation and also octyl methoxycinnamate which becomes very anti-inflammatory (with a percentage inhibition of 93%). The same phenomenon is observed in the case of commercial products. This should be made known as it can have a considerable impact on the results which are displayed on the packaging of sun products. Copyright © 2013 Elsevier B.V. All rights reserved.

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

PubMed Central

Kell, Douglas B

2009-01-01

Background The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. Review We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, since in some circumstances (especially the presence of poorly liganded iron) molecules that are nominally antioxidants can actually act as pro-oxidants. The reduction of redox stress thus requires suitable levels of both antioxidants and effective iron chelators. Some polyphenolic antioxidants may serve both roles. Understanding the exact speciation and liganding of iron in all its states is thus crucial to separating its various pro- and anti-inflammatory activities. Redox stress, innate immunity and pro- (and some anti-)inflammatory cytokines are linked in particular via signalling pathways involving NF-kappaB and p38, with the oxidative roles of iron here seemingly involved upstream of the IkappaB kinase (IKK) reaction. In a number of cases it is possible to identify mechanisms by which ROSs and poorly liganded iron act synergistically and autocatalytically, leading to 'runaway' reactions that are hard to control unless one tackles multiple sites of action simultaneously. Some molecules such as statins and erythropoietin, not traditionally associated with anti-inflammatory activity, do indeed have 'pleiotropic' anti-inflammatory effects that may be of benefit here. Conclusion Overall we argue, by synthesising a widely dispersed literature, that the role of poorly liganded iron has been rather underappreciated in the past, and that in combination with peroxide and superoxide its activity underpins the behaviour of a great many physiological processes that degrade over time. Understanding these requires an integrative, systems-level approach that may lead to novel therapeutic targets. PMID:19133145

Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

PubMed Central

Köhler, Ole; Krogh, Jesper; Mors, Ole; Benros, Michael Eriksen

2016-01-01

Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity of the inflammatory cascade, limited clinical evidence, and the risk for side effects stress cautiousness before clinical application. Thus, despite proof-of-concept studies of anti-inflammatory treatment effects in depression, important challenges remain to be investigated. Within this paper, we review the association between inflammation and depression together with the current evidence on use of anti-inflammatory treatment in depression. Based on this, we address the questions and challenges that seem most important and relevant to future studies, such as timing, most effective treatment lengths and identification of subgroups of patients potentially responding better to different anti-inflammatory treatment regimens. PMID:27640518

Anti-inflammatory actions of clonidine, guanfacine and B-HT 920 against various inflammagen-induced acute paw oedema in rats.

PubMed

Kulkarni, S K; Mehta, A K; Kunchandy, J

1986-02-01

Clonidine (0.1-1.0 mg/kg, i.p.) exhibited anti-inflammatory activity in carrageenan-, formalin-, 5-HT- and histamine-induced paw oedema in rats. Similarly, other two alpha 2-adrenoceptor agonists, guanfacine and B-HT 920, also displayed an anti-inflammatory action in these models. The anti-inflammatory effect of all the three alpha 2-adrenoceptor agonists was reversed by yohimbine. However, prazosin failed to block the anti-inflammatory effect of clonidine. Intracerebroventricularly administered clonidine had a delayed onset of anti-inflammatory action, starting only from 60 min post carrageenan administration. This was in contrast to the systemically administered clonidine which was effective against both phases of carrageenan-induced oedema. On the other hand, irrespective of the route of administration, i.e. peripheral or central, guanfacine and B-HT 920 were effective against the early as well as against the delayed phases of the inflammatory reaction. The studies suggest that it is not the imidazoline moiety but the activation of alpha 2-adrenoceptors which is essential for the anti-inflammatory action of these agents.

Chemically modified tetracycline-3 (CMT-3): a novel inhibitor of the serine proteinase, elastase.

PubMed

Gu, Ying; Lee, Hsi-Ming; Simon, Sanford R; Golub, Lorne M

2011-12-01

Two classes of enzymes play an important role in connective tissue breakdown during various inflammatory diseases: serine proteinases and matrix metalloproteinases (MMPs). Tetracyclines (TCs) exhibit important anti-inflammatory and MMP-inhibitory properties that are unrelated to their antibacterial activities. Of the various TCs and their chemically modified NON-antibiotic analogs (CMTs) tested in vitro and in vivo, CMT-3 (6-demethyl-6-deoxy 4 de-dimethylamino tetracycline) has repeatedly been shown to be the most potent inhibitor of MMP activity and cytokine production. In addition to its anti-MMP function, we have shown that among all CMTs, CMT-3 is the only CMT that can also directly inhibit both the amidolytic activity of human leukocyte elastase (HLE, a serine proteinase) and the extracellular matrix degradation mediated by HLE. In addition, CMT-3 has been found to reduce leukocyte elastase activity in vivo in gingival extracts of rats with experimental periodontal disease. Thus, CMT-3 can inhibit pathologic connective tissue breakdown by (at least) two mechanisms: direct inhibition of neutral proteinases (elastase and MMPs); and protecting their endogenous inhibitors, α(1)-PI and TIMPs, from being digested and inactivated by MMPs and HLE, respectively. The pleiotropic properties of CMT-3 including (but not limited to) inhibition of serine proteinases, MMPs, and cytokines provide impressive therapeutic potential to reduce excessive connective tissue breakdown during various pathologic processes including inflammatory diseases, cancer metastasis and metabolic bone diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

The actions of relaxin on the human cardiovascular system.

PubMed

Sarwar, Mohsin; Du, Xiao-Jun; Dschietzig, Thomas B; Summers, Roger J

2017-05-01

The insulin-like peptide relaxin, originally identified as a hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic, angiogenic, anti-apoptotic and anti-inflammatory effects in both males and females. Relaxin produces these effects by binding to a cognate receptor RXFP1 and activating a variety of signalling pathways including cAMP, cGMP and MAPKs as well as by altering gene expression of TGF-β, MMPs, angiogenic growth factors and endothelin receptors. The peptide has been shown to be effective in halting or reversing many of the adverse effects including fibrosis in animal models of cardiovascular disease including ischaemia/reperfusion injury, myocardial infarction, hypertensive heart disease and cardiomyopathy. Relaxin given to humans is safe and produces favourable haemodynamic changes. Serelaxin, the recombinant form of relaxin, is now in extended phase III clinical trials for the treatment of acute heart failure. Previous clinical studies indicated that a 48 h infusion of relaxin improved 180 day mortality, yet the mechanism underlying this effect is not clear. This article provides an overview of the cellular mechanism of effects of relaxin and summarizes its beneficial actions in animal models and in the clinic. We also hypothesize potential mechanisms for the clinical efficacy of relaxin, identify current knowledge gaps and suggest new ways in which relaxin could be useful therapeutically. This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc. © 2016 The British Pharmacological Society.

Dexamethasone Alleviates Tumor-Associated Brain Damage and Angiogenesis

PubMed Central

Fan, Zheng; Sehm, Tina; Rauh, Manfred; Buchfelder, Michael

2014-01-01

Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA), a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc −; SLC7a11) and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G) resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage. PMID:24714627

Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

PubMed Central

Davinelli, Sergio; Sapere, Nadia; Zella, Davide; Bracale, Renata; Intrieri, Mariano; Scapagnini, Giovanni

2012-01-01

Alzheimer's disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD. PMID:22690271

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

PubMed

Zhu, Fengmei; Du, Bin; Xu, Baojun

2018-05-24

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 E 2 . 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.

Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived inflammatory mediators.

PubMed

Harizi, Hedi; Gualde, Norbert

2006-08-01

Exposure to pathogens induces antigen-presenting cells (APC) such as macrophages and dendritic cells (DC) to produce various endogenous mediators, including arachidonic acid (AA)-derived eicosanoids, cytokines, and nitric oxide (NO). Many secreted products of activated APC can act by themselves in an autocrine manner and modulate their function. Moreover, the cross-interaction between endogenous bioactive molecules regulates the function of professional APC with important consequences for their ability to activate and sustain immune and inflammatory responses, and to regulate immune homeostasis. Although neglected for many years when compared to their role in cardiovascular homeostasis, cancer and inflammation, the importance of eicosanoids in immunology is becoming more defined. The role of prostaglandin (PG) E2 (PGE2), one of the best known and most well studied eicosanoids, is of particular interest. It modulates the activities of professional DC by acting on their differentiation, maturation and their ability to secrete cytokines. Uniquely among haematopoietic cytokines, interleukin-10 (IL-10) is a pleiotropic molecule that displays both immunostimulatory and immunoregulatory activities. IL-10 has attached much attention because of its anti-inflammatory properties. It modulates expression of cytokines, soluble mediators and cell surface molecules by cells of myeloid origin, particularly macrophages and DC. We previously reported that PGE2 is a potent inducer of IL-10 in bone marrow-derived DC (BM-DC), and PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype. BM-DC may be considered as an important model to study complex interactions between endogenous mediators, and autocrine IL-10 plays a pivotal role in the crossregulation of AA-derived lipid mediators, cytokines, and NO, with critical effects on immune and inflammatory responses.

In Vitro Anti-inflammatory Effects of the Phenylbutyric Acid Metabolite Phenylacetyl Glutamine.

PubMed

Hazekawa, Mai; Ono, Kazuhiko; Nishinakagawa, Takuya; Kawakubo-Yasukochi, Tomoyo; Nakashima, Manabu

2018-06-01

Sodium 4-phenylbutyrate (PBA), which exerts a wide range of anti-inflammatory effects, is rapidly cleared from the body (approximately 98%) by urinary excretion by 24 h after oral treatment in humans. PBA was almost entirely excreted to urine as phenylacetyl glutamine (PAGln). However, no data describe the potential anti-inflammatory effects of PAGln. The purpose of this study was to evaluate the anti-inflammatory effects of PAGln on mouse spleen cells and peritoneal cavity cells, and explore the potential mechanism underlying this effect. PAGln was added to mouse spleen cell cultures stimulated by concanavalin A, or mouse peritoneal cavity cell cultures stimulated by lipopolysaccharide. After 72 h of culture, levels of inflammatory cytokines in culture supernatants were measured using a sandwich enzyme-linked immunosorbent assay system, and levels of inflammatory proteins were assessed by Western blotting. PAGln significantly inhibited inflammatory cytokine (interferon-γ, interleukin-6, and tumor necrosis factor-α) production, decrease of cell number in the spleen cell, and suppressed the expression of inflammatory proteins (nuclear factor κB, and inducible nitric oxide synthase). These results suggest that PAGln possesses anti-inflammatory activity via inhibition of T cell activation and Toll-like receptor 4 signaling. This study of the anti-inflammatory mechanism of PAGln provides useful information about its potential for therapeutic applications.

Differential Effects of Vitamins A and D on the Transcriptional Landscape of Human Monocytes during Infection

PubMed Central

Klassert, Tilman E.; Bräuer, Julia; Hölzer, Martin; Stock, Magdalena; Riege, Konstantin; Zubiría-Barrera, Cristina; Müller, Mario M.; Rummler, Silke; Skerka, Christine; Marz, Manja; Slevogt, Hortense

2017-01-01

Vitamin A and vitamin D are essential nutrients with a wide range of pleiotropic effects in humans. Beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. Nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of immune processes. In the present study, we performed a comprehensive RNA-seq-based approach to define the whole immunomodulatory role of vitamins A and D during infection. Using human monocytes as host cells, we characterized the differential role of both vitamins upon infection with three different pathogens: Aspergillus fumigatus, Candida albicans and Escherichia coli. Both vitamins showed an unexpected ability to counteract the pathogen-induced transcriptional responses. Upon infection, we identified 346 and 176 immune-relevant genes that were regulated by atRA and vitD, respectively. This immunomodulatory activity was dependent on the inflammatory stimulus, allowing us to distinguish regulatory patterns which were specific for each stimulatory setting. Moreover, we explored possible direct and indirect mechanisms of vitamin-mediated regulation of the immune response. Our findings highlight the importance of vitamin-monitoring in critically ill patients. Moreover, our results underpin the potential of atRA and vitD as therapeutic options for anti-inflammatory treatment. PMID:28094291

[Pleiotropic effects of atorvastatin in rheumatoid arthritis patients with no history of cardiovascular diseases].

PubMed

Smakotina, S A; Zelendinova, A R; Bondareva, I N; Berns, S A

2015-01-01

To evaluate the effect of atorvastatin (liprimar) on the laboratory values of inflammation and blood lipid composition in rheumatoid arthritis (RA) patients with no history of cardiovascular diseases (CVD). Subjects and methods. Fifty women with grade II RA activity according to DAS28 and radiologic (erosive) Stages I-III were examined; the patients were not former or current smokers; all were seropositive; their mean age was 50.2±9.9 years. All the patients with RA were divided into 2 groups: Group 1 took no atorvastatin and continued to receive standard previously prescribed therapy; Group 2 used atorvastatin in a dose of 20 mg. Lipidogram readings and the levels of Apo-A and Apo-B, neopterin, tumor necrosis factor-α, C-reactive protein, sP-selectin, sE-selectin, interleukin (IL)-6, IL-10, IL-12, and matrix metalloproteinases 3 and 9 were assessed. The patients with RA show obvious blood lipid composition impairments. Incorporation of atorvastatin (liprimar) into combination therapy for RA not only causes a considerable reduction in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apo-B levels, but also positively affects the inflammatory activity of the disease, by lowering the level of proinflammatory cytokines and increasing that of the anti-inflammatory cytokine IL-10. The above changes may underlie the prevention of CVD complications in patients with RA.

The anti-inflammatory effect of Sonchus oleraceus aqueous extract on lipopolysaccharide stimulated RAW 264.7 cells and mice.

PubMed

Li, Qi; Dong, Dan-Dan; Huang, Qiu-Ping; Li, Jing; Du, Yong-Yong; Li, Bin; Li, Huan-Qing; Huyan, Ting

2017-12-01

Sonchus oleraceus L. (Asteraceae) (SO) is a dietary and traditional medicinal plant in China. However, its underlying mechanism of action as an anti-inflammatory agent is not known. This study evaluates the anti-inflammatory activity of aqueous extract of SO. The extract of SO was used to treat RAW 264.7 cells (in the working concentrations of 500, 250, 125, 62.5, 31.3 and 15.6 μg/mL) for 24 h. Pro-inflammatory cytokines and mediators produced in LPS-stimulated RAW 264.7 cells were assessed. Meanwhile, the expression level of TLR-4, COX-2, pSTATs and NF-κB was tested. Moreover, the anti-inflammatory activity of the extract in vivo was assessed using xylene-induced mouse ear oedema model and the anti-inflammatory compounds in the extracts were analyzed by HPLC-MS. SO extract significantly inhibited the production of pro-inflammatory cytokines and mediators at gene and protein levels with the concentration of 31.3 μg/mL, and suppressed the expression of TLR-4, COX-2, NF-κB and pSTAT in RAW 264.7 cells. The anti-inflammatory activity of SO in vivo has significant anti-inflammatory effects with the concentration of 250 and 125 mg/kg, and less side effect on the weights of the mice at the concentration of 250 mg/kg. Moreover, HPLC-MS analysis revealed that the anti-inflammatory compounds in the extract were identified as villosol, ferulaic acid, β-sitosterol, ursolic acid and rutin. This study indicated that SO extract has anti-inflammatory effects in vitro and in vivo, which will be further developed as novel pharmacological strategies in order to defeat inflammatory diseases.

[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.

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.

IN VIVO ANTI-INFLAMMATORY EFFECTS OF TARAXASTEROL AGAINST ANIMAL MODELS

PubMed Central

Wang, Ying; Li, Guan-Hao; Liu, Xin-Yu; Xu, Lu; Wang, Sha-Sha; Zhang, Xue-Mei

2017-01-01

Background: Traditional Chinese medicine Taraxacum officinale has been widely used to treat various inflammatory diseases. Taraxasterol is one of the main active components isolated from Taraxacum officinale. Recently, we have demonstrated that taraxasterol has the in vitro anti-inflammatory effects. This study aims to determine the in vivo anti-inflammatory effects of taraxasterol against animal models. Materials and Methods: Anti-inflammatory effects were assessed in four animal models by using dimethylbenzene-induced mouse ear edema, carrageenan-induced rat paw edema, acetic acid-induced mouse vascular permeability and cotton pellet-induced rat granuloma tests. Results: Our results demonstrated that taraxasterol dose-dependently attenuated dimethylbenzene-induced mouse ear edema and carrageenan-induced rat paw edema, decreased acetic acid-induced mouse vascular permeability and inhibited cotton pellet-induced rat granuloma formation. Conclusion: Our finding indicates that taraxasterol has obvious in vivo anti-inflammatory effects against animal models. It will provide experimental evidences for the traditional use of Taraxacum officinale and taraxasterol in inflammatory diseases. PMID:28480383

Anti-inflammatory Agents: Present and Future

PubMed Central

Dinarello, Charles A.

2012-01-01

Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, when allowed to continue unchecked, inflammation may result in autoimmune or autoinflammatory disorders, neurodegenerative disease, or cancer. A variety of safe and effective anti-inflammatory agents are available, including aspirin and other nonsteroidal anti-inflammatories, with many more drugs under development. In particular, the new era of anti-inflammatory agents includes “biologicals” such as anticytokine therapies and small molecules that block the activity of kinases. Other anti-inflammatories currently in use or under development include statins, histone deacetylase inhibitors, PPAR agonists, and small RNAs. This Review discusses the current status of anti-inflammatory drug research and the development of new anti-inflammatory therapeutics. PMID:20303881

Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives.

PubMed

Cipollina, Chiara; Salvatore, Sonia R; Muldoon, Matthew F; Freeman, Bruce A; Schopfer, Francisco J

2014-01-01

Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. The endogenous detection of these electrophilic ω-3 fatty acid ketone derivatives supports the precept that the benefit of ω-3 PUFA-rich diets can be attributed to the generation of electrophilic oxygenated metabolites that transduce anti-inflammatory actions rather than the suppression of pro-inflammatory AA metabolites. ClinicalTrials.gov NCT00663871.

Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1

PubMed Central

Csiszar, Anna; Labinskyy, Nazar; Jimenez, Rosario; Pinto, John T.; Ballabh, Praveen; Losonczy, Gyorgy; Pearson, Kevin J.; de Cabo, Rafael; Ungvari, Zoltan

2009-01-01

Endothelial-dysfunction, oxidative stress and inflammation are associated with vascular aging and promote the development of cardiovascular-disease. Caloric restriction (CR) mitigates conditions associated with aging, but its effects on vascular dysfunction during aging remain poorly defined. To determine whether CR exerts vasoprotective effects in aging, aortas of ad libitum (AL) fed young and aged and CR-aged F344 rats were compared. Aging in AL-rats was associated with impaired acetylcholine-induced relaxation, vascular oxidative stress and increased NF-κB-activity. Lifelong CR significantly improved endothelial function, attenuated vascular ROS production, inhibited NF-κB activity and down-regulated inflammatory genes. To elucidate the role of circulating factors in mediation of the vasoprotective effects of CR, we determined whether sera obtained from CR-animals can confer anti-oxidant and anti-inflammatory effects in cultured coronary-arterial endothelial cells (CAECs), mimicking the effects of CR. In CAECs cultured in the presence of AL-serum TNFα elicited oxidative-stress, NF-κB-activation and inflammatory gene expression. By contrast, treatment of CAECs with CR-serum attenuated TNFα-induced ROS generation and prevented NF-κB-activation and induction of inflammatory genes. siRNA-knockdown of SIRT1 mitigated the anti-oxidant and anti-inflammatory effects of CR-serum. CR exerts anti-oxidant and anti-inflammatory vascular effects, which are likely mediated by circulating factors, in part, via a SIRT1-dependent pathway. PMID:19549533

Impact of antibiotics on the microcirculation in local and systemic inflammation.

PubMed

Al-Banna, N A; Pavlovic, D; Gründling, M; Zhou, J; Kelly, M; Whynot, S; Hung, O; Johnston, B; Issekutz, T B; Kern, H; Cerny, V; Lehmann, Ch

2013-01-01

The main function of antibiotics is related to their capacity to eliminate a microorganism. In addition to the antimicrobial function of antibiotics, they are known to have anti-inflammatory and vasomodulatory effects on the microcirculation. The ability of non-antimicrobial derivatives of antibiotics to control inflammation illustrates the distinct anti-microbial and anti-inflammatory roles of antibiotics. In this review, we discuss the impact of antibiotics on leukocyte recruitment and the state of the microcirculation. Literature reporting the effect of antibiotics in non-infectious inflammatory conditions is reviewed as well as the studies demonstrating the anti-inflammatory effects of antibiotics in animal models of infection. In addition, the effect of the antibiotics on the immune system is summarized in this review, in order to postulate some mechanisms of action for the proand anti-inflammatory contribution of antibiotics. Literature reported the effect of antibiotics on the production of cytokines, chemotaxis and recruitment of leukocytes, production of reactive oxygen species, process of phagocytosis and autophagy, and apoptosis of leukocytes. Yet, all antibiotics may not necessarily exert an anti-inflammatory effect on the microcirculation. Thus, we suggest a model for spectrum of anti-inflammatory and vasomodulatory effects of antibiotics in the microcirculation of animals in local and systemic inflammation. Although the literature suggests the ability of antibiotics to modulate leukocyte recruitment and microperfusion, the process and the mechanism of action are not fully characterized. Studying this process will expand the knowledge base that is required for the selection of antibiotic treatment based on its anti-inflammatory functions, which might be particularly important for critically ill patients.

Dose-related antihyperglycemic and hypolipidemic effects of two novel thiazolidin-4-ones in a rodent model of metabolic syndrome.

PubMed

Karot, Sarine Sebastian; Surenahalli, Vasantharaju Gowdra; Kishore, Anoop; Mudgal, Jayesh; Nandakumar, Krishnadas; Chirayil, Magith Thambi; Mathew, Geetha; Nampurath, Gopalan Kutty

2016-09-01

The replacement of the thiazolidinedione moiety with a thiazolidinone may yield antidiabetic compounds with similar pleiotropic effects. Hence, the aim of the present study was to explore the dose-related antihyperglycemic and hypolipidemic effects of two synthesized novel thiazolidin-4-one derivatives, one with a nicotinamide and the other with a p-chlorophenoxyacetamide substitution at the N3 position of the thiazolidinone ring (NAT1 and PAT1, respectively), in a rodent model of metabolic syndrome (MetS). Metabolic syndrome was induced in Wistar rats by neonatal administration of monosodium glutamate (i.p.) on 4 consecutive days followed by high-sucrose diet feeding for 6 months. The effects of NAT1 (33 and 66 mg/kg) and molar equivalent doses of PAT1 (40 and 80 mg/kg) on relevant biochemical parameters were evaluated. Because MetS is a state of chronic low-grade inflammation, we also evaluated the effects of these compounds on proinflammatory markers, namely interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and nitric oxide (NO). Both NAT1 and PAT1 attenuated hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, and glucose intolerance. PAT1 exhibited superior antihyperglycemic and antihypoalphalipoproteinemic effects than NAT1. However, NAT1 had a better triglyceride-lowering effect. At the lower dose tested, both compounds significantly reduced elevated malondialdehyde levels. In addition, PAT1 (80 mg/kg) restored hepatic superoxide dismutase enzyme levels. There was a tendency for NAT1 and PAT1 to inhibit elevated hepatic IL-6 and TNF-α levels, but the differences did not reach statistical significance. In addition, PAT1 exhibited in vitro anti-inflammatory activity by reducing proinflammatory ROS and NO levels in RAW264.7 macrophages. The novel thiazolidin-4-ones NAT1 and PAT1 could be potential pleiotropic drug candidates targeting MetS. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

PubMed Central

de Morais Lima, Gedson Rodrigues; Machado, Flavia Danniele Frota; Périco, Larissa Lucena; de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Souza Brito, Alba Regina Monteiro; Pellizzon, Cláudia Helena; Hiruma-Lima, Clélia Akiko; Tavares, Josean Fechine; Barbosa Filho, José Maria; Batista, Leônia Maria

2017-01-01

AIM To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1β. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease. PMID:28293082

Pleiotropic mechanisms facilitated by resveratrol and its metabolites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calamini, Barbara; Ratia, Kiira; Malkowski, Michael G.

2010-07-01

Resveratrol has demonstrated cancer chemopreventive activity in animal models and some clinical trials are underway. In addition, resveratrol was shown to promote cell survival, increase lifespan and mimic caloric restriction, thereby improving health and survival of mice on high-calorie diet. All of these effects are potentially mediated by the pleiotropic interactions of resveratrol with different enzyme targets including COX-1 (cyclo-oxygenase-1) and COX-2, NAD{sup +}-dependent histone deacetylase SIRT1 (sirtuin 1) and QR2 (quinone reductase 2). Nonetheless, the health benefits elicited by resveratrol as a direct result of these interactions with molecular targets have been questioned, since it is rapidly and extensivelymore » metabolized to sulfate and glucuronide conjugates, resulting in low plasma concentrations. To help resolve these issues, we tested the ability of resveratrol and its metabolites to modulate the function of some known targets in vitro. In the present study, we have shown that COX-1, COX-2 and QR2 are potently inhibited by resveratrol, and that COX-1 and COX-2 are also inhibited by the resveratrol 4{prime}-O-sulfate metabolite. We determined the X-ray structure of resveratrol bound to COX-1 and demonstrate that it occupies the COX active site similar to other NSAIDs (non-steroidal anti-inflammatory drugs). Finally, we have observed that resveratrol 3- and 4?-O-sulfate metabolites activate SIRT1 equipotently to resveratrol, but that activation is probably a substrate-dependent phenomenon with little in vivo relevance. Overall, the results of this study suggest that in vivo an interplay between resveratrol and its metabolites with different molecular targets may be responsible for the overall beneficial health effects previously attributed only to resveratrol itself.« less

Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin.

PubMed

Buret, André G

2010-01-01

Exaggerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects.

Immuno-modulation and anti-inflammatory benefits of antibiotics: The example of tilmicosin

PubMed Central

Buret, André G.

2010-01-01

Exagerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects. PMID:20357951

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.

Statins and oxidative stress in the cardiovascular system.

PubMed

Margaritis, Marios; Sanna, Fabio; Antoniades, Charalambos

2017-09-26

Statins are widely established as an important class of medications for primary and secondary prevention of cardiovascular disease. In addition to their lipid-lowering effects, mounting evidence suggests that statins exhibit non-lipid-lowering mediated effects in the cardiovascular system. These so called "pleiotropic" effects are partly due to antioxidant properties of statins. These are mediated by inhibition of the mevalonate pathway, which interferes with small GTP-ase protein prenylation. This, in turn, leads to anti-oxidant effects of statins via a plethora of mechanisms. Statins prevent the activation of the pro-oxidant enzyme NADPH-oxidase by interfering with Rac1 activation and translocation to the membrane, as well as reducing expression of crucial subunits of NADPH-oxidase. Statins also enhance the expression, enzymatic activity and coupling of endothelial nitric oxide synthase (eNOS), through mevalonate-dependent effects. The net result is a restoration of the redox balance in the cardiovascular system, with subsequent anti-atherosclerotic and cardioprotective effects. While the evidence from basic science studies and animal models is strong, more clinical trials are required to establish the relevance of these pleiotropic effects to human cardiovascular disease and potentially lead to expanded indications for statin treatment or alternative therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Why pleiotropic interventions are needed for Alzheimer's disease.

PubMed

Frautschy, Sally A; Cole, Greg M

2010-06-01

Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of beta-amyloid (Abeta) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and synapse loss. We need to develop stage-specific interventions that not only block causal events in pathogenesis (aberrant tau phosphorylation, Abeta production and accumulation, and oxidative damage), but also address damage from these pathways that will not be reversed by targeting prodromal pathways. This approach would not only focus on blocking early events in pathogenesis, but also adequately correct for loss of synapses, substrates for neuroprotective pathways (e.g., docosahexaenoic acid), defects in energy metabolism, and adverse consequences of inappropriate compensatory responses (aberrant sprouting). Monotherapy targeting early single steps in this complicated cascade may explain disappointments in trials with agents inhibiting production, clearance, or aggregation of the initiating Abeta peptide or its aggregates. Both plaque and tangle pathogenesis have already reached AD levels in the more vulnerable brain regions during the "prodromal" period prior to conversion to "mild cognitive impairment (MCI)." Furthermore, many of the pathological events are no longer proceeding in series, but are going on in parallel. By the MCI stage, we stand a greater chance of success by considering pleiotropic drugs or cocktails that can independently limit the parallel steps of the AD cascade at all stages, but that do not completely inhibit the constitutive normal functions of these pathways. Based on this hypothesis, efforts in our laboratories have focused on the pleiotropic activities of omega-3 fatty acids and the anti-inflammatory, antioxidant, and anti-amyloid activity of curcumin in multiple models that cover many steps of the AD pathogenic cascade (Cole and Frautschy, Alzheimers Dement 2:284-286, 2006).

Multitargeting by curcumin as revealed by molecular interaction studies

PubMed Central

Gupta, Subash C.; Prasad, Sahdeo; Kim, Ji Hye; Patchva, Sridevi; Webb, Lauren J.; Priyadarsini, Indira K.

2012-01-01

Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca2+ ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto–enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting binding sites, has also been used to further characterize curcumin’s binding sites. Furthermore, the ability of curcumin to bind directly to carrier proteins improves its solubility and bioavailability. In this review, we focus on how curcumin directly targets signaling molecules, as well as the different forces that bind the curcumin–protein complex and how this interaction affects the biological properties of proteins. We will also discuss various analogues of curcumin designed to bind selective targets with increased affinity. PMID:21979811

Anti-cytokine therapy for prevention of atherosclerosis.

PubMed

Kirichenko, Tatiana V; Sobenin, Igor A; Nikolic, Dragana; Rizzo, Manfredi; Orekhov, Alexander N

2016-10-15

Currently a chronic inflammation is considered to be the one of the most important reasons of the atherosclerosis progression. A huge amount of researches over the past few decades are devoted to study the various mechanisms of inflammation in the development of atherosclerotic lesions. To review current capabilities of anti-inflammatory therapy for the prevention and treatment of atherosclerosis and its clinical manifestations. Appropriate articles on inflammatory cytokines in atherosclerosis and anti-inflammatory prevention of atherosclerosis were searched in PubMed Database from their respective inceptions until October 2015. "The role of inflammatory cytokines in the development of atherosclerotic lesions" describes available data on the possible inflammatory mechanisms of the atherogenesis with a special attention to the role of cytokines. "Modern experience of anti-inflammatory therapy for the treatment of atherosclerosis" describes modern anti-inflammatory preparations with anti-atherosclerotic effect including natural preparations. In "the development of anti-inflammatory herbal preparation for atherosclerosis prevention" an algorithm is demonstrated that includes screening of anti-cytokine activity of different natural products, the development of the most effective combination and estimation of its effect in cell culture model, in animal model of the acute aseptic inflammation and in a pilot clinical trial. A natural preparation "Inflaminat" based on black elder berries (Sambucus nigra L.), violet tricolor herb (Viola tricolor L.) and calendula flowers (Calendula officinalis L.) possessing anti-cytokine activity was developed using the designed algorithm. The results of the following 2-year double blind placebo-controlled clinical study show that "Inflaminat" reduces carotid IMT progression, i.e. has anti-atherosclerotic effect. Anti-cytokine therapy may be a promising direction in moderation of atherogenesis, especially when it begins on the early stages of subclinical atherosclerosis. The use of herbal preparations with anti-cytokine mechanism of action is the most perspective for timely prevention of atherosclerosis, as they have no significant side effects and can be prescribed for long-term administration. Copyright © 2015 Elsevier GmbH. All rights reserved.

Evaluation of analgesic and anti-inflammatory activities of Rubia cordifolia L. by spectrum-effect relationships.

PubMed

Shen, Cai-Hong; Liu, Cui-Ting; Song, Xiao-Juan; Zeng, Wei-Ya; Lu, Xiao-Ying; Zheng, Zuo-Liang; Jie-Pan; Zhan, Ruo-Ting; Ping-Yan

2018-07-15

The objective of the current work was to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and analgesic and anti-inflammatory effects of Rubia cordifolia L. extract (RCE), and to identify active components of RCE. Chemical fingerprints of ten batches of RC from various sources were obtained by HPLC, and similarity and hierarchical clustering analyses were carried out. Pharmacodynamic assays were performed in adjuvant-induced arthritis rat model to assess the analgesic and anti-inflammatory properties of RCE. The spectrum-effect relationships between chemical fingerprints and the analgesic and anti-inflammatory effects of RCE were established by gray correlation analysis. UPLC-ESI-MS was used to identify the structures of potential active components, by reference standards comparison. The results showed that a close correlation existed between chemical fingerprints with analgesic and anti-inflammatory activities, and alizarin, 6-hydroxyrubiadin, purpurin and rubiadin might be the active constituents of RCE. In addition, RCE attenuated pathological changes in adjuvant-induced arthritis. The current findings provide a strong basis for combining chemical fingerprints with analgesic and anti-inflammatory activities in assessing the spectrum-effect relationships of RCE. Copyright © 2018. Published by Elsevier B.V.

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing

PubMed Central

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A.; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space. PMID:29545755

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing.

PubMed

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space.

Different activities of Schinus areira L.: anti-inflammatory or pro-inflammatory effect.

PubMed

Davicino, R; Mattar, A; Casali, Y; Anesini, C; Micalizzi, B

2010-12-01

The anti-inflammatory drugs possess many serious side effects at doses commonly prescribed. It is really important to discover novel regulators of inflammation from natural sources with minimal adverse effects. Schinus areira L. is a plant native from South America and is used in folk medicine as an anti-inflammatory herb. For this study, the activity of aqueous extracts on inflammation and the effect on superoxide anion production in mice macrophages were assayed. Aqueous extracts were prepared by soaking herbs in cold water (cold extract), boiling water (infusion), and simmering water (decoction). Cold extract possess an anti-inflammatory activity. Decoction and infusion showed pro-inflammatory activity. Cold extract increased the production of superoxide anion. It has been proposed to use diverse methods to obtain extracts of S. areira L. with different effects. Cold extract, decoction, and infusion could be utilized as extracts or as pharmacological preparations for topical application.

[In vitro anti-inflammatory and free radical scavenging activities of flavans from Ilex centrochinensis].

PubMed

Li, Lu-jun; Yu, Li-juan; Li, Yan-ci; Liu, Meng-yuan; Wu, Zheng-zhi

2015-04-01

This study was carried out to evaluate the anti-inflammatory and free radical scavenging activities of flavans from flex centrochinensis S. Y. Hu in vitro and their structure-activity relationship. LPS-stimulated RAW 264.7 macrophage was used as inflammatory model. MTT assay for cell availability, Griess reaction for nitric oxide (NO) production, the content of TNF-alpha, IL-1beta, IL-6 and PGE, were detected with ELISA kits; DPPH, superoxide anion and hydroxyl free radicals scavenging activities were also investigated. According to the result, all flavans tested exhibited anti-inflammatory effect in different levels. Among them, compounds 1, 3, 4 and 6 showed potent anti-inflammatory effect through the inhibition of NO, TNF-alpha, IL-lp and IL-6, of which 1 was the most effective inhibitor, however, 2 and 5 were relatively weak or inactive. The order of free radical scavenging activities was similar to that of anti-inflammatory activities. Therefore, these results suggest that 3, 4 and 6, especially of 1, were,in part responsible for the anti-inflammatory and free radical scavenging activity of Ilex centrochinensis. Hydroxyl group at 4'-position of B-ring plays an important role in the anti-inflammatory and free radical scavenging capacities.

Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-κb, STAT3 and pro-inflammatory mediators and enhancement of IκBα and anti-inflammatory cytokines.

PubMed

Ahmad, Sheikh Fayaz; Attia, Sabry M; Bakheet, Saleh A; Zoheir, Khairy M A; Ansari, Mushtaq Ahmad; Korashy, Hesham M; Abdel-Hamied, Hala E; Ashour, Abdelkader E; Abd-Allah, Adel R A

2015-04-01

Naringin has been reported to possess diverse pharmacological properties, including anti-arthritic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-inflammatory effect of naringin in a mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80 mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg) administration. Pro- and anti-inflammatory cytokines were analysed in pleural fluid. We also assessed the effects of naringin on the expression levels of iNOS, inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-β1, nuclear factor kappa B (NF-κB) and inhibitor of kappa B (IκBα) in lung tissue. The histological examinations revealed anti-inflammatory effect of naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated Th2 cytokines. Western blot analyses revealed increased protein expression of NF-κB, STAT3 and COX-2 and decreased IκBα in response to Cg treatment, which were reversed by the treatment with naringin. In the Cg group, mRNA expression levels of pro-inflammatory mediators upregulated and anti-inflammatory mediators downregulated. Naringin reversed these actions.

Personalized medicine: theranostics (therapeutics diagnostics) essential for rational use of tumor necrosis factor-alpha antagonists.

PubMed

Bendtzen, Klaus

2013-04-01

With the discovery of the central pathogenic role of tumor necrosis factor (TNF)-alpha in many immunoinflammatory diseases, specific inhibition of this pleiotropic cytokine has revolutionized the treatment of patients with several non-infectious inflammatory disorders. As a result, genetically engineered anti-TNF-alpha antibody constructs now constitute one of the heaviest medicinal expenditures in many countries. All currently used TNF antagonists may dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favorably, and safety can be severely impaired by immunogenicity, i.e., the ability of a drug to induce anti-drug antibodies (ADA). Assessment of ADA is therefore an important component of the evaluation of drug safety in both pre-clinical and clinical studies and in the process of developing less immunogenic and safer biopharmaceuticals. Therapeutics diagnostics, also called theranostics, i.e., monitoring functional drug levels and neutralizing ADA in the circulation, is central to more effective use of biopharmaceuticals. Hence, testing-based strategies rather than empirical dose-escalation may provide more cost-effective use of TNF antagonists as this allows therapies tailored according to individual requirements rather than the current universal approach to diagnosis. The objective of the present review is to discuss the reasons for recommending theranostics to implement an individualized use of TNF antagonists and to highlight some of the methodological obstacles that have obscured cost-effective ways of using these therapies.

[Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous].

PubMed

Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter

2015-03-29

Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells.

PubMed

Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Nagesh, Rashmi; Ramesh, Govindarajan T; Sharma, S Chidananda

2016-02-01

Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS-induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP-1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases.

Simvastatin promotes NPC1-mediated free cholesterol efflux from lysosomes through CYP7A1/LXRα signalling pathway in oxLDL-loaded macrophages.

PubMed

Xu, Xiaoyang; Zhang, Aolin; Halquist, Matthew S; Yuan, Xinxu; Henderson, Scott C; Dewey, William L; Li, Pin-Lan; Li, Ningjun; Zhang, Fan

2017-02-01

Statins, 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors, are the first-line medications prescribed for the prevention and treatment of coronary artery diseases. The efficacy of statins has been attributed not only to their systemic cholesterol-lowering actions but also to their pleiotropic effects that are unrelated to cholesterol reduction. These pleiotropic effects have been increasingly recognized as essential in statins therapy. This study was designed to investigate the pleiotropic actions of simvastatin, one of the most commonly prescribed statins, on macrophage cholesterol homeostasis with a focus on lysosomal free cholesterol egression. With simultaneous nile red and filipin staining, analysis of confocal/multi-photon imaging demonstrated that simvastatin markedly attenuated unesterified (free) cholesterol buildup in macrophages loaded with oxidized low-density lipoprotein but had little effect in reducing the sizes of cholesteryl ester-containing lipid droplets; the reduction in free cholesterol was mainly attributed to decreases in lysosome-compartmentalized cholesterol. Functionally, the egression of free cholesterol from lysosomes attenuated pro-inflammatory cytokine secretion. It was determined that the reduction of lysosomal free cholesterol buildup by simvastatin was due to the up-regulation of Niemann-Pick C1 (NPC1), a lysosomal residing cholesterol transporter. Moreover, the enhanced enzymatic production of 7-hydroxycholesterol by cytochrome P450 7A1 and the subsequent activation of liver X receptor α underscored the up-regulation of NPC1. These findings reveal a novel pleiotropic effect of simvastatin in affecting lysosomal cholesterol efflux in macrophages and the associated significance in the treatment of atherosclerosis. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

PubMed

Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

2014-03-01

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

Anti-inflammatory effects of insulin.

PubMed

Dandona, Paresh; Chaudhuri, Ajay; Mohanty, Priya; Ghanim, Husam

2007-07-01

This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit. The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease. The anti-inflammatory action of insulin provides a neutralizing effect to balance macronutrient induced inflammation on the one hand and the possibility of using insulin as an anti-inflammatory drug on the other. The actions of macronutrients and insulin described above explain why insulin resistant states like obesity and type 2 diabetes are associated with oxidative stress, inflammation and atherosclerosis. They also suggest that insulin may be antiatherogenic.

Pleiotropic genes for metabolic syndrome and inflammation

PubMed Central

Kraja, Aldi T.; Chasman, Daniel I.; North, Kari E.; Reiner, Alexander P.; Yanek, Lisa R.; Kilpeläinen, Tuomas O.; Smith, Jennifer A.; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D.; Feitosa, Mary F.; Tekola-Ayele, Fasil; Chu, Audrey Y.; Nolte, Ilja M.; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A.; Sun, Yan V.; Ritchie, Marylyn D.; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A.; Im, Hae Kyung; Schnabel, Renate B.; Jørgensen, Torben; Jørgensen, Marit E.; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P.; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Ikram, M. Arfan; Richards, J. Brent; Rotimi, Charles; Wilson, James G.; Lange, Leslie; Ganesh, Santhi K.; Nalls, Mike; Rasmussen-Torvik, Laura J.; Pankow, James S.; Coresh, Josef; Tang, Weihong; Kao, W.H. Linda; Boerwinkle, Eric; Morrison, Alanna C.; Ridker, Paul M.; Becker, Diane M.; Rotter, Jerome I.; Kardia, Sharon L.R.; Loos, Ruth J.F.; Larson, Martin G.; Hsu, Yi-Hsiang; Province, Michael A.; Tracy, Russell; Voight, Benjamin F.; Vaidya, Dhananjay; O’Donnell, Christopher; Benjamin, Emelia J.; Alizadeh, Behrooz Z.; Prokopenko, Inga; Meigs, James B.; Borecki, Ingrid B.

2014-01-01

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. PMID:24981077

Pleiotropic genes for metabolic syndrome and inflammation.

PubMed

Kraja, Aldi T; Chasman, Daniel I; North, Kari E; Reiner, Alexander P; Yanek, Lisa R; Kilpeläinen, Tuomas O; Smith, Jennifer A; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D; Feitosa, Mary F; Tekola-Ayele, Fasil; Chu, Audrey Y; Nolte, Ilja M; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A; Sun, Yan V; Ritchie, Marylyn D; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A; Im, Hae Kyung; Schnabel, Renate B; Jørgensen, Torben; Jørgensen, Marit E; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G; Franco, Oscar H; Ikram, M Arfan; Richards, J Brent; Rotimi, Charles; Wilson, James G; Lange, Leslie; Ganesh, Santhi K; Nalls, Mike; Rasmussen-Torvik, Laura J; Pankow, James S; Coresh, Josef; Tang, Weihong; Linda Kao, W H; Boerwinkle, Eric; Morrison, Alanna C; Ridker, Paul M; Becker, Diane M; Rotter, Jerome I; Kardia, Sharon L R; Loos, Ruth J F; Larson, Martin G; Hsu, Yi-Hsiang; Province, Michael A; Tracy, Russell; Voight, Benjamin F; Vaidya, Dhananjay; O'Donnell, Christopher J; Benjamin, Emelia J; Alizadeh, Behrooz Z; Prokopenko, Inga; Meigs, James B; Borecki, Ingrid B

2014-08-01

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Attenuation of TNF-induced neutrophil adhesion by simvastatin is associated with the inhibition of Rho-GTPase activity, p50 activity and morphological changes.

PubMed

Antoniellis Silveira, Angélica Aparecida; Dominical, Venina Marcela; Morelli Vital, Daiana; Alves Ferreira, Wilson; Trindade Maranhão Costa, Fabio; Werneck, Claudio C; Ferreira Costa, Fernando; Conran, Nicola

2018-05-01

Neutrophil adhesion to the vasculature in response to potent inflammatory stimuli, such as TNF-α (TNF), can contribute to atheroprogression amongst other pathophysiological mechanisms. Previous studies have shown that simvastatin, a statin with known pleiotropic anti-inflammatory properties, can partially abrogate the effects of TNF-induced neutrophil adhesion, in association with the modulation of β 2 -integrin expression. We aimed to further characterize the effects of this statin on neutrophil and leukocyte adhesive mechanisms in vitro and in vivo. A microfluidic assay confirmed the ability of simvastatin to inhibit TNF-induced human neutrophil adhesion to fibronectin ligand under conditions of shear stress, while intravital imaging microscopy demonstrated an abrogation of leukocyte recruitment by simvastatin in the microvasculature of mice that had received a TNF stimulus. This inhibition of neutrophil adhesion was accompanied by the inhibition of TNF-induced RhoA activity in human neutrophils, and alterations in cell morphology and β 2 -integrin activity. Additionally, TNF augmented the activity of the p50 NFκB subunit in human neutrophils and TNF-induced neutrophil adhesion and β 2 -integrin activity could be abolished using pharmacological inhibitors of NFκB translocation, BAY11-7082 and SC514. Accordingly, the TNF-induced elevation of neutrophil p50 activity was abolished by simvastatin. In conclusion, our data provide further evidence of the ability of simvastatin to inhibit neutrophil adhesive interactions in response to inflammatory stimuli, both in vivo and in vitro. Simvastatin appears to inhibit neutrophil adhesion by interfering in TNF-induced cytoskeletal rearrangements, in association with the inhibition of Rho A activity, NFκB translocation and, consequently, β 2 -integrin activity. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Macrolides: a promising pharmacologic therapy for chronic obstructive pulmonary disease

PubMed Central

Qiu, Shilin; Zhong, Xiaoning

2016-01-01

Chronic inflammation plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, there are no effective anti-inflammatory pharmacologic therapies available for COPD so far. Recent evidence suggests that an immunologic mechanism has a role in the pathogenesis of COPD. Macrolides possess anti-inflammatory and immune-modulating effects may be helpful in the treatment of COPD. Several clinical studies have shown that long-term use of macrolides reduces the frequency of COPD exacerbations. However, the subgroups that most effectively respond to long-term treatment of macrolides still need to be determined. The potential adverse events to individuals and the microbial resistance in community populations raises great concern on the long-term use of macrolides. Thus, novel macrolides have anti-inflammatory and immuno-modulating effects, but without antibiotic effects, and are promising as an anti-inflammatory agent for the treatment of COPD. In addition, the combination of macrolides and other anti-inflammatory pharmacologic agents may be a new strategy for the treatment of COPD. PMID:28030992

Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics

PubMed Central

Li, Ping; Zheng, Ying; Chen, Xin

2017-01-01

Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th–20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology. PMID:28785220

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

Expression and Function of Anti-Inflammatory Interleukins: The Other Side of the Vascular Response to Injury

PubMed Central

Cuneo, Anthony A.; Autieri, Michael V.

2012-01-01

Common to multiple vascular diseases, including atherosclerosis, interventional restenosis, and transplant vasculopathy, is a localized inflammatory reaction. Activated vascular smooth muscle cells (VSMC) respond to local inflammation and migrate from the media into the lumen of the vessel where they proliferate and synthesize cytokines which they respond to in an autocrine fashion, sustaining the progression of the lesion. The deleterious effects of pro-inflammatory cytokines, particularly immunomodulatory interleukins, on vascular pathophysiology and development of these maladaptive processes have been the subject of intense study. Although a great deal of attention has been given to the negative effects of pro-inflammatory cytokines and interleukins, relatively little has been reported on the potentially beneficial paracrine and autocrine effects of anti-inflammatory interleukins on the vascular response to injury. The vast majority of emphasis on secretion and function of anti-inflammatory mediators has been placed on leukocytes. Consequently, the role of non-immune cells, and direct effects of anti-inflammatory interleukins on vascular cells is poorly understood. We will review the molecular mechanisms whereby anti-inflammatory interleukins inhibit signal transduction and gene expression in inflammatory cells. We will review studies in which beneficial “indirect” effects of anti-inflammatory interleukins on progression of vascular disease are achieved by modulation of immune function. We will also present the limited studies in which “direct” effects of these interleukins on VSMC and endothelial cells dampen the vascular response to injury. We propose that expression of immunomodulatory cytokines by activated vasculature may represent an auto-regulatory feed back mechanism to promote resolution of the vascular response to injury. PMID:19601851

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.

Anti-inflammatory and antipyretic effects of Sonchus oleraceus in rats.

PubMed

Vilela, Fabiana C; Bitencourt, Andressa D; Cabral, Layla D M; Franqui, Lidiane S; Soncini, Roseli; Giusti-Paiva, Alexandre

2010-02-17

Sonchus oleraceus L. has been used to relieve headaches, general pain, hepatitis, infections, inflammation and rheumatism in Brazilian folk medicine. Nevertheless, scientific information regarding this species is scarce; there are no reports related to its possible anti-inflammatory effects. This study was aimed at evaluating the scientific basis for the traditional use of Sonchus oleraceus using in vivo inflammatory models. Carrageenan-induced paw edema, peritonitis and febrile response induced by lipopolysaccharide tests, as well as fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the anti-inflammatory activity of Sonchus oleraceus hydroethanolic extract (SoHE) in rats. The SoHE at test doses of 100-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced paw edema induced by carragenan, inhibited leukocyte recruitment into the peritoneal cavity and reduced LPS-induced febrile response, and in the model of chronic inflammation using the cotton pellet-induced fibrovascular tissue growth in rats, the SoHE significantly inhibited the formation of granulomatous tissue. The extract administered at 300 mg/kg p.o. had a stronger anti-inflammatory effect than indomethacin (10mg/kg) or dexamethasone (1mg/kg). The hydroethanolic extract of Sonchus oleraceus markedly demonstrated anti-inflammatory action in rats, which supports previous claims of its traditional use. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Low doses of tizanidine synergize the anti-nociceptive and anti-inflammatory effects of ketorolac or naproxen while reducing of side effects.

PubMed

Patiño-Camacho, Selene I; Déciga Campos, Myrna; Beltrán-Villalobos, Karla; Castro-Vidal, Dalia A; Montiel-Ruiz, Rosa M; Flores-Murrieta, Francisco J

2017-06-15

The aim of the present study was to determine whether tizanidine, an alpha2-adrenoceptor agonist, is able to increase the anti-inflammatory and anti-nociceptive effects of naproxen and ketorolac with a low incidence of gastric injury and spontaneous activity in rats. The anti-inflammatory effect was assayed in a carrageenan test, and oral administration of tizanidine (ED 40 =0.94±0.2mg/kg), naproxen (ED 40 =3.18±0.4mg/kg), and ketorolac (ED 40 =16.4±1.9mg/kg) showed a dose-dependent effect on inflammation. The anti-nociceptive effect was assayed in the formalin test, and administration of tizanidine (ED 40 =0.39±0.06mg/kg, p.o.), naproxen (ED 40 =33.9±3.9mg/kg, p.o.) or ketorolac (ED 40 =6.49±1mg/kg, p.o.) each showed a dose-dependent anti-nociceptive effect. The effects of combinations of tizanidine/naproxen and tizanidine/ketorolac were determined considering their ED 40 at a rate of 1:1. Additionally, the tizanidine/naproxen and tizanidine/ketorolac combinations showed anti-inflammatory and anti-nociceptive effects. The tizanidine/ketorolac combination was more potent than tizanidine/naproxen, in both inflammatory (interaction index=0.03 tizanidine/ketorolac and 0.07 tizanidine/naproxen) and nociceptive (interaction index=0.005 tizanidine/ketorolac and 0.01 tizanidine/naproxen) processes. In both cases, tizanidine improved naproxen and ketorolac gastrointestinal tolerability by 50%. Furthermore, co-administration of tizanidine with naproxen or ketorolac did not modify the spontaneous activity in the same way as individual tizanidine administration. Considering that tizanidine increases the anti-inflammatory and anti-nociceptive effects of naproxen or ketorolac, with an increase in gastric tolerability, tizanidine could provide therapeutic advantages in the clinical treatment of inflammation and pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Celecoxib enhances the anti-inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E(2) production.

PubMed

Mor, Adam; Aizman, Elizabeta; Kloog, Yoel

2012-10-01

Celecoxib (Celebrex(®)), a non-steroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor, is widely used to treat arthritis and other inflammatory disorders. Awareness of its anti-proliferative properties has prompted another indication for its use, in preventing colon polyps in high-risk populations. Farnesylthiosalicylic acid (FTS; Salirasib(®)), designed to inhibit oncogenic Ras and currently under evaluation in phase I/II and II clinical trials, was recently shown by our group to exert anti-inflammatory effects on both lymphocytes and mast cells. Here we examined whether celecoxib combined with FTS would enhance this anti-inflammatory activity. While each drug separately inhibited Ras activation in these cells, their combination yielded more marked inhibition as well as further inhibition of ERK phosphorylation, lymphocyte adhesion, and interleukin-2 secretion. The inhibitory effects, moreover, were independent of prostaglandin E(2) secretion. These data point to the promising potential of combined treatment with celecoxib and FTS for inflammatory disorders involving lymphocytes.

Alpha-Lipoic Acid Downregulates IL-1β and IL-6 by DNA Hypermethylation in SK-N-BE Neuroblastoma Cells.

PubMed

Dinicola, Simona; Proietti, Sara; Cucina, Alessandra; Bizzarri, Mariano; Fuso, Andrea

2017-09-26

Alpha-lipoic acid (ALA) is a pleiotropic molecule with antioxidant and anti-inflammatory properties, of which the effects are exerted through the modulation of NF-kB. This nuclear factor, in fact, modulates different inflammatory cytokines, including IL-1b and IL-6, in different tissues and cell types. We recently showed that IL-1b and IL-6 DNA methylation is modulated in the brain of Alzheimer's disease patients, and that IL-1b expression is associated to DNA methylation in the brain of patients with tuberous sclerosis complex. These results prompted us to ask whether ALA-induced repression of IL-1b and IL-6 was dependent on DNA methylation. Therefore, we profiled DNA methylation in the 5'-flanking region of the two aforementioned genes in SK-N-BE human neuroblastoma cells cultured in presence of ALA 0.5 mM. Our experimental data pointed out that the two promoters are hypermethylated in cells supplemented with ALA, both at CpG and non-CpG sites. Moreover, the observed hypermethylation is associated with decreased mRNA expression and decreased cytokine release. These results reinforce previous findings indicating that IL-1b and IL-6 undergo DNA methylation-dependent modulation in neural models and pave the road to study the epigenetic mechanisms triggered by ALA.

6-Gingerol inhibits ROS and iNOS through the suppression of PKC-{alpha} and NF-{kappa}B pathways in lipopolysaccharide-stimulated mouse macrophages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Tzung-Yan, E-mail: joyamen@mail.cgu.edu.tw; Lee, Ko-Chen; Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

2009-04-24

Inflammation is involved in numerous diseases, including chronic inflammatory diseases and the development of cancer. Many plants possess a variety of biological activities, including antifungal, antibacterial and anti-inflammatory activities. However, our understanding of the anti-inflammatory effects of 6-gingerol is very limited. We used lipopolysaccharide (LPS)-stimulated macrophages as a model of inflammation to investigate the anti-inflammatory effects of 6-gingerol, which contains phenolic structure. We found that 6-gingerol exhibited an anti-inflammatory effect. 6-Gingerol could decrease inducible nitric oxide synthase and TNF-{alpha} expression through suppression of I-{kappa}B{alpha} phosphorylation, NF-{kappa}B nuclear activation and PKC-{alpha} translocation, which in turn inhibits Ca{sup 2+} mobilization and disruptionmore » of mitochondrial membrane potential in LPS-stimulated macrophages. Here, we demonstrate that 6-gingerol acts as an anti-inflammatory agent by blocking NF-{kappa}B and PKC signaling, and may be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases.« less

Some Novel Mannich Bases of 5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one and Their Anti-Inflammatory Activity.

PubMed

Koksal, Meric; Ozkan-Dagliyan, Irem; Ozyazici, Tugce; Kadioglu, Beril; Sipahi, Hande; Bozkurt, Ayhan; Bilge, Suleyman S

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1 H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively. © 2017 Deutsche Pharmazeutische Gesellschaft.

Novel enzyme formulations for improved pharmacokinetic properties and anti-inflammatory efficacies.

PubMed

Yang, Lan; Yan, Shenglei; Zhang, Yonghong; Hu, Xueyuan; Guo, Qi; Yuan, Yuming; Zhang, Jingqing

2018-02-15

Anti-inflammatory enzymes promote the dissolution and excretion of sticky phlegm, clean the wound surface and accelerate drug diffusion to the lesion. They play important roles in treating different types of inflammation and pain. Currently, various formulations of anti-inflammatory enzymes are successfully prepared to improve the enzymatic characteristics, pharmacokinetic properties and anti-inflammatory efficacies. The work was performed by systematically searching all available literature. An overall summary of current research about various anti-inflammatory enzymes and their novel formulations is presented. The original and improved enzymatic characteristics, pharmacokinetic properties, action mechanisms, clinical information, storage and shelf life, treatment efficacies of anti-inflammatory enzymes and their different formulations are summarized. The influencing factors such as enzyme type, source, excipient, pharmaceutical technique, administration route and dosage are analyzed. The combined application of enzymes and other drugs are included in this paper. Anti-inflammatory enzymes were widely applied in treating different types of inflammation and diseases with accompanying edema. Their novel formulations increased enzymatic stabilities, improved pharmacokinetic properties, provided different administration routes, and enhanced anti-inflammatory efficacies of anti-inflammatory enzymes but decreased side effects and toxicity. Novel enzyme formulations improve and expand the usage of anti-inflammatory enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of TGF-β1 Stimulation on the Secretome of Human Adipose-Derived Mesenchymal Stromal Cells.

PubMed

Rodríguez, Tania M; Saldías, Alejandro; Irigo, Marcelo; Zamora, Jorge Velasco; Perone, Marcelo J; Dewey, Ricardo A

2015-08-01

Adipose tissue is an attractive source of mesenchymal stromal cells (MSCs) owing to the relative ease of obtaining large volumes with more MSC abundance compared with other sources. Increasing evidence supports the fact that trophic factors secreted by MSCs play a pivotal therapeutic role. Several strategies in regenerative medicine use MSCs, mainly exploiting their immunosuppressive effect and homing capacity to sites of damage. Transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine that, depending on the cell niche, can display either anti-inflammatory or proinflammatory effects. TGF-β1 expression increases in various tissues with damage, especially when accompanied by inflammation. Thus, we analyzed the effect of TGF-β1 on the secretion by adipose-derived mesenchymal stromal cells (ASCs) of a panel of 80 cytokines/chemokines using an antibody array. To avoid a possible effect of fetal bovine serum (FBS) on ASCs secretion, we performed our analysis by culturing cells in FBS-free conditions, only supplemented with 0.1% of bovine serum albumin. We report the cytokine profile secreted by ASCs. We also found that TGF-β1 exposure modulates 8 chemokines and 18 cytokines, including TGF-β1 and -β2, and other important cytokines involved in immunosuppression, allergic responses, and bone resorption. ©AlphaMed Press.

The Anti-Inflammatory Effects and Mechanisms of Eupafolin in Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Macrophages.

PubMed

Chen, Chin-Chaun; Lin, Ming-Wei; Liang, Chan-Jung; Wang, Shu-Huei

2016-01-01

Eupafolin is a flavone isolated from Artemisia princeps Pampanini (family Asteraceae). The aim of this study was to examine the anti-inflammatory effects of eupafolin in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-induced mouse skin and lung inflammation models and to identify the mechanism underlying these effects. Eupafolin decreased the LPS-induced release of inflammatory mediators (iNOS, COX-2 and NO) and proinflammatory cytokines (IL-6 and TNF-α) from the RAW264.7 macrophages. Eupafolin inhibited the LPS-induced phosphorylation of p38 MAPK, ERK1/2, JNK, AKT and p65 and the nuclear translocation of p65 and c-fos. These effects were mainly mediated by the inhibition of JNK. In the mouse paw and lung models, eupafolin effectively suppressed the LPS-induced edema formation and down-regulated iNOS and COX-2 expression. These results demonstrated that eupafolin exhibits anti-inflammatory properties and suggested that eupafolin can be developed as an anti-inflammatory agent.

The Anti-Inflammatory Effects and Mechanisms of Eupafolin in Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Macrophages

PubMed Central

Chen, Chin-Chaun; Lin, Ming-Wei; Liang, Chan-Jung; Wang, Shu-Huei

2016-01-01

Eupafolin is a flavone isolated from Artemisia princeps Pampanini (family Asteraceae). The aim of this study was to examine the anti-inflammatory effects of eupafolin in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-induced mouse skin and lung inflammation models and to identify the mechanism underlying these effects. Eupafolin decreased the LPS-induced release of inflammatory mediators (iNOS, COX-2 and NO) and proinflammatory cytokines (IL-6 and TNF-α) from the RAW264.7 macrophages. Eupafolin inhibited the LPS-induced phosphorylation of p38 MAPK, ERK1/2, JNK, AKT and p65 and the nuclear translocation of p65 and c-fos. These effects were mainly mediated by the inhibition of JNK. In the mouse paw and lung models, eupafolin effectively suppressed the LPS-induced edema formation and down-regulated iNOS and COX-2 expression. These results demonstrated that eupafolin exhibits anti-inflammatory properties and suggested that eupafolin can be developed as an anti-inflammatory agent. PMID:27414646

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.

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 inflammation symptoms in TCM, and its effect is mediated by multiple targets through multiple active ingredients. Although scholars around the world have made studies on the anti-inflammatory studies of CMM from different pathways and aspects and have made substantial progress, further studies are warranted to delineate the inflammation actions in more cogency models, establish the toxicological profiles and quality standards, assess the potentials of CMM in clinical applications, and make more convenient preparations easy to administrate for patients. Development of the clinically anti-inflammatory drugs are also warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The host response in critically ill sepsis patients on statin therapy: a prospective observational study.

PubMed

Wiewel, Maryse A; Scicluna, Brendon P; van Vught, Lonneke A; Hoogendijk, Arie J; Zwinderman, Aeilko H; Lutter, René; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J; Schultz, Marcus J; van der Poll, Tom

2018-01-18

Statins can exert pleiotropic anti-inflammatory, vascular protective and anticoagulant effects, which in theory could improve the dysregulated host response during sepsis. We aimed to determine the association between prior statin use and host response characteristics in critically ill patients with sepsis. We performed a prospective observational study in 1060 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013. Of these, 351 patients (33%) were on statin therapy before admission. The host response was evaluated by measuring 23 biomarkers providing insight into key pathways implicated in sepsis pathogenesis and by analyzing whole-blood leukocyte transcriptomes in samples obtained within 24 h after ICU admission. To account for indication bias, a propensity score-matched cohort was created (N = 194 in both groups for protein biomarkers and N = 95 in both groups for gene expression analysis). Prior statin use was not associated with an altered mortality up to 90 days after admission (38.0 vs. 39.7% in the non-statin users in the propensity-matched analysis). Statin use did not modify systemic inflammatory responses, activation of the vascular endothelium or the coagulation system. The blood leukocyte genomic response, characterized by over-expression of genes involved in inflammatory and innate immune signaling pathways as well as under-expression of genes associated to T cell function, was not different between patients with and without prior statin use. Statin therapy is not associated with a modified host response in sepsis patients on admission to the ICU.

Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Excavatolide B Isolated from the Culture-Type Formosan Gorgonian Briareum excavatum

PubMed Central

Lin, Yen-You; Lin, Sung-Chun; Feng, Chien-Wei; Chen, Pei-Chin; Su, Yin-Di; Li, Chi-Min; Yang, San-Nan; Jean, Yen-Hsuan; Sung, Ping-Jyun; Duh, Chang-Yih; Wen, Zhi-Hong

2015-01-01

In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum and investigated its anti-inflammatory activities. We found that excavatolide B significantly inhibited the mRNA expression of the proinflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-challenged murine macrophages (RAW 264.7). We also examined the anti-inflammatory and anti-nociceptive effects of excavatolide B on intraplantar carrageenan-induced inflammatory responses. Excavatolide B was found to significantly attenuate carrageenan-induced nociceptive behaviors, mechanical allodynia, thermal hyperalgesia, weight bearing deficits and paw edema. In addition, excavatolide B inhibited iNOS, as well as the infiltration of immune cells in carrageenan-induced inflammatory paw tissue. PMID:25923315

Targeting the Hemoglobin Scavenger receptor CD163 in Macrophages Highly Increases the Anti-inflammatory Potency of Dexamethasone

PubMed Central

Graversen, Jonas H; Svendsen, Pia; Dagnæs-Hansen, Frederik; Dal, Jakob; Anton, Gabriele; Etzerodt, Anders; Petersen, Mikkel D; Christensen, Peter A; Møller, Holger J; Moestrup, Søren K

2012-01-01

Synthetic glucocorticoids are potent anti-inflammatory drugs but serious side effects such as bone mobilization, muscle mass loss, immunosuppression, and metabolic alterations make glucocorticoid therapy a difficult balance. The therapeutic anti-inflammatory effect of glucocorticoids relies largely on the suppressed release of tumor-necrosis factor-α and other cytokines by macrophages at the sites of inflammation. We have now developed a new biodegradable anti-CD163 antibody-drug conjugate that specifically targets the glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in macrophages. The conjugate, that in average contains four dexamethasone molecules per antibody, exhibits retained high functional affinity for CD163. In vitro studies in rat macrophages and in vivo studies of Lewis rats showed a strong anti-inflammatory effect of the conjugate measured as reduced lipopolysaccharide-induced secretion of tumor-necrosis factor-α. The in vivo potency of conjugated dexamethasone was about 50-fold that of nonconjugated dexamethasone. In contrast to a strong systemic effect of nonconjugated dexamethasone, the equipotent dose of the conjugate had no such effect, measured as thymus lymphocytes apoptosis, body weight loss, and suppression of endogenous cortisol levels. In conclusion, the study shows antibody-drug conjugates as a future approach in anti-inflammatory macrophage-directed therapy. Furthermore, the data demonstrate CD163 as an excellent macrophage target for anti-inflammatory drug delivery. PMID:22643864

Toxicity induced by chemical warfare agents: insights on the protective role of melatonin.

PubMed

Pita, René; Marco-Contelles, José; Ramos, Eva; Del Pino, Javier; Romero, Alejandro

2013-11-25

Chemical Warfare Agents (CWAs) are substances that can be used to kill, injure or incapacitate an enemy in warfare, but also against civilian population in terrorist attacks. Many chemical agents are able to generate free radicals and derived reactants, excitotoxicity process, or inflammation, and as consequence they can cause neurological symptoms and damage in different organs. Nowadays, taking into account that total immediate decontamination after exposure is difficult to achieve and there are not completely effective antidotes and treatments against all CWAs, we advance and propose that medical countermeasures against CWAs poisoning would benefit from a broad-spectrum multipotent molecule. Melatonin, a versatile and ubiquitous antioxidant molecule, originally discovered as a hormone synthesized mainly in the pineal gland, has low toxicity and high efficacy in reducing oxidative damage, anti-inflammatory effects by regulation of multiple cellular pathways and properties to prevent excitotoxicity, among others. The purpose of this review is to show the multiple and diverse properties of melatonin, as a pleiotropic indole derivative, and its marked potential for improving human health against the most widely used chemical weapons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Assessment of the analgesic, anti-inflammatory and sedative effects of the dichloromethanol extract of Schinus molle.

PubMed

Taylor, A; Oyedeji, O O; Aremu, O; Oyemitan, I; Gwebu, E T; Oyedeji, A O; Nkeh-Chungag, B N

2016-01-01

Determination of the active fraction and compounds of the dichloromethanol extract of Schinus molle seeds and evaluation of their biological effects. Dried seeds of Schinus molle were sequentially extracted in hexane, acetyl acetate and dichloromethane. The dichloromethane extract was separated into two fractions (1 and 2) by column chromatography. Fraction 2 was further separated into its two constituent compounds which were characterized as belonging to the lanosteroid group of compounds. Both factions were tested for their analgesic, anti-inflammatory and sedative effects. The two fractions significantly increased (p<0.05) the tail flick latency though fraction 2 provided better and more long lasting protection against thermal pain. On the other hand, the anti-inflammatory effect of ibuprofen, though inferior to the anti-inflammatory effect of fraction 2 was better than the effects of fraction 1. Fraction 2 significantly (p<0.01) reduced rat paw oedema compared to the saline treatment group throughout the experiments while fraction 2 compared to fraction 1 showed significantly (p<0.01) greater inflammatory effects. On the other hand both fractions lacked significant sedative effects. Given that fraction 2 had only two constituent compounds (isomasticadienonic and Masticatrienonate), one or both of these compounds should be contributing to the observed analgesic and anti-inflammatory effects.

Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

PubMed

Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; da Silva, Josiane Mello; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira; Scio, Elita

2014-01-01

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β -carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: a comparative study with lauric acid.

PubMed

Huang, Wen-Cheng; Tsai, Tsung-Hsien; Chuang, Lu-Te; Li, You-Yi; Zouboulis, Christos C; Tsai, Po-Jung

2014-03-01

Propionibacterium acnes (P. acnes) is a commensal bacterium which is possibly involved in acne inflammation. The saturated fatty acid, lauric acid (C12:0) has been shown to possess antibacterial and anti-inflammatory properties against P. acnes. Little is known concerning the potential effects of its decanoic counterpart, capric acid (C10:0). To examine the antibacterial and anti-inflammatory activities of capric acid against P. acnes and to investigate the mechanism of the anti-inflammatory action. The antimicrobial activity of fatty acids was detected using the broth dilution method. An evaluation of P. acnes-induced ear edema in mice was conducted to evaluate the in vivo anti-inflammatory effect. To elucidate the in vitro anti-inflammatory effect, human SZ95 sebocytes and monocytic THP-1 cells were treated with P. acnes alone or in the presence of a fatty acid. The mRNA levels and secretion of pro-inflammatory cytokines were measured by qRT-PCR and enzyme immunoassay, respectively. NF-κB activation and MAPK expression were analyzed by ELISA and Western blot, respectively. Lauric acid had stronger antimicrobial activity against P. acnes than capric acid in vitro and in vivo. However, both fatty acids attenuated P. acnes-induced ear swelling in mice along with microabscess and significantly reduced interleukin (IL)-6 and CXCL8 (also known as IL-8) production in P. acnes-stimulated SZ95 sebocytes. P. acnes-induced mRNA levels and secretion of IL-8 and TNF-α in THP-1 cells were suppressed by both fatty acids, which inhibited NF-κB activation and the phosphorylation of MAP kinases. Our data demonstrate that both capric acid and lauric acid exert bactericidal and anti-inflammatory activities against P. acnes. The anti-inflammatory effect may partially occur through the inhibition of NF-κB activation and the phosphorylation of MAP kinases. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Salusin-α attenuates hepatic steatosis and atherosclerosis in high fat diet-fed low density lipoprotein receptor deficient mice.

PubMed

Tang, Kun; Wang, Fei; Zeng, Yi; Chen, XueMeng; Xu, XiaoLe

2018-07-05

Salusin-α is an endogenous bioactive peptide and likely to prevent atherosclerosis. But its protective effect against atherosclerosis in vivo remains poorly understood. The aim of the present study was to determine the potential effects of salusin-α on atherosclerosis and its associated metabolic disorders in high fat diet (HFD)-fed low density lipoprotein receptor deficient (LDLr -/- ) mice, and also explore the possible underlying mechanisms involved. Our data showed that after 12 weeks treatment, salusin-α ameliorated HFD-induced weight gain, hyperlipidemia, and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Salusin-α suppressed HFD-induced hepatic steatosis and regulated gene expression of fatty acid synthase, acetyl coenzyme A carboxylase-α, peroxisome proliferator-activated receptor-α, camitine palmitoyltransferase-1α and CYP7A1 in liver. Salusin-α reduced atherosclerotic plaque area and macrophage foam cell formation. Salusin-α prevented hepatic and aortic inflammation as evidenced by the reduced macrophage recruitment and mRNA expression of IL-6 and TNF-α in both liver and aorta. Salusin-α also reduced hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in liver and suppressing reactive oxygen species generation and protein expressions of NADPH-oxidase (NOX) 2 and NOX4 in both liver and aorta. Our present data suggest that salusin-α could reduce hepatic steatosis and atherosclerosis via its pleiotropic effects, including amelioration of lipid profiles, regulation of some key molecules involved in lipid metabolism in liver, anti-oxidative effect and anti-inflammatory action. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Anti-inflammatory effects of ethanolic extract from Sargassum horneri (Turner) C. Agardh on lipopolysaccharide-stimulated macrophage activation via NF-κB pathway regulation.

PubMed

Kim, Mi Eun; Jung, Yun Chan; Jung, Inae; Lee, Hee-Woo; Youn, Hwa-Young; Lee, Jun Sik

2015-01-01

Inflammation is major symptom of the innate immune response by infection of microbes. Macrophages, one of immune response related cells, play a role in inflammatory response. Recent studies reported that various natural products can regulate the activation of immune cells such as macrophage. Sargassum horneri (Turner) C. Agardh is one of brown algae. Recently, various seaweeds including brown algae have antioxidant and anti-inflammatory effects. However, anti-inflammatory effects of Sargassum horneri (Turner) C. Agardh are still unknown. In this study, we investigated anti-inflammatory effects of ethanolic extract of Sargassum horneri (Turner) C. Agardh (ESH) on RAW 264.7 murine macrophage cell line. The ESH was extracted from dried Sargassum horneri (Turner) C. Agardh with 70% ethanol and then lyophilized at -40 °C. ESH was not cytotoxic to RAW 264.7, and nitric oxide (NO) production induced by LPS-stimulated macrophage activation was significantly decreased by the addition of 200 μg/mL of ESH. Moreover, ESH treatment reduced mRNA level of cytokines, including IL-1β, and pro-inflammatory genes such as iNOS and COX-2 in LPS-stimulated macrophage activation in a dose-dependent manner. ESH was found to elicit anti-inflammatory effects by inhibiting ERK, p-p38 and NF-κB phosphorylation. In addition, ESH inhibited the release of IL-1β in LPS-stimulated macrophages. These results suggest that ESH elicits anti-inflammatory effects on LPS-stimulated macrophage activation via the inhibition of ERK, p-p38, NF-κB, and pro-inflammatory gene expression.

Analysis of G-Protein Coupled Receptor 30 (GPR30) on Endothelial Inflammation.

PubMed

Chakrabarti, Subhadeep; Davidge, Sandra T

2016-01-01

The female sex hormone estrogen (the most common form 17-β-estradiol or E2) is known to have both anti-inflammatory and pro-inflammatory effects. Given the diversity of estrogen responses mediated through its three distinct receptors, namely, estrogen receptor α (ERα), ERβ, and the G-protein coupled receptor 30 (GPR30), it is plausible that different receptors have specific modulatory effects on inflammation in different tissues. We have shown that activation of GPR30 exerted anti-inflammatory effects as demonstrated by significant attenuation of tumor necrosis factor (TNF)-mediated upregulation of adhesion molecules in isolated human umbilical vein endothelial cells. Interestingly, estrogen alone had no such effect and blockade of classical ERs restored the anti-inflammatory effect, suggesting that this effect was dependent on GPR30 and opposed to classical ERs. These findings were further validated by the negation of anti-inflammatory GPR30 effects by classical ER agonists. This chapter focuses on multiple pharmacological options to activate GPR30 and the use of TNF activated endothelial cells as a model system for inflammatory response as assessed by adhesion molecule detection through western blotting.

Phytochemical Composition, Antioxidant, Antimicrobial and in Vivo Anti-inflammatory Activity of Traditionally Used Romanian Ajuga laxmannii (Murray) Benth. (“Nobleman’s Beard” – Barba Împăratului)

PubMed Central

Toiu, Anca; Mocan, Andrei; Vlase, Laurian; Pârvu, Alina E.; Vodnar, Dan C.; Gheldiu, Ana-Maria; Moldovan, Cadmiel; Oniga, Ilioara

2018-01-01

In the Romanian folk medicine, aerial parts of Ajuga laxmannii (“nobleman’s beard,” Romanian – “barba boierului” or “avrămească” or “creştinească”) are traditionally used as galactagogue and anti-inflammatory agents. The present study aimed to evaluate the chemical composition (polyphenols, iridoids, and phytosterols), antioxidant, antimicrobial and in vivo anti-inflammatory activity of different extracts of A. laxmannii aerial parts. The major identified bioactive compounds were rutin, 8-O-acetylharpagide and β-sitosterol. The antioxidant activity of A. laxmannii extracts was evaluated using several methods, and the results showed good antiradical effects. Moreover, the antimicrobial evaluation showed a potent antifungal activity against C. albicans and P. funiculosum. Furthermore, the anti-inflammatory effect was determined by monitoring some parameters involved in the inflammatory process. The results obtained showed differences between the analyzed extracts; and therefore the importance of choosing the best solvent in order to extract the appropriate amount of bioactive compounds. A. laxmannii ethanol extract showed an anti-inflammatory effect by reducing total leukocytes, PMN, phagocytosis, and oxidative stress. Compared to diclofenac, only the 50 mg/mL A. laxmannii extract had better anti-inflammatory and anti-oxidative stress effects, and this could justify the importance of a correlation between the activity and the used concentration. These findings strongly suggest that A. laxmannii could be considered as a valuable source of bioactive compounds, which could be further valued as anti-inflammatory agents in the composition of several herbal drugs. PMID:29551972

The efficacy of oral non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy: a systematic review and meta-analysis.

PubMed

Boudreault, Jennifer; Desmeules, François; Roy, Jean-Sébastien; Dionne, Clermont; Frémont, Pierre; Macdermid, Joy C

2014-04-01

To conduct a systematic review and meta-analysis on the efficacy of oral non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy. Systematic review. A literature search was conducted in 4 databases for randomized controlled trials published until 05/2013, comparing the efficacy of oral anti-inflammatory drugs to any other intervention. Studies characteristics were extracted using a standardized form and the methodological quality was evaluated. Results were summarized qualitatively or quantitatively. The mean methodological score of the 12 included studies was 53.6 ± 8.8%. The majority of studies included acute cases and were underpowered to detect differences in adverse events. Compared to a placebo, oral non-steroidal anti-inflammatory drugs were found to provide short-term pain relief (pooled mean difference: -2.69; 95% confidence interval: -1.96 to -3.41) but not function. Oral anti-inflammatory- drugs and corticosteroids injections have similar short-term efficacy in terms of pain reduction as well as in function (pooled standardized mean difference: 0.09; 95% confidence interval: -0.25 to 0.44). Low to moderate grade evidence exists regarding the efficacy of non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy. Oral anti-inflammatory drugs are effective in reducing short-term pain but not function. In terms of pain and function, oral anti-inflammatory drugs in the short term are as effective as corticosteroid injections.

Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.

PubMed

Song, Yanqin; Zhao, Feng; Zhang, Leiming; Du, Yuan; Wang, Tian; Fu, Fenghua

2013-12-01

Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-α, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-α in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect. © 2013.

Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders

PubMed Central

Johnson, Tyler A.; Sohn, Johann; Inman, Wayne D.; Bjeldanes, Leonard F.; Rayburn, Keith

2012-01-01

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica, (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activity in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves were also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with the standard anti-inflammatory agent celastrol (1) but was moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves plant portions displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects ≥ 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of the roots, stems or leaves of stinging nettle may be more effective then traditional tinctures (water, methanol, ethanol) to undergo clinical evaluations for the treatment of inflammatory disorders including arthritis. A chemical investigation into the lipophillic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. PMID:23092723

Adiponectin limits monocytic microparticle-induced endothelial activation by modulation of the AMPK, Akt and NFκB signaling pathways.

PubMed

Ehsan, Mehroz; Singh, Krishna K; Lovren, Fina; Pan, Yi; Quan, Adrian; Mantella, Laura-Eve; Sandhu, Paul; Teoh, Hwee; Al-Omran, Mohammed; Verma, Subodh

2016-02-01

Monocyte-derived microparticles (mono-MPs) are emerging as critical transducers of inflammatory signals, and have been suggested to link cardiovascular risk factors to vascular injury. Since adiponectin has been proposed to exert multiple anti-inflammatory and vasculoprotective effects, we hypothesized that it might serve to limit the production and/or action of mono-MPs. Flow cytometry and western blot studies were conducted on THP-1 cells, THP-1-derived MPs, human umbilical vein endothelial cells (HUVECs), peripheral blood CD14+ monocytes and mice to evaluate the effects of adiponectin on mono-MPs. Adiponectin attenuated lipopolysaccharide (LPS)-evoked MP release from THP-1 monocytes (30% difference) and peripheral blood monocytes (both P < 0.05) as well as dampened LPS-induced mono-MP generation in vivo. Furthermore, peritoneal monocytes from Adipoq(-/-) mice generated significantly greater MPs than those from Adipoq(+/+) littermates in the absence (2.3 fold difference, P < 0.05) and presence (1.6 fold difference, P < 0.05) of LPS. LPS-induced MP expression of NLRP3 inflammasome and its key components, namely cleaved ASC, caspase-1 and IL-1β (pro- and cleaved), were markedly attenuated by adiponectin. HUVECs incubated with MPs from LPS-treated THP-1 cells exhibited increased VCAM-1 levels and adhesion to THP-1 cells. Adiponectin abrogated these effects. From a mechanistic standpoint, the effects of adiponectin on MP release and molecular signaling occurred at least in part through the AMPK, Akt and NFκB pathways. Adiponectin exerts novel effects to limit the production and action of mono-MPs, underscoring yet another pleiotropic effect of this adipokine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

PubMed

Fond, G; Hamdani, N; Kapczinski, F; Boukouaci, W; Drancourt, N; Dargel, A; Oliveira, J; Le Guen, E; Marlinge, E; Tamouza, R; Leboyer, M

2014-03-01

To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation.

PubMed

Tang, Siah Ying; Sivakumar, Manickam; Ng, Angela Min-Hwei; Shridharan, Parthasarathy

2012-07-01

The present study investigated the anti-inflammatory and analgesic activities of novel aspirin oil-in-water (O/W) nanoemulsion and water-in-oil-in-water (W/O/W) nano multiple emulsion formulations generated using ultrasound cavitation techniques. The anti-inflammatory activities of nanoemulsion and nano multiple emulsion were determined using the λ-carrageenan-induced paw edema model. The analgesic activities of both nanoformulations were determined using acetic acid-induced writhing response and hot plate assay. For comparison, the effect of pretreatment with blank nanoemulsion and reference aspirin suspension were also studied for their anti-inflammatory and antinociceptive activities. The results showed that oral administration of nanoemulsion and nano multiple emulsion containing aspirin (60 mg/kg) significantly reduced paw edema induced by λ-carrageenan injection. Both nanoformulations decreased the number of abdominal constriction in acetic acid-induced writhing model. Pretreatment with nanoformulations led to a significant increase in reaction time in hot plate assay. Nanoemulsion demonstrated an enhanced anti-inflammatory and analgesic effects compared to reference suspension while nano multiple emulsion exhibited a mild inhibitory effects in the three experimental animal model tests. The results obtained for nano multiple emulsion were relatively lower than reference. However, administration of blank nanoemulsion did not alter the nociceptive response significantly though it showed slight anti-inflammatory effect. These experimental studies suggest that nanoemulsion and nano multiple emulsion produced a pronounced anti-inflammatory and analgesic effects in rats and may be candidates as new nanocarriers for pharmacological NSAIDs in the treatment of inflammatory disorders and alleviating pains. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of the anti-inflammatory effects of phloretin and phlorizin in lipopolysaccharide-stimulated mouse macrophages.

PubMed

Chang, Wei-Tien; Huang, Wen-Chung; Liou, Chian-Jiun

2012-09-15

Many reports suggest that phloretin and phlorizin have antioxidant properties and can inhibit glucose transportation, the anti-inflammatory effects and mechanism of phloretin and phlorizin remain unclear. This study aims to evaluate the anti-inflammatory effects of phloretin and phlorizin in LPS-stimulated murine RAW264.7 macrophages. RAW264.7 cells were pretreated with various concentrations of phloretin or phlorizin (3-100 μM) and cell inflammatory responses were induced with LPS. Pretreated with 10 μM phloretin significantly inhibited the levels of NO, PGE(2), IL-6, TNF-α, iNOS and COX-2. Furthermore, it was demonstrated that phloretin suppressed the nuclear translocation of NF-κB subunit p65 proteins, and decreased phosphorylation in MAPK pathways. Surprisingly, phlorizin did not suppress the inflammatory response in LPS-stimulated RAW264.7 cells. These results suggest that phloretin has an anti-inflammatory effect that reduces levels of proinflammatory cytokines and mediators in RAW264.7 cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome

PubMed Central

Bulugonda, Ramakrishna K.; kumar, Kotha Anil; Gangappa, D.; Beeda, Harshavardhan; Philip, Gundala Harold; Muralidhara Rao, Dowlathabad; Faisal, Syed M.

2017-01-01

Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future. PMID:28218280

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity

PubMed Central

Herranz-López, María; Olivares-Vicente, Mariló; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

2017-01-01

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. PMID:28825642

Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea.

PubMed

Goswami, Dinesh G; Kant, Rama; Tewari-Singh, Neera; Agarwal, Rajesh

2018-09-01

Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4h after washing NM following its 2h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2h after washing NM following its 2h exposure; however, when treatments were carried out 4h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity.

PubMed

Herranz-López, María; Olivares-Vicente, Mariló; Encinar, José Antonio; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

2017-08-20

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity.

Chebulagic acid Chebulinic acid and Gallic acid, the active principles of Triphala, inhibit TNFα induced pro-angiogenic and pro-inflammatory activities in retinal capillary endothelial cells by inhibiting p38, ERK and NFkB phosphorylation.

PubMed

Shanmuganathan, Sivasankar; Angayarkanni, Narayanasamy

2018-04-17

Tumor necrosis factor-α (TNFα) a pleiotropic cytokine induces pro-inflammatory and pro-angiogenic changes in conditions such as diabetic retinopathy (DR) and neovascular age related macular degeneration (NV-AMD). Hence, inhibition of TNFα mediated changes can benefit the management of DR and NV-AMD. Triphala, an ayurvedic herbal preparation is known to have immunomodulatry functions. In this study we evaluated the alcoholic extract of triphala (AlE) and its compounds Chebulagic acid (CA), Chebulinic acid (CI) and Gallic acid (GA) for their anti-TNFα activity. TNFα induced pro-inflammatory and pro-angiogenic changes in the retinal-choroid microvascular endothelial cells (RF/6A). Treatment with CA/CI/GA and the whole Triphala extract showed characteristic inhibition of MMP-9, cell proliferation/migration and tube formation as well the expression of IL-6, IL-8 and MCP-1 without affecting cell viability. This was mediated by inhibition of p38, ERK and NFκB phosphorylation. Ex vivo angiogenesis assay using chick chorioallantoic membrane (CAM) model also showed that TNFα-induced angiogenesis and it was inhibited by AlE and its active principles. Further, in silico studies revealed that CA, CI and GA are capable of binding the TNFα-receptor-1 to mediate anti-TNFα activity. This study explains the immunomodulatory function of Triphala, evaluated in the context of retinal and choroid vasculopathies in vitro and ex vivo; which showed that CA, CI and GA can be a potential pharmacological agents in the management of DR and NV-AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities.

PubMed

Loued, Soumaya; Berrougui, Hicham; Componova, Pamela; Ikhlef, Souad; Helal, Olfa; Khalil, Abdelouahed

2013-10-01

Paraoxonase 1 (PON1) is associated with HDL and modulates the antioxidant and anti-inflammatory role of HDL. The goals of the present study were to investigate the effect of ageing and the role of PON1 on the anti-inflammatory activity of HDL, and to determine whether extra-virgin olive oil (EVOO) consumption could improve the atheroprotective activity of HDL. HDL and PON1 were isolated from the plasma of ten young (Y-HDL and Y-PON1) and ten elderly (E-HDL and E-PON1) healthy volunteers before and after 12 weeks of EVOO consumption. Inflammation was assessed by measuring intracellular adhesion molecule 1 (ICAM-1) expression. THP-1 (human acute monocytic leukaemia cell line) monocyte chemotaxis was measured using a Boyden chamber. Oxidative damage to HDL was assessed by measuring conjugated diene formation and changes in electrophoretic migration. Y-HDL had more anti-inflammatory activity than E-HDL. The conjugated diene content and the electrophoretic mobility of E-HDL were higher than those of Y-HDL. Y-PON1 had significant anti-inflammatory activity, reducing ICAM-1 expression by 32·64 (SD 2·63)%, while E-PON1 had no significant effect. THP-1 chemotaxis measurements confirmed the ICAM-1 expression results. The 12 weeks of EVOO consumption significantly increased the anti-inflammatory activities of both HDL and PON1. The anti-inflammatory activity of HDL was modulated by PON1 and was lower in the elderly volunteers. EVOO consumption increased the anti-inflammatory effect of HDL and reduced the age-related decrease in anti-atherogenic activity.

Antioxidant and Anti-Inflammatory Activities in Extracts from Minke Whale (Balaenoptera acutorostrata) Blubber

PubMed Central

Stormo, Svein Kristian; Jensen, Ida-Johanne; Østerud, Bjarne; Eilertsen, Karl-Erik

2017-01-01

Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-PUFA) is commonly recognized to reduce cardiovascular disease (CVD). In previous studies, cold-pressed whale oil (CWO) and cod liver oil (CLO) were given as a dietary supplement to healthy volunteers. Even though CWO contains less than half the amount of LC-n3-PUFA of CLO, CWO supplement resulted in beneficial effects on anti-inflammatory and CVD risk markers compared to CLO. In the present study, we prepared virtually lipid-free extracts from CWO and CLO and evaluated the antioxidative capacity (AOC) and anti-inflammatory effects. Oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays were used to test the AOC, and the results indicated high levels of antioxidants present in all extracts. The anti-inflammatory effects of the extracts were tested with lipopolysaccharide- (LPS-) treated THP-1 cells, measuring its ability to reduce cytokine and chemokine secretion. Several CWO extracts displayed anti-inflammatory activity, and a butyl alcohol extract of CWO most effectively reduced TNF-α (50%, p < 0.05) and MCP-1 (85%, p < 0.001) secretion. This extract maintained a stable effect of reducing MCP-1 secretion (60%, p < 0.05) even after long-term storage. In conclusion, CWO has antioxidant and anti-inflammatory activities that may act in addition to its well-known LC-n3-PUFA effects. PMID:29118465

Anti-inflammatory effects of isoacteoside from Abeliophyllum distichum.

PubMed

Nam, Sun-Young; Kim, Hee-Yun; Yoou, Myoung-Schook; Kim, A Hyun; Park, Byoung Jun; Jeong, Hyun-Ja; Kim, Hyung-Min

2015-06-01

Isoacteoside, a dihydroxypheynylethyl glycoside, is a major bioactive component of Abeliophyllum distichum (White Forsythia) which is a deciduous shrub native to the south and central areas of Korea. The present study is designed to evaluate the anti-inflammatory activities and underlying mechanisms of isoacteoside in human mast cell line, HMC-1 cells. We isolated isoacteoside from A. distichum. The anti-inflammatory effect of isoacteoside was investigated in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) secretion and mRNA expression by ELISA and RT-PCR, respectively. In addition, mechanism related to anti-inflammatory was investigated by Western blotting. Isoacteoside significantly suppressed the production and mRNA expression of proinflammatory cytokines including IL-1β, IL-6, IL-8 and TNF-α in PMACI-stimulated HMC-1 cells without cytotoxicity. It was found that anti-inflammatory effects of isoacteoside are mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways. Taken together, the present findings provide new insights that isoacteoside may be a promising anti-inflammatory agent for inflammatory disorders.

Identification and evaluation of anti-inflammatory properties of aqueous components extracted from sesame (Sesamum indicum) oil.

PubMed

Deme, Pragney; Narasimhulu, Chandrakala Aluganti; Parthasarathy, Sampath

2018-06-15

We previously reported that sesame oil (SO) has anti-inflammatory, anti-atherosclerotic and lipid lowering properties in vivo. Our recent studies have shown that, an aqueous extract of sesame oil (SOAE) has also anti-inflammatory and anti-atherosclerotic properties but with no lipid lowering effects. The extent of reduction in atherosclerosis led us to identify components of SOAE and evaluate their anti-inflammatory properties in vitro. Liquid chromatography mass spectrometric method was used to detect and identify components of SOAE. Methoxyphenol derivatives, short and long chain carboxylic acids, dicarboxylic acids, hydroxy and oxo- carboxylic acids were detected. To our surprise, sesamol and its derivatives (lignans), were not present in the SOAE. Among the identified, a combination of methoxy phenol compounds were selected and tested their ability to reduce LPS induced inflammatory gene expression. Monocyte derived macrophages/RAW 264.7 macrophages were pre-treated with these compounds for 2 h, followed by LPS stimulation for 24 h and pro-inflammatory gene expressions were analyzed. These methoxyphenol derivatives showed potent anti-inflammatory properties. In conclusion, the anti-inflammatory molecules associated with SO may contribute the anti-inflammatory and anti-atherosclerotic properties. Also, our results shed light for the development of SOAE based non-pharmacological therapeutics, nutritional supplements and health products for various inflammatory diseases in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

The Anti-Inflammatory Effects of Acupuncture and Their Relevance to Allergic Rhinitis: A Narrative Review and Proposed Model

PubMed Central

McDonald, John L.; Cripps, Allan W.; Smith, Peter K.; Smith, Caroline A.; Xue, Charlie C.; Golianu, Brenda

2013-01-01

Classical literature indicates that acupuncture has been used for millennia to treat numerous inflammatory conditions, including allergic rhinitis. Recent research has examined some of the mechanisms underpinning acupuncture's anti-inflammatory effects which include mediation by sympathetic and parasympathetic pathways. The hypothalamus-pituitary-adrenal (HPA) axis has been reported to mediate the antioedema effects of acupuncture, but not antihyperalgesic actions during inflammation. Other reported anti-inflammatory effects of acupuncture include an antihistamine action and downregulation of proinflammatory cytokines (such as TNF-α, IL-1β, IL-6, and IL-10), proinflammatory neuropeptides (such as SP, CGRP, and VIP), and neurotrophins (such as NGF and BDNF) which can enhance and prolong inflammatory response. Acupuncture has been reported to suppress the expression of COX-1, COX-2, and iNOS during experimentally induced inflammation. Downregulation of the expression and sensitivity of the transient receptor potential vallinoid 1 (TRPV1) after acupuncture has been reported. In summary, acupuncture may exert anti-inflammatory effects through a complex neuro-endocrino-immunological network of actions. Many of these generic anti-inflammatory effects of acupuncture are of direct relevance to allergic rhinitis; however, more research is needed to elucidate specifically how immune mechanisms might be modulated by acupuncture in allergic rhinitis, and to this end a proposed model is offered to guide further research. PMID:23476696

Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

PubMed

Susunaga-Notario, Ana del Carmen; Pérez-Gutiérrez, Salud; Zavala-Sánchez, Miguel Angel; Almanza-Pérez, Julio Cesar; Gutiérrez-Carrillo, Atilano; Arrieta-Báez, Daniel; López-López, Ana Laura; Román-Ramos, Rubén; Flores-Sáenz, José Luis Eduardo; Alarcón-Aguilar, Francisco Javier

2014-07-15

Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa.

Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity.

PubMed

Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; Khan, Amjad A

2014-01-01

The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect.

Effect of Kramecyne on the Inflammatory Response in Lipopolysaccharide-Stimulated Peritoneal Macrophages

PubMed Central

Sánchez-Miranda, E.; Lemus-Bautista, J.; Pérez, S.; Pérez-Ramos, J.

2013-01-01

Kramecyne is a new peroxide, it was isolated from Krameria cytisoides, methanol extract, and this plant was mostly found in North and South America. This compound showed potent anti-inflammatory activity; however, the mechanisms by which this compound exerts its anti-inflammatory effect are not well understood. In this study, we examined the effects of kramecyne on inflammatory responses in mouse lipopolysaccharide- (LPS-) induced peritoneal macrophages. Our findings indicate that kramecyne inhibits LPS-induced production of tumor necrosis factor (TNF-α) and interleukin- (IL-) 6. During the inflammatory process, levels of cyclooxygenase- (COX-) 2, nitric oxide synthase (iNOS), and nitric oxide (NO) increased in mouse peritoneal macrophages; however, kramecyne suppressed them significantly. These results provide novel insights into the anti-inflammatory actions and support its potential use in the treatment of inflammatory diseases. PMID:23573152

The antimicrobial effect of CEN1HC-Br against Propionibacterium acnes and its therapeutic and anti-inflammatory effects on acne vulgaris.

PubMed

Han, Rui; Blencke, Hans-Matti; Cheng, Hao; Li, Chun

2018-01-01

Propionibacterium acnes is a commensal bacterium, which is involved in acne inflammation. An antimicrobial peptide named CEN1HC-Br, which was isolated and characterized form the green sea urchin, has been shown to possess broad-spectrum antibacterial activity. Little is known concerning the potential effects of its antibacterial and anti-inflammatory properties against P. acnes. To examine the potency of CEN1HC-Br in acne treatment, we conducted experiments to analyze the antibacterial and anti-inflammatory activities of CEN1HC-Br both in vitro and in vivo. The antimicrobial activity of CEN1HC-Br was evaluated by minimal inhibitory concentration (MIC) assays using the broth dilution method. To elucidate the in vitro anti-inflammatory effect, HaCaT cells and human monocytes were treated with different concentration of CEN1HC-Br after stimulation by P. acnes. The expression of TLR2 and the secretion of the pro-inflammatory cytokines IL-6, IL-8, IL-1β, TNF-α, IL-12, respectively, were measured by enzyme immunoassays. An evaluation of P. acnes-induced ear edema in rat ear was conducted to compare the in vivo antibacterial and anti-inflammatory effect of CEN1HC-Br, the expression of IL-8, TNF-α, MMP-2 and TLR2 was evaluated by immunohistochemistry and real time-PCR. CEN1HC-Br showed stronger antimicrobial activity against P. acnes than clindamycin. CEN1HC-Br significantly reduced the expression of interleukin IL-12p40, IL-6, IL-1β, TNF-α and TLR2 in monocytes, but they were not influenced by clindamycin. Both CEN1HC-Br and Clindamycin attenuated P. acnes-induced ear swelling in rat along with pro-inflammatory cytokines IL-8, TNF-α, MMP-2 and TLR2. Our data demonstrates that CEN1HC-Br is bactericidal against P. acnes and that it has an anti-inflammatory effect on monocytes. The anti-inflammatory effect may partially occur through TLR2 down-regulation, triggering an innate immune response and the inhibition of pro-inflammatory cytokines. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A Review on the Anti-Inflammatory Activity of Pomegranate in the Gastrointestinal Tract

PubMed Central

Colombo, Elisa; Sangiovanni, Enrico; Dell'Agli, Mario

2013-01-01

Several biological activities of pomegranate have been widely described in the literature, but the anti-inflammatory effect in the gastrointestinal tract has not been reviewed till now. The aim of the present paper is to summarize the evidence for or against the efficacy of pomegranate for coping with inflammatory conditions of the gastro-intestinal tract. The paper has been organized in three parts: (1) the first one is devoted to the modifications of pomegranate active compounds in the gastro-intestinal tract; (2) the second one considering the literature regarding the anti-inflammatory effect of pomegranate at gastric level; (3) the third part considers the anti-inflammatory effect of pomegranate in the gut. In vivo studies performed on the whole fruit or juice, peel, and flowers demonstrate antiulcer effect in a variety of animal models. Ellagic acid was the main responsible for this effect, although other individual ellagitannins could contribute to the biological activity of the mixture. Different preparations of pomegranate, including extracts from peels, flowers, seeds, and juice, show a significant anti-inflammatory activity in the gut. No clinical studies have been found, thus suggesting that future clinical studies are necessary to clarify the beneficial effects of pomegranate in the gastrointestinal tract. PMID:23573120

Pleiotropic effects of polysaccharide capsule loss on selected biological properties of Streptococcus suis.

PubMed

Tanabe, Shin-Ichi; Bonifait, Laetitia; Fittipaldi, Nahuel; Grignon, Louis; Gottschalk, Marcelo; Grenier, Daniel

2010-01-01

In this study, an unencapsulated Streptococcus suis mutant was used to investigate the pleiotropic effects resulting from capsule loss. The capsule deficient mutant of S. suis acquired a biofilm-positive phenotype, which was associated with significantly increased cell surface hydrophobicity. Cell-associated fibrinogen-binding and chymotrypsin-like activities were decreased in the unencapsulated mutant. The mutant did not differ significantly from the encapsulated parent strain for minimal inhibitory concentrations to penicillin G, ampicillin, and tetracycline. However, while the encapsulated strain was highly resistant to the bactericidal action of penicillin G and ampicillin, the unencapsulated mutant was approximately 60-fold more sensitive. Compared with the parent strain, the unencapsulated mutant induced a much higher inflammatory response in monocyte-derived macrophages resulting in an increased secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8. The capsule appears to hinder important adhesins or hydrophobic molecules that mediate biofilm formation, as well as cell wall components capable of stimulating immune cells.

Pleiotropic effects of polysaccharide capsule loss on selected biological properties of Streptococcus suis

PubMed Central

Tanabe, Shin-Ichi; Bonifait, Laetitia; Fittipaldi, Nahuel; Grignon, Louis; Gottschalk, Marcelo; Grenier, Daniel

2010-01-01

In this study, an unencapsulated Streptococcus suis mutant was used to investigate the pleiotropic effects resulting from capsule loss. The capsule deficient mutant of S. suis acquired a biofilm-positive phenotype, which was associated with significantly increased cell surface hydrophobicity. Cell-associated fibrinogen-binding and chymotrypsin-like activities were decreased in the unencapsulated mutant. The mutant did not differ significantly from the encapsulated parent strain for minimal inhibitory concentrations to penicillin G, ampicillin, and tetracycline. However, while the encapsulated strain was highly resistant to the bactericidal action of penicillin G and ampicillin, the unencapsulated mutant was approximately 60-fold more sensitive. Compared with the parent strain, the unencapsulated mutant induced a much higher inflammatory response in monocyte-derived macrophages resulting in an increased secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8. The capsule appears to hinder important adhesins or hydrophobic molecules that mediate biofilm formation, as well as cell wall components capable of stimulating immune cells. PMID:20357962

Blunted activation of NF-{kappa}B and NF-{kappa}B-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayakawa, Kunihiro; Hiramatsu, Nobuhiko; Okamura, Maro

2008-01-04

Geranylgeranylacetone (GGA), an anti-ulcer agent, has anti-inflammatory potential against experimental colitis and ischemia-induced renal inflammation. However, molecular mechanisms involved in its anti-inflammatory effects are largely unknown. We found that, in glomerular mesangial cells, GGA blocked activation of nuclear factor-{kappa}B and consequent induction of monocyte chemoattractant protein 1 (MCP-1) by inflammatory cytokines. It was inversely correlated with induction of unfolded protein response (UPR) evidenced by expression of 78 kDa glucose-regulated protein (GRP78) and suppression of endoplasmic reticulum stress-responsive alkaline phosphatase. Various inducers of UPR including tunicamycin, thapsigargin, A23187, 2-deoxyglucose, dithiothreitol, and AB{sub 5} subtilase cytotoxin reproduced the suppressive effects of GGA.more » Furthermore, attenuation of UPR by stable transfection with GRP78 diminished the anti-inflammatory effects of GGA. These results disclosed a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of GGA.« less

Anti-Inflammatory Activity of Fruit Fractions in Vitro, Mediated through Toll-Like Receptor 4 and 2 in the Context of Inflammatory Bowel Disease

PubMed Central

Nasef, Noha Ahmed; Mehta, Sunali; Murray, Pamela; Marlow, Gareth; Ferguson, Lynnette R.

2014-01-01

Pattern recognition receptors such as Toll-Like Receptor 2 (TLR2) and 4 (TLR4) are important in detecting and responding to stress and bacterial stimuli. Defect or damage in the TLR2 and TLR4 pathways can lead to sustained inflammation, characteristic of inflammatory bowel disease (IBD). The goal of this study was to identify fruit fractions that can be tested further to develop them as complementary therapies for IBD. In order to do this, we identified fruit fractions that mediate their anti-inflammatory response through the TLR4 and TLR2 pathway. Human Embryonic Kidney (HEK)-hTLR4 and hTLR2 cells were stimulated with their respective ligands to induce inflammation. These cells were treated with one of the 12 fractionated fruits and the inflammatory effect measured. 10 of the fruits came up as anti-inflammatory in the hTLR4 assay and nine in the hTLR2 assays. Many of the fruit fractions mediated their anti-inflammatory actions either mainly in their hydrophobic fractions (such as elderberry) or hydrophilic fractions (such as red raspberry), or both. The strongest anti-inflammatory effects were seen for feijoa and blackberry. This study shows that fruits can have multiple fractions eliciting anti-inflammatory effects in a pathway specific manner. This suggests that the compounds found in fruits can act together to produce health benefits by way of reducing inflammation. Exploiting this property of fruits can help develop complimentary therapies for inflammatory diseases. PMID:25415606

Tamarixetin Exhibits Anti-inflammatory Activity and Prevents Bacterial Sepsis by Increasing IL-10 Production.

PubMed

Park, Hee Jo; Lee, Seung Jun; Cho, Joon; Gharbi, Amal; Han, Hee Dong; Kang, Tae Heung; Kim, Yangmee; Lee, Yeongjoon; Park, Won Sun; Jung, In Duk; Park, Yeong-Min

2018-06-22

Sepsis is a systemic inflammatory response to pathogenic infection that currently has no specific pharmaceutical interventions. Instead, antibiotics administration is considered the best available option, despite increasing drug resistance. Alternative strategies are therefore urgently required to prevent sepsis and strengthen the host immune system. One such option is tamarixetin (4'- O-methylquercetin), a naturally occurring flavonoid derivative of quercetin that protects against inflammation. The purpose of this study was to determine whether the anti-inflammatory effects of tamarixetin protect against the specific inflammatory conditions induced in lipopolysaccharide (LPS) or Escherichia coli K1 models of sepsis. Our study showed that tamarixetin reduced the secretion of various inflammatory cytokines by dendritic cells after activation with LPS. It also promoted the secretion of the anti-inflammatory cytokine interleukin (IL)-10 and specifically increased the population of IL-10-secreting immune cells in LPS-activated splenocytes. Tamarixetin showed general anti-inflammatory effects in mouse models of bacterial sepsis and decreased bacteria abundance and endotoxin levels. We therefore conclude that tamarixetin has superior anti-inflammatory properties than quercetin during bacterial sepsis. This effect is associated with an increased population of IL-10-secreting immune cells and suggests that tamarixetin could serve as a specific pharmaceutical option to prevent bacterial sepsis.

The ABP Dendrimer, a Drug-Candidate against Inflammatory Diseases That Triggers the Activation of Interleukin-10 Producing Immune Cells.

PubMed

Fruchon, Séverine; Poupot, Rémy

2018-05-25

The ABP dendrimer, which is built on a phosphorus-based scaffold and bears twelve azabisphosphonate groups at its surface, is one of the dendrimers that has been shown to display immuno-modulatory and anti-inflammatory effects towards the human immune system. Its anti-inflammatory properties have been successfully challenged in animal models of inflammatory disorders. In this review, we trace the discovery and the evaluation of the therapeutic effects of the ABP dendrimer in three different animal models of both acute and chronic inflammatory diseases. We emphasize that its therapeutic effects rely on the enhancement of the production of Interleukin-10, the paradigm of anti-inflammatory cytokines, by different subsets of immune cells, such as monocytes/macrophages and CD4+ T lymphocytes.

Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

PubMed

Hua, Susan; Cabot, Peter J

2013-01-01

The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). A randomized, double blind, controlled animal trial. Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 μL Complete Freund's Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 μL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein injection using liquid scintillation counting (LSC). Administration of liposomes loaded with loperamide HCl, and conjugated with antibody to intercellular adhesion molecule-1 (anti-ICAM-1), exerted analgesic and anti-inflammatory effects exclusively in peripheral painful inflamed tissue. These targeted nanoparticles produced highly significant analgesic and anti-inflammatory effects over the 48 hour time course studied following intravenous administration in rats with Complete Freund's Adjuvant-induced inflammation of the paw. All control groups showed no significant antinociceptive or anti-inflammatory effects. Our biodistribution study demonstrated specific localization of the targeted nanoparticles to peripheral inflammatory tissue and no significant uptake into the brain. In vivo studies were performed in the well-established rodent model of acute inflammatory pain. We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response. The study presents a novel approach of opioid delivery specifically to injured tissues for pain control. The study also highlights a novel anti-inflammatory role for peripheral opioid targeting, which is of clinical relevance. The potential also exists for the modification of these targeted nanoparticles with other therapeutic compounds for use in other painful conditions.

Cecropia pachystachya: A Species with Expressive In Vivo Topical Anti-Inflammatory and In Vitro Antioxidant Effects

PubMed Central

Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira

2014-01-01

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β-carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms. PMID:24877079

Black Cumin (Nigella sativa) and Its Active Constituent, Thymoquinone: An Overview on the Analgesic and Anti-inflammatory Effects.

PubMed

Amin, Bahareh; Hosseinzadeh, Hossein

2016-01-01

For many centuries, seeds of Nigella sativa (black cumin), a dicotyledon of the Ranunculaceae family, have been used as a seasoning spice and food additive in the Middle East and Mediterranean areas. Traditionally, the plant is used for asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and gastrointestinal disturbances. The literature regarding the biological activities of seeds of this plant is extensive, citing bronchodilative, anti-inflammatory, antinociceptive, antibacterial, hypotensive, hypolipidemic, cytotoxic, antidiabetic, and hepatoprotective effects. The active ingredients of N. sativa are mainly concentrated in the fixed or essential oil of seeds, which are responsible for most health benefits. This review will provide all updated reported activities of this plant with an emphasis on the antinociceptive and anti-inflammatory effects. Results of various studies have demonstrated that the oil, extracts, and their active ingredients, in particular, thymoquinone, possess antinociceptive and anti-inflammatory effects, supporting the common folk perception of N. Sativa as a potent analgesic and anti-inflammatory agent. Many protective properties are attributed to reproducible radical scavenging activity as well as an interaction with numerous molecular targets involved in inflammation, including proinflammatory enzymes and cytokines. However, there is a need for further investigations to find out the precise mechanisms responsible for the antinociceptive and anti-inflammatory effects of this plant and its active constituents. Georg Thieme Verlag KG Stuttgart · New York.

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.

Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis.

PubMed

Ramadan, Gamal; Al-Kahtani, Mohammed Ali; El-Sayed, Wael Mohamed

2011-08-01

Turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes have been widely used as dietary spices and to treat different diseases in Ayurveda/Chinese medicine since antiquity. Here, we compared the anti-inflammatory/anti-oxidant activity of these two plants in rat adjuvant-induced arthritis (AIA). Both plants (at dose 200 mg/kg body weight) significantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing/decreasing the production of anti-inflammatory/pro-inflammatory cytokines, respectively, and activating the anti-oxidant defence system. The anti-arthritic activity of turmeric exceeded that of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction. The percentage of disease recovery was 4.6-8.3% and 10.2% more in turmeric compared with ginger and indomethacin (P < 0.05), respectively. The present study proves the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model.

Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory effect of antimicrobial triclocarban in a murine model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Junyan; Qiu Hong; Morisseau, Christophe

The increasing use of the antimicrobial triclocarban (TCC) in personal care products (PCPs) has resulted in concern regarding environmental pollution. TCC is a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs) are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal models. However, the in vivo effects anticipated from a sEHI have not been reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged murine model. Systolic blood pressure, plasma levels of several inflammatory cytokines and chemokine, and metabolomic profile of plasma oxylipins were determined.more » TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. TCC significantly repressed the increased release of inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC significantly shifted the oxylipin profile in vivo in a time-dependent manner towards resolution of inflammation as expected from a sEHI. These results demonstrated that at the doses used TCC is anti-inflammatory in the murine model. This study suggests that TCC may provide some benefits in humans in addition to its antimicrobial activities due to its potent inhibition of sEH. It may be a promising starting point for developing new low volume high value applications of TCC. However these biological effects also caution against the general over use of TCC in PCPs. - Graphical abstract: Display Omitted Research Highlights: > Anti-microbial triclocarban (TCC) is anti-inflammatory in a murine model. > TCC significantly shifted the oxylipin profile in vivo as expected from a sEHI. > TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. > TCC significantly repressed LPS-induced increased release of inflammatory cytokines.« less

Anti-inflammatory effect of a Nuphar lutea partially purified leaf extract in murine models of septic shock.

PubMed

Ozer, J; Levi, T; Golan-Goldhirsh, A; Gopas, J

2015-02-23

Various plant organs of Nuphar lutea (L.) SM. (Nymphaeaceae) are used in traditional medicine for the treatment of arthritis, fever, aches, pains and inflammation. The main purpose of this study was to determine the anti-inflammatory effect of Nuphar lutea leaf extract (NUP) in two septic shock models: (1) Survival of mice challenged with a lethal dose of LPS, determination of pro-inflammatory and anti-inflammatory cytokines in serum, as well as in peritoneal macrophages in cell culture. (2) The effect of NUP in a murine model of fecal-induced peritonitis. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. A significant average survival rate (60%) of LPS lethally-challenged mice was achieved by pre-treatment with NUP. In addition, NUP pre-treatment reduced nuclear NF-κB translocation in peritoneal macrophages. The production of pro-inflammatory cytokines, TNF-α, IL-6 and IL-12, in the sera of LPS-treated mice or in the supernatants of peritoneal macrophages stimulated with LPS for 2-6 h was also decreased by NUP. Pre-treatment with NUP caused a significant increase in the anti-inflammatory cytokine IL-10. The NUP pre-treatment reduced and delayed mortality in mice with fecal-induced peritonitis. Our studies also revealed that NUP pre-treatment induced a dose-dependent phosphorylation of ERK in peritoneal macrophages. Since most of the reports about the anti-inflammatory effect of Nuphar lutea refer to rhizome and root powder and extracts, it is important to clarify the effectiveness of leaf extract as a source for such activity. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Dietary supplementation with rutin has pro-/anti-inflammatory effects in the liver of juvenile GIFT tilapia, Oreochromis niloticus.

PubMed

Zheng, Yao; Zhao, Zhixiang; Fan, Limin; Meng, Shunlong; Song, Chao; Qiu, Liping; Xu, Pao; Chen, Jiazhang

2017-05-01

Dietary supplementation with rutin may have some pharmacological qualities including anti-inflammatory effects. Kupffer cell activation resulted in increased transcription of pro- and anti-inflammatory cytokines. The main purpose of this study was to investigate the pro- and anti-inflammatory activities in juvenile freshwater tilapia, Oreochromis niloticus, in response to 0.1 or 0.3 g/kg dietary supplementation of rutin. Results showed that hepatic IgM, anti-inflammatory-cytokines, and pro-inflammatory cytokines were significantly decreased in groups treated with high doses of rutin. Hepatic IgM and anti-inflammatory cytokines (IL-10 and IFN-γ) transcripts were significantly decreased, whereas the transcripts of the pro-inflammatory cytokines, TNFα and IL-1β were significantly decreased, whereas IL-8 was significantly increased. The number of Kupffer cells in rutin-treated groups was significantly decreased, and scanning electron micrographs showed that rutin enriched the number of gut microvilli and secretion pits. With the phenomena of cell apoptosis occurred in the rutin groups, the present study demonstrated that optimum levels of rutin may be beneficial but excessive level may cause liver impairment, which may be absorbed by the gut and then transported to the liver. Copyright © 2017 Elsevier Ltd. All rights reserved.

Berberine inhibits colitis-associated tumorigenesis via suppressing inflammatory responses and the consequent EGFR signaling-involved tumor cell growth.

PubMed

Li, Dandan; Zhang, Youyu; Liu, Kun; Zhao, Yujie; Xu, Beibei; Xu, Liang; Tan, Li; Tian, Yuan; Li, Cunxi; Zhang, Wenqing; Cao, Hanwei; Zhan, Yan-Yan; Hu, Tianhui

2017-11-01

The anti-inflammatory and anti-tumor effects of berberine, a traditional Chinese medicine, were separately discovered in pathological intestinal tissues. However, whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colitis-associated colorectal cancer (CACRC) remains unknown. In the present study, we found that berberine effectively inhibited colitis-associated tumorigenesis and colonic epithelium hyperproliferation in dextran sulfate sodium (DSS)-treated Apc Min/+ mice. A mechanistic study identified that these inhibitory effects of berberine occurred through blocking interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression in colonic macrophages. An in vitro study on cell lines identified that berberine treatment of Raw 264.7 macrophages resulted in conditioned media with fewer proliferative effects on a cell line with a heterozygous Apc mutation (Immorto-Min colonic epithelium, IMCE). EGFR-ERK signaling act downstream of berberine/pro-inflammatory cytokines axis to regulate CACRC cell proliferation. Furthermore, in vivo administration of IL-6 to DSS-treated Apc Min/+ mice effectively weakened the inhibitory effects of berberine on tumorigenesis and EGFR-ERK signaling in colon tissues. Altogether, the results of our studies have revealed that berberine inhibits the development of CACRC by interfering with inflammatory response-driven EGFR signaling in tumor cell growth. The findings of this study support the possibility that berberine and other anti-inflammatory drugs may be beneficial in the treatment of CACRC.

Anti-inflammatory activities and glycerophospholipids metabolism in KLA-stimulated RAW 264.7 macrophage cells by diarylheptanoids from the rhizomes of Alpinia officinarum.

PubMed

Zhang, Guogai; Zhao, Lifang; Zhu, Jiancheng; Feng, Yifan; Wu, Xia

2018-02-01

Alpinia officinarum is used for its anti-inflammatory activity historically in China. Diarylheptanoids isolated from A. officinarum play important biological roles in the prevention and treatment of inflammatory disorders. Seven diarylheptanoids (1-7) were isolated from A. officinarum. The cell viabilities and anti-inflammatory activities of diarylheptanoids were evaluated by MTT assay and tumor necrosis factor-α production in Kdo2-lipid A-stimulated RAW 264.7 cells in vitro. The relationships between their anti-inflammatories and structure-activities are discussed. The results indicated that compounds 1 and 3-7 had significant anti-inflammatory activities. The relationships between inflammation and phospholipids metabolism were elucidated by multivariate data analysis. Twenty-two potential biomarkers were identified in inflammatory group vs. blank group, and 11 potential biomarkers were identified for inflammatory group vs. drug-treatment groups. Ten common phospholipids were characterized. On the basis of a previous study in our laboratory, we found that phosphatidylethanolamine (18:0/18:1) might be the important glycerophospholipid biomarker in inflammation. In this study, we firstly combined anti-inflammatory activities and glycerophospholipids changes of traditional Chinese medicine. This work suggests that the anti-inflammatory activities of diarylheptanoids might be significantly related to glycerophospholipids and could provide a useful database for investigating the anti-inflammatory effects of traditional Chinese medicine. Copyright © 2017 John Wiley & Sons, Ltd.

Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties

PubMed Central

2013-01-01

For their various bioactivities, biomaterials derived from marine algae are important ingredients in many products, such as cosmetics and drugs for treating cancer and other diseases. This mini-review comprehensively compares the bioactivities and biological functions of biomaterials from red, green, brown, and blue-green algae. The anti-oxidative effects and bioactivities of several different crude extracts of algae have been evaluated both in vitro and in vivo. Natural products derived from marine algae protect cells by modulating the effects of oxidative stress. Because oxidative stress plays important roles in inflammatory reactions and in carcinogenesis, marine algal natural products have potential for use in anti-cancer and anti-inflammatory drugs. PMID:23724847

Anti-inflammatory effect of anthocyanins via modulation of nuclear factor-κB and mitogen-activated protein kinase signaling cascades.

PubMed

Vendrame, Stefano; Klimis-Zacas, Dorothy

2015-06-01

Anthocyanins are a group of bioactive compounds present in plant foods. Although they have consistently shown an anti-inflammatory effect both in vitro and in vivo, their mechanisms of action are not fully understood and have only recently begun to be elucidated. The aim of this review is to highlight the anti-inflammatory activity of anthocyanins, including their effect on the expression of several genes involved in inflammation. The available evidence suggests that their anti-inflammatory action can be attributed primarily to their antioxidant properties, which result in downregulation of the redox-sensitive nuclear factor-κB signaling pathway. Other pathways at least partly involved in the inflammatory response, particularly the mitogen-activated protein kinase pathways, also appear to play a role. A discussion is presented on the most effective dose of anthocyanins, the differential contribution of specific compounds, the comparative effects of anthocyanins versus other anti-inflammatory phenolic compounds, and the extent to which the observed biological activities are exerted by anthocyanins themselves or their metabolites. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

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

Plants from genus Lavandula have been used as anti-inflammatory drugs in Mediterranean traditional medicine. Nowadays, there is a growing interest for complementary medicine, including herbal remedies, to treat inflammatory bowel disease (IBD). To test the anti-inflammatory properties of Lavandula dentata and Lavandula stoechas extracts in two inflammatory experimental models: TNBS model of rat colitis and the carrageenan-induced paw edema in mice, in order to mimic the intestinal conditions and the extra-intestinal manifestations of human IBD, respectively. The extracts were characterized through the qualitative HPLC analysis. Then, they were assayed in vitro and in vivo. In vitro studies were performed in BMDMs and CMT-93 epithelial cells with different concentrations of the extracts (ranging from 0.1 to 100µg/ml). The extracts were tested in vivo in the TNBS model of rat colitis (10 and 25mg/kg) and in the carrageenan-induced paw edema in mice (10, 25 and 100mg/kg). L. dentata and L. stoechas extracts displayed immunomodulatory properties in vitro down-regulating different mediators of inflammation like cytokines and nitric oxide. They also showed anti-inflammatory effects in the TNBS model of colitis as evidenced by reduced myeloperoxidase activity and increased total glutathione content, indicating a decrease of neutrophil infiltration and an improvement of the oxidative state. Besides, both extracts modulated the expression of pro-inflammatory cytokines and chemokines, and ameliorated the altered epithelial barrier function. They also displayed anti-inflammatory effects in the carrageenan-induced paw edema in mice, since a significant reduction of the paw thickness was observed. This was associated with a down-regulation of the expression of different inducible enzymes like MMP-9, iNOS and COX-2 and pro-inflammatory cytokines, all involved in the maintenance of the inflammatory condition. L. dentata and L. stoechas extracts showed intestinal anti-inflammatory 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.

Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro.

PubMed

Nokhbehsaim, Marjan; Deschner, Birgit; Winter, Jochen; Bourauel, Christoph; Jäger, Andreas; Jepsen, Søren; Deschner, James

2012-02-01

Enamel matrix derivative (EMD) used to promote periodontal regeneration has been shown to exert anti-inflammatory effects. This in vitro study was performed to investigate if the anti-inflammatory actions of EMD are modulated by the local cellular environment, such as inflammation or occlusal, i.e., biomechanical, loading. Human periodontal ligament cells were seeded on BioFlex plates and incubated with EMD under normal, inflammatory, and biomechanical loading conditions for 1 and 6 days. In order to mimic inflammatory and biomechanical loading conditions in vitro, cells were stimulated with interleukin (IL)-1β and exposed to dynamic tensile strain, respectively. The gene expression of IL-1β, IL-1 receptor antagonist (IL-1RN), IL-6, IL-8, IL-10, and cyclooxygenase (COX)-2 was analyzed by real-time RT-PCR and the IL-6 protein synthesis by enzyme-linked immunoassay. For statistical analysis, Student's t test, ANOVA, and post-hoc comparison tests were applied (p < 0.05). EMD downregulated significantly the expression of IL-1β and COX-2 at 1 day and of IL-6, IL-8, and COX-2 at 6 days in normal condition. In an inflammatory environment, the anti-inflammatory actions of EMD were significantly enhanced at 6 days. In the presence of low biomechanical loading, EMD caused a downregulation of IL-1β and IL-8, whereas high biomechanical loading significantly abrogated the anti-inflammatory effects of EMD at both days. Neither IL-1RN nor IL-10 was upregulated by EMD. These data suggest that high occlusal forces may abrogate anti-inflammatory effects of EMD and should, therefore, be avoided immediately after the application of EMD to achieve best healing results.

Role of Quzhou Fructus Aurantii Extract in Preventing and Treating Acute Lung Injury and Inflammation.

PubMed

Li, Lili; Zhang, Sheng; Xin, Yanfei; Sun, Junying; Xie, Feng; Yang, Lin; Chen, Zhiqin; Chen, Hao; Liu, Fang; Xuan, Yaoxian; You, Zhenqiang

2018-01-26

Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro. In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.

Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory and Anti-Oxidative Activities

PubMed Central

Lam, Puiyan; Cheung, Fan; Tan, Hor Yue; Wang, Ning; Yuen, Man Fung; Feng, Yibin

2016-01-01

The liver is intimately connected to inflammation, which is the innate defense system of the body for removing harmful stimuli and participates in the hepatic wound-healing response. Sustained inflammation and the corresponding regenerative wound-healing response can induce the development of fibrosis, cirrhosis and eventually hepatocellular carcinoma. Oxidative stress is associated with the activation of inflammatory pathways, while chronic inflammation is found associated with some human cancers. Inflammation and cancer may be connected by the effect of the inflammation-fibrosis-cancer (IFC) axis. Chinese medicinal herbs display abilities in protecting the liver compared to conventional therapies, as many herbal medicines have been shown as effective anti-inflammatory and anti-oxidative agents. We review the relationship between oxidative stress and inflammation, the development of hepatic diseases, and the hepatoprotective effects of Chinese medicinal herbs via anti-inflammatory and anti-oxidative mechanisms. Moreover, several Chinese medicinal herbs and composite formulae, which have been commonly used for preventing and treating hepatic diseases, including Andrographis Herba, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Lycii Fructus, Coptidis Rhizoma, curcumin, xiao-cha-hu-tang and shi-quan-da-bu-tang, were selected for reviewing their hepatoprotective effects with focus on their anti-oxidative and ant-inflammatory activities. This review aims to provide new insight into how Chinese medicinal herbs work in therapeutic strategies for liver diseases. PMID:27043533

Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages

PubMed Central

Ko, Wan-Kyu; Lee, Soo-Hong; Kim, Sung Jun; Jo, Min-Jae; Kumar, Hemant; Han, In-Bo; Sohn, Seil

2017-01-01

Purpose The aim of this study was to investigate the anti-inflammatory effects of Ursodeoxycholic acid (UDCA) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods We induced an inflammatory process in RAW 264.7 macrophages using LPS. The anti-inflammatory effects of UDCA on LPS-stimulated RAW 264.7 macrophages were analyzed using nitric oxide (NO). Pro-inflammatory and anti-inflammatory cytokines were analyzed by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in mitogen-activated protein kinase (MAPK) signaling pathways and nuclear factor kappa-light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) signaling pathways were evaluated by western blot assays. Results UDCA decreased the LPS-stimulated release of the inflammatory mediator NO. UDCA also decreased the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-α (IL-1α), interleukin 1-β (IL-1β), and interleukin 6 (IL-6) in mRNA and protein levels. In addition, UDCA increased an anti-inflammatory cytokine interleukin 10 (IL-10) in the LPS-stimulated RAW 264.7 macrophages. UDCA inhibited the expression of inflammatory transcription factor nuclear factor kappa B (NF-κB) in LPS-stimulated RAW 264.7 macrophages. Furthermore, UDCA suppressed the phosphorylation of ERK, JNK, and p38 signals related to inflammatory pathways. In addition, the phosphorylation of IκBα, the inhibitor of NF-κB, also inhibited by UDCA. Conclusion UDCA inhibits the pro-inflammatory responses by LPS in RAW 264.7 macrophages. UDCA also suppresses the phosphorylation by LPS on ERK, JNK, and p38 in MAPKs and NF-κB pathway. These results suggest that UDCA can serve as a useful anti-inflammatory drug. PMID:28665991

Xanthine-Catechin Mixture Enhances Lithium-Induced Anti-Inflammatory Response in Activated Macrophages In Vitro

PubMed Central

Barbisan, Fernanda; Azzolin, Verônica Farina; Teixeira, Cibele Ferreira; Mastella, Moisés Henrique; Ribeiro, Euler Esteves; do Prado-Lima, Pedro Antonio Schmidt; Praia, Raquel de Souza; Medeiros Frescura Duarte, Marta Maria

2017-01-01

Lithium (Li) is a chemical element used for treating and preventing bipolar disorder (BD) and exerts positive effects such as anti-inflammatory effects as well as undesirable side effects. These effects of Li can be influenced by interaction with some nutritional elements. Therefore, we investigated the potential effects of xanthine (caffeine and theobromine) and catechin molecules present in some food beverages broadly consumed worldwide, such as coffee and tea, on Li-induced anti-inflammatory effects. In the present study, we concomitantly exposed RAW 264.7 macrophages to Li, isolated xanthine and catechin molecules, and a xanthine-catechin mixture (XC mixture). We evaluated the effects of these treatments on cell proliferation, cell cycle progression, oxidative and antioxidant marker expression, cytokine levels, gene expression, and GSK-3β enzyme expression. Treatment with the XC mixture potentialized Li-induced anti-inflammatory effects by intensification of the following: GSK-3β inhibitory action, lowering effect on proinflammatory cytokines (IL-1β, IL-6, and TNFα), and increase in the levels of IL-10 that is an anti-inflammatory cytokine. Despite the controversial nature of caffeine consumption by BD patients, these results suggested that consumption of caffeine, in low concentrations, mixed with other bioactive molecules along with Li may be safe. PMID:29250539

Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Solip; Nguyen, Van Thu; Tae, Nara

Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE{sub 2}, butyl lucidenateD{sub 2} (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting themore » involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum. - Highlights: • The anti-inflammatory effects of selected triterpenes from Ganoderma lucidum are demonstrated. • Heme oxygenase-1 induction is attributable to the anti-inflammatory properties of these triterpenes. • The triterpenes induce heme oxygenase-1 expression via the AKT-Nrf2 pathway. • The mechanism explains the anti-inflammatory effect of triterpenes from G. lucidum.« less

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis

PubMed Central

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero del; Vergnolle, Nathalie

2004-01-01

The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound. PMID:15313880

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis.

PubMed

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero Del; Vergnolle, Nathalie

2004-11-01

1 The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. 2 Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. 3 Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. 4 With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. 5 These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.

Molecular mechanism of action of Pelargonidin-3-O-glucoside, the main anthocyanin responsible for the anti-inflammatory effect of strawberry fruits.

PubMed

Duarte, Larissa Jeremias; Chaves, Vitor Clasen; Nascimento, Marcus Vinicius Pereira Dos Santos; Calvete, Eunice; Li, Mingchuan; Ciraolo, Elisa; Ghigo, Alessandra; Hirsch, Emilio; Simões, Claudia Maria Oliveira; Reginatto, Flávio Henrique; Dalmarco, Eduardo M

2018-05-01

Fragaria x ananassa Duch., popularly called strawberry, is known for its worldwide consumption and important biological activities, and these effects are related to its high concentration of anthocyanins. Pelargonidin-3-O-glucoside (P3G) is a major anthocyanin found in strawberry, and was evaluated for its anti-inflammatory action in experimental models. The effect of strawberry extract and P3G, on leukocyte migration, exudation levels and many inflammatory mediators, was therefore evaluated in an in vivo model. An in vitro study was also carried out to characterize the effect of P3G on mitogen-activated protein kinases, and on nuclear transcript factors NF-κB and AP-1. The results revealed that the strawberry and P3G have important anti-inflammatory proprieties, and the anti-inflammatory mechanism of P3G involves the arrest of IkB-α activation and reduction in JNK MAPK phosphorylation. The results reinforce that strawberry fruits are functional foods that can act as an adjuvant in the treatment of inflammatory conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of the anti-inflammatory properties of NCX 429, a dual-acting compound releasing nitric oxide and naproxen.

PubMed

Amoruso, Angela; Fresu, Luigia Grazia; Dalli, Jesmond; Miglietta, Daniela; Bardelli, Claudio; Federici Canova, Donata; Perretti, Mauro; Brunelleschi, Sandra

2015-04-01

Cyclooxygenase (COX)-inhibiting nitric oxide donors (CINODs) are a new class of drugs that structurally combine a COX inhibitor with a nitric oxide (NO) donating moiety. This combination reduces potential toxicity of the non-steroidal anti-inflammatory drugs (NSAIDs) whilst maintaining the analgesic and anti-inflammatory effects. The present study was undertaken to investigate the anti-inflammatory effects of NCX 429, a naproxen-based CINOD, and to assess the additional properties of NO donation beyond those related to naproxen. We evaluated the in vitro effects of NCX 429 on oxy-radical production, phagocytosis, cytokine release, MMP-9, PPARγ expression and NF-κB activation in human monocytes/MDM and compared to naproxen. Moreover, we compared the in vivo efficacy of NCX 429 and naproxen in a murine model of peritonitis. In all the experiments performed in vitro, NCX 429 reduced the inflammatory responses with equal or higher efficacy compared to naproxen. Moreover, in in vivo experiments, NCX 429, at the lowest dose tested, was able to significantly inhibit cell influx in response to IL-1β administration although naproxen was found to be more potent than NCX 429 at reducing PGE2 in inflammatory exudates. These results demonstrate that both in vitro and in vivo--in a murine model of peritonitis--NCX 429 elicits significant anti-inflammatory activity, beyond the simple COX inhibition or pure NO release. Therefore, NO donation along with COX inhibition may represent a strategy for investigating inflammatory diseases in which pain and function are not fully resolved by analgesics/anti-inflammatory drugs. © 2015.

Physalis angulata extract exerts anti-inflammatory effects in rats by inhibiting different pathways.

PubMed

Bastos, G N T; Silveira, A J A; Salgado, C G; Picanço-Diniz, D L W; do Nascimento, J L M

2008-07-23

Physalis angulata is a popular medicine used in Brazil due to its anti-inflammatory effects, but the pharmacological mechanisms underlying these actions remain to be better understood. In the present work, lyophilized aqueous extract from the roots of Physalis angulata Linneu (AEPa) was used to control the inflammatory response induced by the injection of 1% carrageenan into subcutaneous rat's air pouches. Adenosine deaminase (ADA) activity, nitrite level, and prostaglandin E(2) (PGE(2)) level were used to evaluate the action of inflammatory mediators. Tumor growth factor-beta (TGF-beta) level was used as a bioindicator of immunomodulatory response. Rats were injected with vehicle, indomethacin, or AEPa (0.5 mg/kg, 1 mg/kg, and 5 mg/kg i.p.), 1h before carrageenan administration. AEPa at 0.5 mg/kg had no effect. However, 1mg/kg of AEPa showed significant anti-inflammatory effects, decreasing exudate volume, total number of inflammatory cells, ADA activity, nitrite level, and PGE(2) level in 50%, 41%, 20%, 60%, and 41%, respectively. The anti-inflammatory effects of 5 mg/kg AEPa appeared to be more effective than those of 1 mg/kg AEPa (84%, 80%, 43%, 70%, and 75%, respectively). In addition, TGF-beta level was upregulated to 9700 pg/ml after 5mg/kg AEPa, in comparison with 160 pg/ml in the vehicle-treated group, and 137 pg/ml in the indomethacin-treated group. The results indicate that AEPa exerts powerful anti-inflammatory and immunomodulatory activities, interfering with the cyclooxygenase pathway, lymphocyte proliferation, NO, and TGF-beta production.

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

PubMed

Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

2018-05-12

The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; p< 0.001; random effects: RR=1.90, 95%CI, 0.66-5.44; p=0.233) can significantly increase the risk of lymphoma. Exposition of anti-tumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

Anti-inflammatory activity of D-002: an active product isolated from beeswax.

PubMed

Carbajal, D; Molina, V; Valdés, S; Arruzazabala, M L; Más, R; Magraner, J

1998-10-01

D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.

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.

Pulmonary anti-inflammatory effects and spasmolytic properties of Costa Rican noni juice (Morinda citrifolia L.).

PubMed

Dussossoy, Emilie; Bichon, Florence; Bony, Emilie; Portet, Karine; Brat, Pierre; Vaillant, Fabrice; Michel, Alain; Poucheret, Patrick

2016-11-04

Morinda citrifolia L. (Noni) is a medicinal plant used in Polynesia for many properties such as anti-inflammatory, anti-diabetic and antineoplastic effects. Recent studies showed that noni juice have anti-oxidant and acute anti-inflammatory activities likely due to polyphenols, iridoids and vitamin C content. The present study was undertaken to evaluate chronic anti-inflammatory and spasmolytic effects of noni juice. Therefore, we evaluated the effect of oral or intraperitoneal administrations of noni juice in vivo on the lung inflammation in ovalbumin (OVA) sensitized Brown Norway rat (with prednisolone 10mg/kg intraperitoneously as reference compound) and the ex vivo effect of noni juice on BaCl 2 (calcium signal) or methacholine (cholinergic signal) induced spasms in jejunum segments. We found that noni juice (intraperitoneously 2.17mL/kg and orally 4.55mL/kg) reduced the inflammation in OVA-sensitized Brown Norway rat with regard to the decreased number of inflammatory cells in lung (macrophages minus 20-26%, lymphocytes minus 58-34%, eosinophils minus 53-30%, neutrophils minus 70-28% respectively). Noni juice demonstrated a dose-dependent NO scavenging effect up to 8.1nmol of nitrites for 50µL of noni juice. In addition noni juice inhibited (up to 90%) calcium and cholinergic induced spasms on the jejunum segments model with a rightward shift of the concentration response curve. We describe for the first time that noni juice demonstrate (1) a chronic anti-inflammatory activity on sensitized lungs along with (2) a spasmolytic effect integrating a calcium channel blocker activity component. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Polysaccharides derived from Ganoderma lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury via induction of GM-CSF from macrophages.

PubMed

Nagai, Kenta; Ueno, Yoshitaka; Tanaka, Shinji; Hayashi, Ryohei; Shinagawa, Kei; Chayama, Kazuaki

2017-10-01

Non-steroidal anti-inflammatory drugs often cause ulcers in the human small intestine, but few effective agents exist to treat such injury. Ganoderma lucidum Karst, also known as "Reishi" or "Lingzhi", is a mushroom. We previously reported that a water-soluble extract from G. lucidum fungus mycelia (MAK) has anti-inflammatory effects in murine colitis induced by trinitrobenzene sulfonic acid, and induction of granulocyte macrophage colony-stimulating factor (GM-CSF) by MAK may provide anti-inflammatory effects. However, its effects on indomethacin-induced small intestinal injuries are unknown. The present study investigated the preventative effects of MAK via immunological function and the polysaccharides from MAK on indomethacin-induced ileitis in mice. Peritoneal macrophages (PMs) were stimulated in vitro with MAK and adoptively transferred to C57BL/6 mice intraperitoneally, which were then given indomethacin. Intestinal inflammation was evaluated after 24h. We performed in vivo antibody blockade to investigate the preventive role of GM-CSF, which derived from PMs stimulated with MAK. We then used PMs stimulated with MAK pre-treated by pectinase in an adoptive transfer assay to determine the preventive role of polysaccharides. Indomethacin-induced small intestinal injury was inhibited by adoptive transfer of PMs stimulated in vitro with MAK. In this transfer model, pre-treatment with anti-GM-CSF antibody but not with control antibody reversed the improvement of small intestinal inflammation by indomethacin. Pectinase pretreatment impaired the anti-inflammatory effect of MAK. PMs stimulated by MAK appear to contribute to the anti-inflammatory response through GM-CSF in small intestinal injury induced by indomethacin. The polysaccharides may be the components that elicit the anti-inflammatory effect. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

PubMed

Wu, Ping; Liang, Qin; Feng, Pei; Li, Chunyan; Yang, Chunguang; Liang, Hongsuo; Tang, Huaibo; Shuai, Cijun

2017-04-03

The seeds of Strychnos nux -vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnos nux - vomica . Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.

Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.

PubMed

Yang, Lichao; Guo, Han; Li, Ying; Meng, Xianglan; Yan, Lu; Dan Zhang; Wu, Sangang; Zhou, Hao; Peng, Lu; Xie, Qiang; Jin, Xin

2016-10-10

The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.

Red Pepper (Capsicum baccatum) Extracts Present Anti-Inflammatory Effects In Vivo and Inhibit the Production of TNF-α and NO In Vitro.

PubMed

Allemand, Alexandra; Leonardi, Bianca Franco; Zimmer, Aline Rigon; Moreno, Susana; Romão, Pedro Roosevelt Torres; Gosmann, Grace

2016-08-01

Capsicum baccatum is the most consumed red pepper species in Brazil. Our previous studies demonstrated the anti-inflammatory properties of its crude extract, whose activity is yet to be fully characterized. Herein, we examined the anti-inflammatory in vivo effects of enriched extracts obtained through bioguided fractionation as dichloromethane (DCM), butanol (BUT), and residual aqueous (RAq) extracts and its influence on inflammatory mediators produced by macrophages in vitro. We demonstrated that all C. baccatum extracts presented anti-inflammatory activity in vivo. In addition, we showed that BUT and RAq were more effective in inhibiting the neutrophil migration induced by carrageenan (Cg) to peritoneal cavity and both extracts inhibited paw edema induced by Cg, prostaglandin E2, and histamine in mice. Furthermore, the pretreatment with C. baccatum extracts significantly reduced the levels of myeloperoxidase (MPO) in the paw tissues of mice compared with the carrageenan group. Once again, RAq and BUT caused the greatest reduction in MPO levels. Moreover, it was demonstrated for the first time that C. baccatum inhibited the nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide/interferon gamma (IFN-γ)-stimulated macrophages. These anti-inflammatory effects seem to be at least, in part, independent of capsaicin. Hence, red pepper has bioactive compounds and might be used to develop food-derived extracts to treat related inflammatory diseases.

Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities.

PubMed

Thitimuta, Surached; Pithayanukul, Pimolpan; Nithitanakool, Saruth; Bavovada, Rapepol; Leanpolchareanchai, Jiraporn; Saparpakorn, Patchreenart

2017-03-04

The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE) ( Camellia sinensis L.). The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl₄-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA) oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE's principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl₄-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl₄ intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins.

Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect.

PubMed

Drori, Ariel; Shabat, Yehudit; Ben Ya'acov, Ami; Danay, Ofer; Levanon, Dan; Zolotarov, Lidya; Ilan, Yaron

2016-04-01

Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis.

Chondroprotective and anti-inflammatory role of melanocortin peptides in TNF-α activated human C-20/A4 chondrocytes

PubMed Central

Kaneva, Magdalena K; Kerrigan, Mark JP; Grieco, Paolo; Curley, G Paul; Locke, Ian C; Getting, Stephen J

2012-01-01

BACKGROUND AND PURPOSE Melanocortin MC1 and MC3 receptors, mediate the anti-inflammatory effects of melanocortin peptides. Targeting these receptors could therefore lead to development of novel anti-inflammatory therapeutic agents. We investigated the expression of MC1 and MC3 receptors on chondrocytes and the role of α-melanocyte-stimulating hormone (α-MSH) and the selective MC3 receptor agonist, [DTRP8]-γ-MSH, in modulating production of inflammatory cytokines, tissue-destructive proteins and induction of apoptotic pathway(s) in the human chondrocytic C-20/A4 cells. EXPERIMENTAL APPROACH Effects of α-MSH, [DTRP8]-γ-MSH alone or in the presence of the MC3/4 receptor antagonist, SHU9119, on TNF-α induced release of pro-inflammatory cytokines, MMPs, apoptotic pathway(s) and cell death in C-20/A4 chondrocytes were investigated, along with their effect on the release of the anti-inflammatory cytokine IL-10. KEY RESULTS C-20/A4 chondrocytes expressed functionally active MC1,3 receptors. α-MSH and [DTRP8]-γ-MSH treatment, for 30 min before TNF-α stimulation, provided a time-and-bell-shaped concentration-dependent decrease in pro-inflammatory cytokines (IL-1β, IL-6 and IL-8) release and increased release of the chondroprotective and anti-inflammatory cytokine, IL-10, whilst decreasing expression of MMP1, MMP3, MMP13 genes.α-MSH and [DTRP8]-γ-MSH treatment also inhibited TNF-α-induced caspase-3/7 activation and chondrocyte death. The effects of [DTRP8]-γ-MSH, but not α-MSH, were abolished by the MC3/4 receptor antagonist, SHU9119. CONCLUSION AND IMPLICATIONS Activation of MC1/MC3 receptors in C-20/A4 chondrocytes down-regulated production of pro-inflammatory cytokines and cartilage-destroying proteinases, inhibited initiation of apoptotic pathways and promoted release of chondroprotective and anti-inflammatory cytokines. Developing small molecule agonists to MC1/MC3 receptors could be a viable approach for developing chondroprotective and anti-inflammatory therapies in rheumatoid and osteoarthritis. PMID:22471953

Anti-inflammatory effects, nuclear magnetic resonance identification, and high-performance liquid chromatography isolation of the total flavonoids from Artemisia frigida.

PubMed

Wang, Qinghu; Jin, Jinmei; Dai, Nayintai; Han, Narenchaoketu; Han, Jingjing; Bao, Baiyinmuqier

2016-04-01

The aerial parts of Artemisia frigida Willd. are used to treat joint swelling, renal heat, abnormal menstruation, and sore carbuncle. The anti-inflammatory effects of A. frigida have been well-known in folk medicine, suggesting that components extracted from A. frigida could potentially treat inflammatory disease. With the aim of discovering bioactive compounds, in this study, we extracted total flavonoids from the aerial parts of A. frigida and investigated their anti-inflammatory effects against inflammation induced by carrageenan and egg albumin in rats. At the doses studied, total flavonoids (100 mg/kg, 200 mg/kg, and 400 mg/kg) and some isolated compounds (30 mg/kg) showed significant and dose-dependent anti-inflammatory effects. According to the high-performance liquid chromatography analysis of the total flavonoids from A. frigida, there are five major compounds, namely, 5-hydroxy-3',4'-dimethoxy-7-O-β-d-glucuronide (F1), 5-hydroxy-3',4',5'-trimethoxy-7-O-β-d-glucuronide (F2), 5,7,3'-trihydroxy-6,4'-dimethoxyflavone (F3), 5,3'-dihydroxy-6,7,4'-trimethoxyflavone (F4), and 5,3'-dihydroxy-3,6,7,4'-tetramethoxyflavone (F5), which may explain the anti-inflammatory activity. Copyright © 2016. Published by Elsevier B.V.

In vitro anti-proliferative and anti-inflammatory activity of leaf and fruit extracts from Vaccinium bracteatum Thunb.

PubMed

Landa, Premysl; Skalova, Lenka; Bousova, Iva; Kutil, Zsofia; Langhansova, Lenka; Lou, Ji-Dong; Vanek, Tomas

2014-01-01

The aim of this study was to evaluate in vitro anti-proliferative (tested on MCF-7, MDA-MB-231, and MCF-10A cell lines) and anti-inflammatory (evaluated as inhibition of prostaglandin E2 synthesis catalyzed by cyclooxygenase-2) effect of various extracts from Vaccinium bracteatum leaves and fruits. The highest anti-proliferative effect possessed leaf dichloromethane extract with IC50 values ranging from 93 to 198 μg/mL. In the case of cyclooxygenase-2 inhibition, n-hexane, dichloromethane, and ethanol fruit extracts showed the best activity with IC50 values = 2.0, 5.4, and 12.7 μg/mL, respectively. These results indicate that V. bracteatum leaves and fruits could be useful source of anti-cancer and anti-inflammatory compounds.

Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan-Induced Hind Paw Swelling

PubMed Central

Kim, Jaeyong; Kim, Heesook; Choi, Hakjoon; Jo, Ara; Kang, Huwon; Yun, Hyojeong; Im, Sojeong; Choi, Chulyung

2018-01-01

The fruit of Stauntonia hexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E2 in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation. PMID:29361789

Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan-Induced Hind Paw Swelling.

PubMed

Kim, Jaeyong; Kim, Heesook; Choi, Hakjoon; Jo, Ara; Kang, Huwon; Yun, Hyojeong; Im, Sojeong; Choi, Chulyung

2018-01-22

The fruit of Stauntonia hexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E₂ in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation.

Anti-inflammatory and anti-allergic effect of Agaricus blazei extract in bone marrow-derived mast cells.

PubMed

Song, Hyuk-Hwan; Chae, Hee-Sung; Oh, Sei-Ryang; Lee, Hyeong-Kyu; Chin, Young-Won

2012-01-01

In this study, the anti-inflammatory and anti-allergic effects of the chloroform-soluble extract of Agaricus blazei in mouse bone marrow-derived mast cells (BMMCs) were investigated. The chloroform-soluble extract inhibited IL-6 production in PMA plus A23187-stimulated BMMCs, and down-regulated the phosphorylation of Akt. In addition, this extract demonstrated inhibition of the degranulation of β-hexosaminidase and the production of IL-6, prostaglandin D(2) and leukotriene C(4) in PMA plus A23187-induced BMMCs. In conclusion, the chloroform-soluble extract of Agaricus blazei exerted anti-inflammatory and anti-allergic activities mediated by influencing IL-6, prostaglandin D(2), leukotriene C(4), and the phosphorylation of Akt.

The Synthetic Melanocortin (CKPV)2 Exerts Anti-Fungal and Anti-Inflammatory Effects against Candida albicans Vaginitis via Inducing Macrophage M2 Polarization

PubMed Central

Jia, Zhi-rong; Li, Xian-jing; Wang, Zhuo; Li, Li; Li, Yong-wen; Liu, Gen-yan; Tong, Ming-Qing; Li, Xiao-yi; Zhang, Guo-hui; Dai, Xiang-rong; He, Ling; Li, Zhi-yu; Cao, Cong; Yang, Yong

2013-01-01

In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation. PMID:23457491

Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study.

PubMed

Pérez, David J; Díaz-Reval, M Irene; Obledo-Benicio, Fernando; Zakai, Uzma I; Gómez-Sandoval, Zeferino; Razo-Hernández, Rodrigo Said; West, Robert; Sumaya-Martínez, María Teresa; Pineda-Urbina, Kayim; Ramos-Organillo, Ángel

2017-11-05

There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS • + ) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH• and ABTS • + . On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b achieved significant inflammation inhibition at a lower effective dose 50 (ED 50 ) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant and anti-inflammatory activities of the phenolic extracts of Sapium sebiferum (L.) Roxb. leaves.

PubMed

Fu, Rao; Zhang, Yu-Ting; Guo, Yi-Ran; Huang, Qiu-Lan; Peng, Tong; Xu, Ying; Tang, Lin; Chen, Fang

2013-05-20

The leaves of Sapium sebiferum have long been used in Traditional Chinese Medicine (TCM) for the treatment of eczema, shingles, edema, swelling, ascites, scabs, and snakebites, among other maladies. The present study aimed to investigate the antioxidant and anti-inflammatory effects of the phenolic extracts of Sapium sebiferum leaves using in vitro and in vivo models. The in vitro antioxidant activities of the extracts were measured using common chemical methods (total phenolic content; total flavonoid content; scavenging of DPPH·, ABTS+·, superoxide, and nitrite radicals; reducing power; β-carotene bleaching; and FTC assays). The in vivo topical anti-inflammatory activities were tested using the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis animal model. The SOD and CAT activities and the GSH content of ear tissue were also determined using test kits. The extracts of Sapium sebiferum leaves exhibited strong in vitro antioxidant activities. They also showed significant (P<0.001) and dose-dependent anti-inflammatory activities in an acute dermatitis model at the doses of 0.03 mg/ear, 0.1mg/ear, and 0.3mg/ear. The application of Sapium sebiferum leaf extracts increased the SOD and CAT activities and the GSH content relative to those of the TPA treatment group. The anti-inflammatory effect of the Sapium sebiferum leaf extract was positively correlated with its antioxidant activity. These results demonstrate that Sapium sebiferum leaf extract is an effective anti-inflammatory agent in the TPA-induced dermatitis model, and its anti-inflammatory effect is related, at least in part, to its antioxidant activity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A shift toward T helper 2 responses and an increase in modulators of innate immunity in depressed patients treated with escitalopram.

PubMed

Ho, Pei-Shen; Yeh, Yi-Wei; Huang, San-Yuan; Liang, Chih-Sung

2015-03-01

Depression is hypothesized to involve inflammatory processes, and identifying the key cytokines targeted by antidepressant drugs is critical for tailoring treatment to specific cases. However, investigating a limited number of cytokines at one time cannot provide a broad picture of antidepressant-associated immunomodulation. Cytokines act in a network where one could demonstrate pleiotropism, redundancy, synergy, and antagonism with other cytokine functions. This study was aimed at determining whether escitalopram functions as an anti-inflammatory agent and, if so, how it influences cytokine networks. A total of 24 healthy controls and 26 patients with clinical depression requiring inpatient treatment were recruited. A multiplex assay, an efficient tool to simultaneously measure 27 cytokines, was applied in patients with depression before and after 4-week escitalopram treatment. Healthy controls did not take escitalopram and completed cytokine analyses once. We demonstrated that escitalopram increased the levels of interleukin (IL)-1 receptor antagonist and IL-2. Moreover, escitalopram contributed to a shift toward T helper 2 responses and an increase in modulators of innate immunity, leading to a decrease of immune system activation, both innate and adaptive. We suggest that escitalopram modulates the balance of IL-1 and IL-1 receptor antagonist and improves the function and number of T regulatory cells. However, diverse conclusions could be drawn if only a few cytokines were assessed or different significance levels were used. Further studies should investigate a wide range of cytokines in a reliable and valid way, which is key to disentangling the effects of different antidepressants on inflammatory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages.

PubMed

Wang, Ji; Kang, Yu-Xia; Pan, Wen; Lei, Wan; Feng, Bin; Wang, Xiao-Juan

2016-06-20

Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%-8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders.

PubMed

Johnson, Tyler A; Sohn, Johann; Inman, Wayne D; Bjeldanes, Leonard F; Rayburn, Keith

2013-01-15

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects greater than or equal to 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures (water, methanol, ethanol) in clinical evaluations for the treatment of inflammatory disorders especially arthritis. A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. Published by Elsevier GmbH.

Anti-inflammatory effect of water extracts of Graptopetalum paraguayense supplementation in subjects with metabolic syndrome: a preliminary study.

PubMed

Chen, Shu-Ju; Yen, Chi-Hua; Liu, Jen-Tzu; Tseng, Yu-Fen; Lin, Ping-Ting

2016-03-30

Many studies have demonstrated that Graptopetalum paraguayense has good antioxidant ability; however, few studies have examined its anti-inflammatory effect. The study aimed to investigate the anti-inflammatory effects of water extracts of G. paraguayense (WGP, 4 g day(-1)) in subjects with metabolic syndrome (MS). Intervention was administered for 12 weeks. Levels of inflammatory markers [high sensitivity C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6)] and antioxidant enzymes activities were measured. Forty-two subjects completed the 12 week intervention study (placebo, n = 19; WGP, n = 23). After 12 weeks supplementation, subjects in WGP group had significantly lower levels of inflammatory markers than the baseline (P < 0.05) and the placebo group (CRP, P = 0.07; TNF-α, P = 0.04; IL-6, P = 0.03). The changes in levels of the inflammatory markers were significantly decreased in WGP group (CRP, P = 0.04; TNF-α, P = 0.06; IL-6, P = 0.01) compared to the placebo group. Levels of inflammatory markers were significantly negatively correlated with the antioxidant enzymes activities after supplementation. This study demonstrated a significant reduction in inflammatory status in MS after WGP supplementation. WGP may exert an anti-inflammatory effect on MS in addition to its antioxidant ability. © 2015 Society of Chemical Industry.

Progress with anti-tumor necrosis factor therapeutics for the treatment of inflammatory bowel disease.

PubMed

Fernandes, Carlos; Allocca, Mariangela; Danese, Silvio; Fiorino, Gionata

2015-01-01

Anti-tumor necrosis factor (TNF) therapy is a valid, effective and increasingly used option in inflammatory bowel disease management. Nevertheless, further knowledge and therapeutic indications regarding these drugs are still evolving. Anti-TNF therapy may be essential to achieve recently proposed end points, namely mucosal healing, prevention of bowel damage and prevention of patient's disability. Anti-TNF drugs are also suggested to be more effective in early disease, particularly in early Crohn's disease. Moreover, its efficacy for prevention of postoperative recurrence in Crohn's disease is still debated. Costs and adverse effects, the relevance of drug monitoring and the possibility of anti-TNF therapy withdrawal in selected patients are still debated issues. This review aimed to describe and discuss the most relevant data about the progress with anti-TNF therapy for the management of inflammatory bowel disease.

Antibacterial, anti-inflammatory and anti-oxidatant activities of various isolated compounds from Cratoxylum species.

PubMed

Rodanant, Pirasut; Boonnak, Nawong; Surarit, Rudee; Kuvatanasuchati, Jintakorn; Lertsooksawat, Wannee

2017-05-01

The objective of this study was to investigate the bioactivity of twenty-nine known isolated compounds from Cratoxylum species including three anthraquinones, four triterpenes, and twenty-two xanthones. All isolated compounds were subjected to antibacterial, anti-inflammatory and anti-oxidant activities. Cytotoxicity evaluations were performed by MTT assay. The anti-oxidatant activity was performed using DPPH assay. The anti-inflammatory activity was evaluated from the production of cytokines TNF-α and IL1-β using ELISA assay. Human gingival fibroblasts and monocytes could tolerate both anthraquinones and triterpenes. All isolated anthraquinones showed moderate-to-high antibacterial efficacy while compound A3 also demonstrated moderate anti-inflammatory effect. None of the isolated triterpenes, except for T1, inhibited the expression of TNF-α. A number of isolated xanthones was toxic to HGFs and monocytes. Compound X5, X14 and a 1:1 mixture of X5 and X6 showed comparative anti-inflammatory activity to dexamethasone. Several triterpene and xanthone compounds also expressed antibacterial effect against P. gingivalis. Some isolated xanthones exerted anti-oxidant activity comparable to ascorbic acid. Accordingly, selected pure compounds from plants of Cratoxylum genus might be of benefit in developing medications that are important in treating periodontal diseases.

Membrane stabilization activity as anti-inflammatory mechanisms of Vernonia amygdalina leaves extracts

NASA Astrophysics Data System (ADS)

Nuryanto, MK; Paramita, S.; Iskandar, A.

2018-04-01

Inflammation is a normal process in the human body as a response to injury from healing process. Meanwhile, chronic inflammation will cause new health problems to patients. Anti-inflammatory agents generally used for those conditions, have several side effects to patients. The aim of this research was to find alternative anti-inflammatory agents, especially from natural sources. Vernonia amygdalina knew locally as “daun afrika” belong to family Apiaceae is one of those potential natural sources for alternative anti-inflammatory agents. This plant is known astraditionalmedicine from East Kalimantanfor health problems caused by the muscle stiffness and used as material in this research. The experimental method of anti-inflammatory measurement using membrane stabilization activity for V. amygdalina leaves extracts. The results showed that significant differences of EC50(p<0.05)achieved between indomethacin as the positive control (26.39 ± 2.91 µg/mL) with V. amygdalina leaves extracts for concentration 1% (131.81 ± 2.95 µg/mL) and 10% (62.54 ± 2.05 µg/mL). EC50 of V.amygdalina leaves extracts showed the potential anti-inflammatory activities. It could be concluded that V. amygdalina leaves extracts to have anti-inflammatory activities, which could be further developed as a new natural source of the anti-inflammatory agents.

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

PubMed Central

Kim, Mi Eun; Jung, Inae; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

2017-01-01

The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics. PMID:29104209

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo.

PubMed

Kim, Mi Eun; Jung, Inae; Lee, Jong Suk; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

2017-11-01

The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos , cox-2 , il-1β , tnf-α , and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review

PubMed Central

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-01-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted. PMID:26929767

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review.

PubMed

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-10-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted.

Effect of Anti-TNF Agents on Postoperative Outcomes in Inflammatory Bowel Disease Patients: a Single Institution Experience.

PubMed

Shwaartz, Chaya; Fields, Adam C; Sobrero, Maximiliano; Cohen, Brian D; Divino, Celia M

2016-09-01

Anti-tumor necrosis factor (TNF) agents have been an integral part in the treatment of inflammatory bowel disease. However, a subset of inflammatory bowel disease patients ultimately requires surgery and up to 30 % of them have undergone treatment with anti-TNF agents. Studies assessing the effect of anti-TNF agents on postoperative outcomes have been inconsistent. The aim of this study is to assess postoperative morbidity in inflammatory bowel disease patients who underwent surgery with anti-TNF therapy prior to surgery. This is a retrospective review of 282 patients with inflammatory bowel disease undergoing intestinal surgery between 2013 and 2015 at the Mount Sinai Hospital. Patients were divided into two groups based on treatment with anti-TNF agents (infliximab, adalimumab, certolizumab) within 8 weeks of surgery. Thirty-day postoperative outcomes were recorded. Univariate and multivariate statistical analyses were carried out. Seventy-three patients were treated with anti-TNF therapy within 8 weeks of surgery while 209 patients did not have exposure. Thirty-day anastomotic leak, intra-abdominal abscess, wound infection, extra-abdominal infection, readmission, and mortality rates were not significantly different between the two groups. The use of anti-TNF medications in inflammatory bowel disease patients within 2 months of intestinal surgery is not associated with an increased risk of 30-day postoperative complications.

Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention.

PubMed

Fajardo, Alexandra M; Piazza, Gary A

2015-07-15

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. Copyright © 2015 the American Physiological Society.

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

Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin.

PubMed

Tawara, Shunsuke; Sakai, Takumi; Matsuzaki, Osamu

2016-11-01

Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro. CPB2 activity and tissue factor-induced thrombin generation was examined by a chromogenic assay. C5a inactivation was evaluated by C-terminal cleavage of C5a and inhibition of C5a-induced human neutrophil migration. Clot lysis time prolongation was examined by a tissue-type plasminogen activator-induced clot lysis assay. CPB2 activity in human plasma was increased by TM alfa and thrombin in a concentration-dependent manner. TM alfa inhibited tissue factor-induced thrombin generation and enhanced pro-CPB2 activation in human plasma simultaneously. The mass spectrum of C5a treated with TM alfa, thrombin, and pro-CPB2 was decreased at 156m/z, indicating that TM alfa enhanced the processing of C5a to C-terminal-cleaved C5a, an inactive form of C5a. C5a-induced human neutrophil migration was decreased after C5a treatment with TM alfa, thrombin, and pro-CPB2. TM alfa prolonged the clot lysis time in human plasma, and this effect was completely abolished by addition of a CPB2 inhibitor. TM alfa exerts anti-inflammatory and anti-fibrinolytic effects through CPB2 in the presence of thrombin in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antinociceptive, anti-inflammatory and toxicological evaluation of semi-synthetic molecules obtained from a benzyl-isothiocyanate isolated from Moringa oleifera Lam. in a temporomandibular joint inflammatory hypernociception model in rats.

PubMed

Dos Santos, Alain Oliveira; do Val, Danielle Rocha; da Silveira, Felipe Dantas; Gomes, Francisco Isaac Fernandes; Freitas, Hermany Capistrano; de Assis, Ellen Lima; de Almeida, Diana Kelly Castro; da Silva, Igor Iuco Castro; Barbosa, Francisco Geraldo; Mafezoli, Jair; da Silva, Marcos Reinaldo; de Castro Brito, Gerly Anne; Clemente-Napimoga, Juliana Trindade; de Paulo Teixera Pinto, Vicente de Paulo Teixeira; Filho, Gerardo Cristino; Bezerra, Mirna Marques; Chaves, Hellíada Vasconcelos

2018-02-01

Inflammation is a key component of many clinical conditions that affect the temporomandibular joint (TMJ) and Moringa oleifera Lam. has been used to treat inflammatory diseases. Here, we evaluated the toxicological effects on mice of a naturally-occurring isothiocyanate from M. oleifera and its seven analogue molecules. Further, the anti-nociceptive and anti-inflammatory effects on a rat model of TMJ inflammatory hypernociception were assessed. The systemic toxicological profile was determined in mice over a 14-day period: MC-1 1 μg/kg; MC-D1 1 μg/kg, MC-D3 100 μg/kg, MC-D6 1 μg/kg, MC-D7 1 μg/kg, MC-D8 1 μg/kg, MC-D9 10 μg/kg, and MC-H 1 μg/kg. The safest molecules were assayed for anti-nociceptive efficacy in the formalin (1.5%, 50 μL) and serotonin (255 mg) induced TMJ inflammatory hypernociception tests. The anti-inflammatory effect was evaluated through the vascular permeability assay using Evans blue. Further, the rota-rod test evaluated any motor impairment. Among the tested molecules, MC-D7, MC-D9, and MC-H were not toxic at the survival rate test, biochemical, and hystological analysis. They reduced the formalin-induced TMJ inflammatory hypernociception, but only MC-H decreased the serotonin-induced TMJ inflammation, suggesting an adrenergic receptor-dependent effect. They diminished the plasmatic extravasation, showing anti-inflammatory activity. At the rota-rod test, no difference was observed in comparison with control groups, reinforcing the hypothesis of anti-nociceptive effetc without motor impairment in animals. The analogues MC-D7, MC-D9, and MC-H were safe at the tested doses and efficient in reducing the formalin-induced TMJ hypernociception in rats. Our next steps include determining their mechanisms of anti-nociceptive action. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Interactome of the Glucocorticoid Receptor and Its Influence on the Actions of Glucocorticoids in Combatting Inflammatory and Infectious Diseases

PubMed Central

Petta, Ioanna; Dejager, Lien; Ballegeer, Marlies; Lievens, Sam; Tavernier, Jan; Libert, Claude

2016-01-01

SUMMARY Glucocorticoids (GCs) have been widely used for decades as a first-line treatment for inflammatory and autoimmune diseases. However, their use is often hampered by the onset of adverse effects or resistance. GCs mediate their effects via binding to glucocorticoid receptor (GR), a transcription factor belonging to the family of nuclear receptors. An important aspect of GR's actions, including its anti-inflammatory capacity, involves its interactions with various proteins, such as transcription factors, cofactors, and modifying enzymes, which codetermine receptor functionality. In this review, we provide a state-of-the-art overview of the protein-protein interactions (PPIs) of GR that positively or negatively affect its anti-inflammatory properties, along with mechanistic insights, if known. Emphasis is placed on the interactions that affect its anti-inflammatory effects in the presence of inflammatory and microbial diseases. PMID:27169854

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors.

PubMed

Xiao, L; Ding, M; Fernandez, A; Zhao, P; Jin, L; Li, X

2017-05-09

Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (μCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe clinical treatment of radiculopathy.

CURCUMIN ALLEVIATES LUMBAR RADICULOPATHY BY REDUCING NEUROINFLAMMATION, OXIDATIVE STRESS AND NOCICEPTIVE FACTORS

PubMed Central

Xiao, L.; Ding, M.; Fernandez, A.; Zhao, P.; Jin, L.; Li, X.

2017-01-01

Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (µCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe clinical treatment of radiculopathy. PMID:28485773

The effects of central pro-and anti-inflammatory immune challenges on depressive-like behavior induced by chronic forced swim stress in rats.

PubMed

Pan, Yuqin; Lin, Wenjuan; Wang, Weiwen; Qi, Xiaoli; Wang, Donglin; Tang, Mingming

2013-06-15

Although increasing evidence demonstrates that both chronic stressors and inflammatory immune activation contribute to pathophysiology and behavioral alterations associated with major depression, little is known about the interaction effect of central inflammatory immune activation and stress on depressive-like behavior. Our previous work has shown that 14-day chronic forced swim stress induces significant depressive-like behavior. The present investigation assessed whether pro-inflammatory cytokine and anti-inflammatory cytokine challenges have differential interaction effect on depressive-like behavior induced by chronic forced swim stress in rats. The pro-inflammatory and anti-inflammatory immune challenges were achieved respectively by central administration of lipopolysaccharide (LPS), a pro-inflammatory cytokine inducer, and interleukin-10 (IL-10), an anti-inflammatory cytokine. It was found that either central LPS treatment alone or chronic forced swim stress alone significantly induced depressive-like behavior, including reduced body weight gain, reduced saccharin preference and reduced locomotor activity. However, there was no significant synergistic or additive effect of central LPS treatment and stress on depressive-like behavior. LPS treatment did not exacerbate the depressive-like behavior induced by forced swim stress. Nevertheless, IL-10 reversed depressive-like behavior induced by forced swim stress, a finding indicating that IL-10 has antidepressant effect on behavioral depression induced by stress. The present findings provide new insight into the complexity of the immunity-inflammation hypothesis of depression. Copyright © 2013 Elsevier B.V. All rights reserved.

G-protein coupled receptor 30 (GPR30): a novel regulator of endothelial inflammation.

PubMed

Chakrabarti, Subhadeep; Davidge, Sandra T

2012-01-01

Estrogen, the female sex hormone, is known to exert anti-inflammatory and anti-atherogenic effects. Traditionally, estrogen effects were believed to be largely mediated through the classical estrogen receptors (ERs). However, there is increasing evidence that G-protein coupled receptor 30 (GPR30), a novel estrogen receptor, can mediate many estrogenic effects on the vasculature. Despite this, the localization and functional significance of GPR30 in the human vascular endothelium remains poorly understood. Given this background, we examined the subcellular location and potential anti-inflammatory roles of GPR30 using human umbilical vein endothelial cells as a model system. Inflammatory changes were induced by treatment with tumor necrosis factor (TNF), a pro-inflammatory cytokine involved in atherogenesis and many other inflammatory conditions. We found that GPR30 was located predominantly in the endothelial cell nuclei. Treatment with the selective GPR30 agonist G-1 partially attenuated the TNF induced upregulation of pro-inflammatory proteins such as intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This effect was completely abolished by the selective GPR30 antagonist G-15, suggesting that it was indeed mediated in a GPR30 dependent manner. Interestingly, estrogen alone had no effects on TNF-treated endothelium. Concomitant activation of the classical ERs blocked the anti-inflammatory effects of G-1, indicating opposing effects of GPR30 and the classical ERs. Our findings demonstrate that endothelial GPR30 is a novel regulator of the inflammatory response which could be a potential therapeutic target against atherosclerosis and other inflammatory diseases.

Evaluation of anti-inflammatory and analgesic activity of a novel rigid 3, 4-dihydroxy chalcone in mice.

PubMed

Heidari, M R; Foroumadi, A; Amirabadi, A; Samzadeh-Kermani, A; Azimzadeh, B S; Eskandarizadeh, A

2009-08-01

There have been many reports indicating the analgesic and anti-inflammatory effects of 3,4-dihydroxychalcones. We have designed and synthesized a rigid 3,4-dihydroxychalcone (RDHC) as a possible drug effecting inflammation and nociception. The analgesic and anti-inflammatory effects were evaluated by formalin and hot-plate tests, respectively. The results showed that RDHC induced significant antinociceptive and anti-inflammatory effects (P < 0.01). Maximum analgesia (63.7%) was observed at 37.5 mg/kg in the first phase of the formalin test. The effect of RDHC was higher in the chronic phase (inflammation phase) of the formalin test (86.4%, P < 0.01). In addition, a significant analgesia (maximum possible effect; MPE = 30.1%) was observed in the hot plate test 45 min after injection of 37.5 mg/kg RDHC (P < 0.01). As a result of our findings, this new RDHC could be suggested for further pharmacological studies.

Anti-inflammatory and anti-hyperlipidemic effect of Semecarpus anacardium in a high fat diet: STZ-induced type 2 diabetic rat model.

PubMed

Khan, Haseena Banu Hedayathullah; Vinayagam, Kaladevi Siddhi; Moorthy, Balaji T; Palanivelu, Shanthi; Panchanatham, Sachdanandam

2013-02-01

Semecarpus anacardium, known as marking nut, has been used in indigenous system of medicine against various ailments. To evaluate the antilipidemic and anti-inflammatory effect of S. anacardium Linn. nut milk extract (SA) in Type 2 diabetic rats. Diabetes was induced in rats by feeding them with a high fat diet followed by i.p. of 35 mg/kg body weight of streptozotocin. Diabetic rats were treated with the drugs, SA (200 mg/kg body weight) and metformin (500 mg/kg body weight) for 30 days. Antilipidemic effect of the drug was established by studying the lipoprotein alterations and also the alterations in the lipid profile and lipid metabolizing enzymes in the experimental group of rats. The effect of the drug on the expression of PPAR γ was also studied. To determine the anti-inflammatory effect of the drug, the levels of inflammatory cytokines, TNF-α and IL-6 and also C-reactive protein were determined. Semecarpus anacardium nut milk extract at a dosage of 200 mg/kg orally significantly (p < 0.05) reduced and normalized the alterations in the lipid metabolism in diabetic rats effectively than metformin. SA treatment significantly (p < 0.05) increased the mRNA expression of PPAR γ, thereby establishing the antilipidemic effect of the drug. The increase in the levels of inflammatory cytokines were significantly (p < 0.05) brought down to near normal levels on treatment with the drug SA. The present study thereby establishes the antilipidemic and anti-inflammatory effect of the drug. Thus, by decreasing the alterations in the lipid metabolism and inflammatory status, the drug can effectively improve the insulin sensitivity in rats and can serve as an excellent drug in the treatment of Type 2 diabetes mellitus.

Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells.

PubMed

Hwang, Pai-An; Phan, Nam Nhut; Lu, Wen-Jung; Ngoc Hieu, Bui Thi; Lin, Yen-Chang

2016-01-01

The aim of this study is to investigate the anti-inflammatory effects of low-molecular-weight fucoidan (LMF) and high-stability fucoxanthin (HS-Fucox) in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B. lactis. We used various methods such as transepithelial resistance (TER) assay, cytokine secretion assay, and tight junction protein mRNA expression assay to examine LMF and HS-Fucox anti-inflammatory properties. LMF and HS-Fucox activated probiotic growth and reduced the inflammation of the intestinal epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced the intestinal epithelial barrier and immune function against the lipopolysaccharide effect by inhibiting IL-1β and TNF-α and promoting IL-10 and IFN-γ. These findings suggested that LMF and HS-Fucox, alone or in combination, could be the potential natural compounds to enhance the immune system and have an anti-inflammatory effect on the intestinal cells.

Investigation of the central and peripheral analgesic and anti-inflammatory activity of Draksharishta an Indian Ayurvedic formulation

PubMed Central

Kabir, Ashraf-ul; Samad, Mehdi Bin; D′Costa, Ninadh Malrina; Hannan, Juardar Mohammad

2012-01-01

Rationale: Draksharishta (DRK) is an Ayurvedic formulation approved by the “National formulary of Ayurvedic Medicine 2011”, of Bangladesh. It is widely available in the Bangladeshi market as an effective preparation to treat lumbago, sciatia and arthritic pain of joints. But there are very scientific evidences available to support their common uses. Objectives: Our present studies make an attempt toward identifying probable antinociceptive and anti-inflammatory effect and its mechanisms of DRK. Findings: DRK, at three doses, (10 mL/kg, 20 mL/kg, and 40 mL/kg) showed no involvement of the CNS in antinociceptive activity of the test drug. Both Carrageenan-induced paw edema and acetic acid writhing tests gave significant results (P < 0.05), indicating possible peripheral analgesic and anti-inflammatory action. Formalin-induced paw- licking test showed that DRK had significant effect in suppressing inflammatory pain (P < 0.05) but not neurogenic pain. Conclusions: Hence our study shows anti-inflammatory and peripheral analgesic action for DRK. PMID:24826047

Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii.

PubMed

Pothoulakis, C

2009-10-15

Saccharomyces boulardii, a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as inflammatory bowel disease (IBD), and bacterially mediated or enterotoxin-mediated diarrhoea and inflammation. To discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii. Review of the literature related to the anti-inflammatory effects of this probiotic. Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted-protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor kappaB, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that protects from gut inflammation and IBD. S. boulardii also suppresses 'bacteria overgrowth' and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states.

Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins.

PubMed

González-Trujano, María Eva; Pellicer, Francisco; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

2015-01-01

Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties.

Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

PubMed

Moussaieff, Arieh; Shohami, Esther; Kashman, Yoel; Fride, Ester; Schmitz, M Lienhard; Renner, Florian; Fiebich, Bernd L; Munoz, Eduardo; Ben-Neriah, Yinon; Mechoulam, Raphael

2007-12-01

Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-kappaB (NF-kappaB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-kappaB activation. It had no effect on IKK activity in vitro, and it did not suppress IkappaB alpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-kappaB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFalpha-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders

PubMed Central

SAAVEDRA, Juan M.

2012-01-01

The effects of brain AngII (angiotensin II) depend on AT1 receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT1 receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood–brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT1 receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-β neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT1 receptor blockade, but also from PPARγ (peroxisome-proliferator-activated receptor γ) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer’s disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer’s disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic brain injury. PMID:22827472

AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

PubMed

Chen, Peili; Li, Yan Chun; Toback, F Gary

2015-01-01

Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

Chlorogenic acids from Tithonia diversifolia demonstrate better anti-inflammatory effect than indomethacin and its sesquiterpene lactones.

PubMed

Chagas-Paula, Daniela Aparecida; Oliveira, Rejane Barbosa de; da Silva, Vanessa Cristina; Gobbo-Neto, Leonardo; Gasparoto, Thaís Helena; Campanelli, Ana Paula; Faccioli, Lúcia Helena; Da Costa, Fernando Batista

2011-06-22

T. diversifolia (Hemsl.) A. Gray (Asteraceae) has been used in the traditional medicine in several countries as anti-inflammatory and against other illnesses. It is important to evaluate the anti-inflammatory activity of extracts from the leaves of this species, including an infusion, to identify the main constituents of the extracts, observe their effects and correlate them with the anti-inflammatory activity. An infusion, a leaf rinse extract (LRE) and a polar extract from the rinsed leaves (PE) were obtained and analysed by HPLC-UV-DAD and infrared spectroscopy. The major compounds of these extracts were quantified. The three obtained extracts were evaluated for their anti-inflammatory activities using the paw oedema and croton oil ear oedema assays in mice. Furthermore, neutrophil migration was measured by evaluating myeloperoxidase activity. The PE consists primarily of chlorogenic acids (CAs) and lacks sesquiterpene lactones (STLs). The LRE is rich in STLs and includes a few flavonoids. The infusion is chemically similar to the PE but also contains very low amounts of STLs. The PE and LRE have better mechanisms of action than non-steroidal anti-inflammatory drugs (NSAIDs). Unlike NSAIDs, both the PE and LRE inhibit oedema and neutrophil migration. The pool of CAs from the PE of T. diversifolia has an additional mechanism of action, and its anti-inflammatory effect was greater than what is described in the literature for this class of compounds using the same evaluation models. The similar chemical compositions observed for the infusion and the PE, contrasted with the different activities observed, suggests the presence of antagonist compounds produced during the extraction procedure (infusion); the infusion did not inhibit oedema, however it inhibited neutrophil migration. It suggests that although the great majority of plants present CAs, the category of anti-inflammatory effect of their extracts depends on a suitable pool of compounds and an absence of antagonists, among other factors. CAs from T. diversifolia comprise a good pool of anti-inflammatory compounds with better activity mechanisms than NSAIDs, other active compounds from the leaf extracts (STLs and flavonoids) and CAs from other plant sources. Thus, the PE of T. diversifolia has high potential for the development of new anti-inflammatory phytomedicines. The infusion probably contains antagonists, and therefore it can be useful to treat inflammation processes where neutrophil recruitment is involved and oedema is not. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells.

PubMed

Cianciulli, Antonia; Dragone, Teresa; Calvello, Rosa; Porro, Chiara; Trotta, Teresa; Lofrumento, Dario Domenico; Panaro, Maria Antonietta

2015-02-01

The development of agents that can modulate microglial activation has been suggested as one potential strategy for the treatment or prevention of neurodegenerative diseases. Among these agents, resveratrol, with its anti-inflammatory action, has been described to have neuroprotective effects. In this paper we demonstrate that in LPS-stimulated microglia resveratrol pretreatment reduced, in a dose-dependent manner, pro-inflammatory cytokines IL-1β, TNF-α and IL-6 mRNA expression and increased the release of anti-inflammatory interleukin (IL)-10. Moreover, resveratrol pretreatment up-regulated the phosphorylated forms of JAK1 and STAT3, as well as suppressor of cytokine signaling (SOCS)3 protein expression in LPS activated cells, demonstrating that the JAK-STAT signaling pathway is involved in the anti-inflammatory effect exerted by resveratrol. By supplementing the cultures with an IL-10 neutralizing antibody (IL-10NA) we obtained the opposite effect. Taken together, these data allow us to conclude that the LPS-induced pro-inflammatory response in microglial cells can be markedly reduced by resveratrol, through IL-10 dependent up-regulation of SOCS3, requiring the JAK-STAT signaling pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Anti-angiogenesis effect of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model.

PubMed

Rastegari-Pouyani, Mohsen; Mostafaie, Ali; Mansouri, Kamran; Mortazavi-Jahromi, Seyed Shahabeddin; Mohammadi-Motlagh, Hamid-Reza; Mirshafiey, Abbas

2018-04-01

Angiogenesis is a process through which new capillaries are formed from pre-existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The β-D-mannuronic acid (M2000) is a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti-angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti-proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen-cytodex model and the chick chorioallantoic membrane (CAM) assay were then used to evaluate the anti-angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100 μg/mL) had no cytotoxic effect on human umbilical vein endothelial cells (HUVECs). It was also illustrated that M2000 had little or no anti-proliferative effect on HUVECs. In addition, the anti-angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose-dependent in the in vivo status. This study showed that M2000 could be considered as an anti-angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti-inflammatory effects may partly be attributable to its anti-angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis-related disorders. © 2017 John Wiley & Sons Australia, Ltd.

Evidence for Anti-Inflammatory Effects of Exercise in CKD

PubMed Central

Kosmadakis, George C.; Watson, Emma L.; Bevington, Alan; Feehally, John; Bishop, Nicolette C.; Smith, Alice C.

2014-01-01

CKD is associated with a complex state of immune dysfunction characterized by immune depression, predisposing patients to infections, and immune activation, resulting in inflammation that associates with higher risk of cardiovascular disease. Physical exercise may enhance immune function and exert anti-inflammatory effects, but such effects are unclear in CKD. We investigated the separate effects of acute and regular moderate-intensity aerobic exercise on neutrophil degranulation (elastase release), activation of T lymphocytes (CD69 expression) and monocytes (CD86 and HLA-DR expression), and plasma inflammatory markers (IL-6, IL-10, soluble TNF-receptors, and C-reactive protein) in patients with predialysis CKD. A single 30-minute (acute) bout of walking induced a normal pattern of leukocyte mobilization and had no effect on T-lymphocyte and monocyte activation but improved neutrophil responsiveness to a bacterial challenge in the postexercise period. Furthermore, acute exercise induced a systemic anti-inflammatory environment, evidenced by a marked increase in plasma IL-10 levels (peaked at 1 hour postexercise), that was most likely mediated by increased plasma IL-6 levels (peaked immediately postexercise). Six months of regular walking exercise (30 min/d for 5 times/wk) exerted anti-inflammatory effects (reduction in the ratio of plasma IL-6 to IL-10 levels) and a downregulation of T-lymphocyte and monocyte activation, but it had no effect on circulating immune cell numbers or neutrophil degranulation responses. Renal function, proteinuria, and BP were also unaffected. These findings provide compelling evidence that walking exercise is safe with regard to immune and inflammatory responses and has the potential to be an effective anti-inflammatory therapy in predialysis CKD. PMID:24700875

Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

PubMed Central

Galvez-Llompart, María; Zanni, Riccardo; García-Domenech, Ramón

2011-01-01

One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds. PMID:22272145

Pinosylvin and monomethylpinosylvin, constituents of an extract from the knot of Pinus sylvestris, reduce inflammatory gene expression and inflammatory responses in vivo.

PubMed

Laavola, Mirka; Nieminen, Riina; Leppänen, Tiina; Eckerman, Christer; Holmbom, Bjarne; Moilanen, Eeva

2015-04-08

Scots pine (Pinus sylvestris) is known to be rich in phenolic compounds, which may have anti-inflammatory properties. The present study investigated the anti-inflammatory effects of a knot extract from P. sylvestris and two stilbenes, pinosylvin and monomethylpinosylvin, isolated from the extract. Inflammation is characterized by increased release of pro-inflammatory and regulatory mediators including nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) pathway. The knot extract (EC50 values of 3 and 3 μg/mL) as well as two of its constituents, pinosylvin (EC50 values of 13 and 15 μM) and monomethylpinosylvin (EC50 values of 8 and 12 μM), reduced NO production and iNOS expression in activated macrophages. They also inhibited the production of inflammatory cytokines IL-6 and MCP-1. More importantly, pinosylvin and monomethylpinosylvin exerted a clear anti-inflammatory effect (80% inhibition at the dose of 100 mg/kg) in the standard in vivo model, carrageenan-induced paw inflammation in the mouse, with the effect being comparable to that of a known iNOS inhibitor L-NIL. The results reveal that the Scots pine stilbenes pinosylvin and monomethylpinosylvin are potential anti-inflammatory compounds.

Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models.

PubMed

Hu, Fuliang; Hepburn, H R; Li, Yinghua; Chen, M; Radloff, S E; Daya, S

2005-09-14

The anti-inflammatory effects of ethanol (EEP) and water (WSD) extracts in ICR mice and Wistar rats were analyzed. Both WSD and EEP exhibited significant anti-inflammatory effects in animal models with respect to thoracic capillary vessel leakage in mice, carrageenan-induced oedema, carrageenan-induced pleurisy, acute lung damage in rats. The mechanisms for the anti-inflammatory effects probably involve decreasing prostaglandin-E(2) (PGE(2)) and nitric oxide (NO) levels. In rats with Freund's complete adjuvant (FCA) induced arthritis, propolis extracts significantly inhibited the increase of interleukin-6 (IL-6) in inflamed tissues, but had no significant effect on levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). The results are consistent with the interpretation that EEP and WSD may exert these effects by inhibiting the activation and differentiation of mononuclear macrophages.

Citral inhibits lipopolysaccharide-induced acute lung injury by activating PPAR-γ.

PubMed

Shen, Yongbin; Sun, Zhanfeng; Guo, Xiaotong

2015-01-15

Citral, a component of lemongrass oil, has been reported to have many pharmacological activities such as anti-bacterial and anti-inflammatory effects. However, the effects of citral on acute lung injury (ALI) and the molecular mechanisms have not been reported. The aim of this study was to detect the effects of citral on lipopolysaccharide (LPS)-induced acute lung injury and investigate the molecular mechanisms. LPS-induced acute lung injury model was used to detect the anti-inflammatory effect of citral in vivo. The alveolar macrophages were used to investigate the molecular mechanism of citral in vitro. The results showed that pretreatment with citral remarkably attenuated pulmonary edema, histological severities, TNF-α, IL-6 and IL-1β production in LPS-induced ALI in vivo. In vitro, citral inhibited LPS-induced TNF-α, IL-6 and IL-1β production in alveolar macrophages. LPS-induced NF-κB activation was also inhibited by citral. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, this is the first to demonstrate that citral protects LPS-induced ALI in mice. The anti-inflammatory mechanism of citral is associated with activating PPAR-γ, thereby inhibiting LPS-induced inflammatory response. Copyright © 2014 Elsevier B.V. All rights reserved.

[Dependence of anti-inflammatory effects of high peak-power pulsed electromagnetic radiation of extremely high frequency on exposure parameters].

PubMed

Gapeev, A B; Mikhaĭlik, E N; Rubanik, A V; Cheremis, N K

2007-01-01

A pronounced anti-inflammatory effect of high peak-power pulsed electromagnetic radiation of extremely high frequency was shown for the first time in a model of zymosan-induced footpad edema in mice. Exposure to radiation of specific parameters (35, 27 GHz, peak power 20 kW, pulse widths 400-600 ns, pulse repetition frequency 5-500 Hz) decreased the exudative edema and local hyperthermia by 20% compared to the control. The kinetics and the magnitude of the anti-inflammatory effect were comparable with those induced by sodium diclofenac at a dose of 3 mg/kg. It was found that the anti-inflammatory effect linearly increased with increasing pulse width at a fixed pulse repetition frequency and had threshold dependence on the average incident power density of the radiation at a fixed pulse width. When animals were whole-body exposed in the far-field zone of radiator, the optimal exposure duration was 20 min. Increasing the average incident power density upon local exposure of the inflamed paw accelerated both the development of the anti-inflammatory effect and the reactivation time. The results obtained will undoubtedly be of great importance in the hygienic standardization of pulsed electromagnetic radiation and in further studies of the mechanisms of its biological action.

Pharmacological insight into the anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R.Br. ex Cass.

PubMed

McKinnon, R; Binder, M; Zupkó, I; Afonyushkin, T; Lajter, I; Vasas, A; de Martin, R; Unger, C; Dolznig, H; Diaz, R; Frisch, R; Passreiter, C M; Krupitza, G; Hohmann, J; Kopp, B; Bochkov, V N

2014-10-15

Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data. The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats. The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats. Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

Anti-inflammatory activity of dried flower extracts of Aegle marmelos in Wistar rats.

PubMed

Kumari, K D K P; Weerakoon, T C S; Handunnetti, S M; Samarasinghe, K; Suresh, T S

2014-02-12

Almost all part of the plant Aegle marmelos (Bael tree) has been used in the traditional medicine systems of Asian countries to treat various diseases over many centuries. The water extract of the dried flowers of Aegle marmelos is a commonly used beverage among Sri Lankan population in rural areas. Although extensive investigations done on many parts of the plant there are no experimental data available on the extracts of flowers. Anti-inflammatory effect of the water extract of dried flowers of Aegle marmelos (WEAM) was evaluated in the present study. The anti-inflammatory effect of the WEAM was evaluated by inhibition of the rat paw oedema, induced by carrageenan. The mechanism of the anti-inflammatory effect was assessed by the inhibition of production of nitric oxide (NO) by rat peritoneal cells, infiltration of rat peritoneal cells, anti-histamine effect, membrane stabilization activity, the antioxidant capacity and inhibition of lipid peroxidation by the WEAM. The maximum percentage inhibition of paw oedema was exhibited by the dose of 200 mg/kg at 2 h. The WEAM showed a significant increment of rat peritoneal cell infiltration, inhibition of NO production by rat peritoneal cells and inhibition of wheal formation on the skin of the rat after injection of histamine. The WEAM protected the erythrocyte membrane from heat-induced lysis in a dose-dependent manner and showed a significant anti-oxidant effect and lipid peroxidation inhibition activity. The WEAM possesses significant anti-inflammatory effect by multiple mechanisms in Wistar rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Interplay Between Fiber and the Intestinal Microbiome in the Inflammatory Response12

PubMed Central

Kuo, Shiu-Ming

2013-01-01

Fiber intake is critical for optimal health. This review covers the anti-inflammatory roles of fibers using results from human epidemiological observations, clinical trials, and animal studies. Fiber has body weight–related anti-inflammatory activity. With its lower energy density, a diet high in fiber has been linked to lower body weight, alleviating obesity-induced chronic inflammation evidenced by reduced amounts of inflammatory markers in human and animal studies. Body weight–unrelated anti-inflammatory activity of fiber has also been extensively studied in animal models in which the type and amount of fiber intake can be closely monitored. Fermentable fructose-, glucose-, and galactose-based fibers as well as mixed fibers have shown systemic and local intestinal anti-inflammatory activities when plasma inflammatory markers and tissue inflammation were examined. Similar anti-inflammatory activities have also been demonstrated in some human studies that controlled total fiber intake. The anti-inflammatory activities of synbiotics (probiotics plus fiber) were reviewed as well, but there was no convincing evidence indicating higher efficacy of synbiotics compared with that of fiber alone. Adverse effects have not been observed with the amount of fiber intake or supplementation used in studies, although patients with Crohn’s disease may be more sensitive to inulin intake. Several possible mechanisms that may mediate the body weight–unrelated anti-inflammatory activity of fibers are discussed based on the in vitro and in vivo evidence. Fermentable fibers are known to affect the intestinal microbiome. The immunomodulatory role of the intestinal microbiome and/or microbial metabolites could contribute to the systemic and local anti-inflammatory activities of fibers. PMID:23319119

A Pseudopterane Diterpene Isolated From the Octocoral Pseudopterogorgia acerosa Inhibits the Inflammatory Response Mediated by TLR-Ligands and TNF-Alpha in Macrophages

PubMed Central

González, Yisett; Doens, Deborah; Santamaría, Ricardo; Ramos, Marla; Restrepo, Carlos M.; Barros de Arruda, Luciana; Lleonart, Ricardo; Gutiérrez, Marcelino; Fernández, Patricia L.

2013-01-01

Several diterpenoids isolated from terrestrial and marine environments have been identified as important anti-inflammatory agents. Although considerable progress has been made in the area of anti-inflammatory treatment, the search for more effective and safer compounds is a very active field of research. In this study we investigated the anti-inflammatory effects of a known pseudopterane diterpene (referred here as compound 1) isolated from the octocoral Pseudopterogorgia acerosa on the tumor necrosis factor- alpha (TNF-α) and TLRs- induced response in macrophages. Compound 1 inhibited the expression and secretion of the inflammatory mediators TNF-α, interleukin (IL)-6, IL-1β, nitric oxide (NO), interferon gamma-induced protein 10 (IP-10), ciclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1) induced by LPS in primary murine macrophages. This effect was associated with the inhibition of IκBα degradation and subsequent activation of NFκB. Compound 1 also inhibited the expression of the co-stimulatory molecules CD80 and CD86, which is a hallmark of macrophage activation and consequent initiation of an adaptive immune response. The anti-inflammatory effect was not exclusive to LPS because compound 1 also inhibited the response of macrophages to TNF-α and TLR2 and TLR3 ligands. Taken together, these results indicate that compound 1 is an anti-inflammatory molecule, which modulates a variety of processes occurring in macrophage activation. PMID:24358331

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.

Anti-inflammatory activity effect of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on TPA-induced skin inflammation in mice.

PubMed

Xu, Xue-Tao; Mou, Xue-Qing; Xi, Qin-Mei; Liu, Wei-Ting; Liu, Wen-Feng; Sheng, Zhao-Jun; Zheng, Xi; Zhang, Kun; Du, Zhi-Yun; Zhao, Su-Qing; Wang, Shao-Hua

2016-11-01

2-Substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole, a key structural moiety exiting in many bioactive molecules, has been shown to have excellent selective activity on COX-2. In the present study, the anti-inflammatory activity and the underlying molecular mechanism of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on skin inflammation were assessed by 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. Most of the compounds showed anti-inflammatory activity on TPA-induced skin inflammation. The anti-inflammatory activity of compound 4 showed higher anti-inflammatory activity than celecoxib (3.2-fold). Compound 4 pretreatment resulted in markedly suppression of TPA-induced IL-1β, IL-6, TNF-α, and COX-2, respectively. Furthermore, the mechanical study indicated that the anti-inflammatory activity of compound 4 was associated with its ability to inhibit activation of factor kappa-κB (NF-κB) by blocking IκB kinase (IKK) activities. Accordingly, compound 4 could be used as a potential anti-inflammatory agent for skin inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-inflammatory effects of vitamin E on adjuvant-induced arthritis in rats.

PubMed

Rossato, Mateus Fortes; Hoffmeister, Carin; Tonello, Raquel; de Oliveira Ferreira, Ana Paula; Ferreira, Juliano

2015-04-01

Vitamin E (vit-E) is a lipophilic antioxidant, and its anti-inflammatory activity is still not full characterized. Thus, our goal was to investigate the anti-inflammatory effect of repeated vit-E treatment in the arthritis induced by the intraplantar injection of complete Freund's adjuvant (CFA). We observed an increase in arthritis scores, interleukin-1β and H2O2 levels, neutrophil and macrophage infiltration, thermal hyperalgesia, mechanical allodynia, and loss of function induced by intraplantar CFA injection. These effects were unaltered after 1 day, partially reversed after 3 days, and inhibited after 9 days after vit-E treatment. Furthermore, the concentration of vit-E was reduced and that of tumor necrosis factor-alpha was increased in the CFA-injected paw. Both effects were reversed from 1 to 9 days after vit-E treatment. However, vit-E treatment did not alter CFA-induced edema at any time. Thus, vit-E treatment produced an anti-inflammatory effect of slow onset in CFA, which demonstrates a disease-modifying drug profile.

Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design.

PubMed

Tziona, Paraskevi; Theodosis-Nobelos, Panagiotis; Rekka, Eleni A

2017-01-01

Non-steroidal anti-inflammatory drugs are the oldest and most widely used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX) inhibition, in combination with the weekly acidic character of most of them, major protective mechanisms of the gastrointestinal system are suppressed and deregulated. In this review, several compounds designed to retain anti-inflammatory activity, but devoid of gastrointestinal side effects, are presented. Thus, gastro-protective drugs, selective COX-2 inhibitors, nitric monoxide- and hydrogen sulphide-releasing agents, prodrugs, lipoxygenase (LOX) inhibitors and dual COX/LOX inhibitors are presented. Their mechanism of action, as well as their advantages and disadvantages are discussed. Efforts, aiming to the development of safe non-steroidal anti-inflammatory agents, are evolving, however there are still several problems concerning gastro-protection to be efficiently solved, thus, design of effective and safe agents for the treatment of inflammatory conditions still remains a major challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anti-inflammatory effects of 4′-demethylnobiletin, a major metabolite of nobiletin

PubMed Central

Rakariyatham, Kanyasiri; Zheng, Jinkai; Guo, Shanshan; Tang, Zhonghai; Zhou, Shuangde; Xiao, Hang

2015-01-01

Nobiletin, a citrus flavonoid has been associated with various beneficial biological activities. 4′-Demethylnobiletin (4DN) is a major metabolite of nobiletin and its tissue level was found to be much higher than that of nobiletin after oral administration of nobiletin in mice. Anti-inflammatory effects of 4DN were studied in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. The results showed 4DN not only dose-dependently inhibited LPS-induced nitric oxide production, but also significantly reduced expression of pro-inflammatory mediators, namely PGE2, IL-1β and IL-6. 4DN potently suppressed the expression of iNOS and COX-2 at both protein and mRNA levels. 4DN also inhibited nuclear translocation of NF-κB and AP-1. Furthermore, we demonstrated that 4DN activated transcription factor Nrf2 and its dependent genes including HO-1 and NQO1 whose expression may contribute to anti-inflammatory effects. The results demonstrated anti-inflammatory effects of 4DN and provided a scientific basis for using nobiletin as a nutraceutical to inhibit inflammation–driven diseases. PMID:26770275

Anti-inflammatory activity of animal oils from the Peruvian Amazon.

PubMed

Schmeda-Hirschmann, Guillermo; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Vargas-Arana, Gabriel; Lima, Beatriz; Feresin, Gabriela E

2014-10-28

Animal oils and fats from the fishes Electrophorus electricus and Potamotrygon motoro, the reptiles Boa constrictor, Chelonoidis denticulata (Geochelone denticulata) and Melanosuchus niger and the riverine dolphin Inia geoffrensis are used as anti-inflammatory agents in the Peruvian Amazon. The aim of the study was to assess the topic anti-inflammatory effect of the oils/fats as well as to evaluate its antimicrobial activity and fatty acid composition. The oils/fats were purchased from a traditional store at the Iquitos market of Belen, Peru. The topic anti-inflammatory effect was evaluated by the mice ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) at the dose of 3mg oil/ear. Indomethacine and nimesulide were used as reference anti-inflammatory drugs. The application resembles the traditional topical use of the oils. The antimicrobial effect of the oils/fats was assessed by the microdilution test against reference strains of Escherichia coli, Staphylococcus aureus and Salmonella enteritidis. The fatty acid composition of the oils/fats (as methyl esters) was determined by GC and GC-MS analysis after saponification. All oils/fats showed topic anti-inflammatory activity, with better effect in the TPA-induced mice ear edema assay. The most active drugs were Potamotrygon motoro, Melanosuchus niger and Geochelone denticulata. In the AA-induced assay, the best activity was found for Potamotrygon motoro and Electrophorus electricus oil. The oil of Electrophorus electricus also showed a weak antimicrobial effect with MIC values of 250 µg/mL against Escherichia coli ATCC 25922 and Salmonella enteritidis-MI. The main fatty acids in the oils were oleic, palmitic and linoleic acids. Topical application of all the oils/fats investigated showed anti-inflammatory activity in the mice ear edema assay. The effect can be related with the identity and composition of the fatty acids in the samples. This study gives support to the traditional use of animal oils/fats as ant-inflammatory agents in the Peruvian Amazon. However, new alternative should be encouraged due to the conservation status of several of the animal sources of the crude drugs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The PGC-1 coactivators promote an anti-inflammatory environment in skeletal muscle in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eisele, Petra Sabine; Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich; Furrer, Regula

The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is abundantly expressed in trained muscles and regulates muscle adaptation to endurance exercise. Inversely, mice lacking a functional PGC-1α allele in muscle exhibit reduced muscle functionality and increased inflammation. In isolated muscle cells, PGC-1α and the related PGC-1β counteract the induction of inflammation by reducing the activity of the nuclear factor κB (NFκB). We now tested the effects of these metabolic regulators on inflammatory reactions in muscle tissue of control and muscle-specific PGC-1α/-1β transgenic mice in vivo in the basal state as well as after an acute inflammatory insult. Surprisingly, we observed amore » PGC-1-dependent alteration of the cytokine profile characterized by an increase in anti-inflammatory factors and a strong suppression of the pro-inflammatory interleukin 12 (IL-12). In conclusion, the anti-inflammatory environment in muscle that is promoted by the PGC-1s might contribute to the beneficial effects of these coactivators on muscle function and provides a molecular link underlying the tight mutual regulation of metabolism and inflammation. - Highlights: • Muscle PGC-1s are insufficient to prevent acute systemic inflammation. • The muscle PGC-1s however promote a local anti-inflammatory environment. • This anti-inflammatory environment could contribute to the therapeutic effect of the PGC-1s.« less

Molecular targets and anti-cancer potential of escin.

PubMed

Cheong, Dorothy H J; Arfuso, Frank; Sethi, Gautam; Wang, Lingzhi; Hui, Kam Man; Kumar, Alan Prem; Tran, Thai

2018-05-28

Escin is a mixture of triterpenoid saponins extracted from the horse chestnut tree, Aesculus hippocastanum. Its potent anti-inflammatory and anti-odematous properties makes it a choice of therapy against chronic venous insufficiency and odema. More recently, escin is being actively investigated for its potential activity against diverse cancers. It exhibits anti-cancer effects in many cancer cell models including lung adenocarcinoma, hepatocellular carcinoma and leukemia. Escin also attenuates tumor growth and metastases in various in vivo models. Importantly, escin augments the effects of existing chemotherapeutic drugs, thereby supporting the role of escin as an adjunct or alternative anti-cancer therapy. The beneficial effects of escin can be attributed to its inhibition of proliferation and induction of cell cycle arrest. By regulating transcription factors/growth factors mediated oncogenic pathways, escin also potentially mitigates chronic inflammatory processes that are linked to cancer survival and resistance. This review provides a comprehensive overview of the current knowledge of escin and its potential as an anti-cancer therapy through its anti-proliferative, pro-apoptotic, and anti-inflammatory effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Walnut extract modulates activation of microglia through alteration in intracellular calcium concentration

USDA-ARS?s Scientific Manuscript database

Previous data from our laboratory demonstrated that treatment with walnut extracts (WN) protects cells against oxidative and inflammatory cytotoxicity and promotes anti-inflammatory activities. The current study was undertaken to test whether the anti-inflammatory effects of WN are attributed to its...

The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.

PubMed

Vucković, Sonja M; Tomić, Maja A; Stepanović-Petrović, Radica M; Ugresić, Nenad; Prostran, Milica S; Bosković, Bogdan

2006-11-01

In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

PubMed Central

Schreiber, Dominik; Marx, Lisa; Felix, Silke; Clasohm, Jasmin; Weyland, Maximilian; Schäfer, Maximilian; Klotz, Markus; Lilischkis, Rainer; Erkel, Gerhard; Schäfer, Karl-Herbert

2017-01-01

Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS) cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml), TNF-α (10 ng/ml), and IL-1β (5 ng/ml). Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD. PMID:28824460

Morinda citrifolia lipid transfer protein 1 exhibits anti-inflammatory activity by modulation of pro- and anti-inflammatory cytokines.

PubMed

Campos, Dyély C O; Costa, Andrea S; Luz, Patrícia B; Soares, Pedro M G; Alencar, Nylane M N; Oliveira, Hermógenes D

2017-10-01

Previous reports have demonstrated that a thermostable lipid transfer protein isolated from noni seeds (McLTP 1 ; 9.4kDa) displays anti-nociceptive and anti-inflammatory activities. This work aimed to investigate the underlying mechanisms of the anti-inflammatory activity of McLTP 1 in mice. The protein was solubilised in sterile saline (0.9% NaCl) immediately before the treatment of mice by oral or intraperitoneal routes at doses of 8mg/kg. Given orally or intraperitoneally, McLTP 1 significantly inhibited (p<0.05) cell migration in experimental models of carrageenan-induced peritonitis and the formation of paw oedema induced by carrageenan and dextran. Additionally, McLTP 1 demonstrated the ability to significantly inhibit the production of the cytokines IL-1β, IL-6, and TNF-α (p<0.05) and to promote an increase in the production of the anti-inflammatory cytokine IL-10. The treatment of mice with McLTP 1 by the oral or i.p route reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury. This study suggested that the observed anti-inflammatory effects of McLTP 1 can be related to modulation of pro- and anti-inflammatory cytokine levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

PubMed

Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

Acai Juice Attenuates Atherosclerosis Through Antioxidant and Anti-Inflammatory Effects in ApoE Deficient Mice

USDA-ARS?s Scientific Manuscript database

Introduction: Acai fruit (Euterpe oleracea Mart.) has been shown to exhibit extremely high antioxidant capacity. Antioxidant capacities and anti-inflammatory effects of acai pulp or acai juices have been studied in human, animal and cell culture models. However, their potential effects on atheroscl...

The anti-inflammatory effect of diclofenac is considerably augmented by topical capsaicinoids-containing patch in carrageenan-induced paw oedema of rat.

PubMed

Ercan, Nilufer; Uludag, Mecit Orhan; Agis, Erol Rauf; Demirel-Yilmaz, Emine

2013-12-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in musculoskeletal disorders, but their systemic adverse effects limit their therapeutic benefit in local inflammation. On the other hand, topical preparations of capsaicinoids are widely used for musculoskeletal disorders as a complementary therapy. In this study, the effects of both topical capsaicinoids-containing patch and local subcutaneous capsaicin application on the anti-inflammatory action of NSAID were examined. Carrageenan-induced paw oedema of rats was used as the inflammation model. The volume and weight of the paw oedema and plasma extravasation in the paw were determined after carrageenan injection. The systemic application of diclofenac (3 mg/kg), which is an NSAID, significantly decreased the volume and weight of the paw oedema. Topical capsaicinoids-containing patch application or local capsaicin injection (2, 10, 20 μg/paw) alone did not cause any effect on oedema volume and weight. However, the combination of diclofenac with topical capsaicinoids-containing patch significantly increased the effectiveness of diclofenac on inflammation. Evans blue content of the paws that represents plasma extravasation was decreased by capsaicinoids-containing patch with and without diclofenac and diclofenac combination with the lowest dose of capsaicin injection. The results of this study indicate that topical application of capsaicinoids-containing patch enhances the anti-inflammatory effect of diclofenac and its beneficial effect may not purely relate to its capsaicin content. In the treatment of local inflammatory disorders, the combination of NSAID with topical capsaicinoids-containing patch could increase the anti-inflammatory efficiency of drug without systemic side effects.

Neuroendocrine Factors in the Regulation of Inflammation: Excessive Adiposity and Calorie Restriction

PubMed Central

Fontana, Luigi

2009-01-01

Acute inflammation is usually a self-limited life preserving response, triggered by pathogens and/or traumatic injuries. This transient response normally leads to removal of harmful agents and to healing of the damaged tissues. In contrast, unchecked or chronic inflammation can lead to persistent tissue and organ damage by activated leukocytes, cytokines, or collagen deposition. Excessive energy intake and adiposity cause systemic inflammation, whereas calorie restriction without malnutrition exerts a potent anti-inflammatory effect. As individuals accumulate fat and their adipocytes enlarge, adipose tissue undergoes molecular and cellular alterations, macrophages accumulate, and inflammation ensues. Overweight/obese subjects have significantly higher plasma concentrations of C-reactive protein and several cytokines, including IL-6, IL-8, IL-18, and TNF-alpha. Experimental animals on a chronic CR regimen, instead, have low levels of circulating inflammatory cytokines, low blood lymphocyte levels, reduced production of inflammatory cytokines by the white blood cells in response to stimulation, and cortisol levels in the high normal range. Recent data demonstrate that CR exerts a powerful anti-inflammatory effect also in non-human primates and humans. Multiple metabolic and neuroendocrine mechanisms are responsible for the CR-mediated anti-inflammatory effects, including reduced adiposity and secretion of pro-inflammatory adipokines, enhanced glucocorticoid production, reduced plasma glucose and advanced glycation end-product concentrations, increased parasympathetic tone, and increased ghrelin production. Measuring tissue specific effects of CR using genomic, proteomic and metabolomic techniques in humans will foster the understanding of the complex biological processes involved in the anti-inflammatory and anti-aging effects of CR. PMID:18502597

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 activities. PMID:24242245

Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model

PubMed Central

Shin, Seung Kak; Cho, Jae Hee; Kim, Eui Joo; Kim, Eun-Kyung; Park, Dong Kyun; Kwon, Kwang An; Chung, Jun-Won; Kim, Kyoung Oh; Kim, Yoon Jae

2017-01-01

AIM To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. METHODS An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured. RESULTS In DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05). CONCLUSION Rosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease. PMID:28740344

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice.

PubMed

Rodrigues, Lindaiane Bezerra; Martins, Anita Oliveira Brito Pereira Bezerra; Ribeiro-Filho, Jaime; Cesário, Francisco Rafael Alves Santana; E Castro, Fyama Ferreira; de Albuquerque, Thaís Rodrigues; Fernandes, Maria Neyze Martins; da Silva, Bruno Anderson Fernandes; Quintans Júnior, Lucindo José; Araújo, Adriano Antunes de Sousa; Menezes, Paula Dos Passos; Nunes, Paula Santos; Matos, Isabella Gonçalves; Coutinho, Henrique Douglas Melo; Goncalves Wanderley, Almir; de Menezes, Irwin Rose Alencar

2017-11-01

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent.

PubMed

Katanić, Jelena; Boroja, Tatjana; Mihailović, Vladimir; Nikles, Stefanie; Pan, San-Po; Rosić, Gvozden; Selaković, Dragica; Joksimović, Jovana; Mitrović, Slobodanka; Bauer, Rudolf

2016-12-04

Meadowsweet (Filipendula ulmaria (L.) Maxim, Rosaceae) has been traditionally used in most European countries for the treatment of inflammatory diseases due to its antipyretic, analgesic, astringent, and anti-rheumatic properties. However, there is little scientific evidence on F. ulmaria anti-inflammatory effects regarding its impact on cyclooxygenases enzymatic activity and in vivo assessment of anti-inflammatory potential. This study aims to reveal the anti-inflammatory activity of methanolic extracts from the aerial parts (FUA) and roots (FUR) of F. ulmaria, both in in vitro and in vivo conditions. The characteristic phenolic compounds in F. ulmaria extracts were monitored via high performance thin layer chromatography (HPTLC). The in vitro anti-inflammatory activity of F. ulmaria extracts was evaluated using cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays, and an assay for determining COX-2 gene expression. The in vivo anti-inflammatory effect of F. ulmaria extracts was determined in two doses (100 and 200 mg/kg b.w.) with hot plate test and carrageenan-induced paw edema test in rats. Inflammation was also evaluated by histopathological and immunohistochemical analysis. FUA extract showed the presence of rutoside, spiraeoside, and isoquercitrin. Both F. ulmaria extracts at a concentration of 50μg/mL were able to inhibit COX-1 and -2 enzyme activities, whereby FUA extract (62.84% and 46.43% inhibition, respectively) was double as effective as the root extract (32.11% and 20.20%, respectively). Extracts hardly inhibited the level of COX-2 gene expression in THP-1 cells at a concentration of 25μg/mL (10.19% inhibition by FUA and 8.54% by FUR). In the hot plate test, both extracts in two doses (100 and 200mg/kg b.w.), exhibited an increase in latency time when compared with the control group (p<0.05). In the carrageenan-induced acute inflammation test, FUA at doses of 100 and 200mg/kg b.w., and FUR at 200mg/kg, were able to significantly reduce the mean maximal swelling of rat paw until 6h of treatment. Indomethacin, FUA, and FUR extracts significantly decreased inflammation score and this effect was more pronounced after 24h, compared to the control group (p<0.05). The observed results of in vitro and, for the first time, in vivo anti-inflammatory activity of meadowsweet extracts, provide support of the traditional use of this plant in the treatment of different inflammatory conditions. Further investigation of the anti-inflammatory compounds could reveal the mechanism of anti-inflammatory action of these extracts. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

PubMed Central

Shreedhara, C.S.; Vaidya, V.P.; Vagdevi, H.M.; Latha, K.P.; Muralikrishna, K.S.; Krupanidhi, A.M.

2009-01-01

Objectives: Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models. Materials and Methods: Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy's hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg. Results: The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P < 0.001). The maximum analgesic effect was observed at 120 min at the dose of 100 mg/kg (i.p.) and was comparable to that of standard analgin (150 mg/kg) and the percentage of edema inhibition effect was 46.4% and 77% for 50 mg/kg and 100 mg/kg (i.p) respectively. Anti-inflammatory activity was compared with standard Diclofenac sodium (5 mg/kg). Conclusion: Ethanol extract of Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract. PMID:20336222

Enhanced barrier functions and anti-inflammatory effect of cultured coconut extract on human skin.

PubMed

Kim, Soomin; Jang, Ji Eun; Kim, Jihee; Lee, Young In; Lee, Dong Won; Song, Seung Yong; Lee, Ju Hee

2017-08-01

Natural plant oils have been used as a translational alternative to modern medicine. Particularly, virgin coconut oil (VCO) has gained popularity because of its potential benefits in pharmaceutical, nutritional, and cosmetic applications. Cultured coconut extract (CCE) is an alternative end product of VCO, which undergoes a further bacterial fermentation process. This study aimed to investigate the effects of CCE on human skin. We analyzed the expression of skin barrier molecules and collagens after applying CCE on human explanted skin. To evaluate the anti-inflammatory properties of CCE, the expression of inflammatory markers was analyzed after ultraviolet B (UVB) irradiation. The CCE-treated group showed increased expression of cornified cell envelope components, which contribute to protective barrier functions of the stratum corneum. Further, the expression of inflammatory markers was lower in the CCE-treated group after exposure to UVB radiation. These results suggest an anti-inflammatory effect of CCE against UVB irradiation-induced inflammation. Additionally, the CCE-treated group showed increased collagen and hyaluronan synthase-3 expression. In our study, CCE showed a barrier-enhancing effect and anti-inflammatory properties against ex vivo UVB irradiation-induced inflammation. The promising effect of CCE may be attributed to its high levels of polyphenols and fatty acid components. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effect of COX-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer

DTIC Science & Technology

2006-12-01

drug is it is associated with less side effects than non - steroidal inflammatory drugs ( NSAIDs ), particularly gastroduodenal ulcers. Randomized...Nested case-control study of effects of non - steroidal anti - inflammatory drugs on breast cancer risk and stage. B J Cancer 2000;83:112-120. 18...another non - steroidal anti - inflammatory ; 1 was determined to need neoadjuvant chemotherapy; 1 had a benign core biopsy, and 2

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.

Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition

PubMed Central

Lu, Li; Qin, Aiping; Huang, Hongbiao; Zhou, Ping; Zhang, Chuanyin; Liu, Ningning; Li, Shujue; Wen, Guanmei; Zhang, Change; Dong, Weihua; Wang, Xuejun; Dou, Q. Ping; Liu, Jinbao

2012-01-01

Shikonin, extracted from medicinal Chinese herb (Lithospermum erythrorhizo), was reported to exert anti-inflammatory and anti-cancer effects both in vitro and in vivo. We have found that proteasome was a molecular target of shikonin in tumor cells, but whether shikonin targets macrophage proteasome needs to be investigated. In the current study, we report that shikonin inhibited inflammation in mouse models as efficiently as dexamethasone. Shikonin at 4 μM reduced the Lipopolysaccharides (LPS)-mediated TNFα release in rat primary macrophage cultures, and blocked the translocation of p65-NF-κB from the cytoplasm to the nucleus, associated with decreased proteasomal activity. Consistently, shikonin accumulated IκB-α, an inhibitor of NF-κB, and ubiquitinated proteins in rat primary macrophage cultures, demonstrating that the proteasome is a target of shikonin under inflammatory conditions. Shikonin also induced macrophage cell apoptosis and cell death. These results demonstrate for the first time that proteasome inhibition by shikonin contributes to its anti-inflammatory effect. The novel finding about macrophage proteasome as a target of shikonin suggests that this medicinal compound has great potential to be developed into an anti-inflammatory agent. PMID:21392503

Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition.

PubMed

Lu, Li; Qin, Aiping; Huang, Hongbiao; Zhou, Ping; Zhang, Chuanyin; Liu, Ningning; Li, Shujue; Wen, Guanmei; Zhang, Change; Dong, Weihua; Wang, Xuejun; Dou, Q Ping; Liu, Jinbao

2011-05-11

Shikonin, extracted from medicinal Chinese herb (Lithospermum erythrorhizo), was reported to exert anti-inflammatory and anti-cancer effects both in vitro and in vivo. We have found that proteasome was a molecular target of shikonin in tumor cells, but whether shikonin targets macrophage proteasome needs to be investigated. In the current study, we report that shikonin inhibited inflammation in mouse models as efficiently as dexamethasone. Shikonin at 4 μM reduced the Lipopolysaccharides (LPS)-mediated TNFα release in rat primary macrophage cultures, and blocked the translocation of p65-NF-κB from the cytoplasm to the nucleus, associated with decreased proteasomal activity. Consistently, shikonin accumulated IκB-α, an inhibitor of NF-κB, and ubiquitinated proteins in rat primary macrophage cultures, demonstrating that the proteasome is a target of shikonin under inflammatory conditions. Shikonin also induced macrophage cell apoptosis and cell death. These results demonstrate for the first time that proteasome inhibition by shikonin contributes to its anti-inflammatory effect. The novel finding about macrophage proteasome as a target of shikonin suggests that this medicinal compound has great potential to be developed into an anti-inflammatory agent. Copyright © 2011 Elsevier B.V. All rights reserved.

Echinacea purpurea root extract inhibits TNF release in response to Pam3Csk4 in a phosphatidylinositol-3-kinase dependent manner.

PubMed

Fast, David J; Balles, John A; Scholten, Jeffrey D; Mulder, Timothy; Rana, Jatinder

2015-10-01

Polysaccharides derived from Echinacea have historically been shown to be immunostimulatory. We describe in this work however the anti-inflammatory effect of a water extract of Echinacea purpurea roots (EPRW) that inhibited Pam3Csk4 stimulated production of TNFα by human monocytic THP-1 cells. The polyphenols and alkylamides typically found in Echinacea extracts were absent in EPRW suggesting that the anti-inflammatory component(s) was a polysaccharide. This anti-inflammatory activity was shown to be mediated by the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway as chemical inhibition of PI3K abolished the EPRW anti-inflammatory effect. Demonstration of phosphorylation of Akt and ribosomal S6 proteins, downstream targets of PI3K confirmed EPRW-mediated activation of this pathway. In conclusion, this observation suggests that non-alkylamide/non-polyphenolic phytochemicals from Echinacea may contribute in part to some of the anti-inflammatory therapeutic effects such as reduced severity of symptoms that have been observed in vivo in the treatment of upper respiratory tract infections with Echinacea. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Prospective of curcumin, a pleiotropic signalling molecule from Curcuma longa in the treatment of Glioblastoma.

PubMed

Luthra, Pratibha Mehta; Lal, Neetika

2016-02-15

GBM (Glioblastoma) is the most malignant human brain tumor with median survival of one year. The treatment involves surgery, radiotherapy and adjuvant chemotherapy mostly with the alkylation agents such as temozolomide (TMZ). Dietary polyphenol curcumin, isolated from the rhizome of the Curcuma longa (turmeric), has emerged as remarkable anti-cancer agent in the treatment of various peripheral cancers such as blood, lymphomas, multiple myeloma, melanoma as well as skin, lung, prostate, breast, ovarian, bladder, liver, gastrointestinal tract, pancreatic and colorectal epithelial cancers with a pleiotropic mode of action and also showed promise in alleviation of GBM. In this review, the mechanism of anticancer effect of curcumin in GBM has been discussed extensively. The clinical safety and pharmacokinetics of curcumin has been scrutinized to combat the challenges for the treatment of GBM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Novel anti-inflammatory effects of repaglinide in rodent models of inflammation.

PubMed

Tung, David; Cheung, Peter H; Ciallella, John; Saha, Saurabh

2011-01-01

Repaglinide is an FDA-approved treatment for type 2 diabetes mellitus. The anti-inflammatory effect of repaglinide in the absence of diabetes has not been reported previously. It is the objective of this set of studies to investigate the potential anti-inflammatory effects of repaglinide. The in vivo anti-inflammatory effects of repaglinide were studied in two different models of delay type hyperreactivity (DTH) response induced by sheep red blood cells (sRBC) and 2,5'-dinitrofluorobenzene (DNFB), and in two different rodent models of lipopolysaccharide (LPS) challenge. In mice systemically sensitized with sRBC, which subsequently received a local injection of sRBC in the footpad, local swelling occurred within 24 h after challenge. Repaglinide was efficacious in attenuating this response. In an orthogonal DTH model using DNFB as the antigen, the animals received topical sensitization with DNFB on their shaved backs, followed by topical challenge on the left ears. Repaglinide efficaciously downregulated the resulting ear swelling response. In mice challenged systemically or intratracheally with LPS, repaglinide significantly decreased serum tumor necrosis factor α level and bronchial alveolar lavage fluid MCP-1 levels, respectively. This set of data suggests novel anti-inflammatory effects of repaglinide in nondiabetic animals. However, the high dose required for an efficacious effect would make this application impractical in the clinic. Copyright © 2011 S. Karger AG, Basel.

Polyphenol supplementation as a complementary medicinal approach to treating inflammatory bowel disease.

PubMed

Biasi, F; Astegiano, M; Maina, M; Leonarduzzi, G; Poli, G

2011-01-01

Inflammatory bowel disease (IBD) comprises a group of idiopathic chronic intestinal inflammation syndromes that are very common in developed countries. It is characterized by intermittent episodes of clinical remission and relapse, with recurrent inflammatory injury that can lead to structural damage of the intestine. The uncontrolled intestinal immune response to bacterial antigens leads to the production of abundant cytokines and chemokines, by activated leukocytes and epithelial cells, which trigger inflammatory and oxidative reactions. The current treatment of IBD consists in long-term anti-inflammatory therapy that, however, does not exclude relapses and side effects, frequently resulting in surgical intervention. Polyphenols have been acknowledged to be anti-oxidant and anti-inflammatory and therefore, have been proposed as an alternative natural approach to prevent or treat chronic inflammatory diseases. Most studies have been in animal models of colitis, using chemical inducers or mice defective in anti-inflammatory mediators and in intestinal cell lines treated with pro-inflammatory cytokines or lipid oxidation products. These studies provide evidence that polyphenols can effectively modulate intestinal inflammation. They exert their effects by modulating cell signaling pathways, mainly activated in response to oxidative and inflammatory stimuli, and NF-kB is the principal downstream effector. Polyphenols may thus be considered able to prevent or delay the progression of IBD, especially because they reach higher concentrations in the gut than in other tissues. However, knowledge of the use of polyphenols in managing human IBD is still scanty, and further clinical studies should afford more solid evidence of their beneficial effects.

Vedolizumab is an effective alternative in inflammatory bowel disease patients with anti-TNF-alpha therapy-induced dermatological side effects.

PubMed

Pijls, Philippe A R R; Gilissen, Lennard P L

2016-11-01

The treatment of patients with inflammatory bowel diseases has been revolutionized by the introduction of biological therapy with TNF-alpha blockers. However, TNF-alpha blockers are also associated with a wide variety of dermatological side effects, such as local skin infections, psoriasis and eczema. A new biological therapy, targeting the gut-specific adhesion molecule alpha4beta7 integrin, is the humanized monoclonal IgG1 antibody vedolizumab. Vedolizumab prevents leukocyte migration to the gastrointestinal tract, thereby reducing inflammation. This gut-specific therapy has the potential to reduce systemic side effects, including dermatological ones. We describe 3 inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects, consisting of hidradenitis suppurativa, a folliculitis, scalp psoriasis and a dissecting folliculitis. In all patients, anti-TNF-alpha therapy-induced dermatological side effects diminished after switching to vedolizumab. Vedolizumab may be a viable alternative biological therapy in inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f.) Iwarsson Leaves in Rodent Models

PubMed Central

Alemu, Asnakech

2018-01-01

Background Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and p < 0.05 was considered significant. Results The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p < 0.001). Conclusion The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models. PMID:29675050

Evaluation of the wound healing property of Boesenbergia longiflora rhizomes.

PubMed

Sudsai, Teeratad; Wattanapiromsakul, Chatchai; Nakpheng, Titpawan; Tewtrakul, Supinya

2013-10-28

The rhizomes of Boesenbergia longiflora (Wall.) Kuntze (Zingiberaceae) have been traditionally used for treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer and abscess by decoction with alcohol. The rhizomes of Boesenbergia longiflora were carried out to investigate for anti-inflammatory and wound healing activities in order to support the traditional use. The ethanolic extract of Boesenbergia longiflora and its fractions were tested using relevant in vitro anti-inflammatory and wound healing assays. For the in vitro studies, murine macrophage RAW264.7 cells and mouse fibroblast L929 cells were assessed for anti-inflammatory and fibroblast stimulatory activities, respectively. In vivo anti-inflammatory activity was determined by carrageenan-induced rat paw edema model as well as acute toxicity estimated by the up-and-down method in mice. The present study has demonstrated that the ethanolic extract of Boesenbergia longiflora rhizomes possesses a potent anti-inflammatory and wound healing activities. Among the isolated fractions, the CHCl3 fraction showed potent anti-inflammatory effect through nitric oxide inhibitory activity (IC50=5.5 μg/ml) and reduction of carrageenan-induced rat paw edema (ED50=222.7 mg/kg), whereas this fraction exhibited wound healing property via fibroblast migration on both day 1 (77.3%) and day 2 (100%) as well as enhanced collagen production (187.5 μg/ml) at concentration of 3 μg/ml, compared to that of the controls, 39.4% for fibroblast and 60.8 μg/ml for collagen, respectively. The anti-inflammatory mechanism of the CHCl3 fraction is found to suppress the iNOS and COX-2 mRNA expression. The scientific investigation of wound healing activity of Boesenbergia longiflora rhizomes support the Thai traditional uses for treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer and abscess. The EtOH extract and CHCl3 fraction exert potential wound healing property through NO inhibition, anti-oxidant effect and stimulation of fibroblast migration and collagen production. The phytochemical screening revealed that the CHCl3 fraction of Boesenbergia longiflora rhizomes contains diarylheptanoids, flavonoids and terpenes. The isolation of the compounds responsible for the wound healing effect is now in progress. © 2013 Elsevier Ireland Ltd. All rights reserved.

In Vivo Evaluation of the Anti-Inflammatory Effect of Pistacia lentiscus Fruit Oil and Its Effects on Oxidative Stress

PubMed Central

Bardaa, Sana; Sahnoun, Zouheir; Rebai, Tarek

2016-01-01

In order to find new topical anti-inflammatory agents, we had recourse to a medicinal plant. This work was designed to determine the topical anti-inflammatory effect of Pistacia lentiscus fruit oil (PLFO), using carrageenan-induced paw edema rat model, and to evaluate its effects on oxidative stress. The topical anti-inflammatory activity of PLFO was compared to Inflocine® and estimated by measuring the diameter of paw edema, for 5 hours at a 1-hour interval. After that the rats were scarified and the inflamed paw tissue was removed for the exploration of some parameters of oxidative stress and histopathology. PLFO showed a significant anti-inflammatory activity in comparison with the Inflocine. The percentages of edema inhibition were 70% and % 51.5% (p < 0.01), respectively, after five hours. The treatment with PLFO and Inflocine led to significant increases (p ≤ 0.05) in the activities of CAT, SOD, and GPX and significant decreases in the MDA level and AOPP activity in the paw tissue after Carr injection, in comparison with the Carr group. Therefore, our findings demonstrate that PLFO might accelerate the development of new drugs which could be used scientifically as a source for natural health products in the treatment of topical inflammation. PMID:28070202

Involvement of steroids in anti-inflammatory effects of PK11195 in a murine model of pleurisy.

PubMed Central

da Silva, Marcelo Barreto Spillere; Farges, Roseli Coimbra; Fröde, Tânia Silvia

2004-01-01

BACKGROUND: Studies on peripheral benzodiazepine receptor function have yielded a diverse list of activities of which the anti-inflammatory effects need to be further examined. AIMS: To evaluate the role of steroids, nitric oxide and adenosine-deaminase in the anti-inflammatory effect of PK11195. METHODS: Pleurisy was induced by intrapleural injection of carrageenan in mice pre-treated or not with PK11195. Leukocytes, exudation, adenosine-deaminase (ADA) activity and nitric oxide (NO) level were measured. Steroid involvement was evaluated by pre-treatment with D,L-aminogluthetimide before PK11195. RESULTS: Leukocytes, exudation and NO levels were reduced by PK11195 in the early (4 h) phase. In the late (48 h) phase, PK11195 decreased leukocytes and ADA activity. D,L-aminogluthetimide reversed the effect of PK11195 on exudate (4 h), as well as total and differential leukocytes and NO levels (48 h). CONCLUSIONS: Steroids, NO and ADA are implicated in the anti-inflammatory action of PK11195. PMID:15203550

Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activities.

PubMed

Nujić, Krunoslav; Smith, Marjorie; Lee, Michael; Belamarić, Daniela; Tomašković, Linda; Alihodžić, Sulejman; Malnar, Ivica; Polančec, Denis; Schneider, Klaus; Eraković Haber, Vesna

2012-02-29

In addition to antibacterial activity, some macrolide antibiotics, such as azithromycin and clarithromycin, also exhibit anti-inflammatory properties in vitro and in vivo, although the targets and mechanism(s) of action remain unknown. The aim of the present study was to identify protein targets of azithromycin and clarithromycin which could potentially explain their anti-inflammatory effects. Using chemical proteomics approach, based on compound-immobilized affinity chromatography, valosin containing protein (VCP) was identified as a potential target of the macrolides. Validation studies confirmed the interaction of macrolides and VCP and gave some structural characteristics of this interaction. Cell based assays however, including the use of gene silencing and the study of VCP specific cellular functions in J774.A1 (murine macrophage) and IB3-1 (human cystic fibrotic epithelial) cell lines, failed to confirm an association between the binding of the macrolides to VCP and anti-inflammatory effects. These findings suggest the absence of an abundant high affinity protein target and the potential involvement of other biological molecules in the anti-inflammatory activity of macrolides. Copyright © 2011 Elsevier B.V. All rights reserved.

Discovery and evaluation of novel anti-inflammatory derivatives of natural bioactive curcumin

PubMed Central

Zhang, Yali; Jiang, Xin; Peng, Kesong; Chen, Chengwei; Fu, Lili; Wang, Zhe; Feng, Jianpeng; Liu, Zhiguo; Zhang, Huajie; Liang, Guang; Pan, Zheer

2014-01-01

Curcumin is a natural active product that has various pharmacological activities such as anti-inflammatory effects. Here, we report the synthesis and evaluation of 34 monocarbonyl curcumin analogs as novel anti-inflammatory agents. Among the analogs, the symmetrical heterocyclic type displayed the strongest inhibition of lipopolysaccharide (LPS)-stimulated expression of pro-inflammatory cytokines in macrophages. Analogs S1–S5 and AS29 reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production in a dose-dependent manner and also displayed excellent stability and low cytotoxicity in vitro. In addition, analog S1 dose-dependently inhibited LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, analogs S1 and S4 displayed a significant protective effect on LPS-induced septic death in mouse models, with 40% and 50% survival rates, respectively. These data demonstrate that the heterocyclic monocarbonyl curcumin analogs have potential therapeutic effects in acute inflammatory diseases. PMID:25395833

Anti-Inflammatory Effects of Artemisia Leaf Extract in Mice with Contact Dermatitis In Vitro and In Vivo.

PubMed

Yun, Chanyong; Jung, Youngchul; Chun, Wonjoo; Yang, Beodeul; Ryu, Junghyun; Lim, Chiyeon; Kim, Jung-Hoon; Kim, Hyungwoo; Cho, Su-In

2016-01-01

The leaves of Artemisia argyi Lev. et Vant. and A. princeps Pamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects of Artemisia leaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2 (PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2 in Raw 264.7 cells. These results indicate that Artemisia leaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues.

Anti-Inflammatory Effects of Artemisia Leaf Extract in Mice with Contact Dermatitis In Vitro and In Vivo

PubMed Central

Yun, Chanyong; Jung, Youngchul; Chun, Wonjoo; Yang, Beodeul; Ryu, Junghyun; Cho, Su-In

2016-01-01

The leaves of Artemisia argyi Lev. et Vant. and A. princeps Pamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects of Artemisia leaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2 (PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2 in Raw 264.7 cells. These results indicate that Artemisia leaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues. PMID:27647952

Mushrooms: A Potential Natural Source of Anti-Inflammatory Compounds for Medical Applications

PubMed Central

Elsayed, Elsayed A.; El Enshasy, Hesham; Wadaan, Mohammad A. M.; Aziz, Ramlan

2014-01-01

For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents. PMID:25505823

Anti-inflammatory effects of shea butter through inhibition of iNOS, COX-2, and cytokines via the Nf-κB pathway in LPS-activated J774 macrophage cells.

PubMed

Verma, Nandini; Chakrabarti, Rina; Das, Rakha H; Gautam, Hemant K

2012-01-12

Shea butter is traditionally used in Africa for its anti-inflammatory and analgesic effects. In this study we explored the anti-inflammatory activities of the methanolic extract of shea butter (SBE) using lipopolysaccharide (LPS)-induced murine macrophage cell line J774. It was observed that SBE significantly reduced the levels of LPS-induced nitric oxide, Tumor necrosis factor-α (TNF-α), interleukins, 1β (IL-1β), and -12 (IL-12) in the culture supernatants in a dose dependent manner. Expression of pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were also inhibited by SBE. These anti-inflammatory effects were due to an inhibitory action of SBE on LPS-induced iNOS, COX-2, TNF-α, IL-1β, and IL-12 mRNA expressions. Moreover, SBE efficiently suppressed IκB phosphorylation and NF-κB nuclear translocation induced by LPS. These findings explain the molecular bases of shea butter's bioactivity against various inflammatory conditions and substantiate it as a latent source of novel therapeutic agents.

Synthesis of modified steroids as a novel class of non-ulcerogenic, anti-inflammatory and anti-nociceptive agents.

PubMed

Mohareb, Rafat M; Elmegeed, Gamal A; Abdel-Salam, Omar M E; Doss, Senot H; William, Marian G

2011-01-01

The identification of compounds able to treat both pain and inflammation with limited side effects is one of the prominent goals in biomedical research. This study aimed at the synthesis of new modified steroids with structures justifying non-ulcerogenic, anti-inflammatory and anti-nociceptive activities. The steroid derivatives were synthesized via straightforward and efficient methods and their structures were established based on the analytical and spectral data. The in vivo anti-inflammatory, anti-nociceptive and anti-ulcerogenic activities of some of these compounds were studied. The newly synthesized compounds 8b, 19b, 24 and 31a showed anti-inflammatory, anti-nociceptive and anti-ulcerogenic activity with various intensities. Oedema was significantly reduced by either dose 25 or 50 mg/kg of all tested compounds at 3 and 4 h post-carrageenan. Compound 19b was the most effective in alleviating thermal pain. The analgesic activity of either dose of the compounds 8b, 24, 31a as well as the high dose 19b was significantly higher than that for indomethacin (IND). Gastric mucosal lesions caused in the rats by the administration of 96% EtOH and IND were inhibited by all tested compounds administered at (50 mg/kg) dose in the study. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Review article: Anti-inflammatory mechanisms of action of Saccharomyces boulardii

PubMed Central

Pothoulakis, C.

2009-01-01

SUMMARY Background Saccharomyces boulardii (S. boulardii), a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as Inflammatory Bowel Disease (IBD), and bacterially – or enterotoxin-mediated diarrhea and inflammation. Aim Discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii Methods Review of the literature related to the anti-inflammatory effects of this probiotic. Results Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor κB, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) that protects from gut inflammation and IBD. S. boulardii also suppresses “bacteria overgrowth” and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor, and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. Conclusions The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states. PMID:19706150

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

Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Del-Aguila, Jorge L.; Fernandez, Maria Victoria; Carrell, David; Black, Kathleen; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Bailey, Matthew; Ridge, Perry G.; Hefti, Franz; Fillit, Howard; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Carrillo, Maria; Fleisher, Adam; Reeder, Stephanie; Trncic, Nadira; Burke, Anna; Tariot, Pierre; Reiman, Eric M.; Chen, Kewei; Sabbagh, Marwan N.; Beiden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Green, Robert C.; Marshall, Gad; Johnson, Keith A.; Sperling, Reisa A.; Snyder, Peter; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Bernick, Charles; Munic, Donna; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Relkin, Norman; Chaing, Gloria; Ravdin, Lisa; Paul, Steven; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Friedl, Karl; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Borges-Neto, Salvador; James, Olga; Wong, Terence; Coleman, Edward; Schwartz, Adam; Cellar, Janet S.; Levey, Allan L.; Lah, James J.; Behan, Kelly; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Farlow, Martin R.; Saykin, Andrew J.; Foroud, Tatiana M.; Shen, Li; Faber, Kelly; Kim, Sungeun; Nho, Kwangsik; Marie Hake, Ann; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Petersen, Ronald; Jack, Clifford R.; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Chertkow, Howard; Hosein, Chris; Mintzer, Jacob; Spicer, Kenneth; Bachman, David; Grossman, Hillel; Mitsis, Effie; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Potter, William; Buckholtz, Neil; Hsiao, John; Kittur, Smita; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Johnson, Nancy; Chuang-Kuo; Kerwin, Diana; Bonakdarpour, Borna; Weintraub, Sandra; Grafman, Jordan; Lipowski, Kristine; Mesulam, Marek-Marsel; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Borrie, Michael; Lee, T-Y; Bartha, Rob; Martinez, Walter; Villena, Teresa; Sadowsky, Carl; Khachaturian, Zaven; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Frank, Richard; Fleischman, Debra; Arfanakis, Konstantinos; Shah, Raj C.; deToledo-Morrell, Leyla; Sorensen, Greg; Finger, Elizabeth; Pasternack, Stephen; Rachinsky, Irina; Drost, Dick; Rogers, John; Kertesz, Andrew; Furst, Ansgar J.; Chad, Stevan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Mudge, Benita; Assaly, Michele; Fox, Nick; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Ekstam Smith, Karen; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Natelson Love, Marissa; DeCarli, Charles; Carmichael, Owen; Olichney, John; Maillard, Pauline; Fletcher, Evan; Nguyen, Dana; Preda, Andrian; Potkin, Steven; Mulnard, Ruth A.; Thai, Gaby; McAdams-Ortiz, Catherine; Landau, Susan; Jagust, William; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Thompson, Paul; Donohue, Michael; Thomas, Ronald G.; Walter, Sarah; Gessert, Devon; Brewer, James; Vanderswag, Helen; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Aisen, Paul; Davis, Melissa; Morrison, Rosemary; Harvey, Danielle; Thal, Lean; Beckett, Laurel; Neylan, Thomas; Finley, Shannon; Weiner, Michael W.; Hayes, Jacqueline; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Massoglia, Dino; Brawman-Mentzer, Olga; Schuff, Norbert; Smith, Charles D.; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Koeppe, Robert A.; Lord, Joanne L.; Heidebrink, Judith L.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Trojanowki, John Q.; Shaw, Leslie M.; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Foster, Norm; Montine, Tom; Fruehling, J. Jay; Harding, Sandra; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Petrie, Eric C.; Peskind, Elaine; Li, Gail; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Kuller, Lew; Mathis, Chet; Ann Oakley, Mary; Lopez, Oscar L.; Simpson, Donna M.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Cairns, Nigel J.; Raichle, Marc; Morris, John C.; Householder, Erin; Taylor-Reinwald, Lisa; Holtzman, David; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Varma, Pradeep; MacAvoy, Martha G.; Carson, Richard E.; van Dyck, Christopher H.; Davies, Peter; Holtzman, David; Morris, John C.; Bales, Kelly; Pickering, Eve H.; Lee, Jin-Moo; Heitsch, Laura; Kauwe, John; Goate, Alison; Piccio, Laura; Cruchaga, Carlos

2016-01-01

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes, and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels, and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r, and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects, and complex disease associations in the same locus.

Topical anti-inflammatory potential of Physalin E from Physalis angulata on experimental dermatitis in mice.

PubMed

Pinto, N B; Morais, T C; Carvalho, K M B; Silva, C R; Andrade, G M; Brito, G A C; Veras, M L; Pessoa, O D L; Rao, V S; Santos, F A

2010-08-01

The anti-inflammatory effect of physalin E, a seco-steroid isolated from Physalis angulata L. was evaluated on acute and chronic models of dermatitis induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and oxazolone, respectively, in mouse ear. The changes in ear edema/thickness, production of pro-inflammatory cytokines (TNF-alpha and IFN-gamma), myeloperoxidase (MPO) activity, and histological and immunohistochemical findings were analysed, as indicators of dermal inflammation. Similar to dexamethasone, topically applied Physalin E (0.125; 0.25 and 0.5 mg/ear) potently inhibited the TPA and oxazolone-induced dermatitis, leading to substantial reductions in ear edema/thickness, pro-inflammatory cytokines, and MPO activity. These effects were reversed by mifepristone, a steroid antagonist and confirmed by immunohistochemical and histopathological analysis. The data suggest that physalin E may be a potent and topically effective anti-inflammatory agent useful to treat the acute and chronic skin inflammatory conditions. 2010 Elsevier GmbH. All rights reserved.

Synergistic effect of the interaction between naproxen and citral on inflammation in rats.

PubMed

Ortiz, Mario I; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Aguilar-Robles, Paulina

2010-12-15

The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

Platelets, diabetes and myocardial ischemia/reperfusion injury.

PubMed

Russo, Isabella; Penna, Claudia; Musso, Tiziana; Popara, Jasmin; Alloatti, Giuseppe; Cavalot, Franco; Pagliaro, Pasquale

2017-05-31

Mechanisms underlying the pathogenesis of ischemia/reperfusion injury are particularly complex, multifactorial and highly interconnected. A complex and entangled interaction is also emerging between platelet function, antiplatelet drugs, coronary diseases and ischemia/reperfusion injury, especially in diabetic conditions. Here we briefly summarize features of antiplatelet therapy in type 2 diabetes (T2DM). We also treat the influence of T2DM on ischemia/reperfusion injury and how anti-platelet therapies affect post-ischemic myocardial damage through pleiotropic properties not related to their anti-aggregating effects. miRNA-based signature associated with T2DM and its cardiovascular disease complications are also briefly considered. Influence of anti-platelet therapies and different effects of healthy and diabetic platelets on ischemia/reperfusion injury need to be further clarified in order to enhance patient benefits from antiplatelet therapy and revascularization. Here we provide insight on the difficulty to reduce the cardiovascular risk in diabetic patients and report novel information on the cardioprotective role of widely used anti-aggregant drugs.

Synthesis and anti-inflammatory effect of chalcones and related compounds.

PubMed

Hsieh, H K; Lee, T H; Wang, J P; Wang, J J; Lin, C N

1998-01-01

Mast cell and neutrophil degranulations are the important players in inflammatory disorders. Combined with potent inhibition of chemical mediators released from mast cells and neutrophil degranulations, it could be a promising anti-inflammatory agent. 2',5'-Dihydroxychalcone has been reported as a potent chemical mediator and cyclooxygenase inhibitor. In an effort to continually develop potent anti-inflammatory agents, a novel series of chalcone, 2'- and 3'-hydroxychalcones, 2',5'-dihydroxychalcones and flavanones were continually synthesized to evaluate their inhibitory effects on the activation of mast cells and neutrophils and the inhibitory effect on phlogist-induced hind-paw edema in mice. A series of chalcones and related compounds were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde and the anti-inflammatory activities of these synthetic compounds were studied on inhibitory effects on the activation of mast cells and neutrophils. Some chalcones showed strong inhibitory effects on the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. Almost all chalcones and 4'-hydroxyflavanone exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Some chalcones showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP/cytochalasin B (CB) or phorbol myristate acetate (PMA). 2',3-Dihydroxy-, 2',5'-dihydroxy-4-chloro-, and 2',5'-dihydroxychalcone showed remarkable inhibitory effects on hind-paw edema induced by polymyxin B in normal as well as in adrenalectomized mice. These results indicated that the anti-inflammatory effects of these compounds were mediated, at least partly, through the suppression of chemical mediators released from mast cells and neutrophils.

Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice.

PubMed

Shao, Guoxi; Tian, Yinggang; Wang, Haiyu; Liu, Fangning; Xie, Guanghong

2015-12-01

Melatonin, a secretory product of the pineal gland, has been reported to have antioxidant and anti-inflammatory effects. However, the protective effects of melatonin on lipopolysaccharide (LPS)-induced mastitis have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of melatonin on LPS-induced mastitis both in vivo and in vitro. In vivo, our results showed that melatonin attenuated LPS-induced mammary histopathologic changes and myeloperoxidase (MPO) activity. Melatonin also inhibited LPS-induced inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in mammary tissues. In vitro, melatonin was found to inhibit LPS-induced TNF-α and IL-6 production in mouse mammary epithelial cells. Melatonin also suppressed LPS-induced Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activation in a dose-dependent manner. In addition, melatonin was found to up-regulate the expression of PPAR-γ. Inhibition of PPAR-γ by GW9662 reduced the anti-inflammatory effects of melatonin. In conclusion, we found that melatonin, for the first time, had protective effects on LPS-induced mastitis in mice. The anti-inflammatory mechanism of melatonin was through activating PPAR-γ which subsequently inhibited LPS-induced inflammatory responses. Copyright © 2015 Elsevier B.V. All rights reserved.

Anti-inflammatory effects of Lactobacillus brevis K65 on RAW 264.7 cells and in mice with dextran sulphate sodium-induced ulcerative colitis.

PubMed

Liu, Y-W; Ong, W-K; Su, Y-W; Hsu, C-C; Cheng, T-H; Tsai, Y-C

2016-06-01

Lactic acid bacteria (LAB) with anti-inflammatory effects may be beneficial to the prevention or treatment for inflammation-related diseases, such as inflammatory bowel diseases. In an in vitro assay, heat-killed Lactobacillus brevis K65 (K65) reduced lipopolysaccharide-induced production of nitric oxide, tumour necrosis factor (TNF)-α and prostaglandin E2 in RAW 264.7 cells. In RAW 264.7 cells stably expressing an ind=ucible nitric oxide synthase (iNOS) reporter, viable K65 showed greater inhibition of iNOS production than its heat-killed form. In order to further examine the in vivo anti-inflammatory effect of K65, viable K65 was orally administered to BALB/c mice before and during the period of dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). K65 improved UC symptoms, including reduced the levels of the pro-inflammatory cytokines, TNF-α, interleukin (IL)-6 and IL-1β, and lowered the activity of myeloperoxidase. Furthermore, K65 inhibited TNF-α, cyclo-oxygenase 2, forkhead box P3, and Toll-like receptor 4 mRNA expression in the colonic tissue of DSS-induced UC mice. Taken together, K65, a LAB with in vitro anti-inflammatory activity showed preventive effects on mice with DSS-induced UC by lowering the expression of inflammatory molecules.

Anti-inflammatory effects of a Houttuynia cordata supercritical extract

PubMed Central

Shin, Sunhee; Joo, Seong Soo; Jeon, Jeong Hee; Park, Dongsun; Jang, Min-Jung; Kim, Tae-Ook; Kim, Hyun-Kyu; Hwang, Bang Yeon; Kim, Ki-Yon

2010-01-01

Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in a carrageenan-air pouch model. HSE (200 mg/kg, oral) suppressed exudation and albumin leakage, as well as inflammatory cell infiltration. Dexamethasone (2 mg/kg, i.p.) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content. HSE lowered tumor-necrosis factor (TNF)-α and nitric oxide (NO), as well as prostaglandin E2 (PGE2). Dexamethasone only reduced TNF-α and NO, while indomethacin decreased TNF-α and PGE2. The suppressive activity of HSE on NO and PGE2 production was confirmed in RAW 264.7. These results demonstrate that HSE exerts anti-inflammatory effects by inhibiting both TNF-α-NO and cyclooxygenase II-PGE2 pathways. PMID:20706037

GPER expressed on microglia mediates the anti-inflammatory effect of estradiol in ischemic stroke.

PubMed

Zhao, Tian-Zhi; Ding, Qian; Hu, Jun; He, Shi-Ming; Shi, Fei; Ma, Lian-Ting

2016-04-01

Stroke could lead to serious morbidity, of which ischemic stroke counts for majority of the cases. Inflammation plays an important role in the pathogenesis of ischemic stroke, thus drugs targeting inflammation could be potentially neuroprotective. Estradiol was shown to be neuroprotective as well as anti-inflammatory in animal models of ischemic stroke with unclear mechanism. We hypothesize that the anti-inflammatory and neuroprotective effect of estradiol is mediated by the estradiol receptor G protein-coupled estrogen receptor 1 (GPER) expressed on microglia. We have generated the rat global cerebral ischemic model and the primary microglia culture to study the neuroprotective and anti-inflammatory effect of estradiol. We have further used pharmacological methods and siRNA knockdown approach to study the underlying mechanism. We found that estradiol reduced the level of proinflammatory cytokines including IL-1β and TNF-α, both in vivo and in vitro. We also found that the specific GPER agonist G1 could reduce the level of IL-1β (P = 0 P = 0.0017, one-way ANOVA and post hoc test) and TNF-α (P < 0.0001) in the primary microglia culture. Moreover, the specific GPER antagonist G15 was able to abolish the anti-inflammatory effect of estradiol. Estradiol failed to reduce the level of IL-1β (P = 0.4973, unpaired Student's t-test) and TNF-α (P = 0.1627) when GPER was knocked down. Our studies have suggested that GPER expressed on microglia mediated the anti-inflammatory effect of estradiol after ischemic stroke. Our studies could potentially help to develop more specific drugs to manage inflammation postischemic stroke.

Inhibition of COX-2 and PGE2 in LPS-stimulated RAW264.7 cells by lonimacranthoide VI, a chlorogenic acid ester saponin

PubMed Central

GUAN, FUQIN; WANG, HAITING; SHAN, YU; CHEN, YU; WANG, MING; WANG, QIZHI; YIN, MIN; ZHAO, YOUYI; FENG, XU; ZHANG, JIANHUA

2014-01-01

Lonimacranthoide VI, first isolated from the flower buds of Lonicera macranthoides in our previous study, is a rare chlorogenic acid ester acylated at C-23 of hederagenin. In the present study, the anti-inflammatory effects of lonimacranthoide VI were studied. Lipopolysaccharides (LPS) induced an inflammatory response through the production of prostaglandin E2 (PGE2), and these levels were reduced when lonimacranthoide VI was pre-administered. Additionally, the mechanism of the anti-inflammatory effects of lonimacranthoide VI was investigated by measuring cyclooxygenase (COX) activity and mRNA expression. The results showed that lonimacranthoide VI inhibited mRNA expression and in vitro activity of COX-2 in a dose-dependent manner, whereas only the higher lonimacranthoide VI concentration possibly reduced COX-1 expression and in vitro activity. Taken together, these results indicate that lonimacranthoide VI is an important anti-inflammatory constituent of Lonicera macranthoides and that the anti-inflammatory effect is attributed to the inhibition of PGE2 production through COX activity and mRNA expression. PMID:25054024

6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ.

PubMed

Han, Qinghe; Yuan, Qinghai; Meng, Xiaolin; Huo, Junyuan; Bao, Yuxin; Xie, Guanghong

2017-06-27

6-Shogaol, a pungent agent isolated from Zingiber officinale Roscoe, has been known to have anti-tumor and anti-inflammatory effects. However, the anti-inflammatory effects and biological mechanism of 6-Shogaol in LPS-activated BV2 microglia remains largely unknown. In this study, we evaluated the anti-inflammatory effects of 6-Shogaol in LPS-activated BV2 microglia. 6-Shogaol was administrated 1 h before LPS treatment. The production of inflammatory mediators were detected by ELISA. The expression of NF-κB and PPAR-γ were detected by western blot analysis. Our results revealed that 6-Shogaol inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2 production in a concentration dependent manner. Furthermore, 6-Shogaol inhibited LPS-induced NF-κB activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. In addition, 6-Shogaol could increase the expression of PPAR-γ. Moreover, inhibition of PPAR-γ by GW9662 could prevent the inhibition of 6-Shogaol on LPS-induced inflammatory mediator production. In conclusion, 6-Shogaol inhibits LPS-induced inflammation by activating PPAR-γ.

Synthesis, evaluation and modeling of some triazolothienopyrimidinones as anti-inflammatory and antimicrobial agents.

PubMed

Bekhit, Adnan A; Farghaly, Ahmed M; Shafik, Ragab M; Elsemary, Mona Ma; El-Shoukrofy, Mai S; Bekhit, Alaa El-Din A; Ibrahim, Tamer M

2017-06-01

New triazolotetrahydrobenzothienopyrimidinone derivatives were synthesized. Their structures were confirmed, and their anti-inflammatory, antimicrobial activities and ulcerogenic potentials were evaluated. Compounds 7a, 10a and 11a showed minimal ulcerogenic effect and high selectivity toward human recombinant COX-2 over COX-1 enzyme with IC 50 values of 1.39, 1.22 and 0.56 μM, respectively. Their docking outcome correlated with their biological activity and confirmed the high selectivity binding toward COX-2. Compound 12b displayed antimicrobial activity comparable to that of ampicillin against Escherichia coli while compounds 6 and 11c were similar to ampicillin against Staphylococcus aureus. In addition, compounds 7a, 9a, 10b and 11c showed dual anti-inflammatory/antimicrobial activities. This work represents a promising matrix for developing new potential anti-inflammatory, antimicrobial and dual antimicrobial/anti-inflammatory candidates. [Formula: see text].

Purification and function of two analgesic and anti-inflammatory peptides from coelomic fluid of the earthworm, Eisenia foetida.

PubMed

Li, Chunlong; Chen, Mengrou; Li, Xiaojie; Yang, Meifeng; Wang, Ying; Yang, Xinwang

2017-03-01

The potential application of anti-inflammatory and analgesic compounds in medication and therapeutic care have become of increasing interest. We purified and characterized two novel analgesic and anti-inflammatory peptides, VQ-5 and AQ-5, from the coelomic fluid of the earthworm (Eisenia foetida). Their primary structures were determined as VSSVQ and AMADQ, respectively. Both peptides, especially AQ-5, exhibited analgesic activity in mouse models of persistent neuropathic pain and inflammation. AQ-5 also inhibited tumor necrosis factor alpha and cyclooxygenase-2 production. The mitogen-activated protein kinase signaling pathway, which is involved in analgesic and anti-inflammatory functions, was inhibited by AQ-5. Thus, the analgesic and anti-inflammatory effects of these peptides, especially AQ-5, demonstrated their potential as candidates for the development of novel analgesic medicines. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-inflammatory and in-vitro antibacterial activities of Traditional Chinese Medicine Formula Qingdaisan.

PubMed

Zhao, Xinghua; He, Xin; Zhong, Xiuhui

2016-12-05

Qingdaisan (Formulated Indigo powder, QDS) are widely used for treatment of aphtha, sore throat and bleeding gums in China. The aim of the study is to evaluate the anti-inflammatory, antibacterial and dental ulcer therapeutic effects of QDS. Dimethylbenzene-induced ear edema test and cotton pellet-induced granuloma test were used to evaluate anti-inflammatory activities of QDS on acute and chronic inflammatory. The healing time and local pathologic changes were used to assess the therapeutic effects of QDS on dental ulcer. The antibacterial activities of each component and the whole formulation of QDS were determined by agar well diffusion assay. High-dose and low-dose QDS were tested in this experiment and Gui Lin Watermelon Frost Powder (GLWFP) was used as positive control. Oral treatment with QDS significantly accelerated the healing of ulcerative lesions induced by phenol injury. The dental ulcers of high-dose QDS group were all healed within 6 days. It was shorter than those of low-dose QDS group and GLWFP group. Less quantity of inflammatory cells and plenty fibroblasts were observed in pathological section of QDS groups. QDS also exhibited significant anti-inflammatory activity both in acute and chronic animal models. Although some of the components exhibited antibacterial activities, the whole formulation of QDS didn't show any significant antibacterial activity in vitro. The study showed that QDS has obviously anti-inflammatory activity for both acute and chronic inflammatory, also has a remarkable effect for healing dental ulcer caused by phenol. QDS didn't have antibacterial activity to selected strains in vitro.

The anti-inflammatory effect of cherry blossom extract (Prunus yedoensis) used in soothing skincare product.

PubMed

Zhang, Y Q; Guan, L; Zhong, Z Y; Chang, M; Zhang, D K; Li, H; Lai, W

2014-12-01

Previous investigations suggested that cherry blossoms could provide valuable bioactive materials. However, few observations regarding the anti-inflammatory effect of cherry blossoms were reported. This study was to explore the anti-inflammatory effect of cherry blossom extract (CBE), which was used as a soothing ingredient in skincare product. In vitro study, the anti-inflammatory effect of CBE on the nitric oxide (NO) inhibition assay in lipopolysaccharide (LPS)-treated RAW 264.7 cells was investigated. In vivo study, 40 volunteers were included in a randomized, single-blinded, placebo-controlled trial. 24-hour-occlusive test chambers were applied on the flexor side of the forearm with 3% sodium lauryl sulphate (SLS). Subsequently, the test areas were treated on 9 subsequent days with a cream containing 3% CBE or a placebo. Evaluation included a visual score and determination of erythema value (E value). In vitro study, 2% CBE reduced NO production by 31.83% compared to the placebo. In the SLS irritant patch test, the visual score and erythema value of CBE were lower than that of the placebo on D5 and D9. Cherry blossom extract shows good anti-inflammatory effect in vitro and in vivo and represents a promising functional ingredient in soothing skincare product by reducing skin inflammation. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

The non-peptide GLP-1 receptor agonist WB4-24 blocks inflammatory nociception by stimulating β-endorphin release from spinal microglia

PubMed Central

Fan, Hui; Gong, Nian; Li, Teng-Fei; Ma, Ai-Niu; Wu, Xiao-Yan; Wang, Ming-Wei; Wang, Yong-Xiang

2015-01-01

BACKGROUND AND PURPOSE Two peptide agonists of the glucagon-like peptide-1 (GLP-1) receptor, exenatide and GLP-1 itself, exert anti-hypersensitive effects in neuropathic, cancer and diabetic pain. In this study, we have assessed the anti-allodynic and anti-hyperalgesic effects of the non-peptide agonist WB4-24 in inflammatory nociception and the possible involvement of microglial β-endorphin and pro-inflammatory cytokines. EXPERIMENTAL APPROACH We used rat models of inflammatory nociception induced by formalin, carrageenan or complete Freund's adjuvant (CFA), to test mechanical allodynia and thermal hyperalgesia. Expression of β-endorphin and pro-inflammatory cytokines was measured using real-time quantitative PCR and fluorescent immunoassays. KEY RESULTS WB4-24 displaced the specific binding of exendin (9–39) in microglia. Single intrathecal injection of WB4-24 (0.3, 1, 3, 10, 30 and 100 μg) exerted dose-dependent, specific, anti-hypersensitive effects in acute and chronic inflammatory nociception induced by formalin, carrageenan and CFA, with a maximal inhibition of 60–80%. Spinal WB4-24 was not effective in altering nociceptive pain. Subcutaneous injection of WB4-24 was also antinociceptive in CFA-treated rats. WB4-24 evoked β-endorphin release but did not inhibit expression of pro-inflammatory cytokines in either the spinal cord of CFA-treated rats or cultured microglia stimulated by LPS. WB4-24 anti-allodynia was prevented by a microglial inhibitor, β-endorphin antiserum and a μ-opioid receptor antagonist. CONCLUSIONS AND IMPLICATIONS Our results suggest that WB4-24 inhibits inflammatory nociception by releasing analgesic β-endorphin rather than inhibiting the expression of proalgesic pro-inflammatory cytokines in spinal microglia, and that the spinal GLP-1 receptor is a potential target molecule for the treatment of pain hypersensitivity including inflammatory nociception. PMID:25176008

Advancements in anti-inflammatory therapy for dry eye syndrome.

PubMed

McCabe, Erin; Narayanan, Srihari

2009-10-01

The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting. The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome. Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects. Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.

Antimicrobial and anti-inflammatory potential therapy for opportunistic microorganisms.

PubMed

Assaf, Areej M; Amro, Bassam I; Mashallah, Sundus; Haddadin, Randa N

2016-05-31

Methanolic extracts of six plants (Arbutus andrachne, Chrysanthemum coronarium, Inula viscosa, Origanum syriacum, Punica granatum, and Rosmarinus officinalis) used in traditional medicine for the treatment of bacterial and fungal infections were evaluated. The present study was conducted to evaluate the antimicrobial and anti-inflammatory activity of some medicinal plants in lowering the risk of opportunistic infections of the oral cavity caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Extracts were evaluated separately and in a mixture. The methanolic plant extracts were tested against three opportunistic microorganisms by determining the minimum inhibitory concentration (MIC). They were also evaluated for their ability to suppress the release of the pro-inflammatory cytokine IL-6 while not suppressing the release of the anti-inflammatory cytokine IL-10 from peripheral blood mononuclear cells using ELISA. All extracts showed both antimicrobial and anti-inflammatory activities. However, O. syriacum exhibited the highest antimicrobial activity for the three microorganisms among all of the tested extracts (MIC S. aureus: 1 mg/mL; P. aeruginosa: 2 mg/mL; and C. albicans: 1 mg/mL). The extracts inhibited the expression of the pro-inflammatory cytokine IL-6 with apparent dose-dependent responses while they attenuated the secretion of the anti-inflammatory cytokine IL-10. The mixture of O. syriacum and R. officinalis showed an anti-inflammatory effect, with a synergistic antimicrobial effect. These findings support the idea that a diet rich in plants and herbs may contribute to the reduction of inflammation and microbial growth and may also be preventive against various infections, including those related to the oral cavity.

Effect of Naringin on Monosodium Iodoacetate-Induced Osteoarthritis Pain in Rats.

PubMed

Xu, Qiang; Zhang, Zuo-Fu; Sun, Wei-Xue

2017-08-02

BACKGROUND The aim of the current study was to evaluate the anti-osteoarthritic and anti-inflammatory effect of naringin in a monosodium iodoacetate (MIA)- induced osteoarthritis (OA) model in rats. The anti-osteoarthritic potential of naringin was evaluated against the MIA-induced OA rat model. MATERIAL AND METHODS Wistar rats were used for the study and were divided into the following groups: normal control (saline-treated); group II (MIA-treated): group III (MIA+Naringin), and group IV (MIA+Indomethacin). The potential effect of naringin was evaluated via its effect on the level of proinflammatory cytokines, measuring the weight-bearing distribution, and histopathological analysis. RESULTS The anti-inflammatory effect of naringin was assessed in vitro in lipopolysaccharide-induced RAW 264.6 cells. The results suggest that naringin exerts an anti-inflammatory effect via reducing the production of the prostaglandin E2 (PGE2), nitric oxide (NO), interlukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced RAW cells. Additionally, naringin also supported the recovery of hind-limb weight-bearing, reduced the generation or production of inflammatory mediator and proinflammatory cytokines, and protected the tissue from the damage in the OA model. CONCLUSIONS Naringin appears to be an effective therapeutic drug for the treatment of the OA and OA-related symptoms.

Effect of Naringin on Monosodium Iodoacetate-Induced Osteoarthritis Pain in Rats

PubMed Central

Xu, Qiang; Zhang, Zuo-fu; Sun, Wei-xue

2017-01-01

Background The aim of the current study was to evaluate the anti-osteoarthritic and anti-inflammatory effect of naringin in a monosodium iodoacetate (MIA)- induced osteoarthritis (OA) model in rats. The anti-osteoarthritic potential of naringin was evaluated against the MIA-induced OA rat model. Material/Methods Wistar rats were used for the study and were divided into the following groups: normal control (saline-treated); group II (MIA-treated): group III (MIA+Naringin), and group IV (MIA+Indomethacin). The potential effect of naringin was evaluated via its effect on the level of proinflammatory cytokines, measuring the weight-bearing distribution, and histopathological analysis. Result The anti-inflammatory effect of naringin was assessed in vitro in lipopolysaccharide-induced RAW 264.6 cells. The results suggest that naringin exerts an anti-inflammatory effect via reducing the production of the prostaglandin E2 (PGE2), nitric oxide (NO), interlukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced RAW cells. Additionally, naringin also supported the recovery of hind-limb weight-bearing, reduced the generation or production of inflammatory mediator and proinflammatory cytokines, and protected the tissue from the damage in the OA model. Conclusions Naringin appears to be an effective therapeutic drug for the treatment of the OA and OA-related symptoms. PMID:28765519

Vagal-immune interactions involved in cholinergic anti-inflammatory pathway.

PubMed

Zila, I; Mokra, D; Kopincova, J; Kolomaznik, M; Javorka, M; Calkovska, A

2017-09-22

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

Antinociceptive and anti-inflammatory activities of standardized extract of polymethoxyflavones from Ageratum conyzoides.

PubMed

Faqueti, Larissa G; Brieudes, Vincent; Halabalaki, Maria; Skaltsounis, Alexios L; Nascimento, Leandro F; Barros, Wellinghton M; Santos, Adair R S; Biavatti, Maique W

2016-12-24

Ageratum conyzoides L. is a plant widely used in traditional medicine in tropical and subtropical regions of the world due to its anti-inflammatory, antinociceptive and antibacterial properties. To characterize the standardized extract of polymethoxyflavones (SEPAc) from the plant and evaluate its antinociceptive and anti-inflammatory effects. The SEPAc purified from the ethanol extract of the plant leaves was characterized by high resolution mass spectrometry and the methoxyflavones were quantified by a validated UPLC-PDA method. The antinociceptive and anti-inflammatory activities of the SEPAc were evaluated after oral administration on the acute nocifensive behavior of mice induced by formalin, prostaglandin E2 (PGE2) and proinflammatory cytokines (interleukin-1beta (IL-1β)) and tumor necrosis factor-alpha (TNF-α) in mice. Qualitative analyses revealed the presence of seven methoxyflavones in the SEPAc, also a simple UPLC-PDA method was developed and validated for the quantification of 5,6,7,3',4',5'-hexametoxyflavone; nobiletin; 5'-methoxynobiletin and eupalestin, major compounds in the extract. The SEPAc exhibited antinociceptive and anti-inflammatory activities in both formalin phases, with significant inhibition of the paw edema formation and significant reduction of the nocifensive response induced by an intraplantar injection of PGE2 and intrathecal injection of interleukin-1β. The SEPAc exhibited significant antinociceptive and anti-inflammatory effects. These results provided scientific suggestion of its potential as a source of new medicines to treat inflammatory diseases, such rheumatoid arthritis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Amauroderma rugosum (Blume & T. Nees) Torrend: Nutritional Composition and Antioxidant and Potential Anti-Inflammatory Properties

PubMed Central

Chan, Pui-Mun; Kanagasabapathy, Gowri; Tan, Yee-Shin; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

2013-01-01

Amauroderma rugosum is a wild mushroom that is worn as a necklace by the indigenous communities in Malaysia to prevent fits and incessant crying by babies. The aim of this study was to investigate the nutritive composition and antioxidant potential and anti-inflammatory effects of A. rugosum extracts on LPS-stimulated RAW264.7 cells. Nutritional analysis of freeze-dried mycelia of A. rugosum (KUM 61131) from submerged culture indicated a predominant presence of carbohydrates, proteins, dietary fibre, phosphorus, potassium, and sodium. The ethanol crude extract (EE), its hexane (HF), ethyl acetate (EAF), and aqueous (AF) fractions of mycelia of A. rugosum grown in submerged culture were evaluated for antioxidant potential and anti-inflammatory effects. EAF exhibited the highest total phenolic content and the strongest antioxidant activity based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. HF showed dose-dependent inhibition of NO production in LPS-stimulated RAW264.7 cells and NO radical scavenging activity. Gas chromatographic analysis of HF revealed the presence of ethyl linoleate and ergosterol, compounds with known anti-inflammatory properties. In conclusion, the nutritive compositions and significant antioxidant potential and anti-inflammatory effects of mycelia extracts of A. rugosum have the potential to serve as a therapeutic agent or adjuvant in the management of inflammatory disorders. PMID:24371454

Amomum tsao-ko suppresses lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages via Nrf2-dependent heme oxygenase-1 expression.

PubMed

Li, Bin; Choi, Hee-Jin; Lee, Dong-Sung; Oh, Hyuncheol; Kim, Youn-Chul; Moon, Jin-Young; Park, Won-Hwan; Park, Sun-Dong; Kim, Jai-Eun

2014-01-01

Amomum tsao-ko Crevost et Lemaire, used as a spice in Asia, is an important source of Chinese cuisine and traditional Chinese medicines. A. tsao-ko is reported to exert a variety of biological and pharmacological activities, including anti-proliferative, anti-oxidative and neuroprotective effects. In this study, NNMBS227, consisting of the ethanol extract of A. tsao-ko, exhibited potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS227 in the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-1β) in LPS stimulated macrophages. NNMBS227 also inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of nuclear factor kappa B (NF-κB) p65 caused by stimulation with LPS. In addition, NNMBS227 induced heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. Using tin protoporphyrin (SnPP), an HO activity inhibitor, we confirmed an association between the anti-inflammatory effects of NNMBS227 and the up-regulation of HO-1. These findings suggest that Nrf2-dependent increases in the expression of HO-1 induced by NNMBS227 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy.

PubMed

Dall, Lawrence; Peterson, Sandford; Simmons, Tom; Dall, Amy

2005-03-01

There is some evidence to suggest that host inflammatory response has some effect on the clinical manifestations of cellulitis. The objective of this pilot study was to investigate whether the addition of oral nonsteroidal anti-inflammatory (NSAI) therapy to antibiotic treatment hastens resolution of cellulitis-related inflammation. Patients presenting in the emergency department with signs and symptoms of class II cellulitis were assigned to receive treatment with either antibiotic therapy alone (intravenous, supplemented with oral cephalexin or an equivalent) for 10 days (n = 33) or antibiotic therapy for 10 days plus an oral anti-inflammatory (ibuprofen 400 mg every 6 hours) for 5 days (n = 31). Patients were discharged as soon as possible to complete their therapy on an outpatient basis. The addition of an oral anti-inflammatory agent significantly (P < .05) shortened the time to regression of inflammation and complete resolution of cellulitis. Twenty-four of 29 evaluable patients (82.8%) who received supplemental anti-inflammatory treatment showed regression of inflammation within 1 to 2 days compared with only 3 of 33 patients (9.1%) treated without an anti-inflammatory in the same time frame. All patients receiving adjunctive anti-inflammatory treatment experienced complete resolution of cellulitis in 4 to 5 days or less, while 24.2% (8/33) of patients treated with antibiotic alone required 6 to 7 days, and 6.1% (2/33) required 7 days or more (P < .05). This small preliminary study provides some promising data, suggesting that the supplemental use of anti-inflammatory therapy may hasten the time to regression of inflammation and complete resolution of cellulitis.

Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens.

PubMed

Jin, Jeong Ho; Kim, Ju Sun; Kang, Sam Sik; Son, Kun Ho; Chang, Hyun Wook; Kim, Hyun Pyo

2010-02-17

The roots of Sophora flavescens have long been used in Chinese medicine for the treatment of fever, inflammatory disorders, ulcers and skin burns. Sophora flavescens contains flavonoids and alkaloids. This study was conducted to develop a plant-based anti-inflammatory agent focused on chronic inflammatory disorders. To accomplish this, the alkaloid-free prenylated flavonoid-enriched fraction (PFS) of rhizomes of Sophora flavescens was prepared and its in vitro and in vivo anti-inflammatory activities were then evaluated for the first time. The inhibitory activity of PFS on PGE(2), NO, IL-6 and TNF-alpha production of lipopolysaccharide (LPS)-treated RAW 264.7 cells was measured. Additionally, adjuvant-induced arthritis in rats was used as an animal model of chronic inflammation to establish the in vivo anti-inflammatory effects of PFS. PFS inhibited cyclooxygenase-2 (COX-2)-catalyzed PGE(2) and inducible nitric oxide synthase (iNOS)-catalyzed NO production by lipopolysaccharide (LPS)-treated RAW 264.7 cells at 10-50 microg/ml, and these effects primarily occurred via COX-2 inhibition and iNOS down-regulation, respectively. PFS also inhibited IL-6 and TNF-alpha production. When tested against adjuvant-induced arthritis in rats (chronic inflammation), PFS strongly inhibited arthritic inflammation when administered orally at doses of 10-100mg/kg/day. In addition, PFS administered orally potently inhibited acetic acid-induced writhing in mice. Our results suggest that PFS inhibits chronic inflammatory response and the inhibition of proinflammatory molecules such as COX-2, iNOS and IL-6 may contribute, at least in part, to the anti-inflammatory activity in vivo. Overall, these results indicate that PFS from Sophora flavescens may have the potential for treatment of chronic inflammatory disorders such as rheumatoid arthritis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Curcumin as a natural regulator of monocyte chemoattractant protein-1.

PubMed

Karimian, Maryam Saberi; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

2017-02-01

Monocyte chemoattractant/chemotactic protein-1 (MCP-1), a member of the CC chemokine family, is one of the key chemokines that regulate migration and tissue infiltration of monocytes/macrophages. Its role in the pathophysiology of several inflammatory diseases has been widely recognized, thus making MCP-1 a possible target for anti-inflammatory treatments. Curcumin (diferuloylmethane) is a natural polyphenol derived from the rhizomes of Curcuma Longa L. (turmeric). Anti-inflammatory action underlies numerous pharmacological effects of curcumin in the control and prevention of several diseases. The purpose of this review is to evaluate the effects of curcumin on the regulation of MCP-1 as a key mediator of chemotaxis and inflammation, and the biological consequences thereof. In vitro studies have shown that curcumin can decrease MCP-1 production in various cell lines. Animal studies have also revealed that curcumin can attenuate MCP-1 expression and improve a range of inflammatory diseases through multiple molecular targets and mechanisms of action. There is limited data from human clinical trials showing the decreasing effect of curcumin on MCP-1 concentrations and improvement of the course of inflammatory diseases. Most of the in vitro and animal studies confirm that curcumin exert its MCP-1-lowering and anti-inflammatory effects by down-regulating the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway. As yet, there is limited data from human clinical trials showing the effect of curcumin on MCP-1 levels and improvement of the course of inflammatory diseases. More evidence, especially from human studies, is needed to better assess the effects of curcumin on circulating MCP-1 in different human diseases and the role of this modulatory effect in the putative anti-inflammatory properties of curcumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-Inflammatory Effect of Combination of Scutellariae Radix and Liriopis Tuber Water Extract

PubMed Central

So, Mi-Hye; Choi, You-Kyung

2015-01-01

Scutellariae Radix and Liriopis Tuber have been used to treat the inflammatory diseases in traditional Korean medicine and anti-inflammatory effect of each herb has been shown partially in several articles. However, the combined extract of these medicinal herbs (SL) has not been reported for its anti-inflammatory effects. In this study, we investigated the effects of SL on the creation of several proinflammatory mediators in RAW 264.7 cell mouse macrophages induced by Lipopolysaccharide (LPS). SL inhibited significantly the increase of NO, the release of intracellular calcium, the increase of interleukin-6 (IL-6), macrophage inflammatory proteins (MIP-1α, MIP-1β, and MIP-2), and granulocyte colony-stimulating factor (G-CSF) in LPS-induced RAW 264.7 cell at the concentrations of 25, 50, and 100 μg/mL, and SL inhibited significantly the increase of macrophage colony-stimulating factor (M-CSF) at the concentrations of 25 and 50 μg/mL, and tumor necrosis factor (TNF) at the concentration of 25 μg/mL. These results implicate that SL has anti-inflammatory effects by suppressing the production of various inflammatory mediators in macrophages. But SL did not inhibit significantly the increase of granulocyte macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES); therefore, further study is demanded for the follow-up research to find out the possibility of SL as a preventive and therapeutic medicine for various inflammatory diseases. PMID:26604969

Mast cell: an emerging partner in immune interaction.

PubMed

Gri, Giorgia; Frossi, Barbara; D'Inca, Federica; Danelli, Luca; Betto, Elena; Mion, Francesca; Sibilano, Riccardo; Pucillo, Carlo

2012-01-01

Mast cells (MCs) are currently recognized as effector cells in many settings of the immune response, including host defense, immune regulation, allergy, chronic inflammation, and autoimmune diseases. MC pleiotropic functions reflect their ability to secrete a wide spectrum of preformed or newly synthesized biologically active products with pro-inflammatory, anti-inflammatory and/or immunosuppressive properties, in response to multiple signals. Moreover, the modulation of MC effector phenotypes relies on the interaction of a wide variety of membrane molecules involved in cell-cell or cell-extracellular-matrix interaction. The delivery of co-stimulatory signals allows MC to specifically communicate with immune cells belonging to both innate and acquired immunity, as well as with non-immune tissue-specific cell types. This article reviews and discusses the evidence that MC membrane-expressed molecules play a central role in regulating MC priming and activation and in the modulation of innate and adaptive immune response not only against host injury, but also in peripheral tolerance and tumor-surveillance or -escape. The complex expression of MC surface molecules may be regarded as a measure of connectivity, with altered patterns of cell-cell interaction representing functionally distinct MC states. We will focalize our attention on roles and functions of recently discovered molecules involved in the cross-talk of MCs with other immune partners.

Mast Cell: An Emerging Partner in Immune Interaction

PubMed Central

Gri, Giorgia; Frossi, Barbara; D’Inca, Federica; Danelli, Luca; Betto, Elena; Mion, Francesca; Sibilano, Riccardo; Pucillo, Carlo

2012-01-01

Mast cells (MCs) are currently recognized as effector cells in many settings of the immune response, including host defense, immune regulation, allergy, chronic inflammation, and autoimmune diseases. MC pleiotropic functions reflect their ability to secrete a wide spectrum of preformed or newly synthesized biologically active products with pro-inflammatory, anti-inflammatory and/or immunosuppressive properties, in response to multiple signals. Moreover, the modulation of MC effector phenotypes relies on the interaction of a wide variety of membrane molecules involved in cell–cell or cell-extracellular-matrix interaction. The delivery of co-stimulatory signals allows MC to specifically communicate with immune cells belonging to both innate and acquired immunity, as well as with non-immune tissue-specific cell types. This article reviews and discusses the evidence that MC membrane-expressed molecules play a central role in regulating MC priming and activation and in the modulation of innate and adaptive immune response not only against host injury, but also in peripheral tolerance and tumor-surveillance or -escape. The complex expression of MC surface molecules may be regarded as a measure of connectivity, with altered patterns of cell–cell interaction representing functionally distinct MC states. We will focalize our attention on roles and functions of recently discovered molecules involved in the cross-talk of MCs with other immune partners. PMID:22654879

IL27 controls skin tumorigenesis via accumulation of ETAR-positive CD11b cells in the pre-malignant skin

PubMed Central

Dibra, Denada; Mitra, Abhisek; Newman, Melissa; Xia, Xueqing; Keenan, Camille; Cutrera, Jeffry J.; Mathis, J. Michael; Wang, Xiao-Jing; Myers, Jeffrey; Li, Shulin

2016-01-01

Establishment of a permissive pre-malignant niche in concert with mutant stem are key triggers to initiate skin carcinogenesis. An understudied area of research is finding upstream regulators of both these triggers. IL27, a pleiotropic cytokine with both pro- and anti-inflammatory properties, was found to be a key regulator of both. Two step skin carcinogenesis model and K15-KRASG12D mouse model were used to understand the role of IL27 in skin tumors. CD11b−/− mice and small-molecule of ETAR signaling (ZD4054) inhibitor were used in vivo to understand mechanistically how IL27 promotes skin carcinogenesis. Interestingly, using in vivo studies, IL27 promoted papilloma incidence primarily through IL27 signaling in bone-marrow derived cells. Mechanistically, IL27 initiated the establishment of the pre-malignant niche and expansion of mutated stem cells in K15-KRASG12D mouse model by driving the accumulation of Endothelin A receptor (ETAR)-positive CD11b cells in the skin—a novel category of pro-tumor inflammatory identified in this study. These findings are clinically relevant, as the number of IL27RA-positive cells in the stroma is highly related to tumor de-differentiation in patients with squamous cell carcinomas. PMID:27738312

A Beneficial Effect of Low-Dose Aspirin in a Murine Model of Active Tuberculosis

PubMed Central

Kroesen, Vera Marie; Rodríguez-Martínez, Paula; García, Eric; Rosales, Yaiza; Díaz, Jorge; Martín-Céspedes, Montse; Tapia, Gustavo; Sarrias, Maria Rosa; Cardona, Pere-Joan; Vilaplana, Cristina

2018-01-01

An excessive, non-productive host-immune response is detrimental in active, chronic tuberculosis (TB) disease as it typically leads to tissue damage. Given their anti-inflammatory effect, non-steroidal anti-inflammatory drugs can potentially attenuate excessive inflammation in active TB disease. As such, we investigated the prophylactic and therapeutic effect of low-dose aspirin (LDA) (3 mg/kg/day), either alone or in combination with common anti-TB treatment or BCG vaccination, on disease outcome in an experimental murine model of active TB. Survival rate, bacillary load (BL) in lungs, and lung pathology were measured. The possible mechanism of action of LDA on the host’s immune response was also evaluated by measuring levels of CD5L/AIM, selected cytokines/chemokines and other inflammatory markers in serum and lung tissue. LDA increased survival, had anti-inflammatory effects, reduced lung pathology, and decreased bacillary load in late-stage TB disease. Moreover, in combination with common anti-TB treatment, LDA enhanced survival and reduced lung pathology. Results from the immunological studies suggest the anti-inflammatory action of LDA at both a local and a systemic level. Our results showed a systemic decrease in neutrophilic recruitment, decreased levels of acute-phase reaction cytokines (IL-6, IL-1β, and TNF-α) at late stage and a delay in the decrease in T cell response (in terms of IFN-γ, IL-2, and IL-10 serum levels) that occurs during the course of Mycobacterium tuberculosis infection. An anti-inflammatory milieu was detected in the lung, with less neutrophil recruitment and lower levels of tissue factor. In conclusion, LDA may be beneficial as an adjunct to standard anti-TB treatment in the later stage of active TB by reducing excess, non-productive inflammation, while enhancing Th1-cell responses for elimination of the bacilli. PMID:29740435

Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

PubMed

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.

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

Extracellular cathepsin K exerts antimicrobial activity and is protective against chronic intestinal inflammation in mice.

PubMed

Sina, Christian; Lipinski, Simone; Gavrilova, Olga; Aden, Konrad; Rehman, Ateequr; Till, Andreas; Rittger, Andrea; Podschun, Rainer; Meyer-Hoffert, Ulf; Haesler, Robert; Midtling, Emilie; Pütsep, Katrin; McGuckin, Michael A; Schreiber, Stefan; Saftig, Paul; Rosenstiel, Philip

2013-04-01

Cathepsin K is a lysosomal cysteine protease that has pleiotropic roles in bone resorption, arthritis, atherosclerosis, blood pressure regulation, obesity and cancer. Recently, it was demonstrated that cathepsin K-deficient (Ctsk(-/-) ) mice are less susceptible to experimental autoimmune arthritis and encephalomyelitis, which implies a functional role for cathepsin K in chronic inflammatory responses. Here, the authors address the relevance of cathepsin K in the intestinal immune response during chronic intestinal inflammation. Chronic colitis was induced by administration of 2% dextran sodium sulphate (DSS) in distilled water. Mice were assessed for disease severity, histopathology and endoscopic appearance. Furthermore, DSS-exposed Ctsk(-/-) mice were treated by rectal administration of recombinant cathepsin K. Intestinal microflora was assessed by real-time PCR and 16srDNA molecular fingerprinting of ileal and colonic mucosal and faecal samples. Using Ctsk(-/-) mice, the authors demonstrate a protective role of cathepsin K against chronic DSS colitis. Dissecting the underlying mechanisms the authors found cathepsin K to be present in intestinal goblet cells and the mucin layer. Furthermore, a direct cathepsin K-mediated bactericidal activity against intestinal bacteria was demonstrated, which potentially explains the alteration of intestinal microbiota observed in Ctsk(-/-) mice. Rectal administration of recombinant cathepsin K in DSS-treated Ctsk(-/-) mice ameliorates the severity of intestinal inflammation. These data identify extracellular cathepsin K as an intestinal antibacterial factor with anti-inflammatory potential and suggest that topical administration of cathepsin K might provide a therapeutic option for patients with inflammatory bowel disease.

Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology.

PubMed

Pyle, Chloe J; Uwadiae, Faith I; Swieboda, David P; Harker, James A

2017-09-01

Interleukin-6 is a pleiotropic, pro-inflammatory cytokine that can promote both innate and adaptive immune responses. In humans with respiratory virus infections, such as Respiratory Syncytial Virus (RSV), elevated concentrations of IL-6 are associated with more severe disease. In contrast the polymorphisms in the Il6 promoter which favour lower IL-6 production are associated with increased risk of both RSV and Rhinovirus infections. To determine the precise contribution of IL-6 to protection and pathology we used murine models of respiratory virus infection. RSV infection resulted in increased IL-6 production both in the airways and systemically which remained heightened for at least 2 weeks. IL-6 depletion early, but not late, during RSV or Influenza A virus infection resulted in significantly increased disease associated with an influx of virus specific TH1 and cytotoxic CD8+ T cells, whilst not affecting viral clearance. IL-6 acted by driving production of the immunoregulatory cytokine IL-27 by macrophages and monocytes, which in turn promoted the local maturation of regulatory T cells. Concordantly IL-27 was necessary to regulate TH1 responses in the lungs, and sufficient to limit RSV induced disease. Overall we found that during respiratory virus infection the prototypic inflammatory cytokine IL-6 is a critical anti-inflammatory regulator of viral induced immunopathology in the respiratory tract through its induction of IL-27.

Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology

PubMed Central

Swieboda, David P.

2017-01-01

Interleukin-6 is a pleiotropic, pro-inflammatory cytokine that can promote both innate and adaptive immune responses. In humans with respiratory virus infections, such as Respiratory Syncytial Virus (RSV), elevated concentrations of IL-6 are associated with more severe disease. In contrast the polymorphisms in the Il6 promoter which favour lower IL-6 production are associated with increased risk of both RSV and Rhinovirus infections. To determine the precise contribution of IL-6 to protection and pathology we used murine models of respiratory virus infection. RSV infection resulted in increased IL-6 production both in the airways and systemically which remained heightened for at least 2 weeks. IL-6 depletion early, but not late, during RSV or Influenza A virus infection resulted in significantly increased disease associated with an influx of virus specific TH1 and cytotoxic CD8+ T cells, whilst not affecting viral clearance. IL-6 acted by driving production of the immunoregulatory cytokine IL-27 by macrophages and monocytes, which in turn promoted the local maturation of regulatory T cells. Concordantly IL-27 was necessary to regulate TH1 responses in the lungs, and sufficient to limit RSV induced disease. Overall we found that during respiratory virus infection the prototypic inflammatory cytokine IL-6 is a critical anti-inflammatory regulator of viral induced immunopathology in the respiratory tract through its induction of IL-27. PMID:28953978

Anti-inflammatory, analgesic and antipyretic effects of Lepidagathis anobrya Nees (Acanthaceae).

PubMed

Richard, Sawadogo Wamtinga; Marius, Lompo; Noya, Somé; Innocent Pierre, Guissou; Germaine, Nacoulma-Ouedraogo Odile

2011-01-01

This study investigated the general acute, anti-inflammatory, analgesic and antipyretic effects of methanol extract of Lepidagathis anobrya Nees (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema in rats were used for the evaluation of general acute anti-inflammatory effects. Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were used to evaluate the analgesic and antipyretic activities respectively. The extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of 0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw and ear edemas in rats. In the analgesic and antipyretic tests, the extract has shown a significant inhibition of writhes and hyperpyrexia with all the doses used when compared to the untreated control group. These results clearly show the anti-inflammatory, analgesic and antipyretic effects of the methanol extract of Lepidagathis anobrya and give the scientific basis for its traditional use. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.

The investigation of anti-inflammatory activity of Yi Guanjian decoction by serum metabonomics approach.

PubMed

Shui, Sufang; Cai, Xiaorong; Huang, Rongqing; Xiao, Bingkun; Yang, Jianyun

2017-01-30

Yi Guanjian (YGJ), one of the Chinese herbal medicines most commonly used in western countries, reported to possess significant anti-inflammatary effects that inhibit the process of inflammation. However, the mechanisms underlying its anti-inflammation effects remain largely unresolved. This study was aimed to investigate the anti-inflammatory activity of YGJ and to explore its potential anti-inflammatory mechanisms by serum metabonomics approach. An xylene-induced mouse right-ear-edema model was used as an inflammatory response in vivo model. Ear edema, prostaglandin E2 (PGE 2 ) and Tumor-Necrosis-Factor-alpha (TNF-α) were detected. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after YGJ administration and further integration of metabolic networks. The results showed that YGJ alleviated ear edema and decreased serum PGE 2 and TNF-α levels. Fourteen biomarkers were screened, and the levels were all reversed to different degrees after YGJ administration. These biomarkers were mainly related to linoleic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism and citrate cycle (TCA cycle). In metabolic networks, glycine and pyruvate were node molecules. This indicated that YGJ could significantly inhibit inflammatory response triggered by acute local stimulation and exerted anti-inflammatory activity mainly by regulating node molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of dietary resveratrol supplementation on hepatic and serum pro-/anti-inflammatory activity in juvenile GIFT tilapia, Oreochromis niloticus.

PubMed

Zheng, Yao; Zhao, Zhixiang; Wu, Wei; Song, Chao; Meng, Shunlong; Fan, Limin; Bing, Xuwen; Chen, Jiazhang

2017-08-01

Dietary resveratrol (RES) supplementation may have some pharmacological effects including anti-inflammation. Previous studies have shown that Kupffer cell activation and apoptosis induction increases the transcription of pro- and anti-inflammatory cytokines. The main purpose of this study was to investigate the pro- and anti-inflammatory activities of 0.1 or 0.3 g/kg RES as a dietary supplement in juvenile freshwater tilapia (Oreochromis niloticus). The results showed that hepatic and serum immunoglobulin M (IgM) significantly decreased and increased while anti- and pro-inflammatory cytokines significantly increased and decreased, respectively, in the RES-treated groups. The expression of serum and hepatic IgM and anti-inflammatory cytokines [interleukin (IL)-10] and its inverse inhibitor interferon (IFN)-γ significantly increased while pro-inflammatory cytokine transcription significantly decreased. Hematoxylin-eosin staining and scanning electron microscopy revealed intestinal deformation, irregular goblet cells, and apoptotic cells in the 0.3 g/kg RES groups. RES (0.3 g/kg) also induced necrosis, apoptosis, reduction in Kupffer cell number, compressed sinusoids, and deformation of epidermal cells in the liver of the treated groups. In conclusion, the results of the present study show that high doses of RES were absorbed in the gut and then damaged the liver and intestinal tissue. Copyright © 2017. Published by Elsevier Ltd.

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

PubMed

Ribeiro, Alison; Ferraz-de-Paula, Viviane; Pinheiro, Milena L; Vitoretti, Luana B; Mariano-Souza, Domenica P; Quinteiro-Filho, Wanderley M; Akamine, Adriana T; Almeida, Vinícius I; Quevedo, João; Dal-Pizzol, Felipe; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Palermo-Neto, João

2012-03-05

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor. Copyright © 2012 Elsevier B.V. All rights reserved.

Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kodera, Ryo, E-mail: kodera@cc.okayama-u.ac.jp; Shikata, Kenichi; Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558

Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbationmore » of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.« less

Novel leads from Heliotropium ovalifolium, 4,7,8-trimethoxy-naphthalene-2-carboxylic acid and 6-hydroxy-5,7-dimethoxy-naphthalene-2-carbaldehyde show specific IL-6 inhibitory activity in THP-1 cells and primary human monocytes.

PubMed

Kulkarni-Almeida, Asha; Suthar, Ashish; Goswami, Hitesh; Vishwakarma, Ram; Chauhan, Vijay Singh; Balakrishnan, Arun; Sharma, Somesh

2008-12-01

From our screening program, we identified the anti-inflammatory effects of the extracts of Heliotropium ovalifolium in its ability to inhibit specific cytokines. The H. ovalifolium extract was found to be moderately active with an IC(50) equaling 10 microg/ml for inhibition of interleukin-6 (IL-6) in a human monocytic cell line. Interleukin-6 is a pleiotropic cytokine with implications in the regulation of the immune response, inflammation and hematopoiesis. This prompted us to examine and identify the active molecules that are responsible for the bioactivity in THP-1 cells. Bioassay guided fractionation identified two compounds 4,7,8-trimethoxy-naphthalene-2-carboxylic acid and 6-hydroxy-5,7-dimethoxy-naphthalene-2-carbaldehyde with an IC(50) of 2.4 and 2.0 microM for IL-6 inhibition and an IC(50) of 15.6 and 7.0 microM for tumor necrosis factor-alpha (TNF-alpha) inhibition in THP-1 cells. The protein expression data were supported by the inhibitory effect on mRNA gene expression. The compounds isolated from H. ovalifolium were also non-toxic in human peripheral blood monocytes from normal donors and the activity profile was similar to that obtained on THP-1 cells. Thus, we believe that these scaffolds may be of interest to develop leads for treating rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease and other inflammatory disorders. However, more detailed investigations need to be carried out to explain the efficacy of these compounds as drugs.

Rosuvastatin Attenuates CD40L-Induced Downregulation of Extracellular Matrix Production in Human Aortic Smooth Muscle Cells via TRAF6-JNK-NF-κB Pathway

PubMed Central

Wang, Xiao-Lin; Zhou, Yuan-Li; Sun, Wei; Li, Li

2016-01-01

CD40L and statins exhibit pro-inflammatory and anti-inflammatory effects, respectively. They are both pleiotropic and can regulate extracellular matrix (ECM) degeneration in an atherosclerotic plaque. Statins can decrease both the CD40 expression and the resulting inflammation. However, the effects of CD40L and stains on atherosclerotic plaque ECM production and the underlying mechanisms are not well established. Moreover, prolyl-4-hydroxylase α1 (P4Hα1) is involved in collagen synthesis but its correlations with CD40L and statins are unknown. In the present study, CD40L suppressed P4Hα1 expression in human aortic smooth muscle cells (HASMCs) in a dose- and time-dependent manner, with insignificant changes in MMP2 expression and negative enzymatic activity of MMP9. CD40L increased TRAF6 expression, JNK phosphorylation, NF-κB nuclear translocation as well as DNA binding. Furthermore, silencing TRAF6, JNK or NF-κB genes abolished CD40L-induced suppression of P4Hα1. Lower NF-κB nuclear import rates were observed when JNK or TRAF6 silenced HASMCs were stimulated with CD40L compared to HASMCs with active JNK or TRAF6. Together, these results indicate that CD40L suppresses P4Hα1 expression in HASMCs by activating the TRAF6-JNK- NF-κB pathway. We also found that rosuvastatin inhibits CD40L-induced activation of the TRAF6-JNK- NF-κB pathway, thereby significantly rescuing the CD40L stimulated P4Hα1 inhibition. The results from this study will help find potential targets for stabilizing vulnerable atherosclerotic plaques. PMID:27120457

New insights into the ameliorative effects of ferulic acid in pathophysiological conditions.

PubMed

Ghosh, Sumit; Basak, Priyanka; Dutta, Sayanta; Chowdhury, Sayantani; Sil, Parames C

2017-05-01

Ferulic acid, a natural phytochemical has gained importance as a potential therapeutic agent by virtue of its easy commercial availability, low cost and minimal side-effects. It is a derivative of curcumin and possesses the necessary pharmacokinetic properties to be retained in the general circulation for several hours. The therapeutic effects of ferulic acid are mediated through its antioxidant and anti-inflammatory properties. It exhibits different biological activities such as anti-inflammatory, anti-apoptotic, anti-carcinogenic, anti-diabetic, hepatoprotective, cardioprotective, neuroprotective actions, etc. The current review addresses its therapeutic effects under different pathophysiological conditions (eg. cancer, cardiomyopathy, skin disorders, brain disorders, viral infections, diabetes etc.). Copyright © 2017 Elsevier Ltd. All rights reserved.

Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions

PubMed Central

Mohri, Shinsuke; Takahashi, Haruya; Sakai, Maiko; Takahashi, Shingo; Waki, Naoko; Aizawa, Koichi; Suganuma, Hiroyuki; Ara, Takeshi; Matsumura, Yasuki; Shibata, Daisuke; Goto, Tsuyoshi; Kawada, Teruo

2018-01-01

Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A vicious cycle involving pro-inflammatory mediators between adipocytes and macrophages is a common cause of chronic inflammation in the adipose tissue. Tomato is one of the most popular vegetables and is associated with a reduced risk of diabetes. However, the molecular mechanism underlying the effect of tomato on diabetes is unclear. In this study, we focused on anti-inflammatory compounds in tomato. We found that the extract of tomato reduced plasma glucose and inflammatory markers in mice. We screened anti-inflammatory fractions in tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active compounds were estimated by liquid chromatography-mass spectrometry over a wide range. Surprisingly, a large number of compounds including oxylipin and coumarin derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo-octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation and inhibitor of kappa B α protein degradation. These findings suggest that tomato containing diverse anti-inflammatory compounds ameliorates chronic inflammation in obese adipose tissue. PMID:29329333

UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect

PubMed Central

Couteau, Céline; Chauvet, Catherine; Paparis, Eva; Coiffard, Laurence

2012-01-01

Background To explain observed differences during SPF determination using either an in vivo or in vitro method, we hypothesized on the presence of ingredients having anti-inflammatory properties. Methodology/Principal Findings To research our hypothesis, we studied the 21 UV filters both available on the market and authorized by European regulations and subjected these filters to the phorbol-myristate-acetate test using mice. We then catalogued the 13 filters demonstrating a significant anti-inflammatory effect with edema inhibition percentages of more than 70%. The filters are: diethylhexyl butamido triazone (92%), benzophenone-5 and titanium dioxide (90%), benzophenone-3 (83%), octocrylène and isoamyl p-methoxycinnamate (82%), PEG-25 PABA and homosalate (80%), octyl triazone and phenylbenzimidazole sulfonic acid (78%), octyl dimethyl PABA (75%), bis-ethylhexyloxyphenol methoxyphenyl triazine and diethylamino hydroxybenzoyl hexylbenzoate (70%). These filters were tested at various concentrations, including their maximum authorized dose. We detected a dose-response relationship. Conclusions/Significance The anti-inflammatory effect of a sunscreen ingredient may affect the in vivo SPF value. PMID:23284607

In vitro studies on the relationship between the anti-inflammatory activity of Physalis peruviana extracts and the phagocytic process.

PubMed

Martínez, Willington; Ospina, Luis Fernando; Granados, Diana; Delgado, Gabriela

2010-03-01

The study of plants used in traditional medicine has drawn the attention of researchers as an alternative in the development of new therapeutics agents, such as the American Solanaceae Physalis peruviana, which has significant anti-inflammatory activity. The Physalis peruviana anti-inflammatory effect of ethanol or ether calyces extracts on the phagocytic process was assessed by using an in vitro phagocytosis model (Leishmania panamensis infection to murine macrophages). The Physalis peruviana extracts do not inhibit microorganism internalization and have no parasiticide effect. Most ET and EP extracts negatively affected the parasite's invasion of macrophages (Infected cells increased.). This observation might result from a down-regulation of the macrophage's microbicide ability associated with a selective reduction of proinflammatory cytokines levels. Physalis peruviana's anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which directly or indirectly "blocks" their ability to secrete soluble proinflammatory mediators.

Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases.

PubMed

Piechota-Polanczyk, Aleksandra; Fichna, Jakub

2014-07-01

In this review, we focus on the role of oxidative stress in the aetiology of inflammatory bowel diseases (IBD) and colitis-associated colorectal cancer and discuss free radicals and free radical-stimulated pathways as pharmacological targets for anti-IBD drugs. We also suggest novel anti-oxidative agents, which may become effective and less-toxic alternatives in IBD and colitis-associated colorectal cancer treatment. A Medline search was performed to identify relevant bibliography using search terms including: 'free radicals,' 'antioxidants,' 'oxidative stress,' 'colon cancer,' 'ulcerative colitis,' 'Crohn's disease,' 'inflammatory bowel disease.' Several therapeutics commonly used in IBD treatment, among which are immunosuppressants, corticosteroids and anti-TNF-α antibodies, could also affect the IBD progression by interfering with cellular oxidative stress and cytokine production. Experimental data shows that these drugs may effectively scavenge free radicals, increase anti-oxidative capacity of cells, influence multiple signalling pathways, e.g. MAPK and NF-kB, and inhibit pro-oxidative enzyme and cytokine concentration. However, their anti-oxidative and anti-inflammatory effectiveness still needs further investigation. A highly specific antioxidative activity may be important for the clinical treatment and relapse of IBD. In the future, a combination of currently used pharmaceutics, together with natural and synthetic anti-oxidative compounds, like lipoic acid or curcumine, could be taken into account in the design of novel anti-IBD therapies.

Effects of Lactobacillus plantarum Strain OLL2712 Culture Conditions on the Anti-inflammatory Activities for Murine Immune Cells and Obese and Type 2 Diabetic Mice.

PubMed

Toshimitsu, T; Ozaki, S; Mochizuki, J; Furuichi, K; Asami, Y

2017-04-01

Studies on the health-promoting effects of lactic acid bacteria (LAB) are numerous, but few provide examples of the relationship between LAB function and culture conditions. We verified the effect of differences in culture conditions on Lactobacillus plantarum OLL2712 functionality; this strain exhibits anti-inflammatory activity and preventive effects against metabolic disorders. We measured interleukin-10 (IL-10) and IL-12 production in murine immune cells treated with OLL2712 cells prepared under various culture conditions. The results showed that the IL-10-inducing activities of OLL2712 cells on murine immune cells differed dramatically between OLL2712 groups at different culture phases and using different culture medium components, temperatures, and neutralizing pHs. In particular, exponential-phase cells had much more IL-10-inducing activity than stationary-phase cells. We confirmed that the Toll-like receptor 2 (TLR2) stimulation activity of OLL2712 cells depended on culture conditions in conjunction with IL-10-inducing activity. We also demonstrated functional differences by culture phases in vivo ; OLL2712 cells at exponential phase had more anti-inflammatory activity and anti-metabolic-disorder effects on obese and diabetic mice than those by their stationary-phase counterparts. These results suggest that culture conditions affect the functionality of anti-inflammatory LAB. IMPORTANCE While previous studies demonstrated that culture conditions affected the immunomodulatory properties of lactic acid bacteria (LAB), few have comprehensively investigated the relationship between culture conditions and LAB functionality. In this study, we demonstrated several culture conditions of Lactobacillus plantarum OLL2712 for higher anti-inflammatory activity. We also showed that culture conditions concretely influenced the health-promoting functions of OLL2712 in vivo , particularly against metabolic disorders. Further, we characterized a novel mechanism by which changing LAB culture conditions affected immunomodulatory properties. Our results suggest that culture condition optimization is important for the production of LAB with anti-inflammatory activity. Copyright © 2017 American Society for Microbiology.

Synthesis and biological evaluation of allylated and prenylated mono-carbonyl analogs of curcumin as anti-inflammatory agents.

PubMed

Liu, Zhiguo; Tang, Longguang; Zou, Peng; Zhang, Yali; Wang, Zhe; Fang, Qilu; Jiang, Lili; Chen, Gaozhi; Xu, Zheng; Zhang, Huajie; Liang, Guang

2014-03-03

Curcumin has been shown to possess anti-inflammatory activities but has been limited for its low stability and poor bioavailability. We have previously reported four series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MACs). In continuation of our ongoing research, we designed and synthesized 33 novel allylated or prenylated MACs here, and evaluated their anti-inflammatory effects in RAW 264.7 macrophages. A majority of them effectively inhibited the LPS-induced expression of TNF-α and IL-6, especially IL-6. The preliminary SAR and quantitative SAR analysis were conducted. Compound 14q is the most potent analog among them, and exhibits significant protection against LPS-induced death in septic mice. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

PubMed Central

Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-01-01

Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain. PMID:27559448

Corydalis bungeana Turcz. attenuates LPS-induced inflammatory responses via the suppression of NF-κB signaling pathway in vitro and in vivo.

PubMed

Zhai, Xiao-Ting; Chen, Jia-Quan; Jiang, Cui-Hua; Song, Jie; Li, Dong-Yu; Zhang, Hao; Jia, Xiao-Bin; Tan, Wei; Wang, Shu-Xia; Yang, Yi; Zhu, Fen-Xia

2016-12-24

Corydalis bungeana Turcz. (C. bungeana) is one of traditionally used medicines in China and possesses various biological effects, such as anti-inflammatory, antibacterial activity and inhibition of the immune function of the host. we studied the anti-inflammatory effect and molecular mechanism involved of C. bungeana both in vitro and in vivo model system in which the inflammatory response was induced by LPS treatment. Anti-inflammatory activity of C. bungeana was investigated by LPS-induced RAW 264.7 macrophages and BALB/c mice. The production and expression of pro-inflammatory cytokines were evaluated by Griess reagent, ELISA kits and RT-qPCR, respectively. Phosphorylation status of IκBα and p65 was illustrated by western blot assay. C. bungeana reduced the secretion of NO, TNF-α, IL-6 and IL-1β through inhibiting the protein expression of iNOS, TNF-α, IL-6 and IL-1β in vitro and in vivo. Western blot analysis suggested that C. bungeana supressed NF-κB activation via regulating the phosphorylation of IκBα and p65. Immunohistochemical assay also demostrated the histological inflammatory change in liver tissue. The results indicate that C. bungeana supresses the activation of NF-κB signaling pathway through inhibiting phosphorylation of IκBα and p65, which results in good anti-inflammatory effect. In addition, C. bungeana attenuates inflammatory reaction by supressing the expression of various inflammatory cytokines both in vivo and in vitro. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities.

PubMed

Kashyap, Dharambir; Sharma, Ajay; Tuli, Hardeep S; Punia, Sandeep; Sharma, Anil K

2016-01-01

Plant derived products are not only served as dietary components but also used to treat and prevent the inflammatory associated diseases like cancer. Among the natural products pentacyclic terpenoids including ursolic acid and oleanolic acid are considered as the promising anti-inflammatory therapeutic agents. The current review extensively discusses the anti-inflammatory therapeutic potential of these pentacyclic moieties along with their proposed mechanisms of action. Furthermore, the relevant patents have also been listed to present the health benefits of these promising therapeutic agents to pin down the inflammatory diseases. Expert opinion: Pentacyclic terpenoids are known to negatively down-regulate a variety of extracellular and intracellular molecular targets associated with disease progression. The major anti-inflammatory effects of these molecules have been found to be mediated via inactivation of NFkB, STAT3/6, Akt/mTOR pathways. A number of patents on UA & OA based moieties have been reported between 2010 and 2016. Still there have been only a few compounds which meet the need of sufficient hydro solubility and bioavailability along with higher anti-inflammatory activities. Thus, it is essential to develop novel derivatives of terpenpoids which may not only overcome the solubility issues but also may improve their therapeutic effects. In addition, scientific community may utilize nanotechnology based drug delivery systems so as to increase the bio-availability, selectivity and dosages related problems.

Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid.

PubMed

Siriwardhana, Nalin; Kalupahana, Nishan S; Moustaid-Moussa, Naima

2012-01-01

Marine-based fish and fish oil are the most popular and well-known sources of n-3 polyunsaturated fatty acids (PUFAs), namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These n-3 PUFAs are known to have variety of health benefits against cardiovascular diseases (CVDs) including well-established hypotriglyceridemic and anti-inflammatory effects. Also, various studies indicate promising antihypertensive, anticancer, antioxidant, antidepression, antiaging, and antiarthritis effects. Moreover, recent studies also indicate anti-inflammatory and insulin-sensitizing effects of these fatty acids in metabolic disorders. Classically, n-3 PUFAs mediate some of these effects by antagonizing n-6 PUFA (arachidonic acid)-induced proinflammatory prostaglandin E₂ (PGE₂) formation. Another well-known mechanism by which n-3 PUFAs impart their anti-inflammatory effects is via reduction of nuclear factor-κB activation. This transcription factor is a potent inducer of proinflammatory cytokine production, including interleukin 6 and tumor necrosis factor-α, both of which are decreased by EPA and DHA. Other evidence also demonstrates that n-3 PUFAs repress lipogenesis and increase resolvins and protectin generation, ultimately leading to reduced inflammation. Finally, beneficial effects of EPA and DHA in insulin resistance include their ability to increase secretion of adiponectin, an anti-inflammatory adipokine. In summary, n-3 PUFAs have multiple health benefits mediated at least in part by their anti-inflammatory actions; thus their consumption, especially from dietary sources, should be encouraged. Copyright © 2012 Elsevier Inc. All rights reserved.

Anti-inflammatory effects of Artemisia princeps in antigen-stimulated T cells and regulatory T cells.

PubMed

Chang, Sung Ho; Jung, Eun Jung; Park, Youn Hee; Lim, Dong Gyun; Ko, Na Young; Choi, Wahn Soo; Her, Erk; Kim, Soo Hyun; Choi, Kang Duk; Bae, Jae Ho; Kim, Sun Hee; Kang, Chi Dug; Han, Duck Jong; Kim, Song Cheol

2009-08-01

The aim was to investigate the anti-inflammatory effects of Artemisia princeps extract on the activity of anti-CD3/CD28-stimulated CD4(+)CD25(-) T cells and antigen-expanded regulatory T cells. CD4(+)CD25(-) T cells were activated with coated anti-CD3 and anti-CD28 and cultured in the presence or absence of various concentrations of A. princeps extract. The cultures were pulsed on Day 6 with [(3)H]thymidine and, after harvesting the cells, [(3)H]thymidine incorporation was measured. For analysis of interleukin-2 and interferon-gamma secreted from CD4(+)CD25(-) T cells, culture supernatants were collected on Days 2 and 6. For the analysis of interleukin-10 secreted from the CD4(+)CD25(-) T cells and expanded regulatory T cells, supernatants were collected after 2 and 7 days, respectively. Cytokine levels were determined using an enzyme-linked immunosorbent assay. Potential medicinal components of the A. princeps extract were determined using gas chromatography-mass spectrometry. A. princeps (30 microg/ml) effectively suppressed proliferation of CD4(+)CD25(-) T cells that were stimulated with anti-CD3/CD28 without causing cytotoxicity in spleen cells incubated under conditions lacking antigen stimulation. A. princeps inhibited production of the pro-inflammatory cytokines interleukin-2 and interferon-gamma in anti-CD3/CD28-stimulated CD4(+)CD25(-) T cells. Also, the extract slightly increased production of the anti-inflammatory cytokine interleukin-10 in these cells. In regulatory T cells expanded by anti-CD3/CD28, A. princeps increased production of interleukin-10 and Foxp3. The results suggest that A. princeps may be useful in the treatment of autoimmune diseases and organ transplantation rejection by inhibiting proliferation of inflammatory T cells, suppressing inflammatory processes in antigen-stimulated CD4(+)CD25(-) T cells and increasing activity of expanded regulatory T cells.

Anti-leishmanial, anti-inflammatory and antimicrobial activities of phenolic derivatives from Tibouchina paratropica.

PubMed

Tracanna, María I; Fortuna, Antonio M; Cárdenas, Angel V Contreras; Marr, Alexandra K; McMaster, W Robert; Gómez-Velasco, Anaximandro; Sánchez-Arreola, Eugenio; Hernández, Luis Ricardo; Bach, Horacio

2015-03-01

A new phenolic derivative, 2,8-dihydroxy-7H-furo[2,3-f]chromen-7-one (1), together with isoquercitrin (2), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti-parasitic activity against Leishmania donovani (IC50  = 0.809 µg/mL). In addition, an 85% reduction in the secretion of the pro-inflammatory cytokine IL-6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1, but no effect on the anti-inflammatory IL-10 was observed. Compound 2 showed neither anti-parasitic nor anti-inflammatory properties. In addition, no cytotoxic activities were observed against the human-derived macrophage THP-1 cells. Copyright © 2014 John Wiley & Sons, Ltd.

Influence of the anti-inflammatory compound flosulide on granulocyte function.

PubMed

Zimmerli, W; Sansano, S; Wiesenberg-Böttcher, I

1991-10-24

Polymorphonuclear leukocytes (PMN) are involved in inflammatory reactions. It is thought that oxygen-derived free radicals released from activated PMN may participate in tissue damage during inflammation. We have shown that flosulide (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ), a novel highly potent anti-inflammatory compound, inhibits superoxide production induced by N-formyl-Met-Leu-Phe (FMLP), C5a and PMA without impairing bacterial killing or chemotaxis. Flosulide (10(-5)-10(-7) M) was more potent in inhibiting the FMLP-induced respiratory burst of PMN than the structurally related compound nimesulide. FMLP-induced superoxide generation was also inhibited by two human flosulide metabolites. A good correlation between this in vitro effect and in vivo anti-inflammatory potency in rat adjuvant arthritis was found for flosulide and its metabolites. Indomethacin, piroxicam and ibuprofen did not inhibit the respiratory burst at 10(-5) M. FMLP receptor number was decreased by 36% in the presence of 10(-5) M flosulide. However, a 250-fold molar excess of flosulide could not displace labeled FMLP from the receptor. Inhibition of degranulation of primary and secondary granules was a common effect of all anti-inflammatory compounds tested. At a concentration of 10(-5) M, all drugs inhibited degranulation to about the same degree, independent of their in vivo anti-inflammatory activity.

Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

PubMed Central

Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

2014-01-01

Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10 μg/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection. PMID:24799939

Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice.

PubMed

Kawai, Junya; Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

2014-01-01

Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10  μ g/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3-1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

Anti-inflammatory and anti-pyretic properties of Spirulina platensis and Spirulina lonar: a comparative study.

PubMed

Somchit, Muhammad Nazrul; Mohamed, Nor Azura; Ahmad, Zuraini; Zakaria, Zainul Amiruddin; Shamsuddin, Lokman; Omar-Fauzee, Mohd Sofian; Kadir, Arifah Abdul

2014-09-01

Spirulina spp. is a blue-green algae belongs to the family of Oscillatoriaceae, which having diverse biological activity. The aim of this current study was to evaluate and compare the anti-pyretic and anti-inflammatory activity of Spirulina platensis/SP and Spirulina lonar/SL extracts. In the anti-pyretic study, the ability to reduce the rectal temperature of rats induced pyrexia with 2g/kg Brewer's Yeast (BY) was performed. Rats were dosed either 2 or 4 mg/kg SP or SL. Rectal temperature was taken every hour for 8 hours. Results shown that there were significant dose-dependent (p<0.05) reduction of both treatments. However, SP treatment revealed faster reduction in rectal temperature. For anti-inflammatory activity, the reduction in the volume of paw edema induced by Prostaglandin E2 (100 IU/rat intraplantar) was measured. Rats were dosed orally with 2 or 4 mg/kg SP or SL. The paw edema was measured every 30 minutes for 4 hours using plethysmometer. Results had shown a significant dose dependent reduction in diameter of paw edema (p<0.05). The finding suggests that SP and SL extracts have anti-pyretic and anti-inflammatory properties. However, SP was found to be more effective than SL as anti-pyretic and anti-inflammatory agent.

Anti-inflammatory effects of caper (capparis spinosa l.) Fruit aqueous extract and the isolation of main phytochemicals

USDA-ARS?s Scientific Manuscript database

Caper (Capparis spinosa L.) fruits have been used as food as well as folk medicine in the treatment of inflammatory disorders, such as rheumatism. The present study was carried out to study the anti-inflammatory activities of C. spinosa L. fruit (CSF) aqueous extract and to isolate main phytochemica...

Anti-inflammatory and wound healing activities of Aloe littoralis in rats

PubMed Central

Hajhashemi, V.; Ghannadi, A.; Heidari, A.H.

2012-01-01

Aloe littoralis Baker (Asphodelaceae family) is a well known plant in southern parts of Iran. Because of its use in Iranian folk medicine as a wound-healing agent, the present study was carried out to investigate anti-inflammatory and wound healing activities of this plant in Wistar rats. A. littoralis raw mucilaginous gel (ALRMG) and also two gel formulations prepared from the raw mucilaginous gel were used in this study. Gel formulations (12.5% and 100% v/w Aloe mucilage in a carbomer base) were applied topically (500 mg once daily) for 24 days in the thermal wound model. Also Aloe gel formulation (100%) and ALRMG (500 mg daily) were evaluated in incisional wound model. Carrageenan-induced paw edema was used to assess the anti-inflammatory effect of intraperitoneal injection of ALRMG. In burn wound, ALRMG and Aloe formulated gel (100%) showed significant (P<0.05) healing effect. Topical application of ALMRG and Aloe formulated gel (100%) promoted healing rate of incisional wound. In carrageenan test, ALRMG (2.5 and 5 ml/Kg) revealed significant (P<0.05) anti-inflammatory activity. Results showed that A. littoralis is a potential wound-healing and anti-inflammatory agent in rats. Further studies are needed to find out the mechanism of these biological effects and also the active constituents responsible for the effects. PMID:23181083

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onuma, Hirohisa; Inukai, Kouichi, E-mail: kinukai@ks.kyorin-u.ac.jp; Kitahara, Atsuko

Highlights: • PPARγ activation was involved in the GLP-1-mediated anti-inflammatory action. • Exendin-4 enhanced endogenous PPARγ transcriptional activity in HUVECs. • H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement. • The anti-inflammatory effects of GLP-1 may be explained by PPARγ activation. - Abstract: Recent studies have suggested glucagon-like peptide-1 (GLP-1) signaling to exert anti-inflammatory effects on endothelial cells, although the precise underlying mechanism remains to be elucidated. In the present study, we investigated whether PPARγ activation is involved in the GLP-1-mediated anti-inflammatory action on endothelial cells. When we treated HUVEC cells with 0.2 ng/ml exendin-4, a GLP-1 receptor agonist, endogenousmore » PPARγ transcriptional activity was significantly elevated, by approximately 20%, as compared with control cells. The maximum PPARγ activity enhancing effect of exendin-4 was observed 12 h after the initiation of incubation with exendin-4. As H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement, the signaling downstream from GLP-1 cross-talk must have been involved in PPARγ activation. In conclusion, our results suggest that GLP-1 has the potential to induce PPARγ activity, partially explaining the anti-inflammatory effects of GLP-1 on endothelial cells. Cross-talk between GLP-1 signaling and PPARγ activation would have major impacts on treatments for patients at high risk for cardiovascular disease.« less

Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract.

PubMed

Ojewole, John A O

2005-05-13

In order to scientifically appraise some of the ethnomedical uses of Bryophyllum pinnatum leaves, the present study was undertaken to investigate the antinociceptive, anti-inflammatory and antidiabetic properties of the plant's leaf aqueous extract in experimental animal models. The antinociceptive effect of the herb's leaf extract was evaluated by the 'hot-plate' and 'acetic acid' test models of pain in mice. The anti-inflammatory and antidiabetic effects of the plant's extract were investigated in rats, using fresh egg albumin-induced pedal (paw) oedema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used respectively as reference drugs for comparison. Bryophyllum pinnatum leaf aqueous extract (BPE, 25-800 mg/kg i.p.) produced significant (P<0.05-0.001) antinociceptive effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (BPE, 25-800 mg/kg p.o. or i.p.) also significantly (P<0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (P<0.05-0.001) hypoglycaemia in rats. The results of this experimental animal study suggest that Bryophyllum pinnatum leaf aqueous extract possesses antinociceptive, anti-inflammatory and hypoglycaemic properties. The different flavonoids, polyphenols, triterpenoids and other chemical constituents of the herb are speculated to account for the observed antinociceptive, anti-inflammatory and antidiabetic properties of the plant.

Anti-inflammatory, antioxidant and anti-acetylcholinesterase activities of Bouvardia ternifolia: potential implications in Alzheimer's disease.

PubMed

García-Morales, Giovanni; Huerta-Reyes, Maira; González-Cortazar, Manasés; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Silva-García, Raúl; Román-Ramos, Rubén; Aguilar-Rojas, Arturo

2015-07-01

Bouvardia ternifolia has been used medicinally to treat inflammation. In the present study, we investigate the anti-Alzheimer's potential effect of the hydroalcoholic extract of B. ternifolia through evaluation of anti-inflammatory and antioxidant activities, quantification of the percentage inhibition of acetylcholinesterase activity, protection effect against β-amyloid fibrillar-induce neurotoxicity, and the identification of the main constituents. Our results show that B. ternifolia extract and ethyl acetate fraction induced anti-inflammatory effects by reducing inflammation by >70 %, while antioxidant test revealed significant IC50 values for flavonoid content fraction (30.67 ± 2.09 μg/ml) and ethyl acetate fraction (42.66 ± 0.93 μg/ml). The maximum inhibition of acetylcholinesterase was exhibited by scopoletin content fraction (38.43 ± 3.94 %), while ethyl acetate fraction exerted neuroprotective effect against β-amyloid peptide (83.97 ± 5.03 %). Phytochemical analysis, showed the presence of 3-O-quercetin glucopyranoside (415 mg/g), rutin (229.9 mg/g), ursolic and oleanolic acid (54 and 20.8 mg/g respectively), 3-O-quercetin rhamnopyranoside (12.8 mg/g), chlorogenic acid (9.5 mg/g), and scopoletin (1.38 mg/g). Our findings support the use of B. ternifolia since the extract induced significant neuroprotection against β-amyloid peptide, anti-inflammatory, antioxidant and anti-acetylcholinesterase effects that could be attributed to its contents of polyphenols, coumarins, and triterpenes, and encourage further studies for development of this extract as therapeutic agent in treatment of Alzheimer's disease.

Caffeic acid phenethyl ester inhibits diesel exhaust particle-induced inflammation of human middle ear epithelial cells via NOX4 inhibition.

PubMed

Jo, Sun-Young; Lee, Naree; Hong, Sung-Moon; Jung, Hak Hyun; Chae, Sung-Won

2013-09-01

Otitis media is one of the most common diseases in pediatric populations. Recent research on its pathogenesis has focused on air pollution. Chronic exposure to particulate air pollution is associated with the impairment of middle ear function. However, the mechanisms and the underlying inhibitory pathways, especially in the human middle ear, remain unknown. Caffeic acid phenethyl ester (CAPE) is a biologically active ingredient of propolis, a product of honeybee hives, which has anti-oxidative and anti-inflammatory activities. The aim of this study was to evaluate the inhibitory effect of CAPE on diesel exhaust particle (DEP)-induced inflammation of human middle ear epithelial cells and to determine the underlying pathway of the action of CAPE. The inflammatory damage caused by DEPs and the anti-inflammatory effects of CAPE were determined by measuring the levels of tumor necrosis factor alpha and nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 with real-time reverse transcription polymerase chain reaction and Western blot analysis. The oxidative stress induced by DEPs and the anti-oxidative effects of CAPE were directly evaluated by measuring reactive oxygen species production by use of flow cytometric analysis of 2',7'-dichlorofluorescein diacetate. The effects of CAPE were compared with those of N-acetyl-L-cysteine, which has anti-oxidative and anti-inflammatory effects. Use of CAPE significantly inhibited DEP-induced up-regulation of tumor necrosis factor alpha and NOX4 expression in a dose- and time-dependent manner. The accumulation of reactive oxygen species induced by DEPs was decreased by pretreatment with CAPE. The anti-inflammatory and anti-oxidative effects of CAPE were similar to those of N-acetyl-L-cysteine. The inflammation induced by DEP is reduced by CAPE via the inhibition of NOX4 expression. These findings suggest that CAPE might be used as a therapeutic agent against DEP-induced inflammation of human middle ear epithelial cells.

Anti-inflammatory effects of Houttuynia cordata supercritical extract in carrageenan-air pouch inflammation model

PubMed Central

Kim, Dajeong; Park, Dongsun; Kyung, Jangbeen; Yang, Yun-Hui; Choi, Ehn-Kyoung; Lee, Yoon-Bok; Kim, Hyun-Kyu; Hwang, Bang Yeon

2012-01-01

Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in rat carrageenan-air pouch model. Oral administration of HSE (50-200 mg/kg) suppressed carrageenan-induced exudation and albumin leakage, as well as inflammatory cell infiltration at a high dose (200 mg/kg). Intraperitoneal injection of dexamethasone (2 mg/kg) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content without influence on the cell number. HSE lowered tumor-necrosis factor-α (TNF-α) and nitric oxide (NO), as well as prostaglandin E2 (PGE2). Dexamethasone only reduced TNF-α and NO, while indomethacin decreased PGE2. The results indicate that HSE exhibits anti-inflammatory effects by inhibiting both TNF-α-NO and cyclooxygenase-2-PGE2 pathways. PMID:22787488

Anti-cancer, anti-inflammatory and anti-microbial activities of plant extracts used against hematological tumors in traditional medicine of Jordan.

PubMed

Assaf, Areej M; Haddadin, Randa N; Aldouri, Nedhal A; Alabbassi, Reem; Mashallah, Sundus; Mohammad, Mohammad; Bustanji, Yasser

2013-02-13

Mercurialis annua L., Bongardia chrysogonum L., and Viscum cruciatum Sieb have been traditionally used by local herbalists in Jordan for the treatment of hematopoietic neoplasms. To determine the anti-cancer, anti-inflammatory and anti-microbial potentials of the three extracts against two of the most common hematopoietic malignancies in the Jordanian populations; Burkitt's lymphoma and Multiple myeloma. The anti-cancer activity was tested against the two cell lines (BJAB Burkitt's lymphoma and U266 multiple myeloma) using the MTT and trypan blue assays. The agar dilution assay was used to study the anti-microbial activity against Gram-positive bacteria, Gram-negative bacteria, anaerobic bacteria and yeast. The pro-inflammatory cytokines interleukin (IL) -1β, IL-8 and tumor necrosis factor-α (TNF-α) were measured in the pretreated cell lines using ELISA assay to determine the anti-inflammatory activity of Viscum cruciatum Sieb against the two cell lines. The results show no evidence of stimulation of tumor growth by any of the three extracts comprising cell lines from hematological malignancies, but Viscum cruciatum Sieb showed a selective anticancer activity against BJAB cells, with IC(50) value of 14.21μg/ml. The antimicrobial effect was only noticed with Viscum cruciatum extract by inhibiting Staphylococcus aureus, Candida albicans and Propionibacterium acne, but not Pseudomonas aeruginosa at MIC of 1.25, 1.25, 0.625 and <5mg/ml, respectively. The highest activity was against the anaerobic bacteria Propionibacterium acne. Viscum cruciatum Sieb extract showed an inhibitory effect on the pro-inflammatory cytokine IL-8, but it increased TNF-α and IL-1β secretions in BJAB cells. Whereas, it had an inhibitory effect on TNF-α and IL-1β cytokines while it enhanced IL-8 secretions in U266 cells. Among the three tested herbal extracts used in the traditional medicine in Jordan, only Viscum cruciatum Sieb showed high anti-cancer and anti-microbial potentials. They also had an anti-inflammatory effect. These observations raise the prospects of using Viscum cruciatum Sieb for treatment of diseases associated with some bacterial and fungal infections, for imbalanced cytokine production and for enhancing cancer and other immunotherapies. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Phytochemical distribution in hull and cotyledon of adzuki bean (Vigna angularis L.) and mung bean (Vigna radiate L.), and their contribution to antioxidant, anti-inflammatory and anti-diabetic activities.

PubMed

Luo, Jiaqiang; Cai, Weixi; Wu, Tong; Xu, Baojun

2016-06-15

Total saponin content, total phenolics content, total flavonoids content, condensed tannin content in hull, cotyledon and whole grain of both adzuki bean and mung bean were determined by colorimetric methods. Vitexin and isovitexin contents in mung bean were determined by HPLC. Antioxidant effects were evaluated with DPPH scavenging activity and ferric reducing antioxidant power assay. In vitro anti-inflammatory and anti-diabetic effects of beans were evaluated by protease and aldose reductase inhibitory assays, respectively. The results indicated that the bean hulls were the most abundant in phytochemicals and largely contributed antioxidant activities, anti-inflammatory effects and anti-diabetic effects of whole grains. The result showed that mung bean hull was the most abundant with vitexin at 37.43 mg/g and isovitexin at 47.18 mg/g, respectively. Most of the phytochemicals and bioactivities were most predominantly contributed by the bean hulls with exception for condensed tannin of mung bean; which was more abundant in the cotyledon than its hull. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-{kappa}B, p38MAPK and Akt inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Essafi-Benkhadir, Khadija; Refai, Amira; Riahi, Ichrak

Highlights: Black-Right-Pointing-Pointer Quince peel polyphenols inhibit LPS-induced secretion of TNF-{alpha} and IL-8. Black-Right-Pointing-Pointer Quince peel polyphenols augment LPS-induced secretion of IL-10 and IL-6. Black-Right-Pointing-Pointer Quince peel polyphenols-mediated inhibition of LPS-induced secretion of TNF-{alpha} is partially mediated by IL-6. Black-Right-Pointing-Pointer The anti-inflammatory effects of quince polyphenols pass through NF-{kappa}B, p38MAPK and Akt inhibition. -- Abstract: Chronic inflammation is a hallmark of several pathologies, such as rheumatoid arthritis, gastritis, inflammatory bowel disease, atherosclerosis and cancer. A wide range of anti-inflammatory chemicals have been used to treat such diseases while presenting high toxicity and numerous side effects. Here, we report the anti-inflammatory effectmore » of a non-toxic, cost-effective natural agent, polyphenolic extract from the Tunisian quince Cydonia oblonga Miller. Lipopolysaccharide (LPS) treatment of human THP-1-derived macrophages induced the secretion of high levels of the pro-inflammatory cytokine TNF-{alpha} and the chemokine IL-8, which was inhibited by quince peel polyphenolic extract in a dose-dependent manner. Concomitantly, quince polyphenols enhanced the level of the anti-inflammatory cytokine IL-10 secreted by LPS-treated macrophages. We further demonstrated that the unexpected increase in IL-6 secretion that occurred when quince polyphenols were associated with LPS treatment was partially responsible for the polyphenols-mediated inhibition of TNF-{alpha} secretion. Biochemical analysis showed that quince polyphenols extract inhibited the LPS-mediated activation of three major cellular pro-inflammatory effectors, nuclear factor-kappa B (NF-{kappa}B), p38MAPK and Akt. Overall, our data indicate that quince peel polyphenolic extract induces a potent anti-inflammatory effect that may prove useful for the treatment of inflammatory diseases and that a quince-rich regimen may help to prevent and improve the treatment of such diseases.« less

Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

PubMed

Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

2012-09-01

Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

PubMed

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

Antinociceptive and Anti-Inflammatory Effects of Octacosanol from the Leaves of Sabicea grisea var. grisea in Mice

PubMed Central

de Oliveira, Anderson Marques; Conserva, Lucia M.; de Souza Ferro, Jamylle N.; de Almeida Brito, Fabíola; Lyra Lemos, Rosângela P.; Barreto, Emiliano

2012-01-01

Sabicea species are used in the Amazon for treatment of fever and malaria, which suggests that its chemical constituents may have some effect on pain and inflammation. Phytochemical analysis of the hexane fraction obtained from the crude ethanol extract from Sabicea grisea var. grisea Cham. & Schltdl (Rubiaceae), an endemic plant in Brazil, resulted in the isolation of octacosanol. This study investigated the antinociceptive and anti-inflammatory effects of the octacosanol in different experimental models. The crude ethanolic extract and hexane fraction obtained from the leaves of S. grisea produced an inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the hexane fraction produced a significant inhibition of pain response elicited by acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor antagonist, notably reversed the antinociceptive activity induced by octacosanol in the abdominal constriction test. Furthermore, mice treated with octacosanol did not exhibit any behavioral alteration during the hot plate and rota-rod tests, indicating non-participation of the supraspinal components in the modulation of pain by octacosanol with no motor abnormality. In the formalin test, octacosanol did not inhibit the licking time in first phase (neurogenic pain), but significantly inhibited the licking time in second phase (inflammatory pain) of mice. The anti-inflammatory effect of octacosanol was evaluated using carrageenan-induced pleurisy. The octacosanol significantly reduced the total leukocyte count and neutrophils influx, as well as TNF-α levels in the carrageenan-induced pleurisy. This study revealed that the mechanism responsible for the antinociceptive and anti-inflammatory effects of the octacosanol appears to be partly associated with an inhibition of alpha 2-adrenergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these results demonstrated that the octacosanol from the leaves of S. grisea possesses antinociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes. PMID:22408410

Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells.

PubMed

Lee, Y G; Lee, W M; Kim, J Y; Lee, J Y; Lee, I-K; Yun, B-S; Rhee, M H; Cho, J Y

2008-06-01

Mushrooms are popular both as food and as a source of natural compounds of biopharmaceutical interest. Some mushroom-derived compounds such as beta-glucan have been shown to be immunostimulatory; this study explores the anti-inflammatory properties of hispidin analogues derived from the mushroom, Inonotus xeranticus. We sought to identify the molecular mechanism of action of these hispidin analogues by determining their effects on lipopolysaccharide (LPS)-mediated inflammatory responses in a macrophage cell line. The production of inflammatory mediators was determined by Griess assay, reverse transcription-PCR and ELISA. The inhibitory effect of davalliactone on LPS-induced activation of signalling cascades was assessed by western blotting, immunoprecipitation and direct kinase assay. In activated RAW264.7 cells, davallialactone strongly downregulated LPS-mediated inflammatory responses, including NO production, prostaglandin E2 release, expression of proinflammatory cytokine genes and cell surface expression of co-stimulatory molecules. Davallialactone treatment did not alter cell viability or morphology. Davallialactone was found to exert its anti-inflammatory effects by inhibiting a signalling cascade that activates nuclear factor kappa B via PI3K, Akt and IKK, but not mitogen-activated protein kinases. Treatment with davallialactone affected the phosphorylation of these signalling proteins, but not their level of expression. These inhibitory effects were not due to the interruption of toll-like receptor 4 binding to CD14. In particular, davallialactone strongly inhibited the LPS-induced phosphorylation and kinase activity of Src, implying that Src may be a potential pharmacological target of davallialactone. Our data suggest that davallialactone, a small molecule found in edible mushrooms, has anti-inflammatory activity. Davallialactone can be developed as a pharmaceutically valuable anti-Src kinase agent.

Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

PubMed

Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

2015-06-01

Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

PubMed

Wandji, Bibiane Aimée; Bomba, Francis Desire Tatsinkou; Nkeng-Efouet, Pepin Alango; Piegang, Basile Nganmegne; Kamanyi, Albert; Nguelefack, Télesphore Benoît

2018-02-01

Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

Immune response to Taenia solium cysticerci after anti-parasitic therapy.

PubMed

Singh, Aloukick K; Singh, Satyendra K; Singh, Amrita; Gupta, Kamlesh K; Khatoon, Jahanarah; Prasad, Amit; Rai, Ravi P; Gupta, Rakesh K; Tripathi, Mukesh; Husain, Nuzhat; Prasad, Kashi N

2015-10-01

Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

TWEAK in inclusion-body myositis muscle: possible pathogenic role of a cytokine inhibiting myogenesis.

PubMed

Morosetti, Roberta; Gliubizzi, Carla; Sancricca, Cristina; Broccolini, Aldobrando; Gidaro, Teresa; Lucchini, Matteo; Mirabella, Massimiliano

2012-04-01

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 exert pleiotropic effects, including regulation of myogenesis. Sporadic inclusion-body myositis (IBM) is the most common muscle disease of the elderly population and leads to severe disability. IBM mesoangioblasts, different from mesoangioblasts in other inflammatory myopathies, display a myogenic differentiation defect. The objective of the present study was to investigate TWEAK-Fn14 expression in IBM and other inflammatory myopathies and explore whether TWEAK modulation affects myogenesis in IBM mesoangioblasts. TWEAK, Fn14, and NF-κB expression was assessed by immunohistochemistry and Western blot in cell samples from both muscle biopsies and primary cultures. Mesoangioblasts isolated from samples of IBM, dermatomyositis, polymyositis, and control muscles were treated with recombinant human TWEAK, Fn14-Fc chimera, and anti-TWEAK antibody. TWEAK-RNA interference was performed in IBM and dermatomyositis mesoangioblasts. TWEAK levels in culture media were determined by enzyme-linked immunosorbent assay. In IBM muscle, we found increased TWEAK-Fn14 expression. Increased levels of TWEAK were found in differentiation medium from IBM mesoangioblasts. Moreover, TWEAK inhibited myogenic differentiation of mesoangioblasts. Consistent with this evidence, TWEAK inhibition by Fn14-Fc chimera or short interfering RNA induced myogenic differentiation of IBM mesoangioblasts. We provide evidence that TWEAK is a negative regulator of human mesoangioblast differentiation. Dysregulation of the TWEAK-Fn14 axis in IBM muscle may induce progressive muscle atrophy and reduce activation and differentiation of muscle precursor cells. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The role of tumour necrosis factor-α and tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity

PubMed Central

Westbrook, Aya M.; Wei, Bo; Hacke, Katrin; Xia, Menghang; Braun, Jonathan; Schiestl, Robert H.

2012-01-01

Chronic inflammatory diseases are characterised by systemically elevated levels of tumour necrosis factor (TNF)-α, a proinflammatory cytokine with pleiotropic downstream effects. We have previously demonstrated increased genotoxicity in peripheral leukocytes and various tissues in models of intestinal inflammation. In the present study, we asked whether TNF-α is sufficient to induce DNA damage systemically, as observed in intestinal inflammation, and whether tumour necrosis factor receptor (TNFR) signalling would be necessary for the resultant genotoxicity. In the wild-type mice, 500 ng per mouse of TNF-α was sufficient to induce DNA damage to multiple cell types and organs 1-h post-administration. Primary splenic T cells manifested TNF-α-induced DNA damage in the absence of other cell types. Furthermore, TNFR1−/−TNFR2−/− mice demonstrated decreased systemic DNA damage in a model of intestinal inflammation and after TNF-α injection versus wild-type mice, indicating the necessity of TNFR signalling. Nuclear factor (NF)-κB inhibitors were also able to decrease damage induced by TNF-α injection in wild-type mice. When TNF-α administration was combined with interleukin (IL)-1β, another proinflammatory cytokine, DNA damage persisted for up to 24 h. When combined with IL-10, an anti-inflammatory cytokine, decreased genotoxicity was observed in vivo and in vitro. TNF-α/TNFR-mediated signalling is therefore sufficient and plays a large role in mediating DNA damage to various cell types, subject to modulation by other cytokines and their mediators. PMID:21980144

Anti-inflammatory effects of Melatonin: a mechanistic review.

PubMed

Nabavi, Seyed Mohammad; Nabavi, Seyed Fazel; Sureda, Antoni; Xiao, Janbo; Dehpour, Ahmad Reza; Shirooie, Samira; Silva, Ana Sanches; Baldi, Alessandra; Khan, Haroon; Daglia, Maria

2018-06-14

N-acetyl-5-methoxy-tryptamine (melatonin) is a natural substance produced both by plants, as a secondary metabolite, and animals, by the pineal gland and other tissues. In humans, melatonin participates in numerous functions including the regulation of mood, sleep, reproduction, promotion of immunomodulation, antioxidant defense and as an anti-inflammatory agent. The anti-inflammatory activity of melatonin could yield beneficial effects on intake, particularly against the chronic inflammation which underlies many chronic diseases. This review aims to provide an assessment of the literature data on the anti-inflammatory activity of melatonin, with a particular focus on the mechanisms responsible for this behavior. We can conclude that many in vitro studies and in vivo studies in experimental animal model systems show that melatonin exerts anti-inflammatory activity in a number of chronic diseases which affect different organs in different circumstances. Clinical trials, however, often fail to reach positive results and are thus far inconclusive. Thus, in the future, long-term well-designed investigations on melatonin-rich foods or melatonin food supplements could provide valuable information towards public health recommendations on melatonin, taking into account both the nature of the compound and the optimal dose, for protection from long-term inflammation linked to chronic diseases.

Determining the pharmacological activity of Physalis peruviana fruit juice on rabbit eyes and fibroblast primary cultures.

PubMed

Pardo, Juan Manuel; Fontanilla, Marta Raquel; Ospina, Luis Fernando; Espinosa, Lady

2008-07-01

The pharmacologic activity of compounds isolated from Physalis peruviana has been demonstrated. The use of this fruit juice for treating pterygium has been reported in Colombian traditional medicine. However, studies demonstrating the fruit juice's pharmacologic activity when used in this disease have not been published to date. In the present study the anti-inflammatory and cytostatic activities of P. peruviana fruit juice in a rabbit eye inflammatory model were investigated. A novel rabbit eye inflammation model was developed for studying the juice's anti-inflammatory activity (based on an adaptation of the Draize test). Cytostatic activity was evaluated by measuring and comparing growth rates of cultured fibroblasts exposed and not exposed to various fruit juice concentrations. P. peruviana fruit juice exhibited a mild anti-inflammatory activity compared with methylprednisolone, a known anti-inflammatory drug. An interesting dose-dependent cytostatic effect on cultured fibroblasts was also established. The data found suggest that the P. peruviana fruit juice anti-pterygium effect described in traditional medicine may be related to its inhibiting fibroblast growth. The present study contributes to the pharmacologic knowledge regarding a remedy commonly used in Colombian traditional medicine.

Acai juice attenuates atherosclerosis in apoe deficient mice through antioxidant and anti-inflammatory activities

USDA-ARS?s Scientific Manuscript database

Objective - Acai fruit pulp has received much attention because of its high antioxidant capacity and potential anti-inflammatory effects. In this study, athero-protective effects of açaí juice were investigated in apolipoprotein E deficient (apoE -/-) mice. Methods and Results - ApoE-/- mice were f...

Evaluation of anti-inflammatory effect of statins in chronic periodontitis.

PubMed

Suresh, Snophia; Narayana, Satya; Jayakumar, P; Sudhakar, Uma; Pramod, V

2013-01-01

Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I consists of patients with generalized chronic periodontitis and on statin medication and Group-II consists of patients with generalized chronic periodontitis. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were analyzed for interleukin (IL)-1β using commercially available enzyme-linked immunosorbent assay. The mean GCF IL-1β levels in generalized chronic periodontitis patients who are on statin medication (Group-I) were lower than the generalized chronic periodontitis patients without statin medication (Group-II). Reduction of GCF IL-1β levels in statin users indicate that statins have anti-inflammatory effect on periodontal disease.

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

PubMed Central

Mahony, Chris; Erskine, Lynda; Niven, Jennifer; Greig, Nigel H.; Figg, William Douglas; Vargesson, Neil

2013-01-01

Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently. PMID:23858438

Anti-inflammatory effect and modulation of cytochrome P450 activities by Artemisia annua tea infusions in human intestinal Caco-2 cells.

PubMed

Melillo de Magalhães, Pedro; Dupont, Isabelle; Hendrickx, Aurélie; Joly, Aurélie; Raas, Thomas; Dessy, Stéphanie; Sergent, Thérèse; Schneider, Yves-Jacques

2012-09-15

In an attempt to understand the beneficial health effects of Artemisia annua other than its anti-malaria properties, extracts from different cultivars prepared as tea infusions were investigated using Caco-2 cells on the intestinal inflammation and cytochrome P450 (CYP) activities. The characterisation of their phenolic compound (PC) profile revealed rosmarinic and chlorogenic acids as the main PCs. The extracts, assayed on Caco-2 cells at a plausible intestinal concentration, significantly decreased the secretion of pro-inflammatory cytokines, IL-8 and IL-6. This effect could be attributable at least to their content in rosmarinic acid, detected as a potent anti-inflammatory compound. The extracts also inhibited the activity of CYP3A4, whose expression was induced by 1,25-dihydroxyvitamin D(3), and of CYP1A1, induced by benzo(a)pyrene. Our results highlight the advantage of drinking A. annua infusions for their potent anti-inflammatory effect, linked to PC content, which could synergise their antimalarial activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis.

PubMed

Bermudez, Maria A; Sendon-Lago, Juan; Seoane, Samuel; Eiro, Noemi; Gonzalez, Francisco; Saa, Jorge; Vizoso, Francisco; Perez-Fernandez, Roman

2016-08-01

The aim of the present study was to evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) in uveitis. To do that, uveitis was induced in rats after footpad injection of Escherichia coli lipopolysaccaride (LPS). Human retinal pigment epithelial (ARPE-19) cells after LPS challenge were used to test anti-inflammatory effect of CM-hUCESCs 'ìn vitro'. Real-time PCR was used to evaluate mRNA expression levels of the pro-inflammatory cytokines interkeukin-6, interkeukin-8, macrophage inflammatory protein-1 alpha, tumor necrosis factor alpha, and the anti-inflammatory interkeukin-10. Leucocytes from aqueous humor (AqH) were quantified in a Neubauer chamber, and eye histopathological analysis was done with hematoxylin-eosin staining. Additionally, using a human cytokine antibody array we evaluated CM-hUCESCs to determine mediating proteins. Results showed that administration of CM-hUCESCs significantly reduced LPS-induced pro-inflammatory cytokines both 'in vitro' and 'in vivo', and decreased leucocytes in AqH and ocular tissues. High levels of cytokines with anti-inflammatory effects were found in CM-hUCESCs, suggesting a possible role of these factors in reducing intraocular inflammation. In summary, treatment with CM-hUCESCs significantly reduces inflammation in uveitis. Our data indicate that CM-hUCESCs could be regarded as a potential therapeutic agent for patients suffering from ocular inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases.

PubMed

Pham, Tho X; Park, Young-Ki; Lee, Ji-Young

2016-06-21

We previously demonstrated that the organic extract of Spirulina platensis (SPE), an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs) play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca(2+)/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β), but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα) promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect.

Anti-inflammatory and antiproliferative activities of trifolirhizin, a flavonoid from Sophora flavescens roots

PubMed Central

Zhou, Huiping; Lutterodt, Herman; Cheng, Zhihong; Yu, Liangli (Lucy)

2009-01-01

Trifolirhizin, a pterocarpan flavonoid, was isolated from the roots of Sophora flavescens, and its chemical structure was confirmed by1H and 13C NMR and MS spectra. Its anti-inflammatory activity was examined in lipopolysaccharide (LPS)-stimulated mouse J774A.1 macrophages. Trifolirhizin not only dose-dependently inhibited LPS-induced expression of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but also inhibited lipopolysaccharide (LPS)-induced expression of cyclooxygenase-2 (COX-2). In addition, trifolirhizin showed in vitro inhibitory effects on the growth of human A2780 ovarian and H23 lung cancer cells. These results suggest that trifolirhizin possesses potential anti-inflammatory and anti-cancer activities. PMID:19402641

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.

Characterization, anti-oxidative and anti-inflammatory effects of Costa Rican noni juice (Morinda citrifolia L.).

PubMed

Dussossoy, E; Brat, P; Bony, E; Boudard, F; Poucheret, P; Mertz, C; Giaimis, J; Michel, A

2011-01-07

Noni fruit (Morinda citrifolia L.) juice has been used for more than 2000 years in Polynesia as a traditional folk medicine. The aim of the present study was to finely characterize noni juice from Costa Rica and to evaluate its anti-oxidative and anti-inflammatory activities. A microfiltrated noni juice was prepared with Costarican nonis. HPLC-DAD and Electro Spray Ionization Mass Spectrometric detection (HPLC-ESI-MS) were used to identify phenolic compounds and iridoids. The anti-oxidative activity of noni juice was measured in vitro by both Oxygen Radical Absorbance Capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging methods. The anti-inflammatory effects of noni juice were investigated in vitro by: measuring its effect on nitric oxide and prostaglandin E2 production by activated macrophages, evaluating its inhibitory activities on cyclooxygenase (COX)-1 and -2 and in vivo on a carrageenan-induced paw oedema model in rats. Several polyphenols belonging to the coumarin, flavonoid and phenolic acid groups, and two iridoids were identified. Noni juice demonstrated a mean range free radical scavenging capacity. Furthermore, it also reduced carrageenan-induced paw oedema, directly inhibited cyclooxygenase COX-1 and COX-2 activities and inhibited the production of nitric oxide (NO) and prostaglandins E(2) (PGE(2)) in activated J774 cells, in a dose dependent manner. This study showed that noni's biological effects include: (1) anti-oxidant properties probably associated with phenolic compounds, iridoids and ascorbic acid and (2) anti-inflammatory action through NO and PGE(2) pathways that might also be strengthened by anti-oxidant effects. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Triticum vulgare extract exerts an anti-inflammatory action in two in vitro models of inflammation in microglial cells

PubMed Central

Sanguigno, Luca; Casamassa, Antonella; Funel, Niccola; Minale, Massimiliano; Riccio, Rodolfo; Riccio, Salvatore; Boscia, Francesca; Brancaccio, Paola; Pollina, Luca Emanuele; Anzilotti, Serenella; Di Renzo, Gianfranco

2018-01-01

Triticum vulgare has been extensively used in traditional medicine thanks to its properties of accelerating tissue repair. The specific extract of Triticum vulgare manufactured by Farmaceutici Damor (TVE-DAMOR) is already present in some pharmaceutical formulations used in the treatment of decubitus ulcers, skin lesions and burns. It has been recently suggested that this Triticum vulgare extract may possess potential anti-inflammatory properties. In the light of these premises the aim of the present paper was to verify the anti-inflammatory role of TVE, using the LPS-stimulated microglia model of inflammation. In particular the effect of different concentrations of TVE on the release of several mediators of inflammation such as nitric oxide, IL-6, PGE2 and TNF alpha was evaluated. More important, the anti-inflammatory effect of TVE was confirmed also in primary rat microglia cultures. The results of the present study show that TVE exerts anti-inflammatory properties since it reduces the release of all the evaluated markers of inflammation, such as NO, IL6, TNF alpha and PGE2 in LPS-activated BV2 microglial cells. Intriguingly, TVE reduced microglia activation and NO release also in primary microglia. Indeed, to verify the pathway of modulation of the inflammatory markers reported above, we found that TVE restores the cytoplasmic expression of p65 protein, kwown as specific marker associated with activation of inflammatory response. The evidence for an inhibitory activity on inflammation of this specific extract of Triticum vulgare may open the way to the possibility of a therapeutical use of the Triticum vulgare extract as an anti-inflammatory compound in certain pathological states such as burns, decubitus ulcers, folliculitis and inflammation of peripheral nerve. PMID:29902182

Trauma-induced systemic inflammatory response versus exercise-induced immunomodulatory effects.

PubMed

Fehrenbach, Elvira; Schneider, Marion E

2006-01-01

Accidental trauma and heavy endurance exercise, both induce a kind of systemic inflammatory response, also called systemic inflammatory response syndrome (SIRS). Exercise-related SIRS is conditioned by hyperthermia and concomitant heat shock responses, whereas trauma-induced SIRS manifests concomitantly with tissue necrosis and immune activation, secondarily followed by fever. Inflammatory cytokines are common denominators in both trauma and exercise, although there are marked quantitative differences. Different anti-inflammatory cytokines may be involved in the control of inflammation in trauma- and exercise-induced stress. Exercise leads to a balanced equilibrium between inflammatory and anti-inflammatory responses. Intermittent states of rest, as well as anti-oxidant capacity, are lacking or minor in trauma but are high in exercising individuals. Regular training may enhance immune competence, whereas trauma-induced SIRS often paves the way for infectious complications, such as sepsis.

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

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.

Recent developments in the effects of nitric oxide-donating statins on cardiovascular disease through regulation of tetrahydrobiopterin and nitric oxide.

PubMed

Ma, Sze; Ma, Christopher Cheng-Hwa

2014-11-01

Since the discovery of the importance of nitric oxide (NO) to the human body three decades ago, numerous laboratory and clinical studies have been done to explore its potential therapeutic actions on many organs. In the cardiovascular system, NO works as a volatile signaling molecule regulating the vascular permeability and vascular tone, preventing thrombosis and inflammation, as well as inhibiting the smooth muscle hyperplasia. Thus, NO is important in the prevention and treatment of cardiovascular disease. NO is synthesized by NO synthase (NOS) with tetrahydrobiopterin (BH4) as the crucial cofactor. Many studies have been done to form nitric oxide donors so as to deliver NO directly to the vessel walls. In addition, NO moieties have been incorporated into existing therapeutic agents to enhance the NO bioavailability, including statins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA), the rate-limiting enzyme of the mevalonate pathway. By inhibiting this pathway, statins lower blood cholesterol and exert their pleiotropic effects through activity in reaction cascades, such as Rho/ROCK and Rac 1/NADPH oxidase pathways. Statins have also been observed to implement their non-lipid effects by promoting BH4 synthesis with increase of NO bioavailability. Furthermore, NO-donating statins in laboratory studies have demonstrated to produce better therapeutic effects than their parent's drugs. They offer better anti-inflammatory, anti-proliferative and antithrombotic actions on cardiovascular system. They also cause better revascularization in peripheral ischemia and produce greater enhancement in limb reperfusion and salvage. In addition, it has been shown that NO-donating statin caused less myotoxicity, the most common side effect related to treatment with statins. The initial studies have demonstrated the superior therapeutic effects of NO-donating statins while producing fewer side effects. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Pharmaco-toxicological study of diterpenoids.

PubMed

Delporte, Carla; Backhouse, Nadine; Salinas, Pedro; San-Martín, Aurelio; Bórquez, Jorge; Loyola, Alberto

2003-04-03

Azorella compacta, Azorella yareta and Laretia acaulis (Apiaceae) are native species from the high Andes Mountains, northeastern Chile, and they have being traditionally used to treat asthma, colds and bronchitis, illnesses with inflammation and pain as the main symptoms. Interestingly, there are no scientific reports available on their benefits or toxicity. This study was carried out with the purpose of validating the medicinal use of these species and to discover anti-inflammatory and analgesic new molecules. As a working hypothesis, we have proposed that these medicinal species contain bioactive compounds with anti-inflammatory and analgesic effects. In this context, azorellanol, 13-hydroxy-7-oxoazorellane and 7-deacetylazorellanol, three diterpenoids previously isolated only from these plants, were subjected to farmaco-toxicological evaluation. Their topical anti-inflammatory and analgesic activities along with acute toxicities or innocuosness were also investigated. Our results indicate the absence of toxic and side effects in mice. All compounds presented dose-related inhibition of pain. 13-hydroxy-7-oxoazorellane was the most potent analgesic but it was less effective than sodium naproxen, the reference drug. Azorellanol exhibited the highest topical anti-inflammatory potency on AA (arachidonic acid) and TPA (12-deoxyphorbol 13-tetradecanoate) induced oedema, and it effect was similar to the reference drugs (nimesulide and indomethacin). Probably, its mechanism of action could be explained through the inhibition to cyclo-oxygenase activity. Our results corroborate the anti-inflammatory and analgesic effects of these species, and it justifies their use in folk medicine.

Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer.

PubMed

Schinagl, Alexander; Thiele, Michael; Douillard, Patrice; Völkel, Dirk; Kenner, Lukas; Kazemi, Zahra; Freissmuth, Michael; Scheiflinger, Friedrich; Kerschbaumer, Randolf J

2016-11-08

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer.

Current perspectives in NSAID-induced gastropathy.

PubMed

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.

Sucrose esters from Physalis peruviana calyces with anti-inflammatory activity.

PubMed

Franco, Luis A; Ocampo, Yanet C; Gómez, Harold A; De la Puerta, Rocío; Espartero, José L; Ospina, Luis F

2014-11-01

Physalis peruviana is a native plant from the South American Andes and is widely used in traditional Colombian medicine of as an anti-inflammatory medicinal plant, specifically the leaves, calyces, and small stems in poultice form. Previous studies performed by our group on P. peruviana calyces showed potent anti-inflammatory activity in an enriched fraction obtained from an ether total extract. The objective of the present study was to obtain and elucidate the active compounds from this fraction and evaluate their anti-inflammatory activity in vivo and in vitro. The enriched fraction of P. peruviana was purified by several chromatographic methods to obtain an inseparable mixture of two new sucrose esters named peruviose A (1) and peruviose B (2). Structures of the new compounds were elucidated using spectroscopic methods and chemical transformations. The anti-inflammatory activity of the peruvioses mixture was evaluated using λ-carrageenan-induced paw edema in rats and lipopolysaccharide-activated peritoneal macrophages. Results showed that the peruvioses did not produce side effects on the liver and kidneys and significantly attenuated the inflammation induced by λ-carrageenan in a dosage-dependent manner, probably due to an inhibition of nitric oxide and prostaglandin E2, which was demonstrated in vitro. To our knowledge, this is the first report of the presence of sucrose esters in P. peruviana that showed a potent anti-inflammatory effect. These results suggest the potential of sucrose esters from the Physalis genus as a novel natural alternative to treat inflammatory diseases. Georg Thieme Verlag KG Stuttgart · New York.

Isoflavones: Anti-Inflammatory Benefit and Possible Caveats

PubMed Central

Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

2016-01-01

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. PMID:27294954

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.

Influenza ("Bird Flu"), inflammation and anti-inflammatory/analgesic drugs.

PubMed

Rainsford, K D

2006-03-01

The spectre of an influenza pandemic is being widely mooted. Most of the strategies explored to date for controlling or treating the condition have centred on controlling the spread of the infection, the use of vaccines or anti-viral agents. There has been relatively little discussion about treating the lung and systemic inflammatory reactions that occur during influenza infection. In this review a range of therapeutic agents are proposed to treat the inflammatory reactions, principally in the lung as well as the systemic cytokine-mediated immuno-inflammatory reactions that may be a major cause of the morbidity and mortality associated with influenza infections. Among these are pentoxifylline, the statins, the macrolide antibiotics (e.g. azithromycin, clarithromycin, erythromycin), resveratrol (a component of wine and fruits with inhibitory effects on influenza virus replication) and nutraceuticals (including those that contain flavonoids, the marine oils eicosapentanoic and docosanoic acids or the green-lipped mussel extract, Liprinol which may by virtue of the inhibitory effects on the production or actions of pro-inflammatory cytokines, be useful for their anti-inflammatory actions. The efficacy, mode of actions and side effects of non-steroidal anti-inflammatory drugs (NSAIDs) are considered. There are a number of issues relating to their use in treating the inflammatory reactions in the respiratory tract. Among these are the development of gastro-intestinal ulcers and bleeding and hepato-renal reactions in patients that may because of severe systemic inflammation be prone to the development of these adverse reactions. There are also theoretical issues concerning the impact of COX-1 mediating reduction in prostaglandin and increased cytokine production that might have some negative consequences for respiratory inflammation.In conclusion, further consideration should be given to exploring the actions of these anti-inflammatory agents to control the respiratory inflammatory in influenza infections which can have serious consequences for the outcome of the infection.

Perineural Dexmedetomidine Attenuates Inflammation in Rat Sciatic Nerve via the NF-κB Pathway

PubMed Central

Huang, Yan; Lu, Yi; Zhang, Lei; Yan, Jia; Jiang, Jue; Jiang, Hong

2014-01-01

Recent studies have shown that dexmedetomidine exerts an anti-inflammatory effect by reducing serum levels of inflammatory factors, however, the up-stream mechanism is still unknown. The transcription factor NF-κB enters the nucleus and promotes the transcription of its target genes, including those encoding the pro-inflammatory cytokines IL-6 and TNF-α. In this study, we established a rat model that simulates a clinical surgical procedure to investigate the anti-inflammatory effect of perineural administration of dexmedetomidine and the underlying mechanism. Dexmedetomidine reduced the sciatic nerve levels of IL-6 and TNF-α at both the mRNA and protein level. Dexmedetomidine also inhibited the translocation of activated NF-κB to the nucleus and the binding activity of NF-κB. The anti-inflammatory effect is confirmed to be dose-dependent. Finally, pyrrolidine dithiocarbamate also reduced the levels of IL-6 and TNF-α and the activation of NF-κB. In conclusion, dexmedetomidine inhibited the nuclear translocation and binding activity of activated NF-κB, thus reducing inflammatory cytokines. PMID:24663080

Potent Anti-Inflammatory Activity of Ursolic Acid, a Triterpenoid Antioxidant, Is Mediated through Suppression of NF-κB, AP-1 and NF-AT

PubMed Central

Checker, Rahul; Sandur, Santosh K.; Sharma, Deepak; Patwardhan, Raghavendra S.; Jayakumar, S.; Kohli, Vineet; Sethi, Gautam; Aggarwal, Bharat B.; Sainis, Krishna B.

2012-01-01

Background Ursolic acid (UA), a pentacyclic triterpenoid carboxylic acid, is the major component of many plants including apples, basil, cranberries, peppermint, rosemary, oregano and prunes and has been reported to possess antioxidant and anti-tumor properties. These properties of UA have been attributed to its ability to suppress NF-κB (nuclear factor kappa B) activation. Since NF-κB, in co-ordination with NF-AT (nuclear factor of activated T cells) and AP-1(activator protein-1), is known to regulate inflammatory genes, we hypothesized that UA might exhibit potent anti-inflammatory effects. Methodology/Principal Findings The anti-inflammatory effects of UA were assessed in activated T cells, B cells and macrophages. Effects of UA on ERK, JNK, NF-κB, AP-1 and NF-AT were studied to elucidate its mechanism of action. In vivo efficacy of UA was studied using mouse model of graft-versus-host disease. UA inhibited activation, proliferation and cytokine secretion in T cells, B cells and macrophages. UA inhibited mitogen-induced up-regulation of activation markers and co-stimulatory molecules in T and B cells. It inhibited mitogen-induced phosphorylation of ERK and JNK and suppressed the activation of immunoregulatory transcription factors NF-κB, NF-AT and AP-1 in lymphocytes. Treatment of cells with UA prior to allogenic transplantation significantly delayed induction of acute graft-versus-host disease in mice and also significantly reduced the serum levels of pro-inflammatory cytokines IL-6 and IFN-γ. UA treatment inhibited T cell activation even when added post-mitogenic stimulation demonstrating its therapeutic utility as an anti-inflammatory agent. Conclusions/Significance The present study describes the detailed mechanism of anti-inflammatory activity of UA. Further, UA may find application in the treatment of inflammatory disorders. PMID:22363615

Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors.

PubMed

Endo, Mari; Hori, Masatoshi; Ozaki, Hiroshi; Oikawa, Tetsuro; Hanawa, Toshihiko

2014-06-01

Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action. Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice. DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice. In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

Evidence of anti-inflammatory effect and percutaneous penetration of a topically applied fish oil preparation: a photoacoustic spectroscopy study

NASA Astrophysics Data System (ADS)

Ames, Franciele Q.; Sato, Francielle; de Castro, Lidiane V.; de Arruda, Laura L. M.; da Rocha, Bruno A.; Cuman, Roberto K. N.; Baesso, Mauro L.; Bersani-Amado, Ciomar A.

2017-05-01

This paper investigates the topical anti-inflammatory effect of a fish oil preparation (FOP) in a croton oil (CO) model of skin inflammation. The photoacoustic spectroscopy (PAS) was applied to estimate the percutaneous penetration of the FOP and as a model to evaluate the topical inflammatory response. After applying CO, the groups of mice received a topical application of a FOP on the left ear. The right ear received the vehicle that was used to dilute the CO. After 6 h, ear tissue was collected to determine the percent inhibition of edema, myeloperoxidase (MPO) activity, and cytokine levels and to perform PAS measurements. Treatment with FOP reduced edema and MPO activity, which was at least partially attributed to a decrease in the levels of tumor necrosis factor, interleukin-1β, interleukin-6, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. The topically applied FOP penetrated into the tissue and decreased the area of the bands that characterize inflamed tissue. The present results demonstrated the topical anti-inflammatory effect of the FOP. PAS suggests that FOP anti-inflammatory activity is linked with its ability to penetrate through the skin.

6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ

PubMed Central

Han, Qinghe; Yuan, Qinghai; Meng, Xiaolin; Huo, Junyuan; Bao, Yuxin; Xie, Guanghong

2017-01-01

6-Shogaol, a pungent agent isolated from Zingiber officinale Roscoe, has been known to have anti-tumor and anti-inflammatory effects. However, the anti-inflammatory effects and biological mechanism of 6-Shogaol in LPS-activated BV2 microglia remains largely unknown. In this study, we evaluated the anti-inflammatory effects of 6-Shogaol in LPS-activated BV2 microglia. 6-Shogaol was administrated 1 h before LPS treatment. The production of inflammatory mediators were detected by ELISA. The expression of NF-κB and PPAR-γ were detected by western blot analysis. Our results revealed that 6-Shogaol inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2 production in a concentration dependent manner. Furthermore, 6-Shogaol inhibited LPS-induced NF-κB activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. In addition, 6-Shogaol could increase the expression of PPAR-γ. Moreover, inhibition of PPAR-γ by GW9662 could prevent the inhibition of 6-Shogaol on LPS-induced inflammatory mediator production. In conclusion, 6-Shogaol inhibits LPS-induced inflammation by activating PPAR-γ. PMID:28410218

Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

PubMed Central

Beg, Sarwar; Swain, Suryakanta; Hasan, Hameed; Barkat, M Abul; Hussain, Md Sarfaraz

2011-01-01

Many synthetic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Since the last few decades, herbal drugs have regained their popularity in treatment against several human ailments. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA. The basic aim of this review is to give updated knowledge regarding plants which will be valuable for the scientists working in the field of anti-inflammatory natural chemistry. PMID:22279370

Essential oil of Artemisia argyi suppresses inflammatory responses by inhibiting JAK/STATs activation.

PubMed

Chen, Lin-Lin; Zhang, Hao-Jun; Chao, Jung; Liu, Jun-Feng

2017-05-23

Artemisia argyi is a herbal medicine traditionally used in Asia for the treatment of bronchitis, dermatitis and arthritis. Recent studies revealed the anti-inflammatory effect of essential oil in this plant. However, the mechanisms underlying the therapeutic potential have not been well elucidated. The present study is aimed to verify its anti-inflammatory effect and investigate the probable mechanisms. The essential oil from Artemisia argyi (AAEO) was initially tested against LPS-induced production of inflammatory mediators and cytokines in RAW264.7 macrophages. Protein and mRNA expressions of iNOS and COX-2 were determined by Western blotting and RT-PCR analysis, respectively. The effects on the activation of MAPK/NF-κB/AP-1 and JAK/STATs pathway were also investigated by western blot. Meanwhile, in vivo anti-inflammatory effect was examined by histologic and immunohistochemical analysis in TPA-induced mouse ear edema model. The results of in vitro experiments showed that AAEO dose-dependently suppressed the release of pro-inflammatory mediators (NO, PGE 2 and ROS) and cytokines (TNF-α, IL-6, IFN-β and MCP-1) in LPS-induced RAW264.7 macrophages. It down-regulated iNOS and COX-2 protein and mRNA expression but did not affect the activity of these two enzymes. AAEO significantly inhibited the phosphorylation of JAK2 and STAT1/3, but not the activation of MAPK and NF-κB cascades. In animal model, oral administration of AAEO significantly attenuated TPA-induced mouse ear edema and decreased the protein level of COX-2. AAEO suppresses inflammatory responses via down-regulation of the JAK/STATs signaling and ROS scavenging, which could contribute, at least in part, to the anti-inflammatory effect of AAEO. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

PubMed Central

Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

2014-01-01

Objective To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil. Methods In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-α mRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR. Results Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-β-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC50 12-15 µg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-α mRNA expression in the cells at concentrations of 50 µg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses. Conclusions T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions. PMID:25182441

Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

PubMed Central

Lee, In-Ah; Kamba, Alan; Low, Daren; Mizoguchi, Emiko

2014-01-01

Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1 (CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD), bronchial asthma and several other inflammatory disorders. Based on the data from high-throughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-inflammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivative-mediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine, -based anti-inflammatory therapeutics in the field of IBD and IBD-associated carcinogenesis. PMID:24574789

Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease.

PubMed

Lee, In-Ah; Kamba, Alan; Low, Daren; Mizoguchi, Emiko

2014-02-07

Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1 (CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD), bronchial asthma and several other inflammatory disorders. Based on the data from high-throughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-inflammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivative-mediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine, -based anti-inflammatory therapeutics in the field of IBD and IBD-associated carcinogenesis.

DADLE enhances viability and anti-inflammatory effect of human MSCs subjected to 'serum free' apoptotic condition in part via the DOR/PI3K/AKT pathway.

PubMed

Reddy, L Vinod Kumar; Sen, Dwaipayan

2017-12-15

Nutritional deprivation and inflammation-rich zones are the major causative reasons for poor survivability of transplanted mesenchymal stem cells (MSCs). Therefore in the present study, we demonstrated the cytoprotective and anti-inflammatory effects of activated delta (δ)-opioid receptor (DOR) with synthetic peptide [D-Ala 2 , D-Leu 5 ]-enkephalin (DADLE) treatment on human MSCs cultured in serum-starved condition. Cell viability was measured using MTT and Annexin V/PI assays. Expressions of pro-apoptotic (Bcl2) and anti-apoptotic genes (Bax/Bad), levels of activated p44/42 MAPK, Akt, PI3-kinase-p110γ and cleaved caspase-3 were determined by qPCR and western blot. Levels of secreted cytokines were measured by ELISA. In comparison to the control, DADLE significantly increased cell survivability under serum deprived condition as confirmed by MTT (71% vs 45%) and Annexin V/PI assays (25.9% vs 3.7%). Significant up-regulation of pro-apoptotic Bcl2 (~2.1 folds), down-regulations of anti-apoptotic Bax/Bad (~2.6/2.7 folds) as well as of cleaved caspase-3, increased expression of PI3kinase subunit p110γ and activation of Akt (Ser473) were observed following DADLE treatment in cells under 'serum deprivation' stress. In addition, DADLE treated hMSCs secreted increased levels of anti-inflammatory cytokines (IL10/IL4/TGF-β) under serum deprived condition. LPS stimulated macrophages showed abated release of pro-inflammatory cytokines (IL1/TNFα/IL6) when grown in hMSC conditioned 'serum deprived' media treated with DADLE. Both the cytoprotective and anti-inflammatory effects of DADLE were inhibited by the DOR specific antagonist naltrindole. The DOR signaling pathway improved cell viability and enhanced anti-inflammatory effect of hMSCs subjected to 'serum deprivation' stress that could have potential therapeutic benefits in reparative medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

A REVIEW OF ANTI-INFLAMMATORY AGENTS FOR SYMPTOMS OF SCHIZOPHRENIA

PubMed Central

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

2013-01-01

Schizophrenia is a chronic debilitating mental disorder that affects about 1% of the U.S 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 nonsteroidal anti-inflammatory agents, such as the cyclooxygenase-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. PMID:23151612

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.

Anti-inflammatory effect of thalidomide in paraquat-induced pulmonary injury in mice.

PubMed

Amirshahrokhi, Keyvan

2013-10-01

Thalidomide has been used in inflammatory and autoimmune disorders due to its anti-inflammatory activity. Paraquat (PQ) poisoning causes severe lung injury. PQ-induced pulmonary inflammation and fibrosis are due to its ability to induce oxidative stress, inflammatory and fibrotic reactions. This study was designed to evaluate the anti-inflammatory and anti-fibrotic effect of thalidomide on PQ-induced lung damage in a mouse model. Mice were injected with a single dose of PQ (20mg/kg, i.p.), and treated with thalidomide (25 and 50mg/kg/day, i.p.) for six days. Lung tissues were dissected six days after PQ injection. The results showed that thalidomide ameliorated the biochemical and histological lung alterations induced by PQ. Thalidomide decreased production of inflammatory and fibrogenic cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition thalidomide reduced myeloperoxidase (MPO), nitric oxide (NO), and hydroxyproline content in lung tissue. Taken together, the results of this study suggest that thalidomide might be a valuable therapeutic drug in preventing the progression of PQ-induced pulmonary injury. Copyright © 2013 Elsevier B.V. All rights reserved.

Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review.

PubMed

Gardener, Samantha L; Rainey-Smith, Stephanie R; Martins, Ralph N

2016-01-01

Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti-inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity.

Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition.

PubMed

Ambrozova, Gabriela; Fidlerova, Tana; Verescakova, Hana; Koudelka, Adolf; Rudolph, Tanja K; Woodcock, Steven R; Freeman, Bruce A; Kubala, Lukas; Pekarova, Michaela

2016-11-01

Inflammatory-mediated pathological processes in the endothelium arise as a consequence of the dysregulation of vascular homeostasis. Of particular importance are mediators produced by stimulated monocytes/macrophages inducing activation of endothelial cells (ECs). This is manifested by excessive soluble pro-inflammatory mediator production and cell surface adhesion molecule expression. Nitro-fatty acids are endogenous products of metabolic and inflammatory reactions that display immuno-regulatory potential and may represent a novel therapeutic strategy to treat inflammatory diseases. The purpose of our study was to characterize the effects of nitro-oleic acid (OA-NO2) on inflammatory responses and the endothelial-mesenchymal transition (EndMT) in ECs that is a consequence of the altered healing phase of the immune response. The effect of OA-NO2 on inflammatory responses and EndMT was determined in murine macrophages and murine and human ECs using Western blotting, ELISA, immunostaining, and functional assays. OA-NO2 limited the activation of macrophages and ECs by reducing pro-inflammatory cytokine production and adhesion molecule expression through its modulation of STAT, MAPK and NF-κB-regulated signaling. OA-NO2 also decreased transforming growth factor-β-stimulated EndMT and pro-fibrotic phenotype of ECs. These effects are related to the downregulation of Smad2/3. The study shows the pleiotropic effect of OA-NO2 on regulating EC-macrophage interactions during the immune response and suggests a role for OA-NO2 in the regulation of vascular endothelial immune and fibrotic responses arising during chronic inflammation. These findings propose the OA-NO2 may be useful as a novel therapeutic agent for treatment of cardiovascular disorders associated with dysregulation of the endothelial immune response. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-inflammatory effects of aqueous extract of Mangifera indica in Wistar rats.

PubMed

Oluwole, Oluwafemi Gabriel; Esume, Celestine

2015-05-01

Recent studies in standard laboratories have indicated that a typical mango stem bark aqueous extract (Magnifera indica Linn) possess anti-malaria and anti-fever properties. Recent information also exists in the literature, suggesting its potency as a very effective anti-inflammatory plant extract. This study will therefore contribute immensely to the systemic search for a useful, less toxic and natural bioactive medicinal compound. This study investigated the anti-inflammatory effects of the aqueous extract of Mangifera indica (MI) in a carrageenin-induced rat paw oedema model of acute inflammation. Rats (n=5) were treated orally with MI (50, 100 and 200 mg/kg), acetylsalicylic acid (100 mg/kg) or distilled water (3 mL). Thirty minutes later, acute inflammation was induced with a sub-plantar injection of 0.1 mL of 1% carrageenin solution into the right hind paw of the rats. The paw oedema sizes were measured with the aid of a Vernier calliper over a period of 3 hours. The aqueous extract of MI (50-200 mg/kg, p.o.) produced a dose-dependent and significant inhibition of the acute inflammation induced by the carrageenin in rats when compared with controls. The percentage inhibition of oedema formation produced by MI (200 mg/kg, p.o.) was similar to that elicited by acetylsalicylic acid (100 mg/kg, p.o.). The results of this preliminary investigation suggest that MI contains active compounds with an anti-inflammatory activity. However, more detailed studies using additional models are necessary to further characterise the effects of MI in inflammatory disorders.

Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation

PubMed Central

Rocksén, D; Lilliehöök, B; Larsson, R; Johansson, T; Bucht, A

2000-01-01

Inhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. In this study, the anti-inflammatory effects of the anti-oxidant N-acetylcysteine (NAC) and the glucocorticoid dexamethasone were investigated in mice exposed to aerosolized endotoxin (lipopolysaccharide (LPS)). Powerful reduction of neutrophils in bronchoalveolar lavage fluid (BALF) was obtained by a single i.p. injection of dexamethasone (10 mg/kg), whereas treatment with NAC only resulted in reduction of neutrophils when administered at a high dose (500 mg/kg). Measurement of cytokine and chemokine expression in lung tissue revealed a significant decrease of tumour necrosis factor-alpha, IL-1α, IL-1β, IL-6, IL-12p40, and MIP-1α mRNA when mice where treated with dexamethasone but not when treated with NAC. Analysis of oxidative burst demonstrated a remarkable reduction of oxygen radicals in BALF neutrophils after treatment with dexamethasone, whereas the effect of NAC was not significantly different from that in untreated animals. In conclusion, dexamethasone exerted both anti-inflammatory and anti-oxidative effects in acute airway inflammation, probably by blocking early events in the inflammatory cascade. In contrast, treatment with NAC resulted in a weak reduction of the inflammatory response but no inhibition of proinflammatory cytokines or reduction of oxidative burst in neutrophils. These results demonstrate dramatic differences in efficiency and also indicate that the two drugs have different actions. Combined treatment with NAC and dexamethasone revealed an additive action but no synergy was observed. PMID:11091282

Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

PubMed

Nguyen, Van-Linh; Truong, Cong-Tri; Nguyen, Binh Cao Quan; Vo, Thanh-Niem Van; Dao, Trong-Thuc; Nguyen, Van-Dan; Trinh, Dieu-Thuong Thi; Huynh, Hieu Kim; Bui, Chi-Bao

2017-01-01

Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1β, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration.

PubMed

Ohgi, Yuta; Futamura, Takashi; Kikuchi, Tetsuro; Hashimoto, Kenji

2013-02-01

Accumulating evidence suggests that inflammation may play a role in the pathophysiology of major depressive disorder (MDD). Antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), possess anti-inflammatory effects in vitro. Here, we examined the effects of SSRIs and SNRIs on lipopolysaccharide (LPS)-induced inflammation and depressive-like behavior in male mice. A single administration of LPS (0.5mg/kg, i.p.) increased serum levels of the pro-inflammatory cytokine, tumor necrosis factor-α (TNFα) and the anti-inflammatory cytokine, interleukin-10 (IL-10) in mice. Pretreatment with SSRIs (fluoxetine and paroxetine), SNRIs (venlafaxine and duloxetine), or 5-hydroxytryptophan (5-HTP), a precursor of serotonin, attenuated LPS-induced increases in TNFα, whereas it increased serum levels of IL-10, in mice treated with LPS. In the tail suspension test (TST), LPS increased the immobility time without affecting spontaneous locomotor activity, suggesting that LPS induced depressive-like behavior in mice. Treatment with fluoxetine (30 mg/kg) or paroxetine (10mg/kg) significantly shortened LPS-induced increases of immobility time. These results suggested that antidepressants exert anti-inflammatory effects in vivo, and that the serotonergic system may partially mediate these effects. In addition, the anti-inflammatory effects of antidepressants may help alleviate the symptoms of LPS-induced depression in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Synergistic Interaction of Matricaria Chamomilla Extract with Diclofenac and Indomethacin on Carrageenan-Induced Paw Inflammation in Rats.

PubMed

Ortiz, Mario I; Cariño-Cortés, Raquel; Ponce-Monter, Héctor A; González-García, Martha P; Castañeda-Hernández, Gilberto; Salinas-Caballero, Mireya

2017-11-01

Preclinical Research The coadministration of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase anti-inflammatory activity, thus permitting the use of lower NSAID doses and limiting the side effects. The aim of this study was to explore the interactions between an ethanolic extract of M. chamomilla extract (MCE) with two NSAIDs, diclofenac and indomethacin on carrageenan-induced paw inflammation and gastric injury in rats. Diclofenac, indomethacin and MCE, or combinations with MCE produced an anti-inflammatory effect. Effective dose (ED) values were estimated for the individual drugs, and isobolograms were constructed. The final experimental ED values were 483.7 mg/kg for diclofenac + MCE combination, and 212.6 mg/kg for indomethacin + MCE. These values were lower (p < 0.05) than the theoretical ED values (1186.9 mg/kg for diclofenac + MCE combination, and 1183.8 mg/kg for indomethacin + MCE). These data suggest that the interactions between NSAIDs and MCE that mediate the anti-inflammatory effects at the systemic level are synergistic and may have therapeutic advantages for the clinical treatment of inflammatory processes. Drug Dev Res 78 : 360-367, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Anti-Inflammatory Effects of Hyptis albida Chloroform Extract on Lipopolysaccharide-Stimulated Peritoneal Macrophages

PubMed Central

Sánchez Miranda, Elizabeth; Pérez Ramos, Julia; Fresán Orozco, Cristina; Zavala Sánchez, Miguel Angel; Pérez Gutiérrez, Salud

2013-01-01

We examined the effects of a chloroform extract of Hyptis albida (CHA) on inflammatory responses in mouse lipopolysaccharide (LPS) induced peritoneal macrophages. Our findings indicate that CHA inhibits LPS-induced production of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). During the process, levels of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), and nitric oxide (NO) increased in the mouse peritoneal macrophages; however, the extract suppressed them significantly. These results provide novel insights into the anti-inflammatory actions of CHA and support its potential use in the treatment of inflammatory diseases. PMID:23970974

Antioxidant, anti-inflammatory and anti-septic potential of phenolic acids and flavonoid fractions isolated from Lolium multiflorum.

PubMed

Choi, Ki-Choon; Son, Young-Ok; Hwang, Jung-Min; Kim, Beom-Tae; Chae, Minseon; Lee, Jeong-Chae

2017-12-01

Interest has recently renewed in using Lolium multiflorum Lam. (Poaceae) (called Italian ryegrass; IRG) silage as an antioxidant and anti-inflammatory diet. This study investigated the antioxidant, anti-inflammatory and anti-septic potential of IRG silage and identified the primary components in IRG active fractions. Total 16 fractions were separated from the chloroform-soluble extract of IRG aerial part using Sephadex LH-20 column before HPLC analysis. Antioxidant and anti-inflammatory activities of the fractions at doses of 0-100 μg/mL were investigated using various cell-free and cell-mediated assay systems. To explore anti-septic effect of IRG fractions, female ICR and BALB/c mice orally received 40 mg/kg of phenolic acid and flavonoid-rich active fractions F 7 and F 8 every other day for 10 days, respectively, followed by LPS challenge. The active fractions showed greater antioxidant and anti-inflammatory potential compared with other fractions. IC 50 values of F 7 and F 8 to reduce LPS-stimulated NO and TNF-α production were around 15 and 30 μg/mL, respectively. Comparison of retention times with authentic compounds through HPLC analysis revealed the presence of caffeic acid, ferulic acid, myricetin and kaempferol in the fractions as primary components. These fractions inhibited LPS-stimulated MAPK and NF-κB activation. Supplementation with F 7 or F 8 improved the survival rates of mice to 70 and 60%, respectively, in LPS-injected mice and reduced near completely serum TNF-α and IL-6 levels. This study highlights antioxidant, anti-inflammatory and anti-septic activities of IRG active fractions, eventually suggesting their usefulness in preventing oxidative damage and inflammatory disorders.

The anti-inflammatory effect of tramadol in the temporomandibular joint of rats.

PubMed

Lamana, Simone Monaliza S; Napimoga, Marcelo H; Nascimento, Ana Paula Camatta; Freitas, Fabiana F; de Araujo, Daniele R; Quinteiro, Mariana S; Macedo, Cristina G; Fogaça, Carlos L; Clemente-Napimoga, Juliana T

2017-07-15

Tramadol is a centrally acting analgesic drug able to prevent nociceptor sensitization when administered into the temporomandibular joint (TMJ) of rats. The mechanism underlying the peripheral anti-inflammatory effect of tramadol remains unknown. This study demonstrated that intra-TMJ injection of tramadol (500µg/TMJ) was able to inhibit the nociceptive response induced by 1.5% formalin or 1.5% capsaicin, suggesting that tramadol has an antinociceptive effect, acting directly on the primary nociceptive neurons activating the nitric oxide/cyclic guanosine monophosphate signaling pathway. Tramadol also inhibited the nociceptive response induced by carrageenan (100µg/TMJ) or 5-hydroxytryptamine (225µg/TMJ) along with inhibition of inflammatory cytokines levels, leukocytes migration and plasma extravasation. In conclusion, the results demonstrate that peripheral administration of tramadol has a potential antinociceptive and anti-inflammatory effect. The antinociceptive effect is mediated by activation of the intracellular nitric oxide/cyclic guanosine monophosphate pathway, at least in part, independently from the opioid system. Copyright © 2017 Elsevier B.V. All rights reserved.

[Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].

PubMed

Gapeev, A B; Lushnikov, K V; Shumilina, Iu V; Chemeris, N K

2006-01-01

The anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the action of the known anti-inflammatory drug sodium diclofenac and the antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local inflammatory reaction was induced by intraplantar injection of zymosan into the left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected intraperitoneally 30 min after the initiation of inflammation. The animals were whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of inflammation. The inflammatory reaction was assessed over 3 - 8 h after the initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the average by 26% as compared to the control. Hyperthermia of the inflamed paw decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by about 20%, which was comparable with the effect of a single therapeutic dose of diclofenac (3 - 5 mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2 mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The combined action of clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that both arachidonic acid metabolites and histamine are involved in the realization of anti-inflammatory effects of low-intensity

Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

DTIC Science & Technology

2006-11-01

crucial signals in the development of appropriate defenses. However, exaggerated or prolonged release can lead to pathological conditions ( Sabourin ...gene expression of the inflammatory cytokines ( Sabourin et al., 2000). In this study we examined the expression of four major inflammatory...Med., 117, 2S-4S. Sabourin C. L., Petrali, J. P., and Casillas, R. P., 2000: Alterations in inflammatory cytokine gene expression in sulfur mustard

Ibuprofen: from invention to an OTC therapeutic mainstay.

PubMed

Rainsford, K D

2013-01-01

The discovery of ibuprofen's anti-inflammatory activity by Dr (now Professor) Stewart Adams and colleagues (Boots Pure Chemical Company Ltd, Nottingham, UK) 50 years ago represented a milestone in the development of anti-inflammatory analgesics. Subsequent clinical studies were the basis for ibuprofen being widely accepted for treating painful conditions at high anti-rheumatic doses (≤ 2400 mg/d), with lower doses (≤ 1200 mg/d for ≤ 10 days) for mild-moderate acute pain (e.g. dental pain, headache, dysmenorrhoea, respiratory symptoms and acute injury). The early observations have since been verified in studies comparing ibuprofen with newer cyclo-oxygenase-2 selective inhibitors ('coxibs'), paracetamol and other non-steroidal anti-inflammatory drugs (NSAIDs). The use of the low-dose, non-prescription, over-the-counter (OTC) drug was based on marketing approval in 1983 (UK) and 1984 (USA); and it is now available in over 80 countries. The relative safety of OTC ibuprofen has been supported by large-scale controlled studies. It has the same low gastro-intestinal (GI) effects as paracetamol (acetaminophen) and fewer GI effects than aspirin. Ibuprofen is a racemate. Its physicochemical properties and the short plasma-elimination half-life of the R(-) isomer, together with its limited ability to inhibit cyclo-oxygenase-1 (COX-1) and thus prostaglandin (PG) synthesis, compared with that of S(+)-ibuprofen, are responsible for the relatively low GI toxicity. The R(-) isomer is then converted in the body to the S(+) isomer after absorption in the GI tract. Ex vivo inhibition of COX-1 (thromboxane A(2)) and COX-2 (PGE(2)) at the plasma concentrations of S(+)-ibuprofen corresponding to those found in the plasma following ingestion of 400 mg ibuprofen in dental and other inflammatory pain models provides evidence of the anti-inflammatory mechanism at OTC dosages. R(-)-ibuprofen has effects on leucocytes, suggesting that ibuprofen has anti-leucocyte effects, which underlie its anti-inflammatory actions. Future developments include novel gastro-tolerant forms for 'at risk' patients, and uses in the prevention of neuro-inflammatory states and cancers. © 2012 Blackwell Publishing Ltd.

Dynamic Modulation of Microglia/Macrophage Polarization by miR-124 after Focal Cerebral Ischemia.

PubMed

Hamzei Taj, Somayyeh; Kho, Widuri; Aswendt, Markus; Collmann, Franziska M; Green, Claudia; Adamczak, Joanna; Tennstaedt, Annette; Hoehn, Mathias

2016-12-01

Mononuclear phagocytes respond to ischemic stroke dynamically, undergoing an early anti-inflammatory and protective phenotype followed by the pro-inflammatory and detrimental type. These dual roles of microglia/macrophages suggest the need of subtle adjustment of their polarization state instead of broad suppression. The most abundant brain-specific miRNA, miR-124, promotes neuronal differentiation but can also modulate microglia activation and keeps them in a quiescent state. We addressed whether the intracerebral injection of miR-124 in a mouse model of ischemic stroke before or after the peak phase of the pro-inflammatory polarization modifies the pro-/anti- inflammatory balance. In the sub-acute phase, 48 h after stroke, liposomated miR-124 shifted the predominantly pro-inflammatory polarized microglia/macrophages toward the anti-inflammatory phenotype. The altered immune response improved neurological deficit at day 6 after stroke. When miR-124 was injected 10 days after stroke, the pro-/anti- inflammatory ratio was still significantly reduced although to a lower degree and had no effect on recovery at day 14. This study indicates that miR-124 administration before the peak of the pro-inflammatory process of stroke is most effective in support of increasing the rehabilitation opportunity in the sub-acute phases of stroke. Our findings highlight the important role of immune cells after stroke and the therapeutic relevance of their polarization balance.

Discovery of Indeno[1,2-c]quinoline Derivatives as Potent Dual Antituberculosis and Anti-Inflammatory Agents.

PubMed

Tseng, Chih-Hua; Tung, Chun-Wei; Wu, Chen-Hsin; Tzeng, Cherng-Chyi; Chen, Yen-Hsu; Hwang, Tsong-Long; Chen, Yeh-Long

2017-06-16

A series of indeno[1,2- c ]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H 37 R V . Among the tested compounds, ( E )- N '-[6-(4-hydroxypiperidin-1-yl)-11 H -indeno[1,2- c ]quinolin-11-ylidene]isonicotino-hydrazide ( 12 ), exhibited significant activities against the growth of M. tuberculosis (MIC values of 0.96 μg/mL) with a potency approximately equal to that of isoniazid (INH), an anti-TB drug. Important structure features were analyzed by quantitative structure-activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the anti-TB activity. The anti-inflammatory activity was induced by superoxide anion generation and neutrophil elastase (NE) release using the formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils method. Results indicated that compound 12 demonstrated a potent dual inhibitory effect on NE release and superoxide anion generation with IC 50 values of 1.76 and 1.72 μM, respectively. Our results indicated that compound 12 is a potential lead compound for the discovery of dual anti-TB and anti-inflammatory drug candidates. In addition, 6-[3-(hydroxymethyl)piperidin-1-yl]-9-methoxy-11 H -indeno[1,2- c ]quinolin-11-one ( 4g ) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC 50 values of 0.46 and 0.68 μM, respectively, and is a potential lead compound for the discovery of anti-inflammatory drug candidates.

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

PubMed Central

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-01-01

Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system. PMID:16930490

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

PubMed

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-08-24

Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system.

Increased Growth Inhibitory Effects on Human Cancer Cells and Anti-Inflammatory Potency of Shogaols from Zingiber officinale Relative to Gingerols

PubMed Central

Sang, Shengmin; Hong, Jungil; Wu, Hou; Liu, Jing; Yang, Chung S.; Pan, Min-Hsiung; Badmaev, Vadimir; Ho, Chi-Tang

2009-01-01

Ginger, the rhizome of the plant Zingiber officinale, has received extensive attention due to its antioxidant, anti-inflammatory, and anti-tumor activities. Most researchers have considered gingerols as the active principles and have paid little attention to shogaols, the dehydration products of corresponding gingerols during storage or thermal processing. In this study, we have purified and identified eight major components including three major gingerols and corresponding shogaols from ginger extract and compared their anti-carcinogenic and anti-inflammatory activities. Our results showed that shogaols ([6]-, [8]-, and [10]-) had much stronger growth inhibitory effects than gingerols ([6]-, [8]-, and [10]-) on H-1299 human lung cancer cells and HCT-116 human colon cancer cells, especially when comparing [6]-shogaol with [6]-gingerol (IC50: ~8 µM vs. ~150 µM). In addition, we found that [6]-shogaol had much stronger inhibitory effects on arachidonic acid release and nitric oxide (NO) synthesis than [6]-gingerol. PMID:19877681

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)

Medicinal chemistry and anti-inflammatory activity of nitric oxide-releasing NSAI drugs.

PubMed

Koç And, Esra; Küçükgüzel, S Güniz

2009-05-01

Nitric Oxide, which acts as a non-specific cytotoxic mediator and a biological messenger on immunological competence, has been gaining significantly increasing importance. As an alternative to conventional NSAIDs having significant side effects, pharmacologically improved and therapeutically enhanced NO releasing non-steroidal anti-inflammatory drugs with less side effects are being planned to produce.

The influence of seasonality on the content of goyazensolide and on anti-inflammatory and anti-hyperuricemic effects of the ethanolic extract of Lychnophora passerina (Brazilian arnica).

PubMed

de Albuquerque Ugoline, Bruno César; de Souza, Jacqueline; Ferrari, Fernanda Cristina; Ferraz-Filha, Zilma Schimith; Coelho, Grazielle Brandão; Saúde-Guimarães, Dênia Antunes

2017-02-23

Lychnophora passerina (Mart ex DC) Gardn (Asteraceae), popularly known as Brazilian arnica, is used in Brazilian folk medicine to treat pain, rheumatism, bruises, inflammatory diseases and insect bites. Investigate the influence of the seasons on the anti-inflammatory and anti-hyperuricemic activities of ethanolic extract of L. passerina and the ratio of the goyazensolide content, main chemical constituent of the ethanolic extract, with these activities. Ethanolic extracts of aerial parts of L. passerina were obtained from seasons: summer (ES), autumn (EA), winter (EW) and spring (EP). The sesquiterpene lactone goyazensolide, major metabolite, was quantified in ES, EA, EW and EP by a developed and validated HPLC-DAD method. The in vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. passerina and goyazensolide were assayed on experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase (XOD) inhibition and on carrageenan-induced paw edema in mice. HPLC method using aqueous solution of acetic acid 0.01% (v/v) and acetonitrile with acetic acid 0.01% (v/v) as a mobile phase in a gradient system, with coumarin as an internal standard and DAD detection at 270nm was developed. The validation parameters showed linearity in a range within 10.0-150.0µg/ml, with intraday and interday precisions a range of 0.61-3.82. The accuracy values of intraday and interday analysis within 87.58-100.95%. EA showed the highest goyazensolide content. From the third to the sixth hour after injection of carrageenan, treatments with all extracts at the dose of 125mg/kg were able to reduce edema. Goyazensolide (10mg/kg) showed significant reduction of paw swelling from the second hour assay. This sesquiterpene lactone was more active than extracts and presented similar effect to indomethacin. Treatments with ES, EA and EP (125mg/kg) and goyazensolide (10mg/kg) reduced serum urate levels compared to hyperuricemic control group and were able to inhibit liver XOD activity. One of the mechanisms by which ES, EA, EP and goyazensolide exercise their anti-hyperuricemic effect is by the inhibition of liver XOD activity. Goyazensolide was identified as the main compound present in ES, EA, EW and EP and it is shown to be one of the chemical constituents responsible for the anti-inflammatory and anti-hyperuricemic effects of the ethanolic extracts. The anti-inflammatory and anti-hyperuricemic activities of the ethanolic extracts from L. passerina were not proportionally influenced by the variation of goyazensolide content throughout the seasons. The involvement of goyazensolide on in vivo anti-inflammatory and anti-hyperuricemic activities of L.passerina extracts was confirmed, as well as the possibility of participation of other constituents on these effects. This study demonstrated that the aerial parts of L. passerina may be collected in any season for use as anti-inflammatory agent. For use in hyperuricemia, the best seasons for the collection are summer, autumn and spring. The ethanolic extract of L. passerina and goyazensolide can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Anti-steatotic and anti-inflammatory roles of syringic acid in high-fat diet-induced obese mice.

PubMed

Ham, Ju Ri; Lee, Hae-In; Choi, Ra-Yeong; Sim, Mi-Ok; Seo, Kwon-Il; Lee, Mi-Kyung

2016-02-01

This study examined the effects of syringic acid (SA) on obese diet-induced hepatic dysfunction. Mice were fed high-fat diet (HFD) with or without SA (0.05%, wt/wt) for 16 weeks. SA reduced the body weight, visceral fat mass, serum levels of leptin, TNFα, IFNγ, IL-6 and MCP-1, insulin resistance, hepatic lipid content, droplets and early fibrosis, whereas it elevated the circulation of adiponectin. SA down-regulated lipogenic genes (Cidea, Pparγ, Srebp-1c, Srebp-2, Hmgcr, Fasn) and inflammatory genes (Tlr4, Myd88, NF-κB, Tnfα, Il6), whereas it up-regulated fatty acid oxidation genes (Pparα, Acsl, Cpt1, Cpt2) in the liver. SA also decreased hepatic lipogenic enzyme activities and elevated fatty acid oxidation enzyme activities relative to the HFD group. These findings suggested that dietary SA possesses anti-obesity, anti-inflammatory and anti-steatotic effects via the regulation of lipid metabolic and inflammatory genes. SA is likely to be a new natural therapeutic agent for obesity or non-alcoholic liver disease.

Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity

PubMed Central

2012-01-01

Background As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time. Methods Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p < 0.05 (two-tailed). Results Results indicate that the curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK. Conclusions Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model. PMID:22909087

Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

PubMed

Chen, Chunguang; Kuehn, Carina; Bretzel, Reinhard G; Linn, Thomas

2009-07-20

Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

Inhibitory activity of Sargassum hemiphyllum sulfated polysaccharide in arachidonic acid-induced animal models of inflammation.

PubMed

Hwang, Pai-An; Hung, Yu-Lan; Chien, Shih-Yung

2015-03-01

Sargassum hemiphyllum is a common plant found on the coasts of Taiwan; it has been used as an anti-inflammatory agent in traditional herbal medicine. This study aimed to evaluate the anti-inflammatory effects of S. hemiphyllum sulfated polysaccharide (SHSP) using two different mouse models. In both arachidonic acid-induced ear inflammatory gavage and paint models, SHSP decreased ear swelling and erythema. In addition, SHSP decreased the production of myeloperoxidase, nitric oxide, interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α in a dose-dependent manner. Histological examination results showed that SHSP reduced the area of neutrophilic infiltration in inflamed ears. The anti-inflammatory activity of SHSP has already been demonstrated in vitro. In this study, SHSP extracted from the same species of brown seaweed exhibited anti-inflammatory activity in both oral and topical applications in vivo. Therefore, SHSP may play a role in the treatment of inflammatory diseases. Copyright © 2014. Published by Elsevier B.V.

Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.

PubMed

Lass, Christian; Vocanson, Marc; Wagner, Steffen; Schempp, Christoph M; Nicolas, Jean-Francois; Merfort, Irmgard; Martin, Stefan F

2008-10-01

Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.

Anti-Inflammatory Effect of Supercritical-Carbon Dioxide Fluid Extract from Flowers and Buds of Chrysanthemum indicum Linnén

PubMed Central

Li, Chu-Wen; Zhang, Xiao-Jun

2013-01-01

The aim of this study was to analyze the chemical composition and investigate the anti-inflammatory property of the supercritical-carbon dioxide extract from flowers and buds of C. indicum (CISCFE). The anti-inflammatory effect was evaluated in four animal models including xylene-induced mouse ear edema, acetic acid-induced mouse vascular permeability, carrageenan-induced mouse hind paw edema, and cotton pellet-induced rat granuloma formation. The results indicated that CISCFE significantly attenuated xylene-induced ear edema, decreased acetic acid-induced capillary permeability, reduced carrageenan-induced paw, and inhibited the cotton pellet-induced granuloma formation in a dose-dependent manner. Histopathologically, CISCFE abated inflammatory response of the edema paw. Preliminary mechanistic studies demonstrated that CISCFE decreased the MDA level via increasing the activities of anti-oxidant enzymes (SOD, GPx, and GRd), attenuated the productions of NF-κB, TNF-α, IL-1β, IL-6, PGE2 and NO, and suppressed the activities of iNOS and COX-2. In phytochemical study, 35 compounds were identified by GC-MS, and 5 compounds (chlorogenic acid, luteolin-7-glucoside, linarin, luteolin and acacetin) were reconfirmed and quantitatively determined by HPLC-PAD. This paper firstly analyzed the chemical composition by combining GC-MS with HPLC-PAD and explored possible mechanisms for the anti-inflammatory effect of CISCFE. PMID:24223056

High Hydrostatic Pressure Pretreatment of Whey Protein Isolates Improves Their Digestibility and Antioxidant Capacity

PubMed Central

Iskandar, Michèle M.; Lands, Larry C.; Sabally, Kebba; Azadi, Behnam; Meehan, Brian; Mawji, Nadir; Skinner, Cameron D.; Kubow, Stan

2015-01-01

Whey proteins have well-established antioxidant and anti-inflammatory bioactivities. High hydrostatic pressure processing of whey protein isolates increases their in vitro digestibility resulting in enhanced antioxidant and anti-inflammatory effects. This study compared the effects of different digestion protocols on the digestibility of pressurized (pWPI) and native (nWPI) whey protein isolates and the antioxidant and anti-inflammatory properties of the hydrolysates. The pepsin-pancreatin digestion protocol was modified to better simulate human digestion by adjusting temperature and pH conditions, incubation times, enzymes utilized, enzyme-to-substrate ratio and ultrafiltration membrane molecular weight cut-off. pWPI showed a significantly greater proteolysis rate and rate of peptide appearance regardless of digestion protocol. Both digestion methods generated a greater relative abundance of eluting peptides and the appearance of new peptide peaks in association with pWPI digestion in comparison to nWPI hydrolysates. Hydrolysates of pWPI from both digestion conditions showed enhanced ferric-reducing antioxidant power relative to nWPI hydrolysates. Likewise, pWPI hydrolysates from both digestion protocols showed similar enhanced antioxidant and anti-inflammatory effects in a respiratory epithelial cell line as compared to nWPI hydrolysates. These findings indicate that regardless of considerable variations of in vitro digestion protocols, pressurization of WPI leads to more efficient digestion that improves its antioxidant and anti-inflammatory properties. PMID:28231198

High Hydrostatic Pressure Pretreatment of Whey Protein Isolates Improves Their Digestibility and Antioxidant Capacity.

PubMed

Iskandar, Michèle M; Lands, Larry C; Sabally, Kebba; Azadi, Behnam; Meehan, Brian; Mawji, Nadir; Skinner, Cameron D; Kubow, Stan

2015-05-28

Whey proteins have well-established antioxidant and anti-inflammatory bioactivities. High hydrostatic pressure processing of whey protein isolates increases their in vitro digestibility resulting in enhanced antioxidant and anti-inflammatory effects. This study compared the effects of different digestion protocols on the digestibility of pressurized (pWPI) and native (nWPI) whey protein isolates and the antioxidant and anti-inflammatory properties of the hydrolysates. The pepsin-pancreatin digestion protocol was modified to better simulate human digestion by adjusting temperature and pH conditions, incubation times, enzymes utilized, enzyme-to-substrate ratio and ultrafiltration membrane molecular weight cut-off. pWPI showed a significantly greater proteolysis rate and rate of peptide appearance regardless of digestion protocol. Both digestion methods generated a greater relative abundance of eluting peptides and the appearance of new peptide peaks in association with pWPI digestion in comparison to nWPI hydrolysates. Hydrolysates of pWPI from both digestion conditions showed enhanced ferric-reducing antioxidant power relative to nWPI hydrolysates. Likewise, pWPI hydrolysates from both digestion protocols showed similar enhanced antioxidant and anti-inflammatory effects in a respiratory epithelial cell line as compared to nWPI hydrolysates. These findings indicate that regardless of considerable variations of in vitro digestion protocols, pressurization of WPI leads to more efficient digestion that improves its antioxidant and anti-inflammatory properties.

Design, synthesis and investigation of potential anti-inflammatory activity of O-alkyl and O-benzyl hesperetin derivatives.

PubMed

Huang, Ai-Ling; Zhang, Yi-Long; Ding, Hai-Wen; Li, Bo; Huang, Cheng; Meng, Xiao-Ming; Li, Jun

2018-05-28

Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compounds were investigated for their anti-inflammatory activity by inhibiting interleukin-1β (IL-1β), interleukin-6 (IL-6) and production of nitric oxide (NO) in mouse RAW264.7 macrophages, and the structure-activity relationship of them was discussed. Among them, the compound 1l, 2c demonstrated more effective inhibitory activity of IL-1β and IL-6, meanwhile, the compound 1l showed the best inhibition of NO production. The results of NO inhibition study were basically accord with the molecular docking results of inducible nitric oxide synthase (iNOS). Furthermore, the expression of LPS-induced iNOS and components of NF-κB signaling pathway were reduced by compound 1l. Our results suggest that the inhibitory effect of compound 1l on LPS-stimulated inflammatory mediator production in RAW 264.7 cells is associated with the suppression of NF-κB signaling pathway and inhibition of iNOS protein and iNOS activity. From in vivo study, it was also observed that compound 1l had hepato-protective and anti-inflammatory effects in CCl 4 -induced acute liver injury mouse models. Copyright © 2018 Elsevier B.V. All rights reserved.

Antinociceptive and Anti-Inflammatory Activities of Bridelia retusa Methanolic Fruit Extract in Experimental Animals

PubMed Central

Kumar, Tekeshwar; Jain, Vishal

2014-01-01

Antinociceptive and anti-inflammatory potentials of methanolic extract of Bridelia retusa fruit (BRME) were evaluated against different animal models in rodents. Antinociceptive effects of BRME were assessed in mice using the acetic acid-induced writhing and formalin test. Anti-inflammatory effects of BRME in three different doses, namely, 100, 200, and 400 mg/kg, were evaluated by utilizing different animal models representing various changes associated with inflammation, namely, carrageenan-induced paw oedema, histamine and serotonin-induced paw oedema, arachidonic acid-induced paw oedema, formalin-induced paw oedema, TPA-induced ear oedema, acetic acid-induced vascular permeability, total WBC count in paw fluid, and myeloperoxidase assay. Also BRME was phytochemically evaluated using chromatographic method. The BRME did not exhibit any signs of toxicity up to a dose of 2000 mg/kg. The extract showed statistical significant inhibition of induced nociception and inflammation in dose dependent manner. The higher dose of extract significantly inhibited pain and inflammation against control (P < 0.001). HPLC results revealed the presence of gallic acid and ellagic acid as phytoconstituents in BRME and it was proven as anti-inflammatory agents. The present study scientifically demonstrated the antinociceptive and anti-inflammatory potential of fruit of B. retusa methanolic extract. These effects may be attributed to the presence of polyphenolic phytoconstituents in the extract. PMID:25506619

Anti-inflammatory and antinociceptive effects of Chinese medicine SQ gout capsules and its modulation of pro-inflammatory cytokines focusing on gout arthritis.

PubMed

Kodithuwakku, Nandani Darshika; Pan, Min; Zhu, Yi-lin; Zhang, Yan-yan; Feng, Yi-dong; Fang, Wei-rong; Li, Yun-man

2013-12-12

Shuang-Qi gout capsule is a traditional Chinese medicine prescription, which has been used in the treatment of joint pain, inflammation and gout arthritis. This study evaluates anti-inflammatory and antinociceptive effects of Shuang-Qi gout capsule and its modulation of pro-inflammatory cytokines with special reference to gout arthritis. Anti-inflammatory effect of Shuang-Qi gout capsule was investigated bymice tail-flick response, acetic acid induced writhing response, Xylene-induced auricle inflammation and the hind paw volume of the monosodium urate (MSU) crystal induced rats with different time durations. To investigate the effects on gout arthritis, ankle joint of rats induced by MSU crystals and assessed for edema and histopathological changes. In vitro, prepared serum was incubated with urate crystal induced HUVE cells and the release of TNF-α and IL-1β determined by ELISA. Shuang-Qi gout capsule showed significant and dose dependent anti-inflammatory effect via reducing edema and pain, throughout all the models. The high dose of Shuang-Qi gout capsule and Indomethacin significantly attenuated the edema. Histopathological results showed that high and medium dose of Shuang-Qi gout capsule and Indomethacin reduced gouty joint inflammatory features, while the high dose of Shuang-Qi gout capsule showed a better therapeutic effect. High and medium dose of Shuang-Qi gout capsule significantly reduced the release of TNF-α and IL-1β (p<0.05). Shuang-Qi gout capsule can effectively inhibit the inflammation, analgesia, through the modulation of emission of pro-inflammatory cytokines and the curative effect is dose dependent. Conversely, these MSU induced in vivo and in vitro studies of Shuang-Qi gout capsule suggest that, Shuang-Qi gout capsule may be a potential agent for treatment in gouty arthritis. © 2013 Published by Elsevier Ireland Ltd.

Anti-inflammatory effects of traditional mixed extract of medicinal herbs (MEMH) on monosodium urate crystal-induced gouty arthritis.

PubMed

Nam, Ju-Suk; Jagga, Supriya; Sharma, Ashish Ranjan; Lee, Joon-Hee; Park, Jong Bong; Jung, Jun-Sub; Lee, Sang-Soo

2017-08-01

Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs (MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate (MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mRNA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaOS-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators (IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mRNA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Anti-inflammatory and bronchodilatory constituents of leaf extracts of Anacardium occidentale L. in animal models.

PubMed

Awakan, Oluwakemi Josephine; Malomo, Sylvia Omonirume; Adejare, Abdullahi Adeyinka; Igunnu, Adedoyin; Atolani, Olubunmi; Adebayo, Abiodun Humphrey; Owoyele, Bamidele Victor

2018-01-01

Anacardium occidentale L. leaf is useful in the treatment of inflammation and asthma, but the bioactive constituents responsible for these activities have not been characterized. Therefore, this study was aimed at identifying the bioactive constituent(s) of A. occidentale ethanolic leaf extract (AOEL) and its solvent-soluble portions, and evaluating their effects on histamine-induced paw edema and bronchoconstriction. The bronchodilatory effect was determined by measuring the percentage protection provided by plant extracts in the histamine-induced bronchoconstriction model in guinea pigs. The anti-inflammatory effect of the extracts on histamine-induced paw edema in rats was determined by measuring the increase in paw diameter, after which the percent edema inhibition was calculated. The extracts were analyzed using gas chromatography-mass spectrometry to identify the bioactive constituents. Column chromatography and Fourier transform infrared spectroscopy were used respectively to isolate and characterize the constituents. The bronchodilatory and anti-inflammatory activities of the isolated bioactive constituent were evaluated. Histamine induced bronchoconstriction in the guinea pigs and edema in the rat paw. AOEL, hexane-soluble portion of AOEL, ethyl acetate-soluble portion of AOEL, and chloroform-soluble portion of AOEL significantly increased bronchodilatory and anti-inflammatory activities (P < 0.05). Oleamide (9-octadecenamide) was identified as the most abundant compound in the extracts and was isolated. Oleamide significantly increased bronchodilatory and anti-inflammatory activities by 32.97% and 98.41%, respectively (P < 0.05). These results indicate that oleamide is one of the bioactive constituents responsible for the bronchodilatory and anti-inflammatory activity of A. occidentale leaf, and can therefore be employed in the management of bronchoconstriction and inflammation. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

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.

Anti-inflammatory effect of extract and fractions from the leaves of Byrsonima intermedia A. Juss. in rats.

PubMed

Moreira, Lucimara Q; Vilela, Fabiana C; Orlandi, Lidiane; Dias, Danielle F; Santos, Ana Laura A; da Silva, Marcelo A; Paiva, Renato; Alves-da-Silva, Geraldo; Giusti-Paiva, Alexandre

2011-11-18

Byrsonima intermedia is commonly used for its antiseptic, antimicrobial, and anti-inflammatory properties in the treatment of diarrhea and dysentery in Brazilian folk medicine. The purpose of this study was to examine the anti-inflammatory activity of the aqueous extract and fractions of Byrsonima intermedia leaves. Rats with carrageenan-induced paw edema and fibrovascular tissue growth, which was induced by subcutaneous implantation of a cotton pellet, were used as acute and chronic animal models of inflammation to investigate the anti-inflammatory effects of the aqueous extract and the individual ethyl acetate (EtOAc) and aqueous fractions of Byrsonima intermedia and catechin. High-performance liquid chromatography (HPLC) was used to determine the fingerprint chromatogram of the aqueous extract and fractions of Byrsonima intermedia. The crude aqueous extract at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reducing carrageenan-induced paw edema, as did the ethyl acetate (100mg/kg) and aqueous fractions (30-100mg/kg). In the chronic inflammation rat animal model with fibrovascular tissue growth, the aqueous extract of Byrsonima intermedia (BiAE) at doses of 30-300 mg/kg and the individual EtOAc and aqueous fractions at doses of 30-100mg/kg and catechin significantly reduced the formation of granulomatous tissue. The presence of catechin and phenolic compounds in the extract and fractions of Byrsonima intermedia was confirmed using HPLC. BiAE and the individual EtOAc and aqueous fractions of Byrsonima intermedia exhibited chronic and acute anti-inflammatory efficacy in rats, which supports previous claims of its use in traditional medicine. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effects of LJP 1586 [Z-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride], an amine-based inhibitor of semicarbazide-sensitive amine oxidase activity.

PubMed

O'Rourke, Anne M; Wang, Eric Y; Miller, Andrew; Podar, Erika M; Scheyhing, Kelly; Huang, Li; Kessler, Christina; Gao, Hongfeng; Ton-Nu, Huong-Thu; Macdonald, Mary T; Jones, David S; Linnik, Matthew D

2008-02-01

Semicarbazide-sensitive amine oxidase (SSAO, amine oxidase, copper-containing 3, and vascular adhesion protein-1) is a copper-containing enzyme that catalyzes the oxidative deamination of primary amines to an aldehyde, ammonia, and hydrogen peroxide. SSAO is also involved in leukocyte migration to sites of inflammation, and the enzymatic activity of SSAO is essential to this role. Thus, inhibition of SSAO enzyme activity represents a target for the development of small molecule anti-inflammatory compounds. Here, we have characterized the novel SSAO inhibitor, Z-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride (LJP 1586), and assessed its anti-inflammatory activity. LJP 1586 is a potent inhibitor of rodent and human SSAO activity, with IC(50) values between 4 and 43 nM. The selectivity of LJP 1586 was confirmed with a broad panel of receptors and enzymes that included the monoamine oxidases A and B. Oral administration of LJP 1586 resulted in complete inhibition of rat lung SSAO, with an ED(50) between 0.1 and 1 mg/kg, and a pharmacodynamic half-life of greater than 24 h. In a mouse model of inflammatory leukocyte trafficking oral dosing with LJP 1586 resulted in significant dose-dependent inhibition of neutrophil accumulation, with an effect comparable to that of anti-leukocyte function-associated antigen-1 antibody. In a rat model of LPS-induced lung inflammation, administration of 10 mg/kg LJP 1586 resulted in a 55% significant reduction in transmigrated cells recovered by bronchoalveolar lavage. The results demonstrate that a selective, orally active small molecule inhibitor of SSAO is an effective anti-inflammatory compound in vivo and provide further support for SSAO as a therapeutic anti-inflammatory target.

Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway.

PubMed

Lin, Wen; Wu, Rachel T; Wu, Tienyuan; Khor, Tin-Oo; Wang, Hu; Kong, Ah-Ng

2008-10-15

Sulforaphane (SFN) is a natural isothiocyanate that is present in cruciferous vegetables such as broccoli and cabbage. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents, which is related in part to its potent anti-inflammation properties. In the present study, we compared the anti-inflammatory effect of SFN on LPS-stimulated inflammation in primary peritoneal macrophages derived from Nrf2 (+/+) and Nrf2 (-/-) mice. Pretreatment of SFN in Nrf2 (+/+) primary peritoneal macrophages potently inhibited LPS-stimulated mRNA expression, protein expression and production of TNF-alpha, IL-1beta, COX-2 and iNOS. HO-1 expression was significantly augmented in LPS-stimulated Nrf2 (+/+) primary peritoneal macrophages by SFN. Interestingly, the anti-inflammatory effect was attenuated in Nrf2 (-/-) primary peritoneal macrophages. We concluded that SFN exerts its anti-inflammatory activity mainly via activation of Nrf2 in mouse peritoneal macrophages.

Emodin, a natural inhibitor of protein kinase CK2, suppresses growth, hyphal development, and biofilm formation of Candida albicans.

PubMed

Janeczko, Monika; Masłyk, Maciej; Kubiński, Konrad; Golczyk, Hieronim

2017-06-01

Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a natural secondary plant product, originally isolated from the rhizomes of Rheum palmatum. Many reports show its diuretic, vasorelaxant, antibacterial, antiviral, anti-ulcerogenic, immunosuppressive, hepatoprotective, anti-inflammatory and anticancer potential. Emodin is a pleiotropic molecule capable of interacting with several major molecular targets, e.g. NF-κB, AKT/mTOR and STAT3. The compound can also act as an inhibitor of some protein kinases, with special affinity to protein kinase CK2. The aim of the presented report was to evaluate antifungal properties of emodin and its activity towards CK2 isolated from Candida cells. Our studies revealed that the compound suppressed growth of the cells of reference strains as well as clinical Candida strains, with minimal inhibitory concentration and minimal fungicidal concentration values between 12.5 and 200 μg/mL. Moreover, at a low concentration, the compound was able to effectively stop hyphal formation, thus showing a distinct antivirulent potential. Interestingly, we showed that emodin added to Candida culture inhibited the phosphorylation of many cellular proteins, presumably owing to the inhibition of protein kinase CK2. Notably, the enzyme isolated from the Candida cells was susceptible to emodin with IC 50 of 2.8 μg/mL. Indeed, our computational modelling revealed that emodin was able to occupy the ATP-binding pocket of CK2. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Influence of polyphenol extract from evening primrose (Oenothera paradoxa) seeds on human prostate and breast cancer cell lines.

PubMed

Lewandowska, Urszula; Owczarek, Katarzyna; Szewczyk, Karolina; Podsędek, Anna; Koziołkiewicz, Maria; Hrabec, Elżbieta

2014-02-03

There is growing interest in plant polyphenols which exhibit pleiotropic biological activities, including anti-inflammatory, antioxidant, and anticancer effects. The objective of our study was to evaluate the influence of an evening primrose extract (EPE) from defatted seeds on viability and invasiveness of three human cell lines: PNT1A (normal prostate cells), DU145 (prostate cancer cells) and MDA-MB-231 (breast cancer cells). The results revealed that after 72 h of incubation the tested extract reduced the viability of DU 145 and MDA-MB-231 with IC50 equal to 14.5 μg/mL for both cell lines. In contrast, EPE did not inhibit the viability of normal prostate cells. Furthermore, EPE reduced PNT1A and MDA-MB-231 cell invasiveness; at the concentration of 21.75 μg/mL the suppression of invasion reached 92% and 47%, respectively (versus control). Additionally, zymographic analysis revealed that after 48 h of incubation EPE inhibited metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) activities in a dose-dependent manner. For PNT1A the activities of MMP-2 and MMP-9 decreased 4- and 2-fold, respectively, at EPE concentration of 29 μg/mL. In the case of MDA-MB-231 and DU 145 the decrease in MMP-9 activity at EPE concentration of 29 μg/mL was 5.5-fold and almost 1.9-fold, respectively. In conclusion, this study suggests that EPE may exhibit antimigratory, anti-invasive and antimetastatic potential towards prostate and breast cancer cell lines.

CHP1002, a novel andrographolide derivative, inhibits pro-inflammatory inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW264.7 macrophages via up-regulation of heme oxygenase-1 expression.

PubMed

Zhang, Bo; Yan, Lingdi; Zhou, Peilan; Dong, Zhaoqi; Feng, Siliang; Liu, Keliang; Gong, Zehui

2013-02-01

Andrographolides, a type of diterpene lactone, are widely known to have anti-inflammatory and anti-oxidative properties. CHP1002, a synthetic derivative of andrographolide, has similar anti-inflammatory action in mouse ear swelling test and rat paw edema test. In the present study, the mechanism of anti-inflammatory effects of CHP1002 was investigated in RAW264.7 macrophages. CHP1002 potently suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CHP1002 reduced the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 (PGE2). CHP1002 induced heme oxygenase-1 (HO-1) expression via activation of extracellular signal-regulated kinase (ERK) and NF-E2 related factor 2 transcription factor (Nrf2). Down-regulation of LPS-induced iNOS and COX-2 expressions was partially reversed by the HO-1 inhibitor zinc protoporphyrin (ZnPP). In addition, CHP1002 significantly attenuated LPS-induced TNF-α, IL-1β and IL-6 production. CHP1002 effectively induced HO-1 and was capable of inhibiting some macrophage-derived pro-inflammatory mediators, which may be closely correlated with its anti-inflammatory action. Copyright © 2012 Elsevier B.V. All rights reserved.

ANTI-INFLAMMATORY ACTIVITY OF EUCALYPTUS SPP. AND PISTASCIA LENTISCUS LEAF EXTRACTS.

PubMed

Qabaha, Khaled; Ras, Sari Abu; Abbadi, Jehad; Al-Rimawi, Fuad

2016-01-01

Eucalyptus spp. and Pistascia lentiscus are among the Palestinian trees that are traditionally used in folkloric medicine in treating many diseases; leaves of which are thought to have anti-inflammatory, antibacterial and antioxidant effects. The goal of this study is to evaluate the in vitro inhibitory effect of Eucalyptus spp . and Pistascia lentiscus extracts on Lipopolysacaride (LPS)-induced Interlukin-6 (Il-6) and Tumor Necrosis Factor-α (TNF-α) by polymorphonuclear Cells (PMNCs). Polymorphonuclear cells were isolated from the whole blood using Histopaque (Ficol-1077) method and then cultured in an enriched Roswell Park Memorial Institute (RBMI) medium. Supernatants' Interlukin-6 (IL-6) and Tumor Necrosis Factor (TNF-α) levels were determined 24 hour after LPS stimulation. HPLC was employed to determine the concentration of phenolic compounds in the extracts. The concentrations of TNF-α and IL-6 were compared using paired-samples t test. Eucalyptus spp . and Pistascia lentiscus leaves extracts have shown significant reduction in the levels of both Il-6 and TNF-α Gallic acid; a strong anti-inflammatory agent was found to be the major phenolic compound in both leaf extracts. However, other anti-inflammatory phenolic compounds were detected in Pitascia lentiscus extract including syringic acid and p-coumaric acid, while chlorogenic acid was detected in Eucalyptus spp . leaf extract. Reduction in the levels of Il-6 and TNF-α upon the effect of both Eucalyptus spp . and Pistascia lentiscus extract is an indication of their anti-inflammatory effects. Our results may also indicate that the observed anti-inflammatory effect of the above extracts may be due to the presence of gallic acid and other phenolic compounds. List of Abbreviations and Nomenclature: LPS: Lipopolysacaride, Il-6: Interlukin-6, TNF-α: Tumor Necrosis Factor-α, PMNCs: Polymorphonuclear Cells, HPLC: High Performance Liquid Chromatography, ELISA: Enzyme Linked Immune Sorbent Assay, EDTA: Ethylene Diamine Tetra Acetic acid, PBS: phosphate buffered saline, RPMI: Roswell Park Memorial Institute medium FBS: Fetal Bovine Serum.

Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs

PubMed Central

Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

2014-01-01

Background 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. Aims 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. Methods 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. Results 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. Conclusion 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 should be explored in future studies. PMID:25242268

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

Background 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. Aims 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. Methods 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. Results 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. Conclusion 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 should be explored in future studies.

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 should be explored in future studies.

ANTI-INFLAMMATORY ACTIVITY OF EUCALYPTUS SPP. AND PISTASCIA LENTISCUS LEAF EXTRACTS

PubMed Central

Qabaha, Khaled; Ras, Sari Abu; Abbadi, Jehad; Al-Rimawi, Fuad

2016-01-01

Background: Eucalyptus spp. and Pistascia lentiscus are among the Palestinian trees that are traditionally used in folkloric medicine in treating many diseases; leaves of which are thought to have anti-inflammatory, antibacterial and antioxidant effects. The goal of this study is to evaluate the in vitro inhibitory effect of Eucalyptus spp. and Pistascia lentiscus extracts on Lipopolysacaride (LPS)-induced Interlukin-6 (Il-6) and Tumor Necrosis Factor-α (TNF-α) by polymorphonuclear Cells (PMNCs). Materials and Methods: Polymorphonuclear cells were isolated from the whole blood using Histopaque (Ficol-1077) method and then cultured in an enriched Roswell Park Memorial Institute (RBMI) medium. Supernatants’ Interlukin-6 (IL-6) and Tumor Necrosis Factor (TNF-α) levels were determined 24 hour after LPS stimulation. HPLC was employed to determine the concentration of phenolic compounds in the extracts. The concentrations of TNF-α and IL-6 were compared using paired-samples t test. Results: Eucalyptus spp. and Pistascia lentiscus leaves extracts have shown significant reduction in the levels of both Il-6 and TNF-α Gallic acid; a strong anti-inflammatory agent was found to be the major phenolic compound in both leaf extracts. However, other anti-inflammatory phenolic compounds were detected in Pitascia lentiscus extract including syringic acid and p-coumaric acid, while chlorogenic acid was detected in Eucalyptus spp. leaf extract. Conclusion: Reduction in the levels of Il-6 and TNF-α upon the effect of both Eucalyptus spp. and Pistascia lentiscus extract is an indication of their anti-inflammatory effects. Our results may also indicate that the observed anti-inflammatory effect of the above extracts may be due to the presence of gallic acid and other phenolic compounds. List of Abbreviations and Nomenclature: LPS: Lipopolysacaride, Il-6: Interlukin-6, TNF-α: Tumor Necrosis Factor-α, PMNCs: Polymorphonuclear Cells, HPLC: High Performance Liquid Chromatography, ELISA: Enzyme Linked Immune Sorbent Assay, EDTA: Ethylene Diamine Tetra Acetic acid, PBS: phosphate buffered saline, RPMI: Roswell Park Memorial Institute medium FBS: Fetal Bovine Serum. PMID:28487887

Anti-inflammatory evaluation and characterization of leaf extract of Ananas comosus.

PubMed

Kargutkar, Samira; Brijesh, S

2018-04-01

Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In the present study, the potential anti-inflammatory activity of A. comosus leaf extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to preliminary qualitative phytochemical analysis and quantitative estimations of flavonoids and tannins. The components present in ALE were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and proteinase activity were assessed. Its effect on secretion of pro-inflammatory cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced inflammatory rat model was examined. The preliminary qualitative phytochemical analysis revealed presence of flavonoids, phenols, tannins, carbohydrates, glycosides, and proteins in the extract. Total flavonoids and total tannins were 0.17 ± 0.006 mg equivalent of quercetin/g of ALE and 4.04 ± 0.56 mg equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4-hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid, whereas GC-MS analysis identified the presence of campesterol and ethyl isoallocholate that have been previously reported for anti-inflammatory activity. ALE showed significant inhibition of protein denaturation and proteinase activity and also controlled secretion of tumour necrosis factor-α, interleukin-1β and prostaglandins, as well as the generation of reactive oxygen species by activated macrophages. ALE also significantly decreased carrageenan-induced acute paw edema. The study, therefore, identified the components present in ALE that may be responsible for its anti-inflammatory activity and thus demonstrated its potential use against acute inflammatory diseases.

[Research update of effectiveness and mechanism of essential fatty acids in treating dry eye].

PubMed

Liu, Y; Liang, Q F

2017-03-11

Topical anti-inflammatory therapy has become the significant way of treating dry eye so far. However, as the long-term use of routine anti-inflammatory medications are restricted from their side effects, it is inevitable to explore safer and more effective alternatives. Essential fatty acids have proven to be anti-inflammatory systemically, which makes it possible to treat dry eye. Clinical trials have demonstrated that supplementation with either ω-3 or ω-6 essential fatty acids or both has multifactorial efficacies including improvement of subjective symptoms, alleviation of inflammation of ocular surface and eyelid margin, prolongation of tear break-up time and increase of tear flow secretion. Besides anti-inflammation effects, several basic researches have revealed that other mechanisms of essential fatty acids treating dry eye might lie in the corneal epithelial healing and tear secretion promotion. This review puts emphasis on the effectiveness, feasibility and mechanism of treating dry eye with essential fatty acids. (Chin J Ophthalmol, 2017, 53: 225-229) .

Reducing inappropriate non-steroidal anti-inflammatory prescription in primary care patients with chronic kidney disease.

PubMed

Keohane, David M; Dennehy, Thomas; Keohane, Kenneth P; Shanahan, Eamonn

2017-08-14

Purpose The purpose of this paper is to reduce inappropriate non-steroidal anti-inflammatory prescribing in primary care patients with chronic kidney disease (CKD). Once diagnosed, CKD management involves delaying progression to end stage renal failure and preventing complications. It is well established that non-steroidal anti-inflammatories have a negative effect on kidney function and consequently, all nephrology consensus groups suggest avoiding this drug class in CKD. Design/methodology/approach The sampling criteria included all practice patients with a known CKD risk factor. This group was refined to include those with an estimated glomerular filtration rate (eGFR)<60 ml/min per 1.73m2 (stage 3 CKD or greater). Phase one analysed how many prescriptions had occurred in this group over the preceding three months. The intervention involved creating an automated alert on at risk patient records if non-steroidal anti-inflammatories were prescribed and discussing the rationale with practice staff. The re-audit phase occurred three months' post intervention. Findings The study revealed 728/7,500 (9.7 per cent) patients at risk from CKD and 158 (2.1 per cent) who were subsequently found to have an eGFR<60 ml/min, indicating=stage 3 CKD. In phase one, 10.2 per cent of at risk patients had received a non-steroidal anti-inflammatory prescription in the preceding three months. Additionally, 6.2 per cent had received non-steroidal anti-inflammatories on repeat prescription. Phase two post intervention revealed a significant 75 per cent reduction in the total non-steroidal anti-inflammatories prescribed and a 90 per cent reduction in repeat non-steroidal anti-inflammatory prescriptions in those with CKD. Originality/value The study significantly reduced non-steroidal anti-inflammatory prescription in those with CKD in primary care settings. It also created a CKD register within the practice and an enduring medication alert system for individuals that risk nephrotoxic non-steroidal anti-inflammatory prescription. It established a safe, reliable and efficient process for reducing morbidity and mortality, improving quality of life and limiting the CKD associated health burden.

Anti-inflammatory effect of ethanolic extract of spine, skin and rind of Jack fruit peel - A comparative study.

PubMed

Meera, M; Ruckmani, A; Saravanan, R; Lakshmipathy Prabhu, R

2017-10-09

The present study was conducted to identify the chemical constituents and evaluate the anti-inflammatory activity of crude ethanolic extracts of spine, skin and rind of jack fruit (Artocarpus heterophyllus) peel. Polyphenol and flavonoid contents were assessed using Folin's Ciocalteu reagent and aluminium chloride methods which revealed 316, 355 and 382 mg tannic acid equivalent/g of polyphenol and 96.7, 131.6 and 164.6 mg quercetin equivalent/g of flavonoid in spine, skin and rind, respectively. Anti-inflammatory activity of all three extracts was comparable to diclofenac in vitro and in vivo studies. Skin exhibited maximum anti-inflammatory activity, rind had preferential inhibition on Cyclooxygenase-2 and spine and skin inhibited both Cyclooxygenase-1 and 2 in vitro.

Aurantiamide acetate from baphicacanthus cusia root exhibits anti-inflammatory and anti-viral effects via inhibition of the NF-κB signaling pathway in Influenza A virus-infected cells.

PubMed

Zhou, Beixian; Yang, Zifeng; Feng, Qitong; Liang, Xiaoli; Li, Jing; Zanin, Mark; Jiang, Zhihong; Zhong, Nanshan

2017-03-06

Baphicacanthus cusia root also names "Nan Ban Lan Gen" has been traditionally used to prevent and treat influenza A virus infections. Here, we identified a peptide derivative, aurantiamide acetate (compound E17), as an active compound in extracts of B. cusia root. Although studies have shown that aurantiamide acetate possesses antioxidant and anti-inflammatory properties, the effects and mechanism by which it functions as an anti-viral or as an anti-inflammatory during influenza virus infection are poorly defined. Here we investigated the anti-viral activity and possible mechanism of compound E17 against influenza virus infection. The anti-viral activity of compound E17 against Influenza A virus (IAV) was determined using the cytopathic effect (CPE) inhibition assay. Viruses were titrated on Madin-Darby canine kidney (MDCK) cells by plaque assays. Ribonucleoprotein (RNP) luciferase reporter assay was further conducted to investigate the effect of compound E17 on the activity of the viral polymerase complex. HEK293T cells with a stably transfected NF-κB luciferase reporter plasmid were employed to examine the activity of compound E17 on NF-κB activation. Activation of the host signaling pathway induced by IAV infection in the absence or presence of compound E17 was assessed by western blotting. The effect of compound E17 on IAV-induced expression of pro-inflammatory cytokines was measured by real-time quantitative PCR and Luminex assays. Compound E17 exerted an inhibitory effect on IAV replication in MDCK cells but had no effect on avian IAV and influenza B virus. Treatment with compound E17 resulted in a reduction of RNP activity and virus titers. Compound E17 treatment inhibited the transcriptional activity of NF-κB in a NF-κB luciferase reporter stable HEK293 cell after stimulation with TNF-α. Furthermore, compound E17 blocked the activation of the NF-κB signaling pathway and decreased mRNA expression levels of pro-inflammatory genes in infected cells. Compound E17 also suppressed the production of IL-6, TNF-α, IL-8, IP-10 and RANTES from IAV-infected lung epithelial (A549) cells. These results indicate that compound E17 isolated from B. cusia root has potent anti-viral and anti-inflammatory effects on IAV-infected cells via inhibition of the NF-κB pathway. Therefore, compound E17 could be a potential therapeutic agent for the treatment of influenza. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Shikonin Suppresses NLRP3 and AIM2 Inflammasomes by Direct Inhibition of Caspase-1

PubMed Central

Zorman, Jernej; Sušjan, Petra; Hafner-Bratkovič, Iva

2016-01-01

Shikonin is a highly lipophilic naphtoquinone found in the roots of Lithospermum erythrorhizon used for its pleiotropic effects in traditional Chinese medicine. Based on its reported antipyretic and anti-inflammatory properties, we investigated whether shikonin suppresses the activation of NLRP3 inflammasome. Inflammasomes are cytosolic protein complexes that serve as scaffolds for recruitment and activation of caspase-1, which, in turn, results in cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. NLRP3 inflammasome activation involves two steps: priming, i.e. the activation of NF-κB pathway, and inflammasome assembly. While shikonin has previously been reported to suppress the priming step, we demonstrated that shikonin also inhibits the second step of inflammasome activation induced by soluble and particulate NLRP3 instigators in primed immortalized murine bone marrow-derived macrophages. Shikonin decreased NLRP3 inflammasome activation in response to nigericin more potently than acetylshikonin. Our results showed that shikonin also inhibits AIM2 inflammasome activation by double stranded DNA. Shikonin inhibited ASC speck formation and caspase-1 activation in murine macrophages and suppressed the activity of isolated caspase-1, demonstrating that it directly targets caspase-1. Complexing shikonin with β-lactoglobulin reduced its toxicity while preserving the inhibitory effect on NLRP3 inflammasome activation, suggesting that shikonin with improved bioavailability might be interesting for therapeutic applications in inflammasome-mediated conditions. PMID:27467658

Artemisia asiatica Nakai Attenuates the Expression of Proinflammatory Mediators in Stimulated Macrophages Through Modulation of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathways

PubMed Central

Kim, Eun-Kyung; Tang, Yujiao; Cha, Kwang-Suk; Choi, Heeri; Lee, Chun Bok; Yoon, Jin-Hwan; Kim, Sang Bae; Kim, Jong-Shik; Kim, Jong Moon; Han, Weon Cheol; Choi, Suck-Jun; Lee, Sangmin; Choi, Eun-Ju; Kim, Sang-Hyun

2015-01-01

Abstract The present study aimed to examine the anti-inflammatory effects and potential mechanism of action of Artemisia asiatica Nakai (A. asiatica Nakai) extract in activated murine macrophages. A. asiatica Nakai extract showed dose-dependent suppression of lipopolysaccharide (LPS)-induced nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 activity. It also showed dose-dependent inhibition of nuclear factor-κB (NF-κB) translocation from the cytosol to the nucleus and as an inhibitor of NF-κB-alpha phosphorylation. The extract's inhibitory effects were found to be mediated through NF-κB inhibition and phosphorylation of extracellular signal-regulated kinase 1/2 and p38 in LPS-stimulated J774A.1 murine macrophages, suggesting a potential mechanism for the anti-inflammatory activity of A. asiatica Nakai. To our knowledge, this is the first report of the anti-inflammatory effects of A. asiatica Nakai on J774A.1 murine macrophages; these results may help develop functional foods possessing an anti-inflammatory activity. PMID:26061361

Discovery of Pyrazolo[4,3-c]quinolines Derivatives as Potential Anti-Inflammatory Agents through Inhibiting of NO Production.

PubMed

Tseng, Chih-Hua; Tung, Chun-Wei; Peng, Shin-I; Chen, Yeh-Long; Tzeng, Cherng-Chyi; Cheng, Chih-Mei

2018-04-28

The synthesis and anti-inflammatory effects of certain pyrazolo[4,3- c ]quinoline derivatives 2a ⁻ 2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1 H -pyrazolo[4,3- c ]-quinoline ( 2i ) and 4-(3-amino-1 H -pyrazolo[4,3- c ]quinolin-4-ylamino)benzoic acid ( 2m ) exhibited significant inhibition of LPS-stimulated NO production with a potency approximately equal to that of the positive control, 1400 W. Important structure features were analyzed by quantitative structure⁻activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the inhibitory effects on the accumulation of nitric oxide for RAW 264.7 cells in response to LPS. In addition, our results indicated that their anti-inflammatory effects involve the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression. Further studies on the structural optimization are ongoing.

Anti-inflammatory properties of clovamide and Theobroma cacao phenolic extracts in human monocytes: evaluation of respiratory burst, cytokine release, NF-κB activation, and PPARγ modulation.

PubMed

Zeng, Huawu; Locatelli, Monica; Bardelli, Claudio; Amoruso, Angela; Coisson, Jean Daniel; Travaglia, Fabiano; Arlorio, Marco; Brunelleschi, Sandra

2011-05-25

There is a great interest in the potential health benefits of biologically active phenolic compounds in cocoa (Theobroma cacao) and dark chocolate. We investigated the anti-inflammatory potential of clovamide (a N-phenylpropenoyl-L-amino acid amide present in cocoa beans) and two phenolic extracts from unroasted and roasted cocoa beans, by evaluating superoxide anion (O(2)(-)) production, cytokine release, and NF-κB activation in human monocytes stimulated by phorbol 12-myristate 13-acetate (PMA). The effects of rosmarinic acid are shown for comparison. Clovamide and rosmarinic acid inhibited PMA-induced O(2)(-) production and cytokine release (with a bell-shaped curve and maximal inhibition at 10-100 nM), as well as PMA-induced NF-κB activation; the two cocoa extracts were less effective. In all tests, clovamide was the most potent compound and also enhanced peroxisome proliferator-activated receptor-γ (PPARγ) activity, which may exert anti-inflammatory effects. These findings indicate clovamide as a possible bioactive compound with anti-inflammatory activity in human cells.

Resveratrol inhibits LPS-induced mice mastitis through attenuating the MAPK and NF-κB signaling pathway.

PubMed

Zhang, Xu; Wang, Yanan; Xiao, Chong; Wei, Zhengkai; Wang, Jingjing; Yang, Zhengtao; Fu, Yunhe

2017-06-01

Resveratrol is a natural polyphenol extracted from mangy plants. It has been reported that resveratrol show multitudinous positive role in biology such as anti-oxidant, anti-nociception and anti-inflammatory effects. Therefore, the present study devotes to test the effect of resveratrol on LPS-induced mastitis in mice. Resveratrol was administered intraperitoneally 1 h before LPS treatment. And the anti-inflammatory effect of resveratrol was measured by histopathological examination, MPO assay, real-time PCR and western blotting analysis. The results showed that resveratrol significantly reduced the LPS-induced mammary histopathological changes. Meanwhile, it sharply attenuated the activity of MPO. The result also indicated that the resveratrol can decrease the expression of pro-inflammatory cytokines TNF-α and IL-1β. From the results of western blotting, resveratrol suppressed the expression of phosphorylation of p65 and IκB from NF-κB signal pathway and phosphorylation of p38 and ERK from MAPK signal pathway. These findings suggested that resveratrol may inhibit the inflammatory response in the mastitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two new triterpenes from the roots of Pfaffia glomerata.

PubMed

Lian, Lian; Feng, Yuan; Li, Yan-Wu; Bei, Bei; Tang, Ye-Tian; Wang, Hao; Feng, Qing-Mei; Chen, Gang

2018-04-02

Pfaffia paniculata is a commercialized dietary supplement used as the substitute for the Asian ginseng in Brazil. We conducted the systematic isolation of the EtOAc fraction with anti-inflammatory effect and two new triterpenoids, along with 26 known compounds were characterized by means of MS and NMR analysis. Interestingly, the new compound 1 is the first seco-ring triterpenoid reported in the Pfaffia genus. Furthermore, among the known compounds, 14 and 15 exhibited anti-inflammatory activity in Caco-2 cells, but two new compounds showed no anti-inflammatory.

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

PubMed

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Anti-nociceptive and anti-inflammatory actions of sulforaphane in chronic constriction injury-induced neuropathic pain mice.

PubMed

Wang, Cheng; Wang, Congpin

2017-02-01

Neuropathic pain is still considered as incurable disease as current therapies are not ideal in terms of efficacy and tolerability. It is imperative to search for novel drugs to obtain better treatments. Sulforaphane (SFN), a derivative of glucoraphanin present in cruciferous vegetables, exhibits therapeutic effects on inflammation-related diseases. Since inflammation plays an important role in regulating chronic pain, in the present study, we investigated anti-nociceptive effects of SFN and its underlying mechanisms in a neuropathic pain mouse model, sciatic nerve chronic constriction injury (CCI). SFN (0.1-100 mg/kg) was injected intraperitoneally for 7 days when pain behaviors, including mechanical allodynia and thermal hyperalgesia, reached to the maximum in CCI mice. We observed that SFN dose-dependently attenuated CCI-induced pain behavioral hypersensitivity, accompanied by reduction in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and upregulation of an anti-inflammatory cytokine (IL-10). Moreover, SFN counteracted CCI enhancement of COX2 and iNOS in injured nerves, two key enzymes implicated in inflammation and neuropathic pain. Furthermore, pretreatment of naloxone, an antagonist of opioid receptors, significantly blocked SFN attenuation of behavioral hypersensitivity without affecting SFN modulation of inflammatory cytokines in CCI mice. Interestingly, CCI-induced increase in µ-opioid receptors in injured sciatic nerves was further increased by SFN treatment. Taken together, SFN has both anti-nociceptive and anti-inflammatory actions.

Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal Macrophage Activation.

PubMed

Kozicky, Lisa; Sly, Laura M

2017-12-26

Macrophages are phagocytic innate immune cells, which initiate immune responses to pathogens and contribute to healing and tissue restitution. Macrophages are equally important in turning off inflammatory responses. We have shown that macrophages stimulated with intravenous immunoglobulin (IVIg) can produce high amounts of the anti-inflammatory cytokine, interleukin 10 (IL-10), and low levels of pro-inflammatory cytokines in response to bacterial lipopolysaccharides (LPS). IVIg is a polyvalent antibody, primarily immunoglobulin Gs (IgGs), pooled from the plasma of more than 1,000 blood donors. It is used to supplement antibodies in patients with immune deficiencies or to suppress immune responses in patients with autoimmune or inflammatory conditions. Infliximab, a therapeutic anti-tumor necrosis factor alpha (TNFα) antibody, has also been shown to activate macrophages to produce IL-10 in response to inflammatory stimuli. IVIg and other antibody-based biologics can be tested to determine their effects on macrophage activation. This paper describes methods for derivation, stimulation, and assessment of murine bone marrow macrophages activated by antibodies in vitro and murine peritoneal macrophages activated with antibodies in vivo. Finally, we demonstrate the use of western blotting to determine the contribution of specific cell signaling pathways to anti-inflammatory macrophage activity. These protocols can be used with genetically modified mice, to determine the effect of a specific protein(s) on anti-inflammatory macrophage activation. These techniques can also be used to assess whether specific biologics may act by changing macrophages to an IL-10-producing anti-inflammatory activation state that reduces inflammatory responses in vivo. This can provide information on the role of macrophage activation in the efficacy of biologics during disease models in mice, and provide insight into a potential new mechanism of action in people. Conversely, this may caution against the use of specific antibody-based biologics to treat infectious disease, particularly if macrophages play an important role in host defense against that infection.

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

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.

Passively Administered Pooled Human Immunoglobulins Exert IL-10 Dependent Anti-Inflammatory Effects that Protect against Fatal HSV Encephalitis

PubMed Central

Ramakrishna, Chandran; Newo, Alain N. S.; Shen, Yueh-Wei; Cantin, Edouard

2011-01-01

HSV-1 is the leading cause of sporadic encephalitis in humans. HSV infection of susceptible 129S6 mice results in fatal encephalitis (HSE) caused by massive inflammatory brainstem lesions comprising monocytes and neutrophils. During infection with pathogenic microorganisms or autoimmune disease, IgGs induce proinflammatory responses and recruit innate effector cells. In contrast, high dose intravenous immunoglobulins (IVIG) are an effective treatment for various autoimmune and inflammatory diseases because of potent anti-inflammatory effects stemming in part from sialylated IgGs (sIgG) present at 1–3% in IVIG. We investigated the ability of IVIG to prevent fatal HSE when given 24 h post infection. We discovered a novel anti-inflammatory pathway mediated by low-dose IVIG that protected 129S6 mice from fatal HSE by modulating CNS inflammation independently of HSV specific antibodies or sIgG. IVIG suppressed CNS infiltration by pathogenic CD11b+ Ly6Chigh monocytes and inhibited their spontaneous degranulation in vitro. FcγRIIb expression was required for IVIG mediated suppression of CNS infiltration by CD45+ Ly6Clow monocytes but not for inhibiting development of Ly6Chigh monocytes. IVIG increased accumulation of T cells in the CNS, and the non-sIgG fraction induced a dramatic expansion of FoxP3+ CD4+ T regulatory cells (Tregs) and FoxP3− ICOS+ CD4+ T cells in peripheral lymphoid organs. Tregs purified from HSV infected IVIG treated, but not control, mice protected adoptively transferred mice from fatal HSE. IL-10, produced by the ICOS+ CD4+ T cells that accumulated in the CNS of IVIG treated, but not control mice, was essential for induction of protective anti-inflammatory responses. Our results significantly enhance understanding of IVIG's anti-inflammatory and immunomodulatory capabilities by revealing a novel sIgG independent anti-inflammatory pathway responsible for induction of regulatory T cells that secrete the immunosuppressive cytokine IL-10 and further reveal the therapeutic potential of IVIG for treating viral induced inflammatory diseases. PMID:21655109

Current Perspectives in NSAID-Induced Gastropathy

PubMed Central

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P.

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection. PMID:23576851