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Design of hybrid ?-hairpin peptides with enhanced cell specificity and potent anti-inflammatory activity.  


Antimicrobial peptides (AMPs) have attracted considerable attention for their broad-spectrum antimicrobial activity and reduced tendency to cause bacterial resistance. Emerging concerns over the host cytotoxicity of AMPs, however, may ultimately compromise their development as pharmaceuticals. In order to optimize AMPs with potent cell specificity and anti-inflammatory activity, we designed ?-hairpin hybrid peptides based upon progetrin-1, bovine lactoferricin and cecropin A. The synthetic hybrid peptides LB-PG and CA-PG demonstrated high selectivity over a wide range of microbes from Gram-positive and Gram-negative bacteria in porcine red blood cells. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) show that these peptides kill microbial cells by penetrating the cell membrane and damaging the membrane envelope. Gel retardation demonstrates that the peptides have a high affinity for DNA, indicating an additional possible intracellular bactericidal mechanism. Moreover, the hybrid peptides inhibit the expression of LPS-induced proinflammatory cytokines and chemokines, such as tumor necrosis factor-? (TNF-?), inducible nitric oxide synthase (iNOS), macrophage inflammatory protein-1? (MIP-1?) and monocyte chemoattractant protein 1(MCP-1), following LPS stimulation in RAW264.7 cells. Our results indicate that these hybrid peptides have considerable potential for future development as antimicrobial and anti-inflammatory agents. PMID:23046754

Liu, YiFan; Xia, Xi; Xu, Liang; Wang, YiZhen



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

PubMed Central

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

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



Potent anti-inflammatory effects of systemically-administered curcumin modulates periodontal disease in vivo  

PubMed Central

Background Curcumin is a plant-derived dietary spice with various biological activities, including anti-tumoral and anti-inflammatory. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression; but no studies evaluated the effects of curcumin on periodontal disease in vivo. Methods Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats intragastrically daily in two doses (30 and 100 mg/Kg) during 15 days. Control animals received ligatures but only the corn oil vehicle by gavage and no treatment negative control animals were included. Bone resorption was assessed by microcomputer tomography and the inflammatory status was evaluated by stereometric analysis. RT-qPCR and ELISA were used to determine the expression of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and prostaglandin E2 (PGE2) synthase on the gingival tissues. Modulation of p38 mitogen-activated protein kinase (MAPK) and NK-kB activation was assessed by western blot. Results Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at mRNA and protein levels and dose-dependently inhibited activation of NF-kB in the gingival tissues. p38 MAPK activation was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction on the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers. Conclusions Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests it may have a therapeutic potential in periodontal diseases.

Guimaraes, Morgana R.; Coimbra, Leila S.; de Aquino, Sabrina Garcia; Spolidorio, Luis C.; Kirkwood, Keith L.; Junior, Carlos Rossa



Total synthesis and biological evaluation of viscolin, a 1,3-diphenylpropane as a novel potent anti-inflammatory agent.  


Total synthesis of viscolin, an anti-inflammatory 1,3-diphenylpropane isolated from Viscum coloratum, employing the Wittig reaction is reported. Key steps in the synthesis of viscolin depend on the selection of protecting groups to maintain the para hydroxyl group that is the most critical chemical structure influencing the biological activity of viscolin and the utilization of microwave-assisted Wittig olefination reaction. Anti-inflammatory potency of the synthetic viscolin, its precursor product 16, and its analogue 17, through their effects on reactive oxygen species (ROS), nitric oxide (NO), and pro-inflammatory cytokine production in leukocytes and microglial cells were evaluated. Excellent inhibition of ROS and NO production in inflammatory cells could confer the synthetic viscolin to be a potent anti-inflammatory agent for the treatment of oxidative stress-induced diseases. PMID:17046255

Su, Chung-Ren; Shen, Yuh-Chiang; Kuo, Ping-Chung; Leu, Yann-Lii; Damu, Amooru G; Wang, Yea-Hwey; Wu, Tian-Shung



Targeting the hemoglobin scavenger receptor CD163 in macrophages highly increases the anti-inflammatory potency of dexamethasone.  


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-? 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-?. 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

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



Potent Anti-Inflammatory Activity of Novel Microtubule-Modulating Brominated Noscapine Analogs  

PubMed Central

Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules.

Zughaier, Susu; Karna, Prasanthi; Stephens, David; Aneja, Ritu



Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease  

Microsoft Academic Search

1.In the brains of patients with Alzheimer's disease (AD) signs of neuronal degeneration are accompanied by markers of microglial activation, inflammation, and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons in AD suggests that peroxynitrite contributes to the pathogenesis of the disease.2.A drug with antioxidant and anti-inflammatory activity may prevent neuronal degeneration in AD. Celastrol, a

Anthony C. Allison; Ramon Cacabelos; Valter R. M. Lombardi; Xoan A. Álvarez; Carmen Vigo



Camphoratins A-J, Potent Cytotoxic and Anti-inflammatory Triterpenoids from the Fruiting Body of Taiwanofungus camphoratus  

PubMed Central

Ten new triterpenoids, camphoratins A–J (1–10), along with 12 known compounds were isolated from the fruiting body of Taiwanofungus camphoratus. Their structures were established by spectroscopic analysis and chemical methods. Compound 10 is the first example of a naturally occurring ergosteroid with an unusual cis-C/D ring junction. Compounds 2–6 and 11 showed moderate to potent cytotoxicity with EC50 values ranging from 0.3 to 3 ?M against KB and KB-VIN human cancer cell lines. Compounds 6, 10, 11, 14–16, 18, and 21 exhibited anti-inflammatory NO-production inhibition activity with IC50 values of less than 5 ?M, which was more potent than the nonspecific NOS inhibitor N?-nitro-L-arginine methyl ester (L-NAME).

Wu, Shwu-Jen; Leu, Yann-Lii; Chen, Chou-Hsiung; Chao, Chih-Hua; Shen, De-Yang; Chan, Hsiu-Hui; Lee, E-Jian; Wu, Tian-Shung; Wang, Yea-Hwey; Shen, Yuh-Chiang; Qian, Keduo; Bastow, Kenneth F.; Lee, Kuo-Hsiung




PubMed Central

Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective, if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by: i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and ii) enhanced epidermal lipid synthesis and secretion. Since barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamine. In four immunologically-diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis), or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, while H1/2r antagonists improved inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly-systemic to a topical approach.

Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis; Park, Kyungho; Roelandt, Truus; Oda, Yuko; Hupe, Melanie; Crumrine, Debra; Lee, Hae-Jin; Gschwandtner, Maria; Thyssen, Jacob P.; Trullas, Carles; Tschachler, Erwin; Feingold, Kenneth R.; Elias, Peter M.



Paeonol attenuates high-fat-diet-induced atherosclerosis in rabbits by anti-inflammatory activity.  


Cortex Moutan (Paeonia suffruticosa Andrews, Ranunculaceae) has several uses in traditional medicine, such as analgesic, antipyretic, and anti-inflammatory applications and use in the prevention of thromboembolic diseases. Paeonol, a main active component in Cortex Moutan, possesses various pharmacological activities, particularly an anti-atherosclerosis effect. However, so far there have been no reports evaluating the anti-inflammatory action of paeonol in atherosclerosis therapy. The purpose of this study was to investigate the association of the therapeutic effect of paeonol on atherosclerotic rabbits with its anti-inflammatory action. The atherosclerotic model was developed in 24 rabbits fed a high-fat diet for 12 weeks. Twelve rabbits on the high-fat diet then were administered with paeonol (p.o) for a subsequent 6 weeks at the doses of 75 mg/kg and 150 mg/kg. Histological analysis showed significant improvement in atherosclerosis plaque in the paeonol groups. Moreover, the blood levels of TNF- alpha, IL-1 beta, and CRP and the translocation of NF- kappaB to the nucleus were significantly suppressed in paeonol groups, as was the inhibition of lipid peroxidation. In conclusion, these findings suggest that the anti-inflammatory action of paeonol may contribute to its anti-atherosclerosis effect. PMID:19003727

Li, Houkai; Dai, Min; Jia, Wei



Potent 2'-aminoanilide inhibitors of cFMS as potential anti-inflammatory agents.  


A series of 2'-aminoanilides have been identified which exhibit potent and selective inhibitory activity against the cFMS tyrosine kinase. Initial SAR studies within this series are described which examine aroyl and amino group substitutions, as well as the introduction of hydrophilic substituents on the benzene core. Compound 47 inhibits the isolated enzyme (IC(50)=0.027 microM) and blocks CSF-1-induced proliferation of bone marrow-derived macrophages (IC(50)=0.11 microM) and as such, serves as a lead candidate for further optimization studies. PMID:17904845

Patch, Raymond J; Brandt, Benjamin M; Asgari, Davoud; Baindur, Nand; Chadha, Naresh K; Georgiadis, Taxiarchis; Cheung, Wing S; Petrounia, Ioanna P; Donatelli, Robert R; Chaikin, Margery A; Player, Mark R



A disease-relevant high-content screening assay to identify anti-inflammatory compounds for use in cystic fibrosis.  


Chronic lung inflammation caused by bacterial pathogenesis through activation of nuclear factor kappa B (NF?B)-responsive proinflammatory genes is a major hurdle in the management of lung disease in cystic fibrosis (CF) patients. The authors generated a disease-relevant cell-based high-content screen to identify novel anti-inflammatory compounds for treating lung inflammation in CF. The human bronchial epithelial cell line KKLEB, harboring the most common form of mutation that causes CF, was modified to express an NF?B-responsive green fluorescent protein (GFP) reporter. After creation, the cell line was tested for its ability to respond to disease-relevant inflammatory stimuli elicited by treatment of cells with filtrates of Pseudomonas aeruginosa isolated from the airways of a CF patient. P. aeruginosa filtrates potently activated NF?B-responsive GFP reporter expression in cells. Subsequently, the assay was optimized for high-throughput screening (HTS) through generation of a Z factor (~0.5) and by testing its tolerance to the commonly used solvents ethanol and DMSO. A pilot library of clinically approved compounds was screened for assay validation. Several compounds with known NF?B inhibitory activity were identified, including several steroidal compounds that have been clinically tested in CF. Thus, the assay can be used in a broader HTS campaign to find anti-inflammatory agents for use in CF. PMID:20944057

Giddings, Angela M; Maitra, Rangan



The anti-inflammatory compound BAY-11-7082 is a potent inhibitor of protein tyrosine phosphatases.  


The families of protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) function in a coordinated manner to regulate signal transduction events that are critical for cellular homeostasis. Aberrant tyrosine phosphorylation, resulting from disruption of either PTP or PTK function, has been shown to be the cause of major human diseases, including cancer and diabetes. Consequently, the characterization of small-molecule inhibitors of these kinases and phosphatases may not only provide molecular probes with which to define the significance of particular signaling events, but also may have therapeutic implications. BAY-11-7082 is an anti-inflammatory compound that has been reported to inhibit I?B kinase activity. The compound has an ?,?-unsaturated electrophilic center, which confers the property of being a Michael acceptor; this suggests that it may react with nucleophilic cysteine-containing proteins, such as PTPs. In this study, we demonstrated that BAY-11-7082 was a potent, irreversible inhibitor of PTPs. Using mass spectrometry, we have shown that BAY-11-7082 inactivated PTPs by forming a covalent adduct with the active-site cysteine. Administration of the compound caused an increase in protein tyrosine phosphorylation in RAW 264 macrophages, similar to the effects of the generic PTP inhibitor sodium orthovanadate. These data illustrate that BAY-11-7082 is an effective pan-PTP inhibitor with cell permeability, revealing its potential as a new probe for chemical biology approaches to the study of PTP function. Furthermore, the data suggest that inhibition of PTP function may contribute to the many biological effects of BAY-11-7082 that have been reported to date. PMID:23578302

Krishnan, Navasona; Bencze, Gyula; Cohen, Philip; Tonks, Nicholas K



Potent Anti-Inflammatory Activity of Ursolic Acid, a Triterpenoid Antioxidant, Is Mediated through Suppression of NF-?B, AP-1 and NF-AT  

PubMed Central

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-?B (nuclear factor kappa B) activation. Since NF-?B, 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-?B, 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-?B, 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-?. 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.

Checker, Rahul; Sandur, Santosh K.; Sharma, Deepak; Patwardhan, Raghavendra S.; Jayakumar, S.; Kohli, Vineet; Sethi, Gautam; Aggarwal, Bharat B.; Sainis, Krishna B.



Aspirin-triggered 15-Epi-Lipoxin A4 (LXA4) and LXA4 Stable Analogues Are Potent Inhibitors of Acute Inflammation: Evidence for Anti-inflammatory Receptors  

PubMed Central

Lipoxins are bioactive eicosanoids that are immunomodulators. In human myeloid cells, lipoxin (LX) A4 actions are mediated by interaction with a G protein–coupled receptor. To explore functions of LXA4 and aspirin-triggered 5(S),6(R),15(R)-trihydroxy-7,9,13-trans-11-cis–eicosatetraenoic acid (15-epi-LXA4) in vivo, we cloned and characterized a mouse LXA4 receptor (LXA4R). When expressed in Chinese hamster ovary cells, the mouse LXA4R showed specific binding to [3H]LXA4 (Kd ? 1.5 nM), and with LXA4 activated GTP hydrolysis. Mouse LXA4R mRNA was most abundant in neutrophils. In addition to LXA4 and 15-epi-LXA4, bioactive LX stable analogues competed with both [3H]LXA4 and [3H]leukotriene D4 (LTD4)– specific binding in vitro to neutrophils and endothelial cells, respectively. Topical application of LXA4 analogues and novel aspirin-triggered 15-epi-LXA4 stable analogues to mouse ears markedly inhibited neutrophil infiltration in vivo as assessed by both light microscopy and reduced myeloperoxidase activity in skin biopsies. The 15(R)-16-phenoxy-17,18, 19,20-tetranorLXA4 methyl ester (15-epi-16-phenoxy-LXA4), an analogue of aspirin triggered 15-epi-LXA4, and 15(S)-16-phenoxy-17,18,19,20-tetranor-LXA4 methyl ester (16-phenoxy-LXA4) were each as potent as equimolar applications of the anti-inflammatory, dexamethasone. Thus, we identified murine LXA4R, which is highly expressed on murine neutrophils, and showed that both LXA4 and 15-epi-LXA4 stable analogues inhibit neutrophil infiltration in the mouse ear model of inflammation. These findings provide direct in vivo evidence for an anti-inflammatory action for both aspirin-triggered LXA4 and LXA4 stable analogues and their site of action in vivo.

Takano, Tomoko; Fiore, Stefano; Maddox, Jane F.; Brady, Hugh R.; Petasis, Nicos A.; Serhan, Charles N.



Identification of Magnolia officinalis L. bark extract as the most potent anti-inflammatory of four plant extracts.  


This study was designed to compare the anti-inflammatory potential of a Magnolia officinalis L. bark extract solely or in combination with extracts prepared from either Polygonum aviculare L., Sambucus nigra L., or Isodon japonicus L. in bacterial lipopolysaccharide (LPS) stimulated human gingival fibroblasts (HGF-1) and human U-937 monocytes, as cell models of periodontal disease. HGF-1 and U-937 cells were incubated with LPS from either Porphyromonas gingivalis or Escherichia coli together with the four plant extracts alone or in combination. Secretion of anti-inflammatory cytokines from HGF-1 and U-937 cells was measured by means of a multiplexed bead assay system. Magnolia officinalis L. bark extract, at concentrations of 1 ?g/mL and 10 ?g/mL, reduced interleukin 6 (IL-6) and interleukin-8 (IL-8) secretion from HGF-1 cells to 72.5 ± 28.6% and reduced matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) secretion from U-937 cells to 8.87 ± 7.97% compared to LPS-treated cells (100%). The other three extracts also reduced secretion of these inflammatory markers but were not as effective. Combination of 9 ?g/mL Magnolia officinalis L. extract with 1 ?g/mL of each of the other extracts maintained the anti-inflammatory effect of Magnolia officinalis L. extract. Combination of 5 ?g/mL Magnolia officinalis L. extract with 5 ?g/mL Isodon japonicus L. extract also maintained the anti-inflammatory potential of the Magnolia officinalis L. extract, whereas increasing concentrations of any of the other plant extracts in the combination experiments reduced the Magnolia officinalis L. extract efficacy in U-937 cells. PMID:23711140

Walker, Joel M; Maitra, Amarnath; Walker, Jessica; Ehrnhoefer-Ressler, Miriam M; Inui, Taichi; Somoza, Veronika



Potent inhibition of human 5-lipoxygenase and microsomal prostaglandin E? synthase-1 by the anti-carcinogenic and anti-inflammatory agent embelin.  


Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) possesses anti-inflammatory and anti-carcinogenic properties in vivo, and these features have been related to interference with multiple targets including XIAPs, NF?B, STAT-3, Akt and mTOR. However, interference with these proteins requires relatively high concentrations of embelin (IC??>4 ?M) and cannot fully explain its bioactivity observed in several functional studies. Here we reveal human 5-lipoxygenase (5-LO) and microsomal prostaglandin E? synthase (mPGES)-1 as direct molecular targets of embelin. Thus, embelin potently suppressed the biosynthesis of eicosanoids by selective inhibition of 5-LO and mPGES-1 with IC??=0.06 and 0.2 ?M, respectively. In intact human polymorphonuclear leukocytes and monocytes, embelin consistently blocked the biosynthesis of various 5-LO products regardless of the stimulus (fMLP or A23187) with IC??=0.8-2 ?M. Neither the related human 12- and 15-LO nor the cyclooxygenases-1 and -2 or cytosolic phospholipase A? were significantly affected by 10 ?M embelin. Inhibition of 5-LO and mPGES-1 by embelin was (I) essentially reversible after wash-out, (II) not impaired at higher substrate concentrations, (III) unaffected by inclusion of Triton X-100, and (IV) did not correlate to its proposed antioxidant properties. Docking simulations suggest concrete binding poses in the active sites of both 5-LO and mPGES-1. Because 5-LO- and mPGES-1-derived eicosanoids play roles in inflammation and cancer, the interference of embelin with these enzymes may contribute to its biological effects and suggests embelin as novel chemotype for development of dual 5-LO/mPGES-1 inhibitors. PMID:23623753

Schaible, Anja M; Traber, Heidi; Temml, Veronika; Noha, Stefan M; Filosa, Rosanna; Peduto, Antonella; Weinigel, Christina; Barz, Dagmar; Schuster, Daniela; Werz, Oliver



Potent analgesic and anti-inflammatory actions of a novel thymulin-related peptide in the rat  

PubMed Central

The present study examines the effect of PAT (peptide analogue of thymulin) in two rat models of inflammatory hyperalgesia induced by either (1.25 ?g in 50 ?l saline) or i.p. (50 ?g in 100 ?l) injections of endotoxin ET. Pretreatment with PAT (1, 5 or 25 ?g in 100 ?l saline, i.p.) decreased, in a dose dependent manner, both mechanical hyperalgesia, determined by the paw pressure (PP) test and thermal hyperalgesia determined by the hot plate (HP), the paw immersion (PI) and the tail flick (TF) tests. Compared to the tripeptides K(D)PT and K(D)PV, known to antagonize interleukin (IL)-1? or IL-1? and PGE2 mechanisms, PAT, at lower dosages, exerted stronger anti-hyperalgesic effects. When compared with the effect of a steroidal (dexamethasone) and a non-steroidal (indomethacin) anti-inflammatory drugs (NSAID), PAT demonstrated equal analgesic actions. Pretreatment with PAT, reduced significantly the increased concentration of IL-1?, IL-6, TNF-? and NGF due to injection of ET. Injection of i.p. ET produced sickness behaviour characterized by hyperalgesia and fever. Pretreatment with PAT prevented the hyperalgesia and maintained the body temperature within the normal range and was accompanied by a down-regulation of the levels of pro-inflammatory cytokines and PGE2 in the liver. PAT, in all doses used, did not result in any evident changes in the physiological parameters or in the normal behaviour of the rats. The anti-hyperalgesic and anti-inflammatory effects of PAT can be attributed, at least partially, to the down-regulation of pro-inflammatory mediators.

Safieh-Garabedian, Bared; Dardenne, Mireille; Pleau, Jean Marie; Saade, Nayef E



A rapid and highly predictive in vitro assay for non-steroidal anti-inflammatory agents.  


The inhibition of the production of malonyldialdehyde (MDA) in guinea-pig lung homogenates, incubated in the presence of 50 microM arachidonic acid and 1.4 mM adrenaline, has been exploited as a simple and reliable assay to test in vitro non-steroidal anti-inflammatory agents (NSAIA). The inhibitory potencies of a series of reference NSAIA, which correlated fairly well with in vivo anti-inflammatory activity as determined by carrageenin oedema, are herewith reported. The specificity of the assay was also evaluated by testing up to forty miscellaneous drugs: none of these significantly reduced the MDA production. PMID:3141307

Luzzani, F; Ventura, P; Zuccari, G; Clavenna, G



Approaches to Nonsteroidal Anti-inflammatory Drug Use in the High-Risk Patient  

Microsoft Academic Search

Nonsteroidal anti-inflammatory drugs (NSAIDs) are probably the most common cause of gastroduodenal injury in the United States today. Approximately half of patients who regularly take NSAIDs have gastric erosions, and 15%–30% have ulcers when they are examined endoscopically. However, the incidence of clinical gastrointestinal (GI) events caused by NSAIDs is much lower. Clinical upper GI events may occur in 3%–4.5%

Loren Laine



Inhibition of cholesteryl ester transfer protein by anacetrapib does not impair the anti-inflammatory properties of high density lipoprotein.  


Cholesteryl ester transfer protein (CETP) is a target of therapeutic intervention for coronary heart disease. Anacetrapib, a potent inhibitor of CETP, has been shown to reduce LDL-cholesterol by 40% and increase HDL-cholesterol by 140% in patients, and is currently being evaluated in a phase III cardiovascular outcomes trial. HDL is known to possess anti-inflammatory properties, however with such large increases in HDL-cholesterol, it is unclear whether CETP inhibition perturbs HDL functionality such as anti-inflammatory effects on endothelial cells. The purpose of the present study was to determine whether CETP inhibition by anacetrapib affects the anti-inflammatory properties of HDL. HDL was isolated from either hamsters treated with vehicle or anacetrapib for 2weeks, or from normal human subjects treated either placebo, 20mg, or 150mg anacetrapib daily for 2weeks. Anacetrapib treatment increased plasma HDL cholesterol levels by 65% and between 48 and 82% in hamsters and humans, respectively. Pre-incubation of human aortic endothelial cells with HDL isolated from both control and anacetrapib treated hamsters suppressed TNF? induced expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Similar results were obtained with human HDL samples pre and post treatment with placebo or anacetrapib. Further, HDL inhibited TNF?-induced MCP-1 secretion, monocyte adhesion and NF-?B activation in endothelial cells, and the inhibition was similar between control and anacetrapib treated groups. These studies demonstrate that anacetrapib treatment does not impair the ability of HDL to suppress an inflammatory response in endothelial cells. PMID:23269286

Han, Seongah; Levoci, Lauretta; Fischer, Paul; Wang, Sheng-Ping; Gagen, Karen; Chen, Ying; Xie, Dan; Fisher, Timothy; Ehrhardt, Anka G; Peier, Andrea M; Johns, Douglas G



A Herbal Composition of Scutellaria baicalensis and Eleutherococcus senticosus Shows Potent Anti-Inflammatory Effects in an Ex Vivo Human Mucosal Tissue Model.  


Background. Patients seek an effective alternative to pharmacotherapy including herbal treatment options for allergic rhinitis and rhinosinusitis. Material and Methods. Nasal mucosal tissue was obtained from 12 patients, fragmented, preincubated with tissue culture medium, S. baicalensis and/or E. senticosus and/or vitamin C (each compound 0.2??g/mL and 2??g/mL) for 1 hour at 37°C/5% CO2, and stimulated with anti-IgE for 30 minutes and 6 hours to imitate the allergic early and late phases. Furthermore, Staphylococcus aureus superantigen B (SEB) stimulation for 6 hours was used to imitate T-cell activation. Results. The combination of S. baicalensis and E. senticosus had a more potent suppressive effect on the release of PGD2, histamine, and IL-5 than S. baicalensis alone. The combination also resulted in a significant inhibition of SEB-induced cytokines comparable or superior to an established topical corticosteroid, fluticasone propionate. Vitamin C increased ciliary beat frequency, but had no anti-inflammatory effects. Discussion. The combination of S. baicalensis and E. senticosus may be able to significantly block allergic early-and late-phase mediators and substantially suppress the release of proinflammatory, and Th1-, Th2-, and Th17-derived cytokines. PMID:22272213

Zhang, Nan; Van Crombruggen, Koen; Holtappels, Gabriele; Bachert, Claus



Mechanisms by which licochalcone e exhibits potent anti-inflammatory properties: studies with phorbol ester-treated mouse skin and lipopolysaccharide-stimulated murine macrophages.  


In this study we found that licochalcone E (LicE), a recently isolated retrochalcone from Glycyrrhiza inflata, exhibits potent anti-inflammatory effects in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage models. Topical application of LicE (0.5-2 mg) effectively inhibited TPA-induced (1) ear edema formation; (2) phosphorylation of stress-activated protein kinase/c-Jun-N-terminal kinase (SAPK/JNK), c-Jun, and extracellular signal regulated kinase 1/2; and (3) expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins in mouse skin. The treatment of RAW 264.7 cells with LicE (2.5-7.5 ?mol/L) induced a profound reduction in LPS-induced (1) release of NO and prostaglandin E2; (2) mRNA expression and secretion of interleukin (IL)-6, IL-1? and tumor necrosis factor-?; (3) promoter activity of iNOS and COX-2 and expression of their corresponding mRNAs and proteins; (4) activation of AKT, p38 mitogen activated protein kinase (MAPK), SAPK/JNK and c-Jun; (5) phosphorylation of inhibitor of ?B (I?B) kinase-?? and I?B?, degradation of I?B?, translocation of p65 (RelA) to the nucleus and transcriptional activity of nuclear factor (NF)-?B; and (6) transcriptional activity of activator protein (AP)-1. These results indicate that the LicE inhibition of NF-?B and AP-1 transcriptional activity through the inhibition of AKT and MAPK activation contributes to decreases in the expression of pro-inflammatory cytokines and the inducible enzymes iNOS and COX-2. PMID:23708096

Lee, Han Na; Cho, Han Jin; Lim, Do Young; Kang, Young-Hee; Lee, Ki Won; Park, Jung Han Yoon



Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages  

PubMed Central

In this study we found that licochalcone E (LicE), a recently isolated retrochalcone from Glycyrrhiza inflata, exhibits potent anti-inflammatory effects in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage models. Topical application of LicE (0.5–2 mg) effectively inhibited TPA-induced (1) ear edema formation; (2) phosphorylation of stress-activated protein kinase/c-Jun-N-terminal kinase (SAPK/JNK), c-Jun, and extracellular signal regulated kinase 1/2; and (3) expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins in mouse skin. The treatment of RAW 264.7 cells with LicE (2.5–7.5 ?mol/L) induced a profound reduction in LPS-induced (1) release of NO and prostaglandin E2; (2) mRNA expression and secretion of interleukin (IL)-6, IL-1? and tumor necrosis factor-?; (3) promoter activity of iNOS and COX-2 and expression of their corresponding mRNAs and proteins; (4) activation of AKT, p38 mitogen activated protein kinase (MAPK), SAPK/JNK and c-Jun; (5) phosphorylation of inhibitor of ?B (I?B) kinase-?? and I?B?, degradation of I?B?, translocation of p65 (RelA) to the nucleus and transcriptional activity of nuclear factor (NF)-?B; and (6) transcriptional activity of activator protein (AP)-1. These results indicate that the LicE inhibition of NF-?B and AP-1 transcriptional activity through the inhibition of AKT and MAPK activation contributes to decreases in the expression of pro-inflammatory cytokines and the inducible enzymes iNOS and COX-2.

Lee, Han Na; Cho, Han Jin; Lim, Do Young; Kang, Young-Hee; Lee, Ki Won; Park, Jung Han Yoon



Synthesis of novel 3,5-diaryl pyrazole derivatives using combinatorial chemistry as inhibitors of tyrosinase as well as potent anticancer, anti-inflammatory agents.  


In the present article, we have synthesized a combinatorial library of 3,5-diaryl pyrazole derivatives using 8-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (1) and hydrazine hydrate in absolute ethyl alcohol under the refluxed conditions. The structures of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their anticancer activity against five cell lines (breast cancer cell line, prostate cancer cell line, promyelocytic leukemia cell line, lung cancer cell line, colon cancer cell line) and anti-inflammatory activity against TNF-alpha and IL-6. Out of 15 compounds screened, 2a and 2d exhibited promising anticancer activity (61-73% at 10 microM concentration) against all selected cell lines and IL-6 inhibition (47% and 42% at 10 microM concentration) as in comparison to standard flavopiridol (72-87% inhibition at 0.5 microM) and dexamethasone (85% inhibition at 1 microM concentration), respectively. Cytotoxicity of the compounds checked using CCK-8 cell lines and found to be nontoxic to slightly toxic. Out of 15, four 3,5-diaryl pyrazole derivatives exhibiting potent inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase. The IC(50) values of compounds (2a, 2d, 2h and 2l) for monophenolase inhibition were determined to range between 1.5 and 30 microM. Compounds 2a, 2d, 2h and 2l also inhibited diphenolase significantly with IC(50) values of 29.4, 21.5, 2.84 and 19.6 microM, respectively. All four 3,5-diaryl pyrazole derivatives were active as tyrosinase inhibitors (2a, 2d, 2h and 2l), and belonging to competitive inhibitors. Interestingly, they all manifested simple reversible slow-binding inhibition against diphenolase. PMID:20638287

Bandgar, Babasaheb P; Totre, Jalinder V; Gawande, Shrikant S; Khobragade, C N; Warangkar, Suchita C; Kadam, Prasad D



Potent anti-inflammatory\\/analgesic effects of lornoxicam in comparison to other nsaids: A c-fos study in the rat  

Microsoft Academic Search

This study evaluates the anti-inflammatory\\/analgesic effects of lornoxicam, a new non-steroidal anti-inflammatory drug, using\\u000a the method of c-Fos protein immunoreactivity in the carrageenan model of inflammatory nociception in the rat. The immunohistochemical\\u000a revelation of inflammatory\\/nociceptive stimulation evoked c-Fos expression in spinal neurons was used as an indirect marker\\u000a of neurons involved in spinal nociceptive transmission. Lornoxicam (0.1, 0.3, 1, 3

J. Buritova; J. M. Besson



Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents.  


A novel series of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines (5a-o) has been synthesized and the structures of newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their in vitro and in vivo anti-inflammatory activity, and also for their antioxidant activity. Compounds 5b, 5c, 5d and 5n were found to be selective COX-2 inhibitors. Compound 5c was found to potent inhibitor of the carrageenin induced paw edema in rats. Most of the compounds exhibited good DPPH and superoxide radical scavenging activity, while compounds 5c, 5d, 5i and 5k exhibited good hydroxyl radical scavenging activity. Molecular docking result, along with the biological assay data, suggested that compound 5c was a potential anti-inflammatory agent. PMID:22901385

Bandgar, Babasaheb P; Adsul, Laxman K; Chavan, Hemant V; Jalde, Shivkumar S; Shringare, Sadanand N; Shaikh, Rafique; Meshram, Rohan J; Gacche, Rajesh N; Masand, Vijay



Potent Anti-Inflammatory and Neuroprotective Effects of TGF?1 Are Mediated through the Inhibition of ERK and p47phox-Ser345 Phosphorylation and Translocation in Microglia  

PubMed Central

TGF?1 is one of the most potent endogenous immune modulators of inflammation. The molecular mechanism of its anti-inflammatory effect on the activation of the transcription factor NF-kB has been well studied, however, the potential effects of TGF?1 on other pro-inflammatory signaling pathways is less clear. In this study, using the well-established lipopolysaccharide (LPS) and the 1-methyl-4-phenylpyridinium (MPP+)-mediated models of Parkinson’s disease (PD), we demonstrate TGF?1 exerts significant neuroprotection in both models via its anti-inflammatory properties. The neuroprotective effects of TGF?1 are mainly attributed to its ability to inhibit the production of reactive oxygen species (ROS) from microglia during their activation or reactivation. Moreover, we demonstrate that TGF?1 inhibited LPS-induced NADPH oxidase (PHOX) subunit p47phox translocation from the cytosol to the membrane in microglia within 10 min. Mechanistic studies show that TGF?1 fails to protect dopaminergic neurons in cultures from PHOX knockout mice, and significantly reduced LPS-induced translocation of the PHOX cytosolic subunits p47phox to the cell membrane. In addition, LPS-induced ERK phosphorylation and subsequent serine345 (Ser345) phosphorylation on p47phox were significantly inhibited by TGF?1 pretreatment. Taken together, our results show that TGF?1 exerted potent anti-inflammatory and neuroprotective properties, either through the prevention of the direct activation of microglia by LPS, or indirectly through the inhibition of reactive microgliosis elicited by MPP+. The molecular mechanisms of TGF?1-mediated anti-inflammatory properties is through the inhibition of PHOX activity by preventing the ERK-dependent phosphorylation of Ser345 on p47phox in microlgia to reduce oxidase activities induced by LPS.

Qian, Li; Wei, Sung-Jen; Zhang, Dan; Hu, Xiaoming; Xu, Zongli; Wilson, Belinda; El-Benna, Jamel; Hong, Jau-Shyong; Flood, Patrick M



Fasting induces an anti-inflammatory effect on the neuroimmune system which a high-fat diet prevents  

PubMed Central

The neuroimmunological and behavioral consequences of a high-fat diet (HFD) are not well delineated. This is especially true when short term (24 h) fasting is used as a physiologic stressor. In this study, we examined the impact of a HFD on learning and memory and depressive-like behaviors to understand how fasting impacts neuroimmunity and if obesity modulates the response. Mice were fed diets containing either 10% (LFD mice) or 60% (HFD mice) calories from fat for 10-12 wks. Gene transcripts for 26 pro-/anti-inflammatory cytokines and markers of macrophage activation were examined in adipose tissue and whole brain. Mouse learning and memory (spontaneous alternation, novel object) and depressive like behaviors (saccharin preference, burrowing, forced swim) were studied in the fed and fasted state as were gene transcripts for F4/80, CD11b, IL-1alpha, IL-1beta, IL-1R1, IL-1R2, IL-1RA, IL-6 and TNF-alpha in cortex, hippocampus and hypothalamus. In the fed state, HFD mice compared to LFD mice had reduced locomotor activity, were adverse to saccharin and burrowed less. After fasting, LFD mice verse HFD mice lost 18% vs 5% of their body weight, respectively. In addition, HFD mice failed to down-regulate gene transcripts for the myeloid-cell associated proteins F4/80, CD11b and IL-1alpha in the brain, failed to appropriately explore a novel object, failed to reduce locomotor activity and had increased saccharin consumption and burrowing. These data indicate that fasting induces an anti-inflammatory effect on the neuroimmune system which a HFD prevents. This breakdown appears linked to the IL-1 system because of the association of this cytokine with memory and learning.

Lavin, Desiree N.; Joesting, Jennifer J.; Chiu, Gabriel S.; Moon, Morgan L.; Meng, Jia; Dilger, Ryan N.; Freund, Gregory G.



Nicotinic acid conjugates of nonsteroidal anti-inflammatory drugs (NSAID's) and their anti-inflammatory properties.  


A series of nicotinic acid conjugates with non-steroidal anti-inflammatory drugs (NSAID's) have been effectively synthesized using TBTU in high yield and purity. All the synthesized conjugates were evaluated for their in vitro anti-inflammatory activity. PMID:23481139

Gund, Machhindra; Khan, Fazlur-Rahman Nawaz; Khanna, Amit; Krishnakumar, Varadhan



Anti-inflammatory ingredients.  


There is a growing public awareness and concern among individuals regarding the condition of their skin, with a concomitant desire to use natural products to treat skin conditions. The increased interest in these products has spurred scientific and clinical studies evaluating the composition and clinical usefulness of natural products in the treatment of inflammatory skin dermatoses. There are numerous natural ingredients that have been demonstrated to possess anti-inflammatory properties that make formulations containing these ingredients attractive treatment options. This article summarizes the active ingredients, anti-inflammatory properties, clinical effects, and therapeutic potential of colloidal oatmeal, feverfew, licorice, aloe vera, chamomile, and turmeric. Potential therapeutic indications include erythema induced by ultraviolet light, rosacea, atopic dermatitis, sensitive and irritated skin, drug-induced skin eruptions, and psoriasis. These products may be particularly well suited as alternatives to pharmacologic therapies in chronic conditions for which long-term use is required. PMID:18681154

Wu, Jessica



Anti-inflammatory effects of high-dose inhaled fluticasone versus oral prednisone in asthma exacerbations  

Microsoft Academic Search

The objective of the present study was to investigate the kinetics of high doses of inhaled steroid fluticasone in comparison with oral steroid prednisone on plasma protein leakage and bronchial eosinophilia in adults with moderate asthma exacerbations. The study design was a randomised, double-blind, placebo-controlled prospective trial. In total, 45 patients treated at the emergency department for moderate asthma exacerbations

J. Belda; G. Margarit; C. Martinez; J. Bellido-Casado; P. Casan; M. Torrejon; M. Brufal; F. Rodriguez-Jerez; J. Sanchis



Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity.  


The purpose of this study was to investigate the anti-inflammatory and antiobesity effect of combinational mulberry leaf extract (MLE) and mulberry fruit extract (MFE) in a high-fat (HF) diet-induced obese mice. Mice were fed a control diet or a HF diet for nine weeks. After obesity was induced, the mice were administered with single MLE at low dose (133?mg/kg/day, LMLE) and high dose (333?mg/kg/day, HMLE) or combinational MLE and MFE (MLFE) at low dose (133?mg MLE and 67?mg MFE/kg/day, LMLFE) and high dose (333?mg MLE and 167?mg MFE/kg/day, HMLFE) by stomach gavage for 12 weeks. The mulberry leaf and fruit extract treatment for 12 weeks did not show liver toxicity. The single MLE and combinational MLFE treatments significantly decreased plasma triglyceride, liver lipid peroxidation levels and adipocyte size and improved hepatic steatosis as compared with the HF group. The combinational MLFE treatment significantly decreased body weight gain, fasting plasma glucose and insulin, and homeostasis model assessment of insulin resistance. HMLFE treatment significantly improved glucose control during intraperitoneal glucose tolerance test compared with the HF group. Moreover, HMLFE treatment reduced protein levels of oxidative stress markers (manganese superoxide dismutase) and inflammatory markers (monocyte chemoattractant protein-1, inducible nitric oxide synthase, C-reactive protein, tumour necrosis factor-? and interleukin-1) in liver and adipose tissue. Taken together, combinational MLFE treatment has potential antiobesity and antidiabetic effects through modulation of obesity-induced inflammation and oxidative stress in HF diet-induced obesity. PMID:24000381

Lim, Hyun Hwa; Lee, Sung Ok; Kim, Sun Yeou; Yang, Soo Jin; Lim, Yunsook



Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal  

Microsoft Academic Search

BACKGROUND: Enprocal is a high-protein micro-nutrient rich formulated supplementary food designed to meet the nutritional needs of the frail elderly and be delivered to them in every day foods. We studied the potential of Enprocal to improve gut and immune health using simple and robust bioassays for gut cell proliferation, intestinal integrity\\/permeability, immunomodulatory, anti-inflammatory and anti-oxidative activities. Effects of Enprocal

Jagat R Kanwar; Rupinder K Kanwar



Simultaneous analysis of several non-steroidal anti-inflammatory drugs in human urine by high-performance liquid chromatography with normal solid-phase extraction  

Microsoft Academic Search

A practical and reproducible high-performance liquid chromatographic method using normal solid-phase extraction has been developed for the simultaneous analysis of twelve non-steroidal anti-inflammatory drugs (NSAIDs) in human urine. A urine specimen mixed with acetate buffer pH 5.0 was purified by solid-phase extraction on a Sep-Pak Silica cartridge. The analyte was chromatographed by a reversed-phase Inertsil ODS-2 column using a phosphate

Toshio Hirai; Shozo Matsumoto; Ikuo Kishi



Confirmatory analysis of non-steroidal anti-inflammatory drugs in bovine milk by high-performance liquid chromatography with fluorescence detection  

Microsoft Academic Search

HPLC with fluorescence detection is considered for confirmatory analysis of group B veterinary drugs by the European Union legislation. A procedure for confirming the presence of anti-inflammatory non-steroidal drug (NSAID) residues in bovine milk by reversed phase high-performance liquid chromatography with fluorescence detection is herein described. The native fluorescence of nine drugs belonging to different NSAID sub-classes, namely flurbiprofen, carprofen,

Pasquale Gallo; Serena Fabbrocino; Geraldine Dowling; Marco Salini; Maurizio Fiori; Giuseppe Perretta; Luigi Serpe



PXS-4681A, a Potent and Selective Mechanism-Based Inhibitor of SSAO/VAP-1 with Anti-Inflammatory Effects In Vivo.  


Semicarbazide-sensitive amine oxidase (SSAO), also known as vascular adhesion protein-1 (VAP-1), is a member of the copper-dependent amine oxidase family that is associated with various forms of inflammation and fibrosis. To investigate the therapeutic potential of SSAO/VAP-1 inhibition, potent and selective inhibitors with drug-like properties are required. PXS-4681A [(Z)-4-(2-(aminomethyl)-3-fluoroallyloxy)benzenesulfonamide hydrochloride] is a mechanism-based inhibitor of enzyme function with a pharmacokinetic and pharmacodynamic profile that ensures complete, long-lasting inhibition of the enzyme after a single low dose in vivo. PXS-4681A irreversibly inhibits the enzyme with an apparent Ki of 37 nM and a kinact of 0.26 min(-1) with no observed turnover in vitro. It is highly selective for SSAO/VAP-1 when profiled against related amine oxidases, ion channels, and seven-transmembrane domain receptors, and is superior to previously reported inhibitors. In mouse models of lung inflammation and localized inflammation, dosing of this molecule at 2 mg/kg attenuates neutrophil migration, tumor necrosis factor-?, and interleukin-6 levels. These results demonstrate the drug-like properties of PXS-4681A and its potential use in the treatment of inflammation. PMID:23943052

Foot, Jonathan S; Yow, Tin T; Schilter, Heidi; Buson, Alberto; Deodhar, Mandar; Findlay, Alison D; Guo, Lily; McDonald, Ian A; Turner, Craig I; Zhou, Wenbin; Jarolimek, Wolfgang




PubMed Central

Volatile oil of Psidium guajava leaves obtained by steam distillation was given orally to study its effects on the exudation and proliferative phases of the inflammatory reaction, using technique of carragenin induced paw edema and cotton pellets in male albino rats. The anti inflammatory activity as compared with ketorolac tromethamine. In carragenin induced edemas,. 0.8ml/kg of the volatile oil ad anti-inflammatory activity as that of ketorolac tromethamine. The oil was also found to be potent in cotton pellet granuom studies. Preliminary investigation revealed that the volatile oil fraction consist sesqueterpene which may be responsible for its anti inflammatory activity.

Kavimani, S.; Ilango, R.; Vertichelvan, T.



Anti-inflammatory iridoids of botanical origin.  


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 nonsteroidal 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 antiinflammatory 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

Viljoen, A; Mncwangi, N; Vermaak, I



A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity.  


The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. The above activities have been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection. PMID:9927043

Suh, N; Wang, Y; Honda, T; Gribble, G W; Dmitrovsky, E; Hickey, W F; Maue, R A; Place, A E; Porter, D M; Spinella, M J; Williams, C R; Wu, G; Dannenberg, A J; Flanders, K C; Letterio, J J; Mangelsdorf, D J; Nathan, C F; Nguyen, L; Porter, W W; Ren, R F; Roberts, A B; Roche, N S; Subbaramaiah, K; Sporn, M B



Cholinergic Anti-Inflammatory Pathway Activity and High Mobility Group Box-1 (HMGB1) Serum Levels in Patients with Rheumatoid Arthritis  

PubMed Central

High Mobility Group Box-1 (HMGB1) is a cytokine implicated in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. The cholinergic anti-inflammatory pathway, a vagus nerve-dependent mechanism, inhibits HMGB1 release in experimental disease models. Here, we examine the relationship between vagus nerve activity and HMGB1 in patients with RA. We compared RR interval variability, an index of cardiac vagal modulation, HMGB1 and hsCRP serum levels, and disease activity scores in thirteen RA patients and eleven age- and sex-matched controls. In RA patients, serum levels of HMGB1 and hsCRP were elevated as compared with controls (HMGB1 = 71 ng/mL [45–99] vs. 18 ng/mL [0–40], P < 0.0001; hsCRP = 14.5 mg/L [0.7–59] vs. 1 mg/L [0.4–2.9], P < 0.001). RR interval variability in RA patients was significantly decreased as compared with controls (HF = 38 msec2 [14–80] vs. 288 msec2 [38–364], P < 0.0001; rMSSD = 20.9 ± 9.79 msec, 52.6 ± 35.3 msec, P < 0.01). HMGB1 levels and RR interval variability were significantly related (rho = ?0.49, P < 0.01). HMGB1 serum levels significantly correlated with disease activity scores (DAS-28) in patients with RA (P = 0.004). The study design does not enable a determination of causality, but the results are consistent with the hypothesis that decreased cholinergic anti-inflammatory pathway activity is associated with increased HMGB1 levels in patients with RA.

Goldstein, Richard S; Bruchfeld, Annette; Yang, Lihong; Qureshi, Abdul R; Gallowitsch-Puerta, Margot; Patel, Nirav B; Huston, Brett J; Chavan, Sangeeta; Rosas-Ballina, Mauricio; Gregersen, Peter K; Czura, Christopher J; Sloan, Richard P; Sama, Andrew E; Tracey, Kevin J



Statins as Anti-Inflammatory Agents in Atherogenesis: Molecular Mechanisms and Lessons from the Recent Clinical Trials  

PubMed Central

Ample evidence exists in support of the potent anti-inflammatory properties of statins. In cell studies and animal models statins exert beneficial cardiovascular effects. By inhibiting intracellular isoprenoids formation, statins suppress vascular and myocardial inflammation, favorably modulate vascular and myocardial redox state and improve nitric oxide bioavailability. Randomized clinical trials have demonstrated that further to their lipid lowering effects, statins are useful in the primary and secondary prevention of coronary heart disease (CHD) due to their anti-inflammatory potential. The landmark JUPITER trial suggested that in subjects without CHD, suppression of low-grade inflammation by statins improves clinical outcome. However, recent trials have failed to document any clinical benefit with statins in high risk groups, such in heart failure or chronic kidney disease patients. In this review, we aim to summarize the existing evidence on statins as an anti-inflammatory agent in atherogenesis. We describe the molecular mechanisms responsible for the anti-inflammatory effects of statins, as well as clinical data on the non lipid-lowering, anti-inflammatory effects of statins on cardiovascular outcomes. Lastly, the controversy of the recent large randomized clinical trials and the issue of statin withdrawal are also discussed.

Antonopoulos, Alexios S; Margaritis, Marios; Lee, Regent; Channon, Keith; Antoniades, Charalambos



Electrophilic cyclopentenone neuroprostanes are anti-inflammatory mediators formed from the peroxidation of the omega-3 polyunsaturated fatty acid docosahexaenoic acid.  


The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) possesses potent anti-inflammatory properties and has shown therapeutic benefit in numerous inflammatory diseases. However, the molecular mechanisms of these anti-inflammatory properties are poorly understood. DHA is highly susceptible to peroxidation, which yields an array of potentially bioactive lipid species. One class of compounds are cyclopentenone neuroprostanes (A(4)/J(4)-NPs), which are highly reactive and similar in structure to anti-inflammatory cyclopentenone prostaglandins. Here we show that a synthetic A(4)/J(4)-NP, 14-A(4)-NP (A(4)-NP), potently suppresses lipopolysaccharideinduced expression of inducible nitric-oxide synthase and cyclooxygenase-2 in macrophages. Furthermore, A(4)-NP blocks lipopolysaccharide-induced NF-kappaB activation via inhibition of Ikappa kinase-mediated phosphorylation of IkappaBalpha. Mutation on Ikappa kinase beta cysteine 179 markedly diminishes the effect of A(4)-NP, suggesting that A(4)-NP acts via thiol modification at this residue. Accordingly, the effects of A(4)-NP are independent of peroxisome proliferator-activated receptor-gamma and are dependent on an intact reactive cyclopentenone ring. Interestingly, free radical-mediated oxidation of DHA greatly enhances its anti-inflammatory potency, an effect that closely parallels the formation of A(4)/J(4)-NPs. Furthermore, chemical reduction or conjugation to glutathione, both of which eliminate the bioactivity of A(4)-NP, also abrogate the anti-inflammatory effects of oxidized DHA. Thus, we have demonstrated that A(4)/J(4)-NPs, formed via the oxidation of DHA, are potent inhibitors of NF-kappaB signaling and may contribute to the anti-inflammatory actions of DHA. These findings have implications for understanding the anti-inflammatory properties of omega-3 fatty acids, and elucidate novel interactions between lipid peroxidation products and inflammation. PMID:18490445

Musiek, Erik S; Brooks, Joshua D; Joo, Myungsoo; Brunoldi, Enrico; Porta, Alessio; Zanoni, Giuseppe; Vidari, Giovanni; Blackwell, Timothy S; Montine, Thomas J; Milne, Ginger L; McLaughlin, BethAnn; Morrow, Jason D



Pharmacology of LY315920/S-5920, [[3-(aminooxoacetyl)-2-ethyl-1- (phenylmethyl)-1H-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: A new class of anti-inflammatory drugs, SPI.  


LY315920 is a potent, selective inhibitor of recombinant human, group IIA, nonpancreatic secretory PLA2 (sPLA2). In a chromogenic isolated enzyme assay, LY315920 inhibited sPLA2 activity with an IC50 of 9 +/- 1 nM or 7.3 x 10(-6) mole fraction, which approached the stiochiometric limit of this assay. The true potency of LY315920 was defined using a deoxycholate/phosphatidylcholine assay with a mole fraction of 1.5 x 10(-6). LY315920 was 40-fold less active against human, group IB, pancreatic sPLA2 and was inactive against cytosolic PLA2 and the constitutive and inducible forms of cyclooxygenase. Human sPLA2-induced release of thromboxane A2 (TXA2) from isolated guinea pig lung bronchoalveolar lavage cells was inhibited by LY315920 with an IC50 of 0.79 microM. The release of TXA2 from these cells by N-formyl-methionyl-leucyl-phenylalanine or arachidonic acid was not inhibited. The i.v. administration of LY315920, 5 min before harvesting the bronchoalveolar lavage cells, resulted in the inhibition of sPLA2-induced production of TXA2 with an ED50 of 16.1 mg/kg. Challenge of guinea pig lung pleural strips with sPLA2 produced contractile responses that were suppressed in a concentration-dependent manner by LY315920 with an apparent KB of 83 +/- 14 nM. Contractile responses induced by arachidonic acid were not altered. Intravenous or oral administration of LY315920 to transgenic mice expressing the human sPLA2 protein inhibited serum sPLA2 activity in a dose-related manner over a 4-h time course. LY315920 is a potent and selective sPLA2 inhibitor and represents a new class of anti-inflammatory agent designated SPI. This agent is currently undergoing clinical evaluation and should help to define the role of sPLA2 in various inflammatory disease states. PMID:10027849

Snyder, D W; Bach, N J; Dillard, R D; Draheim, S E; Carlson, D G; Fox, N; Roehm, N W; Armstrong, C T; Chang, C H; Hartley, L W; Johnson, L M; Roman, C R; Smith, A C; Song, M; Fleisch, J H



Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe  

PubMed Central

Background Statins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients. Methods 46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n?=?24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n?=?22) for 12 weeks. The primary endpoint was a change in hs-CRP. Results Baseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4?±?14.2 vs. -22.4?±?14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6?±?5.9 vs. 0.0?±?6.7 mg/dL; p?anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10. Trial registration UMIN000003746



Synthesis and anti-inflammatory activity of aromatic glucosinolates.  


Aromatic GLs are important members of the glucosinolate family of compounds because of their potential biological activity and medicinal properties. This study has shown success in the high yielding synthesis of some important aromatic GLs as well as the results of testing for anti-inflammatory properties of the synthetic GLs. 3,4-Dimethoxyphenylglucosinolate was found to be the most active anti-inflammatory of the seven glucosinolates assayed. PMID:23978357

Vo, Quan V; Trenerry, Craige; Rochfort, Simone; Wadeson, Jenny; Leyton, Carolina; Hughes, Andrew B



[Simultaneous analysis of 4 non-steroidal anti-inflammatory drug residues in mutton muscle using high performance liquid chromatography assisted by ultrasonic-microwave extraction].  


A method for the simultaneous determination of 4 non-steroidal anti-inflammatory drug (NSAID) residues, including flunixin meglumine, meloxicam, diclofenac sodium and ketoprofen, in mutton muscle was developed using high performance liquid chromatography assisted by ultrasonic-microwave extraction. The NSAIDs were extracted with acidified ethanol and purified by a diatomite column. The subsequent analysis of NSAIDs was achieved on a Hypersil C18 column (250 mm x 4.6 mm, 5 microm) with the mobile phase of acetonitrile-0.2% triethylamine (40 : 60, v/v, pH 3.5 adjusted by phosphoric acid) at a flow rate of 0.8 mL/min at 30 degrees C. The detection wavelength was set at 255 nm. The 4 NSAIDs were well separated within 20 min. The correlation coefficients for 4 NSAIDs were from 0.999 3 to 0.999 8 with the limits of detection (LOD, S/N = 3) of 5-10 microg/kg and the limits of quantification (LOQ, S/N = 10) of 15-30 microg/kg. The recoveries were in the range of 65.3% - 99.6% with the relative standard deviations (RSDs) less than 15%. This method is simple, rapid and highly sensitive, and can meet the requirement for the qualitative and quantitative analysis. PMID:21381422

Kang, Yongfeng; Zou, Shiwen; Duan, Wuping; Li, Yan; Sun, Tao



Investigation of retention behaviour of non-steroidal anti-inflammatory drugs in high-performance liquid chromatography by using quantitative structure-retention relationships.  


In this paper, a quantitative structure-retention relationship (QSRR) method is employed to model the retention behaviour in reversed-phase high-performance liquid chromatography of arylpropionic acid derivatives, largely used non-steroidal anti-inflammatory drugs (NSAIDs). Computed molecular descriptors and the organic modifier content in the mobile phase are associated into a comprehensive model to describe the effect of both solute structure and eluent composition on the isocratic retention of these drugs in water-acetonitrile mobile phases. Multilinear regression (MLR) combined with genetic algorithm (GA) variable selection is used to extract from a large set of computed 3D descriptors an optimal subset. Based on GA-MLR analysis, a five-dimensional QSRR model is identified. All the four selected molecular descriptors belong to the category of GEometry, Topology, and Atom-Weights AssemblY (GETAWAY) descriptors. The related multilinear model exhibits a quite good fitting and predictive performance. This model is further improved using an artificial neural network (ANN) learned by error back-propagation. Finally, the ANN-based model displays a remarkably better performance as compared with the MLR counterpart and, based on external validation, is able to predict with good accuracy the behaviour of unknown arylpropionic NSAIDs in the range of mobile phase composition of analytical interest (between 35 and 75% acetonitrile (v/v)). PMID:17904471

Carlucci, Giuseppe; D'Archivio, Angelo Antonio; Maggi, Maria Anna; Mazzeo, Pietro; Ruggieri, Fabrizio



Confirmatory analysis of non-steroidal anti-inflammatory drugs in bovine milk by high-performance liquid chromatography with fluorescence detection.  


HPLC with fluorescence detection is considered for confirmatory analysis of group B veterinary drugs by the European Union legislation. A procedure for confirming the presence of anti-inflammatory non-steroidal drug (NSAID) residues in bovine milk by reversed phase high-performance liquid chromatography with fluorescence detection is herein described. The native fluorescence of nine drugs belonging to different NSAID sub-classes, namely flurbiprofen, carprofen, naproxen, vedaprofen, 5-hydroxy-flunixin, niflumic acid, mefenamic acid, meclofenamic acid and tolfenamic acid, allowed for detection in bovine milk down to 0.25-20.0 microg/kg. Confirmation of the nine NSAIDs is attained by fluorescence detection at characteristic excitation and emission wavelengths. The procedure described is simple and selective. Limits of quantification (LOQs) ranging between 0.25 and 20 microg/kg were measured; satisfactory trueness and within-laboratory reproducibility data were calculated at LOQ spiking levels, apart from 5-hydroxy-flunixin. The procedure developed is used in our laboratory for confirmation of each one of the above mentioned NSAIDs in bovine milk, to support results after HPLC quantitative analysis with UV-vis detection. PMID:20227702

Gallo, Pasquale; Fabbrocino, Serena; Dowling, Geraldine; Salini, Marco; Fiori, Maurizio; Perretta, Giuseppe; Serpe, Luigi



In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo.  


Hyperforin, a major constituent of St. John's Wort (Hypericum perforatum, HP), provides anti-inflammatory, anti-tumor, and anti-bacterial properties. Previous studies have shown anti-oxidative properties of St. John's Wort extracts; however, its free radical scavenging activity in skin cells or skin has not been assessed in detail so far. Therefore, the free radical scavenging activity of hyperforin was tested in the H(2)DCFDA-assay in vitro in HaCaT keratinocytes irradiated with solar simulated radiation. Hyperforin (EC(50) 0.7 ?M corresponding to 0.42 ?g/ml) was much more effective compared to Trolox (EC(50) 12 ?g/ml) and N-acetylcysteine (EC(50) 847 ?g/ml) without showing phototoxicity. The radical protection factor of a cream containing 1.5%w/w of a hyperforin-rich HP extract was determined to be 200 × 10(14) radicals/mg, indicating a high radical scavenging activity. The cream was further applied ex vivo on porcine ear skin and significantly reduced radical formation after infrared irradiation. Finally, the UV-protective effect of the HP cream was tested on 20 volunteers in a randomized, double-blind, vehicle-controlled study. HP cream significantly reduced UVB-induced erythema as opposed to the vehicle. Occlusive application of HP cream on non-irradiated test sites did not cause any skin irritation. Taken together, these results demonstrate that hyperforin is a powerful free radical scavenger. PMID:22430217

Meinke, Martina C; Schanzer, Sabine; Haag, Stefan F; Casetti, Federica; Müller, Marcel L; Wölfle, Ute; Kleemann, Anke; Lademann, Juergen; Schempp, Christoph M



Anti-inflammatory effects of yerba maté extract (Ilex paraguariensis) ameliorate insulin resistance in mice with high fat diet-induced obesity.  


The aim of the present study was to evaluate the effects of yerba maté extract upon markers of insulin resistance and inflammatory markers in mice with high fat diet-induced obesity. The mice were introduced to either standard or high fat diets. After 12 weeks on a high fat diet, mice were randomly assigned to one of the two treatment conditions, water or yerba maté extract at 1.0 gkg(-1). After treatment, glucose blood level and hepatic and soleus muscle insulin response were evaluated. Serum levels of TNF-? and IL-6 were evaluated by ELISA, liver tissue was examined to determine the mRNA levels of TNF-?, IL-6 and iNOS, and the nuclear translocation of NF-?B was determined by an electrophoretic mobility shift assay. Our data show improvements in both the basal glucose blood levels and in the response to insulin administration in the treated animals. The molecular analysis of insulin signalling revealed a restoration of hepatic and muscle insulin substrate receptor (IRS)-1 and AKT phosphorylation. Our data show that the high fat diet caused an up-regulation of the TNF-?, IL-6, and iNOS genes. Although after intervention with yerba maté extract the expression levels of those genes returned to baseline through the NF-?B pathway, these results could also be secondary to the weight loss observed. In conclusion, our results indicate that yerba maté has a potential anti-inflammatory effect. Additionally, these data demonstrate that yerba maté inhibits hepatic and muscle TNF-? and restores hepatic insulin signalling in mice with high fat diet-induced obesity. PMID:21238540

Arçari, Demétrius P; Bartchewsky, Waldemar; dos Santos, Tanila W; Oliveira, Karim A; DeOliveira, Carlorine C; Gotardo, Érica M; Pedrazzoli, José; Gambero, Alessandra; Ferraz, Lucio F C; Carvalho, Patricia de O; Ribeiro, Marcelo L



Anti-inflammatory Activity of a High-molecular-weight Cranberry Fraction on Macrophages Stimulated by Lipopolysaccharides from Periodontopathogens  

Microsoft Academic Search

Periodontitis is a chronic inflammatory disease affecting oral tissues. The continuous, high production of cytokines by host cells triggered by periodontopathogens is thought to be responsible for the destruction of tooth-supporting tissues. Macrophages play a critical role in this host inflammatory response to periodontopathogens. The aim of this study was to investigate the effect of non-dialyzable material prepared from cranberry

C. Bodet; F. Chandad; D. Grenier



Anti-inflammatory effect of antidiabetic thiazolidinediones prevents bone resorption rather than cartilage changes in experimental polyarthritis  

Microsoft Academic Search

BACKGROUND: Rosiglitazone and pioglitazone are high-affinity peroxisome proliferator-activated receptor (PPAR)-? agonists with potent anti-diabetic properties and potential anti-inflammatory effects. We compared the ability of a range of oral doses of these thiazolidinediones, including those sufficient to restore insulin sensitization, to inhibit the pathogenesis of adjuvant-induced arthritis (AIA). METHODS: AIA was induced in Lewis rats by a subcutaneous injection of 1

Meriem Koufany; David Moulin; Arnaud Bianchi; Mikhaela Muresan; Sylvie Sebillaud; Patrick Netter; Georges Weryha; Jean-Yves Jouzeau



Stereochemical resolution of enantiomeric 2-aryl propionic acid non-steroidal anti-inflammatory drugs on a human serum albumin based high-performance liquid chromatographic chiral stationary phase  

Microsoft Academic Search

Summary  The native enantioselectivity in binding of human serum albumin (HSA) towards 2-aryl propionic acid non-steroidal anti-inflammatory drugs (2-APA-NSAIDs, the profens) was found to be preserved when the protein was immobilized within a commercially available diol high-performance liquid chromatographic column. High capacity factors were obtained, reflecting the previously observed extensive binding of the 2-APA-NSAIDs to free HSA. The capacity factors were

T. A. G. Noctor; G. Felix; I. W. Wainer



Anti-inflammatory Agents: Present and Future  

PubMed Central

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.

Dinarello, Charles A.



High mobility group box 1 promotes small intestinal damage induced by nonsteroidal anti-inflammatory drugs through Toll-like receptor 4.  


Release of high mobility group box 1 (HMGB1) from damaged cells, which is involved in many types of tissue injuries, activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor 2 (TLR2), TLR4, and receptor for advanced glycation end-products (RAGE). Our objective was to determine the role of HMGB1 in nonsteroidal anti-inflammatory drug (NSAID)-induced damage of the small intestine. Oral indomethacin (10 mg/kg) induced damage to the small intestine and was associated with increases in intestinal HMGB1 expression and serum HMGB1 levels. In wild-type mice, recombinant human HMGB1 aggravated indomethacin-induced small intestinal damage; enhanced the mRNA expression levels of tumor necrosis factor ? (TNF-?), monocyte chemotactic protein 1, and KC; activated nuclear factor kappa B; and stimulated phosphorylation of the mitogen-activated protein kinases p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). In contrast, blocking HMGB1 action with neutralizing antibodies prevented damage and inhibited both inflammatory cytokine overexpression and activation of these intracellular signaling pathways. TLR2-knockout (KO) and RAGE-KO mice exhibited high sensitivities to indomethacin-induced damage, similar to wild-type mice, whereas TLR4-KO mice exhibited less severe intestinal damage and lower levels of TNF-? mRNA expression. Exogenous HMGB1 aggravated the damage in TLR2- and RAGE-KO mice but did not affect the damage in TLR4-KO mice. Thus, our results suggest that HMGB1 promotes NSAID-induced small intestinal damage through TLR4-dependent signaling pathways. PMID:22634181

Nadatani, Yuji; Watanabe, Toshio; Tanigawa, Tetsuya; Machida, Hirohisa; Okazaki, Hirotoshi; Yamagami, Hirokazu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo



Anti-inflammatory Asterosaponins from the Starfish Astropecten monacanthus.  


Four new asterosaponins, astrosteriosides A-D (1-3 and 5), and two known compounds, psilasteroside (4) and marthasteroside B (6), were isolated from the MeOH extract of the edible Vietnamese starfish Astropecten monacanthus. Their structures were elucidated by chemical and spectroscopic methods including FTICRMS and 1D and 2D NMR experiments. The effects of the extracts and isolated compounds on pro-inflammatory cytokines were evaluated by measuring the production of IL-12 p40, IL-6, and TNF-? in LPS-stimulated bone marrow-derived dendritic cells. Compounds 1, 5, and 6 exhibited potent anti-inflammatory activity comparable to that of the positive control. Further studies are required to confirm efficacy in vivo and the mechanism of effects. Such potent anti-inflammatory activities render compounds 1, 5, and 6 important materials for further applications including complementary inflammation remedies and/or functional foods and nutraceuticals. PMID:24047259

Thao, Nguyen Phuong; Cuong, Nguyen Xuan; Luyen, Bui Thi Thuy; Thanh, Nguyen Van; Nhiem, Nguyen Xuan; Koh, Young-Sang; Ly, Bui Minh; Nam, Nguyen Hoai; Kiem, Phan Van; Minh, Chau Van; Kim, Young Ho



Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal  

PubMed Central

Background Enprocal is a high-protein micro-nutrient rich formulated supplementary food designed to meet the nutritional needs of the frail elderly and be delivered to them in every day foods. We studied the potential of Enprocal to improve gut and immune health using simple and robust bioassays for gut cell proliferation, intestinal integrity/permeability, immunomodulatory, anti-inflammatory and anti-oxidative activities. Effects of Enprocal were compared with whey protein concentrate 80 (WPC), heat treated skim milk powder, and other commercially available milk derived products. Results Enprocal (undigested) and digested (Enprocal D) selectively enhanced cell proliferation in normal human intestinal epithelial cells (FHs74-Int) and showed no cytotoxicity. In a dose dependent manner Enprocal induced cell death in Caco-2 cells (human colon adencarcinoma epithelial cells). Digested Enprocal (Enprocal D: gut enzyme cocktail treated) maintained the intestinal integrity in transepithelial resistance (TEER) assay, increased the permeability of horseradish peroxidase (HRP) and did not induce oxidative stress to the gut epithelial cells. Enprocal D upregulated the surface expression of co-stimulatory (CD40, CD86, CD80), MHC I and MHC II molecules on PMA differentiated THP-1 macrophages in coculture transwell model, and inhibited the monocyte/lymphocyte (THP-1/Jurkat E6-1 cells)-epithelial cell adhesion. In cytokine secretion analyses, Enprocal D down-regulated the secretion of proinflammatory cytokines (IL-1? and TNF-?) and up-regulated IFN-?, IL-2 and IL-10. Conclusion Our results indicate that Enprocal creates neither oxidative injury nor cytotoxicity, stimulates normal gut cell proliferation, up regulates immune cell activation markers and may aid in the production of antibodies. Furthermore, through downregulation of proinflammatory cytokines, Enprocal appears to be beneficial in reducing the effects of chronic gut inflammatory diseases such as inflammatory bowel disease (IBD). Stimulation of normal human fetal intestinal cell proliferation without cell cytotoxicity indicates it may also be given as infant food particularly for premature babies.

Kanwar, Jagat R; Kanwar, Rupinder K



Potent anti-inflammatory effect of a novel furan-2,5-dione derivative, BPD, mediated by dual suppression of COX-2 activity and LPS-induced inflammatory gene expression via NF-?B inactivation  

PubMed Central

BACKGROUND AND PURPOSE We previously reported that 3-(benzo[d]-1,3-dioxol-5-yl)-4-phenylfuran-2,5-dione (BPD) showed strong inhibitory effects on PGE2 production. However, the exact mechanism for the anti-inflammatory effect of BPD is not completely understood. In this study, we investigated the molecular mechanism involved in the effects of BPD on inflammatory mediators in LPS-stimulated macrophages and animal models of inflammation. EXPERIMENTAL APPROACH The expressions of COX-2, inducible NOS (iNOS), TNF-?, IL-6 and IL-1?, in LPS-stimulated RAW 264.7 cells and murine peritoneal macrophages, were determined by Western blot and/or qRT-PCR, respectively. NF-?B activation was investigated by EMSA, reporter gene assay and Western blotting. Anti-inflammatory effects of BPD were evaluated in vivo in carrageenan-induced paw oedema in rats and LPS-induced septic shock in mice. KEY RESULTS BPD not only inhibited COX-2 activity but also reduced the expression of COX-2. In addition, BPD inhibited the expression of iNOS, TNF-?, IL-6 and IL-1? at the transcriptional level. BPD attenuated LPS-induced DNA-binding activity and the transcription activity of NF-?B; this was associated with a decrease in the phosphorylation level of inhibitory ?B-? (I?B-?) and reduced nuclear translocation of NF-?B. Furthermore, BPD suppressed the formation of TGF-?-activated kinase-1 (TAK1)/TAK-binding protein1 (TAB1), which was accompanied by a parallel reduction of phosphorylation of TAK1 and I?B kinase (IKK). Pretreatment with BPD inhibited carrageenan-induced paw oedema and LPS-induced septic death. CONCLUSION AND IMPLICATIONS Taken together, our data indicate that BPD is involved in the dual inhibition of COX-2 activity and TAK1-NF-?B pathway, providing a molecular basis for the anti-inflammatory properties of BPD.

Shin, Ji-Sun; Park, Seung-Jae; Ryu, Suran; Kang, Han Byul; Kim, Tae Woo; Choi, Jung-Hye; Lee, Jae-Yeol; Cho, Young-Wuk; Lee, Kyung-Tae



Bioactive Compounds, Antioxidant, Xanthine Oxidase Inhibitory, Tyrosinase Inhibitory and Anti-Inflammatory Activities of Selected Agro-Industrial By-products  

PubMed Central

Evaluation of abundantly available agro-industrial by-products for their bioactive compounds and biological activities is beneficial in particular for the food and pharmaceutical industries. In this study, rapeseed meal, cottonseed meal and soybean meal were investigated for the presence of bioactive compounds and antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities. Methanolic extracts of rapeseed meal showed significantly (P < 0.01) higher phenolics and flavonoids contents; and significantly (P < 0.01) higher DPPH and nitric oxide free radical scavenging activities when compared to that of cottonseed meal and soybean meal extracts. Ferric thiocyanate and thiobarbituric acid tests results showed rapeseed meal with the highest antioxidant activity (P < 0.01) followed by BHT, cotton seed meal and soybean meal. Rapeseed meal extract in xanthine oxidase and tyrosinase inhibitory assays showed the lowest IC50 values followed by cottonseed and soybean meals. Anti-inflammatory assay using IFN-?/LPS stimulated RAW 264.7 cells indicated rapeseed meal is a potent source of anti-inflammatory agent. Correlation analysis showed that phenolics and flavonoids were highly correlated to both antioxidant and anti-inflammatory activities. Rapeseed meal was found to be promising as a natural source of bioactive compounds with high antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities in contrast to cotton and soybean meals.

Oskoueian, Ehsan; Abdullah, Norhani; Hendra, Rudi; Karimi, Ehsan



An emerging role for anti-inflammatory agents for chemoprevention.  


There have been a number of promising recent developments in the prevention of colorectal cancer. This book examines in detail important aspects of the current status of and future prospects for chemoprevention of colorectal tumors, particularly using anti-inflammatory drugs. Research into the mechanisms that lead from early colorectal adenoma to colorectal cancer is discussed. The role and modes of action of available anti-inflammatory drugs, such as aspirin, celecoxib, and sulindac are described and recent data from trials of aspirin are reviewed. In addition, the possible impact of nutritional agents with anti-inflammatory properties is considered, and strategies applicable in those with a high level of genetic risk are evaluated. An important feature of the book is its interdisciplinary perspective, offering highly relevant information for gastroenterologists, internists, general practitioners, oncologists, colorectal and gastroenterological surgeons, and public health practitioners. PMID:22893197

Chan, Andrew T; Detering, Elmar



Gastrointestinal and Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs  

PubMed Central

Nonsteroidal anti-inflammatory drugs (NSAIDs) confer a gastrointestinal (GI) side effect profile and concerns regarding adverse cardiovascular effects have emerged associated with considerable morbidity and mortality. NSAIDs are highly effective in treating pain and inflammation, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although they may increase cardiovascular adverse events. The selection of an appropriate analgesic or anti-inflammatory agent with or without gastroprotective therapy should be individualized.

Al-Saeed, Abdulwahed



The topical anti-inflammatory and analgesic properties of bromfenac in rodents  

Microsoft Academic Search

Bromfenac [2-amino-3-(4-bromobenzoyl) benzeneacetic acid sodium slat sesquihydrate] is an anti-inflammatory\\/analgesic agent that possesses potent topical activity in rats, guinea pigs, and mice. In rat models of acute (carrageenan paw edema) and chronic (adjuvant arthritis) inflammation, preparations of bromfenac at concentrations as low as 0.01–0.32% (0.01–0.32 mg bromfenac) produced significant anti-inflammatory activity when applied to the injected paw or to the

J. C. Nolan; L. E. Wagner; C. E. Gathright; D. J. Stephens; L. F. Sancilio



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

PubMed Central

The increasing use of the anti-microbial 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. 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.

Liu, Jun-Yan; Qiu, Hong; Morisseau, Christophe; Hwang, Sung Hee; Tsai, Hsing-Ju; Ulu, Arzu; Chiamvimonvat, Nipavan; Hammock, Bruce D



Anti-Inflammatory Agents for Cancer Therapy  

PubMed Central

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

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



Evaluation of the anti-inflammatory activity of Aegle marmelos (Bilwa) root  

PubMed Central

Aims and objectives: The purpose of this study was to evaluate and compare the anti-inflammatory activity of the aqueous root bark extract of Aegle marmelos (Bilwa) in experimental acute and chronic inflammatory animal models. Materials and Methods: Aqueous extract of root bark of Bilwa was prepared and tested for anti-inflammatory activity in albino rats weighing 150-280 grams. The animals were randomly divided into 3 groups of 6 each; one group served as control and other two groups received indomethacin and Bilwa orally 1 hour prior to experimentation. The in vivo anti-inflammatory activity was studied using the acute (Carrageenan induced paw edema) and chronic (Cotton pellet induced granuloma) animal models. Anti-inflammatory activity was expressed as Percent inhibition (PI). Statistical analysis was performed using One-way analysis of variance (ANOVA) followed by Scheffe's post hoc test. P < 0.05 was considered statistically significant. Results: The PI with indomethacin and Bilwa in carrageenan induced paw edema were 52.7% and 46% and in cotton pellet induced granuloma were 24.7% and 9.2% respectively. Indomethacin showed highly significant anti-inflammatory activity in both the models. However, Bilwa showed highly significant activity in acute model and but a trend of anti-inflammatory activity in chronic model studied. Conclusions: As Bilwa showed significant anti-inflammatory activity in the models studied, it can be a promising anti-inflammatory agent.

Benni, Jyoti M.; Jayanthi, M.K.; Suresha, R.N.



Anti-inflammatory sesquiterpenes from Curcuma zedoaria  

Microsoft Academic Search

From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti-inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4), curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8), dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures were elucidated on the basis of spectroscopic data. The anti-inflammatory effect of

H. Makabe; N. Maru; A. Kuwabara; T. Kamo; M. Hirota



In vitro analysis of the cytotoxic and anti-inflammatory effects of antioxidant compounds used as additives in ultra high-molecular weight polyethylene in total joint replacement components  

PubMed Central

Ultra high-molecular weight polyethylene (UHMWPE) remains the most commonly used material in modern joint replacement prostheses. However, UHMWPE wear particles, formed as the bearing articulates, are one of the main factors leading to joint replacement failure via the induction of osteolysis and subsequent aseptic loosening. Previous studies have shown that the addition of antioxidants such as vitamin E to UHMWPE can improve wear resistance of the polymer and reduce oxidative fatigue. However, little is known regarding the biological consequences of such antioxidant chemicals. This study investigated the cytotoxic and anti-inflammatory effects of a variety of antioxidant compounds currently being tested experimentally for use in hip and knee prostheses, including nitroxides, hindered phenols, and lanthanides on U937 human histocyte cells and human peripheral blood mononuclear cells (PBMNCs) in vitro. After addition of the compounds, cell viability was determined by dose response cytotoxicity studies. Anti-inflammatory effects were determined by quantitation of TNF-? release in lipopolysaccharide (LPS)-stimulated cells. This study has shown that many of these compounds were cytotoxic to U937 cells and PBMNCs, at relatively low concentrations (micromolar), specifically the hindered phenol 3,5-di-tert-butyl-4-hydroxyhydrocinnamate (HPAO1), and the nitroxide 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO). Lanthanides were only cytotoxic at very high concentrations and were well tolerated by the cells at lower concentrations. Cytotoxic compounds also showed reduced anti-inflammatory effects, particularly in PBMNCs. Careful consideration should therefore be given to the use of any of these compounds as potential additives to UHMWPE. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 407–413, 2013.

Bladen, C L; Tzu-Yin, L; Fisher, J; Tipper, J L



In vitro analysis of the cytotoxic and anti-inflammatory effects of antioxidant compounds used as additives in ultra high-molecular weight polyethylene in total joint replacement components.  


Ultra high-molecular weight polyethylene (UHMWPE) remains the most commonly used material in modern joint replacement prostheses. However, UHMWPE wear particles, formed as the bearing articulates, are one of the main factors leading to joint replacement failure via the induction of osteolysis and subsequent aseptic loosening. Previous studies have shown that the addition of antioxidants such as vitamin E to UHMWPE can improve wear resistance of the polymer and reduce oxidative fatigue. However, little is known regarding the biological consequences of such antioxidant chemicals. This study investigated the cytotoxic and anti-inflammatory effects of a variety of antioxidant compounds currently being tested experimentally for use in hip and knee prostheses, including nitroxides, hindered phenols, and lanthanides on U937 human histocyte cells and human peripheral blood mononuclear cells (PBMNCs) in vitro. After addition of the compounds, cell viability was determined by dose response cytotoxicity studies. Anti-inflammatory effects were determined by quantitation of TNF-? release in lipopolysaccharide (LPS)-stimulated cells. This study has shown that many of these compounds were cytotoxic to U937 cells and PBMNCs, at relatively low concentrations (micromolar), specifically the hindered phenol 3,5-di-tert-butyl-4-hydroxyhydrocinnamate (HPAO1), and the nitroxide 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO). Lanthanides were only cytotoxic at very high concentrations and were well tolerated by the cells at lower concentrations. Cytotoxic compounds also showed reduced anti-inflammatory effects, particularly in PBMNCs. Careful consideration should therefore be given to the use of any of these compounds as potential additives to UHMWPE. PMID:22915524

Bladen, C L; Tzu-Yin, L; Fisher, J; Tipper, J L



Indigenous New Zealand honeys exhibit multiple anti-inflammatory activities.  


Recent evidence suggests a potential role for honeys in mediating clinical inflammation and tissue damage. Here, we investigated the anti-inflammatory activity of a selection of previously untested indigenous New Zealand (NZ) honeys. We found that several, but not all, New Zealand rewarewa, manuka and kanuka honey samples exhibited potent, dose-dependent reduction of human neutrophil superoxide production in vitro. This inhibitory activity did not correlate with levels of known phenolic-based free radical scavengers. Furthermore, the active honeys did not scavenge superoxide generated in a cell-free xanthine/xanthine oxidase assay. In C57BL/6?J mice, topical application of manuka and rewarewa honey samples with the highest in vitro activity suppressed arachidonic acid-induced ear oedema, and rewarewa honey suppressed both oedema and leukocyte (monocyte and neutrophil) infiltration. Together, these findings demonstrate that some indigenous NZ honeys exhibit clinically relevant anti-inflammatory activity. Further investigation is warranted to identify the active component(s) and mechanisms responsible for these activities and to determine potential applications for anti-inflammatory honeys in the topical treatment of clinical inflammation. PMID:21978989

Leong, Aidan G; Herst, Patries M; Harper, Jacquie L



The açaí flavonoid velutin is a potent anti-inflammatory agent: blockade of LPS-mediated TNF-? and IL-6 production through inhibiting NF-?B activation and MAPK pathway.  


Recent studies have shown that some flavonoids are modulators of proinflammatory cytokine production. In this study, velutin, a unique flavone isolated from the pulp of açaí fruit (Euterpe oleracea Mart.), was examined for its effects in reducing lipopolysaccharide-induced proinflammatory cytokine tumor necrosis factor (TNF)-? and interleukin (IL)-6 production in RAW 264.7 peripheral macrophages and mice peritoneal macrophages. Three other structurally similar and well-studied flavones, luteolin, apigenin and chrysoeriol, were included as controls and for comparative purposes. Velutin exhibited the greatest potency among all flavones in reducing TNF-? and IL-6 production. Velutin also showed the strongest inhibitory effect in nuclear factor (NF)-?B activation (as assessed by secreted alkaline phosphatase reporter assay) and exhibited the greatest effects in blocking the degradation of inhibitor of NF-?B as well as in inhibiting mitogen-activated protein kinase p38 and JNK phosphorylation; all of these are important signaling pathways involved in production of TNF-? and IL-6. The present study led to the discovery of a strong anti-inflammatory flavone, velutin. This compound effectively inhibited the expression of proinflammatory cytokines TNF-? and IL-6 in low micromole levels by inhibiting NF-?B activation and p38 and JNK phosphorylation. PMID:22137267

Xie, Chenghui; Kang, Jie; Li, Zhimin; Schauss, Alexander G; Badger, Thomas M; Nagarajan, Shanmugam; Wu, Tong; Wu, Xianli



The anti-inflammatory profile of fluticasone propionate.  


Fluticasone propionate is a new corticosteroid based on the androstane nucleus. It is more lipophilic than beclomethasone dipropionate (BDP) and budesonide, and binds more avidly to human lung tissue. It has an absolute affinity (KD) of 0.5 nM for the glucocorticoid receptor and a relative receptor affinity 1.5- and 3.0-times greater than that of beclomethasone-17-monopropionate (17-BMP) and budesonide, respectively. The rate of association with the receptor is faster and the rate of dissociation slower than with standard corticosteroids. As a result, the half-life of the corticosteroid-receptor complex is > 10 h. Fluticasone propionate is also highly selective for the glucocorticoid receptor, with little or no activity at other steroid receptors. Pretreatment with fluticasone propionate significantly inhibits the increase in mast cell numbers in the nasal mucosa of rats chronically exposed to toluene di-isocyanate (TDI), and suppresses TDI-induced mast cell degranulation. It is more potent in vitro than dexamethasone, BDP and budesonide in inhibiting anti-CD3-induced human T-lymphocyte proliferation, in attenuating tumour necrosis factor-alpha-induced endothelial cell adhesion molecule expression, and in increasing secretory leucocyte protease inhibitor levels in airway epithelial cells. It is also more potent and longer-acting than other corticosteroids in inhibiting oedema formation, interleukin-5 (IL-5)-induced blood eosinophilia, and IL-5- or platelet activating factor-stimulated eosinophil accumulation in the lung. Fluticasone propionate therefore has increased intrinsic glucocorticoid potency and high topical anti-inflammatory activity. PMID:7604948

Johnson, M



Cannabinoids as novel anti-inflammatory drugs  

PubMed Central

Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of ?9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.

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



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


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

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



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

PubMed Central

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.

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



Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory, and free radical scavenging effects of Rumex nepalensis.  


Evaluation of the topical anti-inflammatory activity of chloroform and ethyl acetate extracts of RUMEX NEPALENSIS roots in a TPA-induced acute inflammation mouse model demonstrated a significant reduction in ear edema. The extracts were further tested on purified enzymes for COX-1 and COX-2 inhibition to elucidate their mechanism of action, and a strong inhibition was observed. Six anthraquinones and two naphthalene derivatives were isolated from the ethyl acetate extract. Among the isolated compounds, emodin was found to be a potent inhibitor with slight selectivity towards COX-2, and nepodin exhibited selectivity towards COX-1. Emodin, endocrocin, and nepodin also exhibited significant topical anti-inflammatory activity in mice. Interestingly, nepodin showed better radical scavenging activity than trolox and ascorbic acid against DPPH and ABTS radicals. The strong radical scavenging activity of chloroform and ethyl acetate extracts could be explained by the presence of nepodin as well as by the high phenolic content of the ethyl acetate extract. Thus, the anti-inflammatory effect of R. NEPALENSIS roots was assumed to be mediated through COX inhibition by anthraquinones and naphthalene derivatives and through the radical scavenging activities of naphthalene derivatives. PMID:20379952

Gautam, Raju; Karkhile, Kailas V; Bhutani, Kamlesh K; Jachak, Sanjay M



Comparison of Analgesic and Anti-Inflammatory Activity of Meloxicam Gel with Diclofenac and Piroxicam Gels in Animal Models: Pharmacokinetic Parameters after Topical Application  

Microsoft Academic Search

Meloxicam, a non-steroidal anti-inflammatory drug, is a preferential inhibitor of cyclooxygenase-2 and has demonstrated potent analgesic and anti-inflammatory activity after oral administration. The present work was carried out to elucidate the anti-inflammatory and analgesic activity of a newer topical gel formulation of meloxicam (1% w\\/w gel) and compare it with 0.5% w\\/w piroxicam and 1% w\\/w diclofenac gels in experimental

S. K. Gupta; P. Bansal; R. K. Bhardwaj; J. Jaiswal; T. Velpandian



Anti-inflammatory sesquiterpenes from Curcuma zedoaria.  


From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti-inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4), curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8), dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures were elucidated on the basis of spectroscopic data. The anti-inflammatory effect of isolated components on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears were examined. Compounds 1 and 2 suppressed the TPA-induced inflammation of mouse ears by 75% and 53%, respectively, at a dose of 1.0 micromol. Their activities are comparable to that of indomethacin, the normally used anti-inflammatory agent. PMID:16901812

Makabe, H; Maru, N; Kuwabara, A; Kamo, T; Hirota, M



Gastrointestinal delivery of anti-inflammatory nanoparticles.  


The concept of nanomedicine has risen to be the future of medicine. Advantages of using nanoobjects as vectors for drug delivery systems are numerous, such as fewer side effects due to a low drug dose, and high specificity between drug and target. Unlike systemic therapy, targeting a specific target is more efficient and less costly. In inflammatory bowel disease, including ulcerative colitis and Crohn disease, the colon represents the targeted organ. A large number of drugs are candidates for loading into nanoparticles (NPs). Small molecules, such as tripeptides and siRNA, or larger molecules, such as proteins (hormones, antibodies (Ab), etc.), can be encapsulated alone or in a complex form inside the NPs. In our studies, once NPs are synthesized and loaded with anti-inflammatory compounds, they are delivered to the colon. An efficient technique has been developed for specific NP targeting to digestive tract regions, including the colon, using a hydrogel based on electrostatic interactions between positive ions and negative polysaccharides. An in situ double cross-linking process, mediated by Ca²? and SO?²?, of chitosan and alginate administered to the mouse gastrointestinal (GI) tract by double gavage, is used for gel formation. When the drug is given in NPs, NPs are targeted to the colon, and NP degradation by aggressive environmental conditions in the GI tract is significantly reduced. Using a biomaterial (hydrogel) associated with nanotechnology, lower doses of drug can be loaded efficiently and delivered to the colon to reduce colonic inflammation. PMID:22568903

Laroui, Hamed; Sitaraman, Shanthi V; Merlin, Didier



Anti-Inflammatory and Pro-Resolving Lipid Mediators  

PubMed Central

The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that non-steroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held to be a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution possessing potent anti-inflammatory and pro-resolving actions. A lipid mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3-polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates in addition to the lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. These new chemical mediator families were coined resolvins and protectins, given their potent bioactions. In this annual review, we present recent advances on the biosynthesis and stereospecific actions of these new pro-resolving mediators, which have also proven to be organ protective and anti-fibrotic.

Serhan, Charles N.; Yacoubian, Stephanie; Yang, Rong



An anti-inflammatory and immunomodulatory polysaccharide from Orbignya phalerata  

Microsoft Academic Search

A polysaccharide, a glucan with mean Mr of 1.0×106 (MP1), was isolated from the mesocarp of fruits of Orbignya phalerata. Chemical and spectroscopic studies indicated that MP1 has a highly branched glucan type structure composed of ?-(1?4) linked d-glucopyranose residues with (3?4), (4?6), and with (3?6) branching points. MP1 enhanced phagocytosis in vivo and exhibited anti-inflammatory activity.

Bernadete Pereira da Silva; José Paz Parente



Anti-inflammatory effectiveness of topically administered corticosteroids in the cornea without epithelium.  


The present studies demonstrate that modification of the derivative of a given steriod base alters its anti-inflammatory potential as measured by suppression of leukocyte invasion of the cornea. A comparison of each drug's corneal bioavailability with its anti-inflammatory effectiveness shows the acetate derivative of prednisolone to be a more potent anti-inflammatory agent than the phosphate derivative. Similarly, the free alcohol derivative of dexamethasone proved to be more potent than the phosphate derivative. Increasing the concentration of prednisolone acetate from 0.125 per cent to 1.0 per cent results in a significant increase in its anti-inflammatory effectiveness in the cornea following topical administration. The same increase in prednisolone phosphate concentration does not produce a significant increase in its ability to suppress polymorphonuclear leukocyte infiltration of the cornea. When the epithelium of the inflamed cornea is intact, prednisolone acetate, 1.0 per cent ophthalmic suspension, is the most effective of the corticosteroid preparations studied. In the absence of an intact epithelium, prednisolone acetate, 1.0 per cent ophthalmic suspension, again produces the greatest mean reduction in polymorphonuclear leukocytic infiltration of the cornea although here one cannot demonstrate a statistically significant difference from the anti-inflammatory effect produced by prednisolone phosphate, 1.0 per cent ophthalmic solution, or dexamethasone alcohol, 0.1 per cent ophthalmic suspension. Overall, therefore, prednisolone acetate 1.0 per cent is the most effective of the topical agents studied for suppression of corneal inflammation. PMID:1116925

Kupferman, A; Leibowitz, H M



Design and synthesis of 2-phenoxynicotinic acid hydrazides as anti-inflammatory and analgesic agents.  


A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for their analgesic and anti-inflammatory activities. Several compounds having an unsubstituted phenyl/4-pyridyl or C-4 methoxy substituent on the terminal phenyl ring showed moderate to high analgesic or anti-inflammatory activity in comparison to mefenamic acid as the reference drug. The compounds with highest anti-inflammatory activity were subjected to in vitro COX-1/COX-2 inhibition assays and showed moderate to good COX-1 and weak COX-2 inhibition activities. PMID:20806271

Moradi, Alireza; Navidpour, Latifeh; Amini, Mohsen; Sadeghian, Hamid; Shadnia, Hooman; Firouzi, Omidreza; Miri, Ramin; Ebrahimi, Seyed Esmaeil Sadat; Abdollahi, Mohammad; Zahmatkesh, Mona Haddad; Shafiee, Abbas



Antioxidant, Anti-inflammatory and Cytotoxicity of Phaleria macrocarpa (Boerl.) Scheff Fruit  

PubMed Central

Background Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) originates from Papua Island, Indonesia and grows in tropical areas. The different parts of the fruit of P. macrocarpa were evaluated for antioxidant, anti-inflammatory, and cytotoxic activities. Methods Phaleria macrocarpa fruit were divided into pericarp, mesocarp and seed. All parts of the fruit were reflux extracted with methanol. The antioxidant activity of the extracts were characterized in various in vitro model systems such as FTC, TBA, DPPH radical, reducing power and NO radical. Anti-inflammatory assays were done by using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-? and cytotoxic activities were determined by using several cancer cell lines and one normal cell line Results The results showed that different parts (pericarp, mesocarp, and seed) of Phaleria macrocarpa fruit contain various amount of total phenolic (59.2 ± 0.04, 60.5 ± 0.17, 47.7 ± 1.04 mg gallic acid equivalent/g DW) and flavonoid compounds (161.3 ± 1.58, 131.7 ± 1.66, 35.9 ± 2.47 mg rutin equivalent/g DW). Pericarp and mesocarp showed high antioxidant activities by using DPPH (71.97%, 62.41%), ferric reducing antioxidant power (92.35%, 78.78%) and NO scavenging activity (65.68%, 53.45%). Ferric thiocyanate and thiobarbituric acid tests showed appreciable antioxidant activity in the percentage hydroperoxides inhibitory activity from pericarp and mesocarp in the last day of the assay. Similarly, the pericarp and mesocarp inhibited inducible nitric oxide synthesis with values of 63.4 ± 1.4% and 69.5 ± 1.4% in macrophage RAW 264.7 cell lines induced by LPS/IFN-? indicating their notable anti-inflammatory potential. Cytotoxic activities against HT-29, MCF-7, HeLa and Chang cell lines were observed in all parts. Conclusions These results indicated the possible application of P. macrocarpa fruit as a source of bioactive compounds, potent as an antioxidant, anti inflammatory and cytotoxic agents.



Regulation of pro-and anti-inflammatory host responses.  


Sepsis is a very heterogeneous clinical syndrome broadly defined as the systemic host response to an infection. Until recently, the concept that mortality is the consequence of an uncontrolled hyperinflammatory response of the host was widely accepted. However, although some patients may die rapidly from septic shock accompanied by an overwhelming systemic inflammatory response syndrome triggered by a highly virulent pathogen, most patients survive the initial phase of sepsis, showing multiple organ failure days or weeks later. These patients often demonstrate signs of immune suppression rather than enhanced inflammation. As such, sepsis is now considered a misbalance between proinflammatory reactions (designed to kill invading pathogens but at the same time responsible for tissue damage) and anti-inflammatory responses (designed to limit excessive inflammation, but at the same time making the host more vulnerable for secondary infections). This chapter discusses key components of the pro- and anti-inflammatory response to sepsis and the regulation thereof. PMID:21659750

van der Poll, Tom; van Zoelen, Marieke A D; Wiersinga, W Joost



The role of anti-inflammatory drugs in colorectal cancer.  


A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle are key risk factors for colorectal cancer (CRC). Prevention of CRC has long been considered a plausible approach for the population and individuals at high risk for developing this disease. A significant effort has been made in the development of novel drugs for both prevention and treatment over the past two decades. This review highlights recent advances in our understanding of the role of nonsteroidal anti-inflammatory drugs in CRC prevention and adjuvant treatment. Moreover, we focus on the molecular mechanisms underlying the antitumor effects of these drugs in CRC. The knowledge of how anti-inflammatory agents inhibit cancer formation and progression may provide a rationale for the development of more effective chemopreventive and chemotherapeutic agents with less toxicity. PMID:23020877

Wang, Dingzhi; DuBois, Raymond N



Gastroscopic evaluation of anti-inflammatory agents*  

PubMed Central

Gastroscopy was performed in 164 patients with rheumatoid arthritis (RA) and 85 with osteoarthritis (OA) to assess the effects of anti-inflammatory agents on the stomach. The main criterion for entry into the trial was the absence of active gastric lesions on pretreatment endoscopy. The patients were divided into groups to receive one of 12 anti-inflammatory drugs or combinations of these. Gastroscopy repeated at three to six and at 12 months disclosed gastric lesions in 78 cases (31%), patients in both disease categories being similarly affected. Lesions occurred in 41 of the 177 patients (23%) receiving a single drug and in 37 of the 72 (51%) receiving combined treatment. All the anti-inflammatory drugs caused gastric damage, the greatest offender being aspirin (13 out of 26 patients) and the least sulindac and diflunisal (two out of 19 (11%) and two out of 20 (10%) patients respectively). Corticosteroids caused gastric damage in only three out of 21 patients (14%), a lower incidence than expected. The indiscriminate prescribing of anti-inflammatory drugs to patients with OA is to be deplored. A lack of correlation between the patients' subjective complaints of gastric discomfort and the gastroscopic findings emphasises the unreliability of patients' complaints and the importance of gastroscopy in assessing gastric tolerance. It was not possible to assess minimal prescribing doses or minimum periods of treatment below which gastric damage may be guaranteed not to occur. ImagesFIG 1

Caruso, I; Porro, G Bianchi



Increased gastric juice epidermal growth factor after non-steroidal anti-inflammatory drug ingestion  

Microsoft Academic Search

Epidermal growth factor (EGF), present in saliva and gastric juice, is a potent mitogen and an important element of mucosal defence. Changes in salivary and gastric juice epidermal growth factor in response to non-steroidal anti-inflammatory drug (NSAIDs) ingestion were measured to assess the role of EGF in gastric mucosal adaptation to NSAIDs. Patients with arthritis underwent endoscopy with collection of

S M Kelly; J R Jenner; R J Dickinson; J O Hunter



Anti-inflammatory activities of selected synthetic homoisoflavanones.  


Four homoisoflavanones of the 3-benzylidene-4-chromanone type, some of which were previously isolated from Caesalpinia pulcherrima, were synthesised to determine their anti-inflammatory activity and cytotoxicity. A range of four different homoisoflavanones (compounds 4a-4d) were synthesised from the corresponding substituted phenols. ¹H- and ¹³C-NMR data together with high-resolution mass spectroscopy data were employed to elucidate the structures. Anti-inflammatory activity was determined in mice with acute croton oil-induced auricular dermatitis. In vitro cytotoxicity was tested against a Chinese hamster ovarian cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Compound 4a exhibited a tendency to inhibit oedema in a dose-dependent manner after 3 and 6 h of treatment. Compounds 4b-4d also inhibited oedema, although a clear dose-response relationship was not observed. Compounds 4a-4c were found to be less cytotoxic than compound 4d. Compound 4b was the least cytotoxic. Compounds 4a-4d exhibited anti-inflammatory activity and varying levels of cytotoxicity. PMID:21950651

Shaikh, Mahidansha M; Kruger, Hendrik G; Bodenstein, Johannes; Smith, Peter; du Toit, Karen



Anti-Inflammatory Activities of Natural Products Isolated from Soft Corals of Taiwan between 2008 and 2012.  


This review reports details on the natural products isolated from Taiwan soft corals during the period 2008-2012 focusing on their in vitro and/or in vivo anti-inflammatory activities. Chemical structures, names, and literature references are also reported. This review provides useful and specific information on potent anti-inflammatory marine metabolites for future development of immune-modulatory therapeutics. PMID:24152566

Wei, Wen-Chi; Sung, Ping-Jyun; Duh, Chang-Yih; Chen, Bo-Wei; Sheu, Jyh-Horng; Yang, Ning-Sun



Highly potent aminopyridines as Syk kinase inhibitors.  


A novel class of potent Syk inhibitors has been developed from rational design. Highly potent aminopyridine derivatives bearing a 4-trifluoromethyl-2-pyridyl motif and represented by compound 13b IC(50): 0.6 nM were identified. Substitution by a 2-pyrazinyl motif and SAR expansion in position 4 of the central core provided diverse potent non-cytotoxic Syk inhibitors showing nanomolar activity inhibiting human mast cell line LAD2 degranulation. PMID:22877633

Castillo, Marcos; Forns, Pilar; Erra, Montse; Mir, Marta; López, Manel; Maldonado, Mónica; Orellana, Adelina; Carreño, Cristina; Ramis, Isabel; Miralpeix, Montserrat; Vidal, Bernat



Synthesis of some novel chalcones, flavanones and flavones and evaluation of their anti-inflammatory activity.  


A novel series of synthetic 2'-hydroxychalcones (1a-h), 2'-methoxychalcones (2a-l), flavanones (3a-k) and flavones (4a-f) have been synthesized and evaluated for their anti-inflammatory activity in carrageenan induced rat paw oedema model. Compounds 1a, 1e-g, 2e-g, 3j, and 4f showed potent anti-inflammatory activity comparable to the reference drug indomethacin with insignificant ulceration. Compound 1f showed mild inhibition against the enzymatic activity of ovine COX-1 and COX-2 (in-vitro). Compound 1f also exhibited inhibitory activity in LPS induced TNF-? production. PMID:23693150

Bano, Sameena; Javed, Kalim; Ahmad, Shamim; Rathish, I G; Singh, Surender; Chaitanya, M; Arunasree, K M; Alam, M S



Topical anti-inflammatory constituents of lipophilic leaf fractions of Alchornea floribunda and Alchornea cordifolia  

Microsoft Academic Search

The leaves of Alchornea floribunda and Alchornea cordifolia are used traditionally as topical anti-inflammatory agents. In this study, two highly lipophilic fractions AFLF and ACLF isolated from A. floribunda and A. cordifolia leaves respectively were investigated for topical anti-inflammatory effects using xylene-induced mice ear oedema as a model of inflammation. AFLF and ACLF at 5?mg per ear showed significant (p?

F. B. C. Okoye; P. O. Osadebe; C. S. Nworu; N. N. Okoye; E. O. Omeje; C. O. Esimone



Structure and function of papiliocin with antimicrobial and anti-inflammatory activities isolated from the swallowtail butterfly, Papilio xuthus.  


Papiliocin is a novel 37-residue cecropin-like peptide isolated recently from the swallowtail butterfly, Papilio xuthus. With the aim of identifying a potent antimicrobial peptide, we tested papiliocin in a variety of biological and biophysical assays, demonstrating that the peptide possesses very low cytotoxicity against mammalian cells and high bacterial cell selectivity, particularly against Gram-negative bacteria as well as high anti-inflammatory activity. Using LPS-stimulated macrophage RAW264.7 cells, we found that papiliocin exerted its anti-inflammatory activities by inhibiting nitric oxide (NO) production and secretion of tumor necrosis factor (TNF)-? and macrophage inflammatory protein (MIP)-2, producing effects comparable with those of the antimicrobial peptide LL-37. We also showed that the innate defense response mechanisms engaged by papiliocin involve Toll-like receptor pathways that culminate in the nuclear translocation of NF-?B. Fluorescent dye leakage experiments showed that papiliocin targets the bacterial cell membrane. To understand structure-activity relationships, we determined the three-dimensional structure of papiliocin in 300 mm dodecylphosphocholine micelles by NMR spectroscopy, showing that papiliocin has an ?-helical structure from Lys(3) to Lys(21) and from Ala(25) to Val(36), linked by a hinge region. Interactions between the papiliocin and LPS studied using tryptophan blue-shift data, and saturation transfer difference-NMR experiments revealed that Trp(2) and Phe(5) at the N-terminal helix play an important role in attracting papiliocin to the cell membrane of Gram-negative bacteria. In conclusion, we have demonstrated that papiliocin is a potent peptide antibiotic with both anti-inflammatory and antibacterial activities, and we have laid the groundwork for future studies of its mechanism of action. PMID:21965682

Kim, Jin-Kyoung; Lee, Eunjung; Shin, Soyoung; Jeong, Ki-woong; Lee, Jee-Young; Bae, Su-Young; Kim, Soo-Hyun; Lee, Juneyoung; Kim, Seong Ryul; Lee, Dong Gun; Hwang, Jae-Sam; Kim, Yangmee



Antioxidant, anti-inflammatory, and antiproliferative activities of Taxillus sutchuenensis.  


Inflammation is related to several chronic diseases, including cancer and atherosclerosis. Taxillus sutchuenensis (Lecomte) Danser is a special folk medicinal plant in Taiwan. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antiproliferative activities of the aqueous-thanol extract from T. sutchuenensis (AETS) and its fractions. TEAC, DPPH radicals, total phenolic compounds, total flavonoid content, inhibition of NO production in LPS-induced RAW264.7 cells, and inhibition of cancer cell proliferation were tested. Among all fractions, the ethyl-acetate (EA) fraction showed the highest TEAC and DPPH radical scavenging activities. The EA fraction also had the highest polyphenol and flavonoid content. The EA fractions also decreased LPS-induced NO production and the expression of iNOS and COX-2 in RAW264.7 cells. The antiproliferative activities of the aqueous/ethanol extract and fractions were studied in vitro using A549 cells, and the results were consistent with their antioxidant capacities. EA fractions had the highest antiproliferative activity with an IC(50) of 454.38 ± 1.48 ?g/ml. Quercetin also had antioxidant, anti-inflammatory, and antiproliferative activities. Quercetin might be an important bioactive compound in T. sutchuenensis. The experimental data indicated that T. sutchuenensis is a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds. PMID:22419427

Liu, Chia-Yu; Lin, Ying-Chih; Deng, Jeng-Shyan; Liao, Jung-Chun; Peng, Wen-Huang; Huang, Guan-Jhong



Molecular Targets of Dietary Polyphenols with Anti-inflammatory Properties  

PubMed Central

There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process.

Yoon, Joo-Heon



Evaluation of marine brown algae Sargassum ilicifolium extract for analgesic and anti-inflammatory activity  

PubMed Central

Background: The methanolic extract of Sargassum ilicifolium (Pheophyceae) was used to evaluate its analgesic and anti-inflammatory activity in the present study. Materials and Methods: Analgesic activity was tested using Acetic acid writhing method and Eddy hot plate method in Male albino mice and Wister rats respectively at a dose level of 1, 10, 50, 100mg/kg p.o. At the same dose, its anti-inflammatory activity was also tested using Carrageenan induced rat paw edema method Result Acetic acid writhing test and Eddy's hot plate episodes were significantly and dose dependently reduced. Carrageenan (a standard inflammatory agent) induced paw edema in rats was significantly reduced after intraperitonal administration of methanolic extract. Results: showed dose dependant significant activity in comparison with standard and control. Conclusion: Methanolic extracts of the brown seaweeds Sargassum ilicifolium have potent analgesic and anti-inflammatory activity at moderate doses.

Simpi, Chandraraj C.; Nagathan, Channabasappa V.; Karajgi, Santosh R.; Kalyane, Navanath V.



Anti-inflammatory principles from Cordyceps sinensis.  


In order to explore the anti-inflammatory principles of the mycelia of Cordyceps sinensis, the crude extract and partially purified fractions were examined for their inhibition of superoxide anion generation and elastase release. Further chemical investigation of the bioactive fractions has resulted in the identification of 50 compounds, including five constituents, cordysinins A-E (1-5), reported from a natural source for the first time. In addition, compounds were examined for their anti-inflammatory activity. 1-(5-Hydroxymethyl-2-furyl)-?-carboline displayed the most significant inhibition of superoxide anion generation and elastase release with IC50 values of 0.45±0.15 and 1.68±0.32 ?M, respectively. PMID:21848266

Yang, Mei-Lin; Kuo, Ping-Chung; Hwang, Tsong-Long; Wu, Tian-Shung



Anti-inflammatory activity of cassia aauriculata.  


Cassia auriculata is widely distributed even in poor soil in Sri Lanka, India, Burma and cultivated in tropics. Based on Physical and Chemical methods, the flower of C. auriculata was found to contain a flavonol glycoside 5-O-methylquercetin 7-O-glucoside. The 50% acetone extract of the flower of C. auriculata showed marked anti-inflammatory activity (56%) in carrageenin induced oedema in rats. PMID:22557154

Manogaran, S; Sulochana, N




PubMed Central

Cassia auriculata is widely distributed even in poor soil in Sri Lanka, India, Burma and cultivated in tropics. Based on Physical and Chemical methods, the flower of C. auriculata was found to contain a flavonol glycoside 5-O-methylquercetin 7-O-glucoside. The 50% acetone extract of the flower of C. auriculata showed marked anti-inflammatory activity (56%) in carrageenin induced oedema in rats.

Manogaran, S.; Sulochana, N.



Non-steroidal anti-inflammatory drugs  

Microsoft Academic Search

The discovery and commercialization of asprin over 100 years ago, and the introduction of other non-steroidal anti-inflammatory\\u000a drugs (NSAIDs) have had a profound impact on the practice of medicine and the treatment of the inflammatory conditions. Widespread\\u000a access and over-the-counter availability of these agents has lead to the impression that these drugs are safe and relatively\\u000a void of toxicity. NSAID

Ali J. Olyaei; Andrew Whelton; Til Sturmer; George A. Porter


Anti-inflammatory bioactivities in plant extracts.  


The medical ethnobotanical knowledge propagated over generations in the coastal regions of the Eastern Mediterranean, including Lebanon, is one that has built on several ancient cultures and civilizations of these regions. Recent interest in medical ethnobotany and the use of medicinal herbs in treating or preventing ailments has rejuvenated interest in folk medicine practices, especially those transcendent across generations. According to Eastern Mediterranean folk medicine practices, herbal remedies that treat many inflammation-related ailments were typically based on plant bioactive water extracts or decoctions. Studies have shown that active anti-inflammatory ingredients in water extracts include many natural chemicals such as phenols, alkaloids, glycosides, and carbohydrates. The intent of this manuscript is twofold: first, to review the literature that describes anti-inflammatory bioactivities in plant extracts of different plant genera; and second, to evaluate indigenous folk remedies used by folk doctors to treat inflammatory ailments in this region of the world. For this aim, the reported literature of five plant genera assumed to possess anti-inflammatory bioactivities and typically prescribed by folk doctors to treat inflammation-related ailments is reviewed. PMID:17472460

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



Anti-inflammatory phloroglucinol derivatives from Hypericum empetrifolium  

PubMed Central

Phytochemical investigation of Hypericum empetrifolium Willd. (Clusiaceae), a species native to Greece and Turkey has led to the bioassay-guided identification of two acylphloroglucinol derivatives with potent in vitro anti-inflammatory activity. Using NMR spectroscopy and mass spectrometry, the acylphloroglucinol derivatives were characterized as 3-geranyl-1-(2?-methylpropanoyl)phloroglucinol (1) and 3-geranyl-1-(2?-methylbutanoyl)phloroglucinol (2). Hypotheses are proposed regarding the biosynthetic origin of these and similar acylphloroglucinols from related Hypericum species. Compounds 1 and 2 were evaluated for in vitro inhibitory activity against COX-1, COX-2 and 5-LOX catalyzed LTB4 formation. Compound 1 displayed good activity (IC50 values: 6.0, 29.9, and 2.2 ?M, respectively) in all three assays. Compound 2 showed good activity (IC50 value: 5.8 ?M) against LTB4 formation and moderate activity (IC50 value: 26.2 ?M) against COX-1.

Crockett, Sara L.; Wenzig, Eva-Maria; Kunert, Olaf; Bauer, Rudolf



Erdosteine: antitussive and anti-inflammatory effects.  


Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on lipoperoxidation (8-isoprostane) proved discriminant between treatments, with antioxidant and anti-inflammatory effects the main determinants of the erdosteine multifactorial properties. In addition, antitussive effects may be regarded as related to its anti-inflammatory properties via the improvement of mucociliary clearance and the reduction of chemokines from epithelial cells. Finally, a sort of "sensitization" of 2-adrenoceptors can also be speculated due to the same mechanisms of action; if confirmed by further controlled studies, this particular property would suggest a novel therapeutic role of erdosteine in COPD. PMID:18185958

Dal Negro, Roberto W



Novel N-phenylcarbamothioylbenzamides with anti-inflammatory activity and prostaglandin E2 inhibitory properties  

PubMed Central

A number of 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl) benzamides (1a–h) were synthesized via reaction of 2-((4-ethylphenoxy)methyl)benzoyl isothiocyanate (2) as a key intermediate with several substituted primary aromatic amines. The new compounds were characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), infrared spectrometry (IR), mass spectrometry (MS), and elemental analysis. The anti-inflammatory activity of 1a–h was investigated by acute carrageenan-induced paw edema in mice using the reference drug indomethacin. The results obtained indicated that, of the derivatives developed, 1a and 1d–h exhibited significantly higher anti-inflammatory activity (26.81%–61.45%) when compared with the reference drug indomethacin (22.43%) (P = 0.0490 for 1a, 0.0015 for 1d, 0.0330 for 1f, and P < 0.001 for 1e and 1h). Moreover, the ulcer incidence of 20% for 1e and 1h was clearly lower when compared with the indomethacin group (in which the ulcer incidence was 80%). Of particular note, the ulcer index of 0.2 for 1e was significantly less than that in the indomethacin group (0.6, P = 0.014). Additionally, prostaglandin E2 (PGE2) inhibitory properties were found to be high with 1e (68.32 pg/mL), significantly different from those of the placebo group (530.13 pg/mL, P < 0.001), and equipotent to the effect observed in the indomethacin-pretreated group (96.13 pg/mL, P > 0.05). Moreover, the PGE2 level of 54.15 pg/mL with 1h was also significantly different from that of the placebo group (P < 0.001) and of the indomethacin group (P < 0.05). The significant inhibition of PGE2 observed with 1e (68.32 pg/mL) and 1h (54.15 pg/mL) agree with their observed ulcer incidences. Our overall findings for N-phenylcarbamothioylbenzamides 1a–h clearly suggest that the compounds exhibit an anti-inflammatory effect, potently inhibit PGE2 synthesis, and markedly demonstrate low ulcer incidence.

Limban, Carmen; Missir, Alexandru Vasile; Fahelelbom, Khairi Mustafa Salem; Al-Tabakha, Moawia Mohammad; Caproiu, Miron Teodor; Sadek, Bassem



Novel N-phenylcarbamothioylbenzamides with anti-inflammatory activity and prostaglandin E2 inhibitory properties.  


A number of 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl) benzamides (1a-h) were synthesized via reaction of 2-((4-ethylphenoxy)methyl)benzoyl isothiocyanate (2) as a key intermediate with several substituted primary aromatic amines. The new compounds were characterized by proton nuclear magnetic resonance ((1)H-NMR), carbon-13 nuclear magnetic resonance ((13)C-NMR), infrared spectrometry (IR), mass spectrometry (MS), and elemental analysis. The anti-inflammatory activity of 1a-h was investigated by acute carrageenan-induced paw edema in mice using the reference drug indomethacin. The results obtained indicated that, of the derivatives developed, 1a and 1d-h exhibited significantly higher anti-inflammatory activity (26.81%-61.45%) when compared with the reference drug indomethacin (22.43%) (P = 0.0490 for 1a, 0.0015 for 1d, 0.0330 for 1f, and P < 0.001 for 1e and 1h). Moreover, the ulcer incidence of 20% for 1e and 1h was clearly lower when compared with the indomethacin group (in which the ulcer incidence was 80%). Of particular note, the ulcer index of 0.2 for 1e was significantly less than that in the indomethacin group (0.6, P = 0.014). Additionally, prostaglandin E2 (PGE2) inhibitory properties were found to be high with 1e (68.32 pg/mL), significantly different from those of the placebo group (530.13 pg/mL, P < 0.001), and equipotent to the effect observed in the indomethacin-pretreated group (96.13 pg/mL, P > 0.05). Moreover, the PGE2 level of 54.15 pg/mL with 1h was also significantly different from that of the placebo group (P < 0.001) and of the indomethacin group (P < 0.05). The significant inhibition of PGE2 observed with 1e (68.32 pg/mL) and 1h (54.15 pg/mL) agree with their observed ulcer incidences. Our overall findings for N-phenylcarbamothioylbenzamides 1a-h clearly suggest that the compounds exhibit an anti-inflammatory effect, potently inhibit PGE2 synthesis, and markedly demonstrate low ulcer incidence. PMID:24039398

Limban, Carmen; Missir, Alexandru Vasile; Fahelelbom, Khairi Mustafa Salem; Al-Tabakha, Moawia Mohammad; Caproiu, Miron Teodor; Sadek, Bassem



An online coupled peritoneal macrophage/cell membrane chromatography and high-performance liquid chromatography/mass spectrometry method to screen for anti-inflammatory components from the Chinese traditional medicine Chloranthus multistachys Pei.  


Cell membrane chromatography (CMC) is a chromatographic biological affinity method that uses specific cell membranes as the stationary phase. In this study, a novel peritoneal macrophage/cell membrane chromatography (PM/CMC)-online-high performance liquid chromatography/mass spectrometry (HPLC/MS) method was established to screen for the anti-inflammatory components from traditional Chinese medicines using hydrocortisone and dexamethasone as standards. The stationary phase of the CMC employed mouse peritoneal macrophage cell membranes. This method was applied to the purification and identification of components in extracts of Chloranthus multistachys Pei. The major component retained by CMC was identified as isofraxidin by HPLC/MS. In vitro experiments revealed that IF was able to inhibit the production of nitric oxide and tumor necrosis factor-? in lipopolysaccharide-stimulated mice and peritoneal macrophages in a dose-dependent manner. The results demonstrated that the PM/CMC-online-HPLC/MS is an effective screening system for the rapid detection, enrichment, and identification of target components from complex samples. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23760986

Li, Weifeng; Xing, Wei; Wang, Sicen; Fan, Ting; Huang, Huimin; Niu, Xiaofeng; He, Langchong



Anti-inflammatory and antinociceptive activities of indole-imidazolidine derivatives.  


Non-steroidal anti-inflammatory drugs (NSAIDs) represent a group of approximately 50 different medicines that are widely prescribed for the management of inflammation and that exhibit variable anti-inflammatory, anti-pyretic and analgesic activities. Most NSAIDs also exhibit a shared set of adverse effects, particularly related to gastrointestinal complications; thus, the development of new drugs for the treatment of chronic inflammation and pain continues to be an issue of high interest. Hydantoin and indole derivatives are reported to possess various pharmacological effects, including anti-inflammatory and analgesic activities. Therefore, the aim of this study was to evaluate the potential anti-inflammatory and antinociceptive activities of hybrid molecules containing imidazole and indole nuclei. The anti-inflammatory activities of 5-(1H-Indol-3-yl-methylene)-2-thioxo-imidazolidin-4-one (LPSF/NN-56) and 3-(4-Bromo-benzyl)-5-(1H-indol-3-yl-methylene)-2thioxo-imidazolidin-4-one (LPSF/NN-52) were evaluated using air pouch and carrageenan-induced peritonitis models as well as an acetic acid-induced vascular permeability model followed by IL-1? and TNF-? quantification. To evaluate the antinociceptive activities of the compounds, acetic acid-induced nociception, formalin and hot plate tests were also performed. The anti-inflammatory activities of the compounds were evidenced by a reduction in both leukocyte migration and the release of TNF-? and IL-1? in air pouch and peritonitis models. Upon acetic acid-induced nociception, a decrease in the level of abdominal writhing in the groups treated with LPSF/NN-52 (52.1%) or LPSF/NN-56 (63.1%) was observed. However, in the hot plate test, none of the derivatives tested exhibited an inhibition of nociception. These results indicate that the compounds tested exhibited promising anti-inflammatory and antinociceptive activities that likely involved the modulation of the immune system. PMID:21855654

Guerra, Aline Stamford Henrique da Silva; Malta, Diana Jussara do Nascimento; Laranjeira, Luana Priscilla Morais; Maia, Maria Bernadete Souza; Colaço, Nathália Cavalcanti; de Lima, Maria do Carmo Alves; Galdino, Suely Lins; Pitta, Ivan da Rocha; Gonçalves-Silva, Teresinha



Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity  

PubMed Central

Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 µg ml?1 mPE was sufficient to inhibit interleukin-1?-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-?B, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues.

Hua, J; Scott, R.W.; Diamond, G



Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity.  


Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 ?g ml(-1) mPE was sufficient to inhibit interleukin-1?-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-?B, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues. PMID:21040516

Hua, J; Scott, R W; Diamond, G



Evaluation of the anti-inflammatory and analgesic activities of Liu-Shen-Wan and its individual fractions.  


Liu-Shen-Wan (LSW), a famous traditional Chinese medicine for treatment of upper respiratory tract inflammation, was evaluated for its anti-inflammatory and analgesic activities. Acetic acid-elevated vascular permeability, carboxymethylcellulose sodium (CMC-Na)-induced leukocyte migration and ear edema induced by picryl chloride were used to test anti-inflammatory activity. Moreover, acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. It was observed that LSW exerted significant anti-inflammatory and analgesic activities in these models at doses of 30 and 90mg/kg crude drug in vivo. In addition, LSW potently inhibited proliferation of human peripheral blood mononuclear cell (PBMC) stimulated by streptococcal pyrogenic exotoxin at doses of 0.5-5microg/ml in vitro. LSW was then partitioned with chloroform, methanol, water and mineral fraction. Several fractions inhibited inflammation and pain in varying degrees. Among them, chloroform fraction was the most active in hot-plate and writhing tests, and exerted the remarkable inhibitory effect on human PBMC proliferation. Methanol and water fractions had more suppressive activities in vascular permeability, leukocyte migration and PC-DTH tests. These results suggest that LSW has significantly anti-inflammatory and analgesic activities. The chloroform fraction is a key fraction of LSW to the overall anti-inflammatory and analgesic effects, while methanol and water fractions also partly contribute to anti-inflammatory activities of LSW. PMID:17368990

Ma, Hong-Yue; Kou, Jun-Ping; Wang, Jing-Rong; Yu, Bo-Yang



Anti-inflammatory property of 401 (MCD-peptide), a peptide from the venom of the bee Apis mellifera (L.)  

PubMed Central

1 Peptide 401, a potent mast cell degranulating factor from bee venom, substantially inhibited the oedema provoked by subplantar injection of carrageenin or intra-articular injection of turpentine in the rat. The ED50 of 401 was c. 0.1 mg/kg. The anti-inflammatory effect was assessed by measurement of the increased 125I-albumin content of an injected site in comparison with an uninjected contralateral site. 2 Peptide 401 also suppressed the increased vascular permeability due to intradermal injection of various smooth muscle spasmogens (histamine, bradykinin, 5-hydroxytryptamine (5-HT), and prostaglandins). 3 Other comparable mast cell degranulating agents (48/80 and melittin) showed little evidence of anti-inflammatory activity when tested at comparable dosage on turpentine arthritis and carrageenin oedema. 4 The anti-inflammatory effects were not abolished by pretreatment with mepyramine and methysergide, which abolished the increased vascular permeability produced by local injection of 401. 5 The anti-inflammatory action of 401 was not affected by regional denervation or pretreatment with phenoxybenzamine, and was reduced but not abolished by adrenalectomy. 6 Measurement of skin temperature, fractional extraction of 86Rb and blood flow in perfused mesentery gave no evidence that the anti-inflammatory action of 401 was due to reduced tissue perfusion. 7 It is concluded that 401 may exert its anti-inflammatory action directly by making the vascular endothelium anergic to phlogistic stimuli.

Hanson, Jennifer M.; Morley, J.; Soria-Herrera, C.



Lyprinol—is it a Useful Anti-inflammatory Agent?  

Microsoft Academic Search

The New Zealand green lipped mussel preparation Lyprinol is available without a prescription from a supermarket, pharmacy or Web. The Food and Drug Administration have recently warned Lyprinol USA about their extravagant anti-inflammatory claims for Lyprinol appearing on the web. These claims are put to thorough review. Lyprinol does have anti-inflammatory mechanisms, and has anti-inflammatory effects in some animal models

Sheila A. Doggrell


Evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities of ethanolic extract of Ammi majus seeds in albino rats and mice.  


Pharmacological and biochemical studies on the Ammi majus seeds L. (family Umbelliferae) grown in Egypt are limited. Furocoumarins are the major constituents in the plant seeds. In the present study, the evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities on albino rats and mice was done. After 2 months of administration, both the doses (50 and 100 mg/kg body weight [bwt], respectively) of the alcoholic extract of the A. majus seed result in a significant decrease in the concentrations of cholesterol, triglycerides, and low-density lipoprotein and increase in the concentration of high-density lipoprotein. The extract was found to inhibit the rat paw edema at both the doses, which means that it exerts a significant anti-inflammatory activity compared with control-untreated groups at the intervals of 30 and 60 minutes posttreatment. The antipyretic effect of the extract was quite obvious; it showed that 100 mg/kg bwt was more potent in lowering body temperature starting after 1 hour of treatment than the lower dose (50 mg/kg bwt). It is worth to mention that the A. majus extract with its coumarin contents as well as the tested biological activities of the plant was investigated for the first time in the current study. In conclusion, ethanolic extract of the A. majus seeds had antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities that are dose dependant. PMID:22550046

Koriem, Khaled M M; Asaad, Gihan F; Megahed, Hoda A; Zahran, Hanan; Arbid, Mahmoud S



Anti-inflammatory, antipyretic, and analgesic effects of Lawsonia inermis L. (henna) in rats.  


Crude ethanolic extract of Lawsonia inermis L. (0.25-2.0 g/kg) produced significant and dose-dependent anti-inflammatory, analgesic, and antipyretic effects in rats. The extract also produced significant increases in pentobarbitone-induced sleeping time. Using a liquid-liquid extraction procedure, the extract was fractionated into chloroform, butanol, and water fractions, and these were tested for the above activities. The butanol and chloroform fractions showed more potent anti-inflammatory, analgesic, and antipyretic effects than the crude extracts, while the aqueous extract showed significantly less effect. As compared with the other extracts, the butanolic extract (500 mg/kg) was the most effective in the analgesic test. From the chloroform extract, a pure compound was isolated and identified, using chromatographic and spectroscopic techniques, as 2-hydroxy-1,4-naphthaquinone (lawsone). The isolated compound was found to possess significant anti-inflammatory, analgesic, and antipyretic activity. It potentiated significantly the pentobarbitone-induced sleeping time. The anti-inflammatory effect of lawsone (500 mg/kg) was not significantly different from that of the reference drug phenylbutazone (100 mg/kg). PMID:8966192

Ali, B H; Bashir, A K; Tanira, M O



Anti-inflammatory and antimicrobial properties of pyrroloquinazoline alkaloids from Adhatoda vasica Nees.  


Adhatoda vasica Nees, Acanthaceae, is well known plant in Ayurveda and Unani medicine. The purpose of this study was to characterize the most bioactive phytochemicals viz., vasicine, vasicinone, vasicine acetate, 2-acetyl benzyl amine, vasicinolone present in the chloroform fraction having anti-inflammatory and antimicrobial activities. The anti-inflammatory activity was tested by using carrageenan and CFA-model induced paw oedema. The antimicrobial activity of isolated compounds was assessed by using the microdilution method. The observed results revealed that vasicine showed most potent anti-inflammatory effects (59.51%) at the dose of 20.0mg/kg at 6h after carrageenan injection and maximum inhibition rate was observed of vasicinone (63.94%) at the dose of 10.0mg/kg at 4 days after CFA injection. The strong antibacterial activity was exhibited by vasicine at 20?g/ml dose against E. coli and also demonstrated maximum antifungal activity against C. albicans at the dose of >55?g/ml. All the five alkaloids demonstrated significant anti-inflammatory and antimicrobial activities. PMID:23357363

Singh, Bharat; Sharma, Ram Avtar



Antimicrobial and anti-inflammatory activities of leaf extract of Valeriana wallichii DC.  


Valeriana wallichii DC (Valerianaceae) is one of the most widely used traditional remedies for various complications associated with nervous system and digestion. No antimicrobial and anti-inflammatory studies have so far been carried out on the aerial parts of the plant. The present work was focused to evaluate the antimicrobial (antifungal and antibacterial) and anti-inflammatory properties of V. wallichii using reported methods. Chloroform fraction (VW-2) and hexane fraction (VW-3) exhibited significant activity against S. aureus and B. subtilus, respectively. The chloroform fraction (VW-2) showed significant activity against S. aureus with 0.27 mg/ml MIC, where 0.31 mg/ml MIC was deduced for VW-3 fraction against B. subtilus. VW-3 fraction was also found to be the most potent inhibitor of M. canis, showing 70% inhibition with an MIC value of 0.19 mg/ml. Considerable inhibitory activity was also observed for VW-2 and water fraction (VW-6) against M. canis and A. flavus. A remarkable anti-inflammatory like activity was observed for the crude extract at a dose of 200 mg/kg at all observed durations. Other doses of the sample also showed excellent activity. Looking to these results it may be concluded that V. wallichii may be a potential source for activity guided isolation of natural products with antimicrobial and anti-inflammatory-like properties. PMID:23009985

Khuda, Fazli; Iqbal, Zafar; Zakiullah; Khan, Ayub; Nasir, Fazli



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

PubMed Central

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.

Buret, Andre G.



Amentoflavone, a plant biflavone: A new potential anti-inflammatory agent  

Microsoft Academic Search

Biflavonoid is one of unique classes of naturally-occurring bioflavonoids. Certain biflavonoids including amentoflavone were\\u000a previously reported to have inhibitory effect on the group II phospholipase A2 activity. Amentoflavone was also found to inhibit cyclooxygenase from guinea-pig epidermis without affecting lipoxygenase.\\u000a In this study, anti-inflammatory and analgesic activities of amentoflavone were evaluated. When amentoflavone was administered\\u000a intraperitoneally, it showed a potent

Hee Kee Kim; Kun Ho Son; Hyeun Wook Chang; Sam Sik Kang; Hyun Pyo Kim



Nuclear Factor kappa B Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms  

Microsoft Academic Search

Sulforaphane (SFN), an aliphatic isothiocyanate, is a known cancer chemopreventive agent. Aiming to inves- tigate anti-inflammatory mechanisms of SFN, we here report a potent decrease in lipopolysaccharide (LPS)- induced secretion of pro-inflammatory and pro-carcino- genic signaling factors in cultured Raw 264.7 macro- phages after SFN treatment, i.e. NO, prostaglandin E2, and tumor necrosis factor . SFN did not directly inter-

Elke Heiss; Christian Herhaus; Karin Klimo; Helmut Bartsch; Clarissa Gerhauser



The anti-inflammatory non-antibiotic helper compound diclofenac: an antibacterial drug target  

Microsoft Academic Search

Diclofenac sodium (Dc) was found to possess antibacterial activity against both drug-sensitive and drug-resistant clinical\\u000a isolates of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Mycobacterium spp., in addition to its potent anti-inflammatory activity. The time-kill curve study indicates that this non-steroidal drug\\u000a exhibits bactericidal activity against Listeria, E. coli, and M. tuberculosis. The antibacterial activity of Dc comes, in part,

K. Mazumdar; S. G. Dastidar; J. H. Park; N. K. Dutta



Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents  

Microsoft Academic Search

PROSTAGLANDINSand glucocorticoids are potent mediators of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibition of prostaglandin production. The pharmacological target of NSAIDs is cyclooxygenase (COX, also known as PGH synthase), which catalyses the first committed step in arachidonic-acid metabolism1,2. Two isoforms of the membrane protein COX are known3: COX-1, which is constitu-tively expressed in most tissues, is responsible

Ravi G. Kurumbail; Anna M. Stevens; James K. Gierse; Joseph J. McDonald; Roderick A. Stegeman; Jina Y. Pak; Daniel Gildehaus; Julie M. Iyashiro; Thomas D. Penning; Karen Seibert; Peter C. Isakson; William C. Stallings



High-performance liquid chromatography analysis of anti-inflammatory pharmaceuticals with ultraviolet and electrospray-mass spectrometry detection in suspected counterfeit homeopathic medicinal products  

Microsoft Academic Search

A simple high-performance liquid chromatography (HPLC) method with both ultraviolet (UV) and electrospray ionisation mass spectrometry (ESI-MS) detection has been developed for the determination of seven pharmaceuticals in counterfeit homeopathic preparations. Naproxen, Ketoprofen, Ibuprofen, Diclofenac, Piroxicam, Nimesulide and Paracetamol were separated by reversed phase chromatography with acetonitrile–water (0.1% acetic acid) mobile phase, and detected by UV at 245nm and by

Alessia Panusa; Giuseppina Multari; Giampaolo Incarnato; Luigi Gagliardi



Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries  

PubMed Central

Background Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries. Methods and Findings Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7–58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%. Conclusions Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs. Please see later in the article for the Editors' Summary

McGettigan, Patricia; Henry, David



Corneal reepithelialization and anti-inflammatory agents.  

PubMed Central

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

Srinivasan, B D



Corneal reepithelialization and anti-inflammatory agents.  


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

Srinivasan, B D



Toxicity of non-steroidal anti-inflammatory drugs: a review of melatonin and diclofenac sodium association.  


Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the purpose of anti-inflammation, antipyretic, and analgesia. For this aim, they are used for the alleviation of pain, fever, and inflammation associated with rheumatoid arthritis, sports injuries, and temporary pain. However, treatment with NSAIDs may be accompanied by adverse effects such as gastrointestinal damage and platelet dysfunction. As with the other NSAIDs, diclofenac sodium (sodium-(o-((2,6-dichlorophenyl)-amino)-phenyl)-acetate) (DS), an NSAID, has potent anti-inflammatory, analgesic, and antipyretic effects. However, treatment with DS may cause some adverse cerebral and cerebellar effects such as convulsions, disorientation, hallucination, and loss of consciousness. Melatonin (MLT) is a free-radical scavenger and possesses antioxidant properties. It has been reported to easily cross the blood-brain barrier, and is found in high concentrations in the brain after exogenous administration. It is also a neuroprotector in a wide range of conditions affecting the central nervous system CNS due to its free-radical scavenging activities and lipophilic-hydrophilic properties. Neuroprotective actions of MLT have been discovered in both in vitro and in vivo, and are a powerful scavenger of oxygen and nitrogen free radicals. Thus, MLT can protect the cell membrane, organelles, and core against free-radical damage. Therefore, it has been postulated that exogenous MLT acts as a neuroprotector contrary to DS neurotoxicity. In this review, we aimed to discuss the possible neuroprotective effects of MLT on DS toxicity. PMID:22374720

Aygün, D; Kaplan, S; Odaci, E; Onger, M E; Altunkaynak, M E



A mechanistic approach to the in vivo anti-inflammatory activity of sesquiterpenoid compounds isolated from Inula viscosa.  


The present study was designed to examine the anti-inflammatory activity of the sesquiterpenoids ilicic acid and inuviscolide, isolated from Inula viscosa, on cell degranulation, leukotriene biosynthesis, neurogenic drive and glucocorticoid-like interactions. Swiss female mice were used to measure the ear oedema induced by phorbol esters or ethyl phenylpropiolate (EPP), and the paw oedema induced by phospholipase A(2) (PLA(2)) or serotonin. Drug treatment consisted of one topically-applied dose in the ear models and a subcutaneous or intraperitoneal injection in the paw models. Quantitative analysis of leukotriene B(4) (LTB(4)) formation was performed on rat peritoneal neutrophils by high performance liquid chromatography (HPLC). The lactone inuviscolide reduced the PLA(2)-induced oedema (ID(50): 98 micromol/kg). The effect on serotonin-induced oedema was not changed by modifiers of the glucocorticoid response. Ilicic acid showed minor in vivo effects, but was slightly more potent than inuviscolide on the 12-O-tetradecanoylphorbol 13-acetate (TPA) acute oedema test (ID(50): 0.650 micromol per ear). Inuviscolide reduced LTB(4) generation in intact cells, with an IC(50) value of 94 microM. On the basis of the reported results, inuviscolide is the main anti-inflammatory sesquiterpenoid from Inula viscosa, and may act by interfering with leukotriene synthesis and PLA(2)-induced mastocyte release of inflammatory mediators. PMID:11731914

Hernández, V; del Carmen Recio, M; Máñez, S; Prieto, J M; Giner, R M; Ríos, J L



Fermentation improves anti-inflammatory effect of sipjeondaebotang on LPS-stimulated RAW 264.7 cells.  


Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E(2) and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-?, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-?B in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE(2), NO and TNF-? production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) MAPK phosphorylation as well as NF-?B p65 translocation by reduced I?B? degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-?B signaling in RAW 264.7 cells. PMID:22809034

Oh, You-Chang; Cho, Won-Kyung; Jeong, Yun Hee; Im, Ga Young; Yang, Min Cheol; Ma, Jin Yeul



In vitro evaluation of Lactobacillus crispatus K313 and K243: high-adhesion activity and anti-inflammatory effect on Salmonella braenderup infected intestinal epithelial cell.  


Currently, there is an increasing interest in the use of probiotics as an alternative strategy to antimicrobial compounds. In this study, two high adhesive strains Lactobacillus crispatus K313 adhering to HT-29 cells as well as Lb. crispatus K243 adhering to collagen type IV were isolated from chicken intestines. SDS-PAGE analysis revealed the presence of the potential S-proteins SlpA and SlpB in Lb. crispatus K243 and K313. SlpA and SlpB, rich in hydrophobic amino acids, were proved to be involved in adhering to collagen type IV and HT-29 cells, respectively, based on the LiCl treatment assay. After removal of S-proteins, the viability and tolerance of the two Lb. crispatus strains to simulated gastric and small intestinal juice were reduced, indicating the protective role of S-proteins against the hostile environments. Lb. crispatus K313 exhibited the stronger autoaggregation ability and inhibitive activity against Salmonella braenderup H9812 adhesion to HT-29 cells than the strain K243. To elucidate the inhibitive mechanism, cultured epithelial cells were exposed with Lb. crispatus strains, and followed by a challenge with S. braenderup H9812. The pro-inflammatory signaling factors (IL-8, CXCL1 and CCL20) from HT-29 were detected by real-time PCR technology. The results showed that both of Lb. crispatus strains down-regulated the transcription level of those pro-inflammatory genes induced by S. braenderup H9812 by 36.2-58.8%. ELISA analysis was further confirmed that Lb. crispatus K243 and K313 inhibited the IL-8 secretion triggered by S. braenderup H9812 by 32.8% and 47.0%, indicating that the two isolates could attenuate the pro-inflammatory signaling induced by S. braenderup H9812, and have the potential application in clinical practice to prevent diarrhea. PMID:22542524

Sun, Zhilan; Huang, Lihua; Kong, Jian; Hu, Shumin; Zhang, Xiaowei; Kong, Wentao



Evaluation of anti-inflammatory and anti oxidant activity of a poly herbal formulation - Chyavana drink  

PubMed Central

The study was designed to evaluate the anti-inflammatory and antioxidant activity of a poly herbal formulation-Chyavana drink. The inflammation was induced in albino rats by carrageenan. The formulation was effective when compared with a known anti-inflammatory drug. The antioxidant activity was studied by invitro methods. The DPPH radical scavenging activity was found to be showing higher percentage of inhibition and reducing power at high concentrations. The phenolic content of Chyavana drink was observed to be high showing a good antioxidant effect.

Poornima, K.; Thangal, Haseeb Koya; Karpagavalli, S.



The vagus nerve and the nicotinic anti-inflammatory pathway  

Microsoft Academic Search

Physiological anti-inflammatory mechanisms are selected by evolution to effectively control the immune system and can be exploited for the treatment of inflammatory disorders. Recent studies indicate that the vagus nerve (which is the longest of the cranial nerves and innervates most of the peripheral organs) can modulate the immune response and control inflammation through a 'nicotinic anti-inflammatory pathway' dependent on

Luis Ulloa



Anti-inflammatory activity of some Saudi Arabian medicinal plants  

Microsoft Academic Search

Five plants which have been used for the treatment of rheumatism, arthritis and gout in the traditional medicine of Saudi Arabia, were evaluated for their anti-inflammatory properties. Of these the ethanolic extract of Capparis decidua and the aqueous extract of Capparis spinosa were found to possess significant anti-inflammatory activity against carrageenan induced oedema in rats. These two plants were also

A. M. Ageel; N. S. Parmar; J. S. Mossa; M. A. Al-Yahya; M. S. Al-Said; M. Tariq



Anti-inflammatory Effect of Palmitoylethanolamide on Human Adipocytes  

Microsoft Academic Search

Obesity leads to the appearance of an inflammatory process, which can be initiated even with a moderate weight gain. Palmitoylethanolamide (PEA) is an endogenous lipid, secreted by human adipocytes, that possesses numerous anti-inflammatory properties. The main purpose of this study was to investigate the anti-inflammatory effect of PEA on human adipocytes, as well as in a murine model. The production

Laurence Hoareau; Marion Buyse; Franck Festy; Palaniyandi Ravanan; Marie-Paule Gonthier; Isabel Matias; Stefania Petrosino; Frank Tallet; Christian Lefebvre d'Hellencourt; Maya Cesari; Vincenzo Di Marzo; Régis Roche



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

PubMed Central

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.

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



Inhibition of the NF-?B signaling pathway mediates the anti-inflammatory effects of petrosaspongiolide M  

Microsoft Academic Search

Petrosaspongiolide M (PT) is a potent secretory phospholipase A2 inhibitor and anti-inflammatory agent. This marine metabolite reduced the production of nitrite, prostaglandin E2, and tumor necrosis factor-? in the mouse air pouch injected with zymosan. These effects were also observed in mouse peritoneal macrophages stimulated with zymosan. Inhibition of these inflammatory mediators was related to reductions in inducible nitric oxide

Inmaculada Posadas; Maria Carmen Terencio; Antonio Randazzo; Luigi Gomez-Paloma; Miguel Payá; Maria José Alcaraz



Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress  

Microsoft Academic Search

Curcumin, a widely used spice and coloring agent in food, has been shown to possess potent antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. The mechanism(s) of such pleiotropic action by this yellow pigment is unknown; whether induction of distinct antioxidant genes contributes to the beneficial activities mediated by curcumin remains to be investigated. In the present

Roberto Motterlini; Roberta Foresti; Rekha Bassi; Colin J Green



Synthesis and evaluation of the antioxidant and anti-inflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts  

Microsoft Academic Search

In the present work a series of novel coumarin-3-carboxamides and their hybrids with the alpha-lipoic acid were designed, synthesized and tested as potent antioxidant and anti-inflammatory agents. The new compounds were evaluated for their antioxidant activity, their activity to inhibit in vitro lipoxygenase and their in vivo anti-inflammatory activity. In general, the derivatives were generally found to present antioxidant and

Georgia Melagraki; Antreas Afantitis; Olga Igglessi-Markopoulou; Anastasia Detsi; Maria Koufaki; Christos Kontogiorgis; Dimitra J. Hadjipavlou-Litina



Synthesis and anti-inflammatory activity of 2-substituted-((N, N-disubstituted)-1, 3-benzoxazole)-5-carboxamides.  


A series of 2-substituted-((N, N-disubstituted)-1, 3-benzoxazole)-5-carboxamides derivatives were synthesized by the reaction of 2-substituted-5-carbomethoxy benzoxazole with different secondary amines. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, 1H NMR, MS) & elemental analysis. All these compounds were screened for anti-inflammatory activity using carrageenan induced rat paw edema method. All of these compounds exhibited significant activity. Among the tested compounds Ve, Vg, Vf and Va were considered to have potent anti-inflammatory activity and was comparable with standard. PMID:20939181

Reena, M; Kiran, G; Rajyalakshmi, G; Venkateshwa, Rao J; Sarangapani, M



Anti-inflammatory effects of escin are correlated with the glucocorticoid receptor/NF-?B signaling pathway, but not the COX/PGF2? signaling pathway  

PubMed Central

In China, escin has been widely used in the clinic as a potent anti-inflammatory drug. Previous studies have indicated that escin exerts its anti-inflammatory effect by enhancing the release of glucocorticoids (GCs) and prostaglandin-F2? (PGF2?), and this has been documented in the drug description. However, our previous studies demonstrated that escin did not increase the secretion of GCs, but instead elevated the protein expression of the GC receptor (GR), which may have repressed nuclear factor (NF)-?B-mediated gene expression. The aim of this study was to determine the functions of NF-?B and PGF2? with regard to the anti-inflammatory effect of escin. We investigated the anti-inflammatory effects of dexamethasone, diclofenac and escin against carrageenan-induced paw edema in rats, and observed that escin exerted a GC-like anti-inflammatory effect. In addition, we studied the role of PGF2? in the anti-inflammatory effect exerted by escin in an acetic acid-induced capillary permeability model in mice. The results revealed that the coadministration of escin and diclofenac, a potent prostaglandin-synthesis inhibitor, did not affect the anti-inflammatory effect of escin. Furthermore, we investigated the function of NF-?B with regard to the anti-inflammatory effect exerted by escin in lipopolysaccharide (LPS)-treated mice, and demonstrated that escin significantly inhibited the expression of NF-?B. These results suggest that escin has a GC-like anti-inflammatory effect, and that its mechanisms may be correlated with the GC receptor/NF-?B signaling pathway, but not the COX/PGF2? signaling pathway.




Anti-inflammatory constituents of Sappan Lignum.  


We performed an in vitro assay for seven compounds from methanolic extract of Sappan Lignum (CSE) that inhibit the chemical mediators of inflammation using the J774.1 cell line: brazilin (1), sappanchalcone (2), protosappanin A (3), protosappanin B (4), protosappanin C (5), protosappanin D (6), and protosappanin E (7). Those compounds were evaluated for their inhibitory effects on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production and their suppressive effects on tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA expression. As a result, we clarified that 1 inhibited NO production, and almost no inhibition in PGE(2). On the contrary, 2, 6, and 7 inhibited both NO and PGE(2) production and suppressed TNF-alpha, IL-6, COX-2, and iNOS mRNA expression. An examination of carrageenin-induced mouse paw edema suggested that the CSE contained active compounds other than 1, the main constituent in CSE. It was thus revealed that several compounds and mechanisms contributed to the anti-inflammatory effect of CSE. PMID:19420769

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



Evaluation of the anti-inflammatory effect of chalcone and chalcone analogues in a zebrafish model.  


The aim of this study was to investigate novel chalcones with potent anti-inflammatory activities in vivo. Chalcone and two chalcone analogues (compound 5 and 9) were evaluated using a caudal fin-wounded transgenic zebrafish line "Tg(mpx:gfp)" to visualize the effect of neutrophil recruitment dynamically. Results showed that treatment with compound 9 not only affected wound-induced neutrophil recruitment, but also affected Mpx enzymatic activity. Moreover, protein expression levels of pro-inflammatory factors (Mpx, NF?B, and TNF?) were also regulated by compound 9. Taken together, our results provide in vivo evidence of the anti-inflammatory effects of synthesized chalcone analogues on wound-induced inflammation. PMID:23385341

Chen, Yau-Hung; Wang, Wei-Hua; Wang, Yun-Hsin; Lin, Zi-Yu; Wen, Chi-Chung; Chern, Ching-Yuh



Assessment of Anti-inflammatory Activity of Taxus Baccata Linn. Bark Extract.  


Taxus baccata (L) known as Sthauneyaka in Sanskrit(1) has wide range of biological activities including analgesic, anti-malarial, anti-rheumatic, sedative, anti-spasmodic, aphrodisiac and anti-asthmatic. In the present study, the dried and powdered bark of Taxus baccata (L) was extracted with 95% ethanol and ether at room temperature and screened for their anti--inflammatory activity by Carrageenan-induced paw edema method in rat. 95% ethanol extract exhibits potent anti-inflammatory activity at 200mg/kg four hours after administration in comparison with ether extract, as well reference standard, Aspirin. The observed pharmacological activities provide a scientific basis for the folklore use of the plant in treating acute inflammation. PMID:22557354

Dutta, Satyajit; Mariappan, G; Sarkar, Dipankar; Sarkar, Piyali



Anti-inflammatory and anticancer drugs from nature.  


Over the centuries, plant extracts have been used to treat various diseases. Until now, natural products have played an important role in anticancer therapy as there are more than 500 compounds from terrestrial and marine plants or microorganisms, which have antioxidant, antiproliferative, or antiangiogenic properties and are therefore able to reduce tumor growth. The recent discovery of new natural products has been accelerated by novel technologies (high throughput screening of natural products in plants, animals, marine organisms, and microorganisms). Vincristine, irinotecan, etoposide, and paclitaxel are examples of compounds derived from plants that are used in cancer treatment. Similarly, actinomycin D, mitomycin C, bleomycin, doxorubicin, and L-asparaginase are drugs derived from microorganisms. In this review, we describe the molecular mechanisms of natural compounds with anti-inflammatory and anticancer activities. PMID:24114478

Orlikova, Barbora; Legrand, Noémie; Panning, Jana; Dicato, Mario; Diederich, Marc



Thalidomide has anti-inflammatory properties in neonatal immune cells.  


Neonates demonstrate functional immaturity and dysregulation of immune responses leading to systemic inflammation and enhanced apoptosis of immune cells. Thalidomide has already been proven to differentially regulate immune responses and support anti-apoptosis in immunodeficiency syndromes. Thus, it was the aim of this study to evaluate the effects of thalidomide on the cytokine response and apoptosis of neonatal immune cells. After whole blood culture and stimulation of cord and adult blood samples, the intracytoplasmic expression and the secreted amounts of IL-2, TNF-?, IFN-?, IL-6, IL-10 and IL-8 were assessed by flow cytometry and Cytokine Bead Array. Apoptosis was detected using Annexin-V staining. Bcl-2 expression was analysed using the Cytokine Bead Array Apoptosis Kit. Exposure to thalidomide (100 µg/ml) reduced the intracytoplasmic pro-inflammatory cytokine production of neonatal monocytes and the IFN-? production of neonatal lymphocytes. In supernatants, the addition of thalidomide resulted in reduction of TNF-?, IL-6, IL-10 and, by trend, IFN-?. While stimulated neonatal lymphocytes exhibited susceptibility to apoptosis, thalidomide tended to diminish apoptotic cells. Bcl-2 expression tended to be increased after addition of thalidomide. The potent anti-inflammatory effects of thalidomide and its anti-apoptotic properties in cord blood immune cells provide the basis for future strategies to optimise treatment of neonatal infections and immunodeficiency syndromes. PMID:22710762

Puzik, Alexander; Thiel, Annette; Faust, Kirstin; Härtel, Christoph



Is licofelone, a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase, a promising alternative in anti-inflammatory therapy?  


As prostaglandins and leukotrienes are critical in inflammation, dual cyclo-oxygenase and 5-lipoxygenase enzymes inhibitors, especially licofelone, are being developed by pharmaceutical companies. Experimental data indicate that licofelone shares the antipyretic, analgesic, anti-inflammatory and anti-platelet activities of conventional nonsteroidal anti-inflammatory drugs (NSAIDs), and exhibits anti-allergic properties. Although licofelone may lead to similar adverse effects on the kidney than available NSAIDs, it appeared to induce less gastrointestinal damaging effects than nonselective NSAIDs in animals. Unfortunately, preliminary clinical studies provided less impressive data with respect to efficacy. Finally, the experimental promise of licofelone as a safe and potent anti-inflammatory and analgesic agent remains to be proved in humans. PMID:14748764

Bannwarth, Bernard



Anti-inflammatory drugs, eicosanoids and the annexin A1/FPR2 anti-inflammatory system.  


The action of anti-inflammatory and anti-allergic drugs on the eicosanoid system is briefly reviewed. In addition to the aspirin-like drugs, which directly inhibit the cyclo-oxygenase enzymes, other drugs such as the glucocorticoids and the cromones also inhibit the formation of eicosanoids. In the latter cases this is bought about through the release of a protein factor that acts through formyl peptide receptors on the target cell surface. Of growing interest, is the observation that this receptor is also a target for other eicosanoids, such as lipoxins and resolvins that modulate host defence systems. PMID:22123264

Yazid, Samia; Norling, Lucy V; Flower, Rod J



Acai juice attenuates atherosclerosis in apoe deficient mice through antioxidant and anti-inflammatory activities  

Technology Transfer Automated Retrieval System (TEKTRAN)

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...


Simultaneous Determination of Clobutinol Together with Some Anti?inflammatory Drugs in Urine by HPLC  

Microsoft Academic Search

An isocratic high performance liquid chromatography method is described for simultaneous determination of clobutinol hydrochloride together with some anti?inflammatory drugs, such as diclofenac, meloxicam, and nimesulide in urine. For the development and optimization of the system, three different buffers containing ammonium acetate, tetraethylammonium hydrogen sulfate (THAS), and tetrabutylammonium hydrogen sulfate (THBS) were investigated, because it has been proven that different

Eleftheria T. Malliou; Catherine K. Markopoulou; John E. Koundourellis



Anti-inflammatory activity of macrolide antibiotics.  


The effect of four macrolide antibiotics (roxithromycin, clarithromycin, erythromycin, and azithromycin) on the generation of some mediators and cytokines involved in the inflammatory process has been studied both in vivo and in vitro. Rat carrageenin pleurisy was used as a model of acute inflammation, and the macrolides were administered (10, 20, and 40 mg/kg p.o.) 1 h before the carrageenin challenge. Exudate volume and leukocyte accumulation were both dose-dependently reduced by roxithromycin, clarithromycin and erythromycin in either normal or adrenalectomized animals. Furthermore, in normal rats, prostaglandin (PG)E(2), nitrate plus nitrite, and tumor necrosis factor-alpha levels in pleural exudate were significantly reduced by these macrolides. Roxithromycin appeared more effective than erythromycin and clarithromycin, whereas azithromycin only slightly affected the inflammatory reaction. None of the macrolides were able to modify leukotriene B(4) exudate levels. In vitro experiments have shown that the four macrolides (5-80 microM) reduced in a concentration-dependent manner the production of 6-keto-PGF(1alpha), NO(2)(-), tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by lipopolysaccharide-stimulated J774 macrophages. In J774 cells, the inhibition of 6-keto-PGF(1alpha) and NO(2)(-) production by roxithromycin and erythromycin was not dependent on direct inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activity because it appears to be related to the inhibition of cyclooxygenase-2 and inducible nitric oxide synthase protein expression. In conclusion, the present study shows that macrolide antibiotics have anti-inflammatory activity, which likely depends on their ability to prevent the production of proinflammatory mediators and cytokines, and suggest that these agents, particularly roxithromycin, can exert therapeutic effects independently of their antibacterial activity. PMID:10604943

Ianaro, A; Ialenti, A; Maffia, P; Sautebin, L; Rombolà, L; Carnuccio, R; Iuvone, T; D'Acquisto, F; Di Rosa, M



Anti-Inflammatory Cytokine IL-10 and Mammary Gland Development.  

National Technical Information Service (NTIS)

This investigation seeks to determine the relationship between anti- inflammatory cytokine IL-10 and mammary gland development. To achieve this goal, the authors propose to compare mammary glands from wild type and IL-10 knockout female mice at different ...

S. Kuo



Anti-inflammatory and analgesic activities of Melanthera scandens  

PubMed Central

Objective To evaluate the anti-inflammatory and analgesic activities of leaf extract of Melanthera scandens (M. scandens). Methods The crude leaf extract (39–111 mg/kg) of M. scandens was investigated for anti-inflammatory and analgesic activities using various experimental models. The anti-inflammatory activity was investigated using carragenin, egg-albumin induced oedema models, while acetic acid, formalin-induced paw licking and thermal-induced pain models were used to evaluate the antinociceptive property. Results The extract caused a significant (P<0.05 – 0.001) dose-dependent reduction of inflammation and pains induced by different agents used. Conclusions The leaf extract possesses anti-inflammatory and analgesic effects which may be mediated through the phytochemical constituents of the plant.

Okokon, Jude E; Udoh, Anwanga E; Frank, Samuel G; Amazu, Louis U



Anti-inflammatory activity of Bacopa monniera in rodents  

Microsoft Academic Search

The ethanol extract of Bacopa monniera (Scrophulariaceae) exhibited marked anti-inflammatory activity against carrageenan-induced paw edema in mice and rats, an acute inflammatory model. To assess the possible mechanism of anti-inflammatory action against carrageenan, the ethanol extract was treated with chemical mediators (histamine, serotonin, bradykinin, prostaglandin E2 and arachidonic acid)-induced edema in rats. The extract selectively inhibited prostaglandin E2-induced inflammation. Thus,

Shabana Channa; Ahsana Dar; Shazia Anjum; Muhammad Yaqoob; Atta-ur-Rahman



Anti-inflammatory glucocorticoid drugs: reflections after 60 years  

Microsoft Academic Search

This review considers the problem of the serious concomitant side effects of powerful anti-inflammatory drugs modelled upon\\u000a the principal human glucocorticoid hormone, cortisol. The very nature of the original bio-assays to validate their cortisol-like\\u000a hormonal and anti-inflammatory activities ensured that pleiotropic toxins were selected for clinical studies. Other complicating\\u000a factors have been (1) considerable reliance on bio-assays conducted in laboratory

Michael W. Whitehouse



Anti-inflammatory agents from Sandoricum koetjape Merr.  


The anti-inflammatory activity of the stem extracts of Sandoricum koetjape was investigated on topical administration using the TPA (tetradecanoylphorbol acetate)-induced mouse ear inflammation model. Bioassay-guided chromatographic fractionation of active fractions led to the isolation 3-oxo-12-oleanen-29-oic acid and katonic acid as the bioactive principles responsible for the anti-inflammatory acitivity. The percentage of inhibition exhibited by 3-oxo-12-oleanen-29-oic acid was almost equivalent to indomethacin. PMID:15070182

Rasadah, M A; Khozirah, S; Aznie, A A; Nik, M M



Anti-inflammatory activity of Syzygium cumini bark  

Microsoft Academic Search

The ethanolic extract of the bark of Syzygium cumini was investigated for its anti-inflammatory activity in animal models. The extract did not show any sign of toxicity up to a dose of 10.125 g\\/kg, p.o. in mice. Significant anti-inflammatory activity was observed in carrageenin (acute), kaolin-carrageenin (subacute), formaldehyde (subacute)-induced paw oedema and cotton pellet granuloma (chronic) tests in rats. The

S Muruganandan; K Srinivasan; S Chandra; S. K Tandan; J Lal; V Raviprakash



Anti-inflammatory steroid signalling in the human peritoneum  

Microsoft Academic Search

Peritoneal surface epithelial (PSE) cells participate in adhesion formation following inflammatory injury yet adjacent ovarian SE (OSE) cells regenerate without scarification after ovulation. OSE cells show inflammation-associated expression of 11b hydroxysteroid dehydrogenase type 1 (11bHSD1) enzyme, enabling intracrine generation of anti-inflammatory cortisol to minimise tissue damage. We asked if human PSE cells show an 11bHSD1 response to pro-\\/anti-inflammatory stimulation and

K S Fegan; M T Rae; H O D Critchley; S G Hillier



Anti-inflammatory management for tendon injuries - friends or foes?  

Microsoft Academic Search

Acute and chronic tendon injuries are very common among athletes and in sedentary population. Most physicians prescribe anti-inflammatory managements to relieve the worst symptoms of swelling and pain, including non-steroidal anti-inflammatory drugs, corticosteroids and physical therapies. However, experimental research shows that pro-inflammatory mediators such as prostaglandins may play important regulatory roles in tendon healing. Noticeably nearly all cases of chronic

Kai-Ming Chan; Sai-Chuen Fu



Anti-inflammatory effect of microalgal extracts from Tetraselmis suecica  

Microsoft Academic Search

The aim of the present study was to examine the anti-inflammatory activities of extracts from Tetraselmis suecica with respect to nitric oxide (NO) production, tumor necrosis factor (TNF)-? and interlukin (IL)-6 release in lipopolysaccharide\\u000a (LPS)-stimulated RAW 264.7 cells. We prepared methanolic extracts and water extract using protease. Of all the prepared extracts,\\u000a 80% methanol extract exhibited the strongest anti-inflammatory effect.

Wol Soon Jo; Yoo Jin Choi; Hyoun Ji Kim; Byung Hyouk Nam; Sook Hee Hong; Gye An Lee; Sang Wha Lee; Su Yeong Seo; Min Ho Jeong



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


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. PMID:22209877

Nuji?, Krunoslav; Smith, Marjorie; Lee, Michael; Belamari?, Daniela; Tomaškovi?, Linda; Alihodži?, Sulejman; Malnar, Ivica; Polan?ec, Denis; Schneider, Klaus; Erakovi? Haber, Vesna



Anti-inflammatory substances can influence some glial cell types but not others.  


In rat microglial enriched cultures, expressing Toll-like receptor 4, we studied cytokine release after exposure with 1ng/ml LPS for 0.5-24h. Dexamethasone and corticosterone exposure served as controls. We focused on whether naloxone, ouabain, and bupivacaine, all agents with reported anti-inflammatory effects on astrocytes, could affect the release of TNF-? and IL-1? in microglia. Our results show that neither ultralow (10(-12)M) nor high (10(-6)M) concentrations of these agents had demonstrable effects on cytokine release in microglia. The results indicate that anti-inflammatory substances exert specific influences on different glial cell types. Astrocytes seem to be functional targets for anti-inflammatory substances while microglia respond directly to inflammatory stimuli and are thus more sensitive to anti-inflammatory substances like corticoids. The physiological relevance might be that astrocyte dysfunction influences neuronal signalling both due to direct disturbance of astrocyte functions and in the communication within the astrocyte networks. When the signalling between astrocytes is working, then microglia produce less pro-inflammatory cytokines. PMID:24120988

Forshammar, Johan; Jörneberg, Per; Björklund, Ulrika; Westerlund, Anna; Lundborg, Christopher; Biber, Björn; Hansson, Elisabeth



Comparative pharmacokinetics of three non-steroidal anti-inflammatory drugs in five bird species.  


Information on the pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in birds is scarce. Choice of drug and of dosage is usually empirical, since studies of anti-inflammatory drugs are lacking. In this study, three common veterinary non-steroidal anti-inflammatory drugs (NSAIDs) were administered intravenously to five different bird species. Sodium salicylate, flunixin and meloxicam were selected as anti-inflammatory drugs. These NSAIDs were administered intravenously to chickens (Gallus gallus), ostriches (Struthio camelus), ducks (Anas platyrhynchos), turkeys (Meleagris gallopavo) and pigeons (Columba livia). Plasma concentrations of the drugs were determined by validated high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. Most bird species exhibited rapid elimination of these drugs. Ostriches had the fastest elimination rate for all three NSAIDs, but there were some interesting species differences. Chickens had a half-life that was approximately 10-fold as long as the other bird species for flunixin. The half-life of chickens and pigeons was three-fold as long as the other bird species for meloxicam, and, for salicylic acid, the half-life in pigeons was at least three-five-fold longer than in the other bird species. PMID:12524015

Baert, K; De Backer, P



Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.  

PubMed Central

GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized.

van der Velden, V H



The anti-inflammatory and hepatoprotective effects of fractions from Cudrania cochinchinensis var. gerontogea.  


Various fractions of the ethanol extract from the root wood of Cudrania cochinchinensis var. gerontogea (Moraceae) were evaluated for their anti-inflammatory effects on carrageenan-induced edema and hepatoprotective activities on carbon tetrachloride (CCl4)-induced and D-galactosamine-(D-GalN) induced acute hepatotoxicity in rats. The fractions (n-hexane, CHCl3, EtOAc, n-BuOH, and H2O) displayed significant inhibitory activity against carrageenan-induced edema, and the active anti-inflammatory components were further localized in the n-BuOH fraction, which exhibited the greatest anti-inflammatory effect, an effect 5% greater than indomethacin (which was used as a standard reference substance). Each fraction exerted a significant hepatoprotective effect by reducing enzymatic alteration (sGOT and sGPT) and by improving hepatic lesions, including liver centrilobular inflammation, cell necrosis, fatty change, ballooning degeneration in CCl4-induced acute hepatitis; and necrosis of the portal area in D-GalN-induced acute liver injury. The n-BuOH and EtOAc fractions had the greatest hepatoprotective effects on CCl4-induced liver injury; in contrast, the CHCl3 fraction was most potent against D-GalN intoxication, which is comparable to silymarin, as a recognized hepatoprotective drug. PMID:10467456

Lin, C C; Lee, H Y; Chang, C H; Yang, J J



Anti-inflammatory and analgesic effects of ketoprofen in palm oil esters nanoemulsion.  


Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen. PMID:21099145

Sakeena, M H F; Yam, M F; Elrashid, S M; Munavvar, A S; Azmin, M N



Anti-inflammatory effects of phosphatidylcholine  

PubMed Central

We recently showed that mucus from patients with ulcerative colitis, a chronic inflammatory disorder of the colon, is characterized by a low level of phosphatidylcholine (PC) while clinical studies reveal that therapeutic addition of PC using slow release preparations is beneficial. The positive role of PC in this disease is still elusive. Here we tested the hypothesis that exogenous application of PC has anti-inflammatory properties using three model systems. First, human Caco-2 cells were treated with TNF-a? to induce a pro-inflammatory response via activation of NF-?B. Second, latex bead phagosomes were analyzed for their ability to assemble actin in vitro, a process linked to pro-inflammatory signaling and correlating with the growth versus killing of mycobacteria in macrophages. The third system used was the rapid assembly of plasma membrane actin in macrophages in response to sphingosine 1- phosphate (S1P). TNF-a induced a pro-inflammatory response in Caco-2 cells including 1) assembly of plasma membrane actin; 2) activation of both MAP kinases ERK and p38; 3) transport of NF-?B subunits to the nucleus and 4) subsequent up-regulation of the synthesis of pro-inflammatory gene products. Exogenous addition of most PCs tested significantly inhibited these processes. Other phospholipids like sphingomyelin or phosphatidyl-ethanolamine showed no effects in these assays. PC also inhibited latex bead phagosome actin assembly, the killing of M. tuberculosis in macrophages and the S1P-induced actin assembly in macrophages. TNF-a induces the activation of signaling molecules and the reorganization of the actin cytoskeleton in human intestinal cells. Exogenous application of PC blocks pro-inflammatory signaling in Caco-2 cells, in phagosomes in vitro and facilitates intracellular survival of mycobacteria. We provide further evidence that actin assembly by membranes is part of the pro-inflammatory response. Collectively, these results provide a molecular foundation for the clinical studies showing a beneficial effect of PC therapy in ulcerative colitis.

Treede, Irina; Braun, Annika; Sparla, Richard; Kuhnel, Mark; Giese, Thomas; Turner, Jerrold R.; Anes, Elsa; Kulaksiz, Hassan; Fullekrug, Joachim; Stremmel, Wolfgang; Griffiths, Gareth; Ehehalt, Robert



Topical anti-inflammatory activity of Eupatilin, a lipophilic flavonoid from mountain wormwood ( Artemisia umbelliformis Lam.).  


Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the major lipophilic flavonoid from Artemisia umbelliformis Lam. and Artemisia genipi Weber, two mountain wormwoods used for the production of the celebrated alpine liqueur genepy. The topical anti-inflammatory activity of eupatilin was investigated using the inhibition of the Croton-oil-induced dermatitis in the mouse ear as the end point. The oedematous response and the leukocyte infiltration were evaluated up to 48 h after the induction of phlogosis, comparing eupatilin with hydrocortisone and indomethacin as representatives of steroid and non-steroid anti-inflammatory drugs, respectively. At maximum development, eupatilin significantly reduced edema in a dose-dependent manner (ID(50) = 0.28 micromol/cm(2)), showing an anti-inflammatory potency comparable to that of indomethacin (ID(50) = 0.26 micromol/cm(2)) and only 1 order of magnitude lower than that of hydrocortisone (ID(50) = 0.03 micromol/cm(2)). Within 48 h, eupatilin (0.30 micromol/cm(2)) caused a global inhibition of the oedematous response (42%) higher than that of an equimolar dose of indomethacin (18%) and fully comparable to that of 0.03 micromol/cm(2) of hydrocortisone (55%). Moreover, the effect of eupatilin on the granulocytes infiltrate (32% inhibition) was similar to that of indomethacin (35% inhibition) and comparable to that of hydrocortisone (42% reduction), as confirmed by histological analysis. When our results are taken together, they show that eupatilin is endowed with potent in vivo topical anti-inflammatory activity, qualitatively similar to that of hydrocortisone and intermediate in terms of potency between those of steroid and non-steroid drugs. PMID:19663482

Giangaspero, Anna; Ponti, Cristina; Pollastro, Federica; Del Favero, Giorgia; Della Loggia, Roberto; Tubaro, Aurelia; Appendino, Giovanni; Sosa, Silvio



IL35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines  

Microsoft Academic Search

It remains unknown whether newly identified anti-inflammatory\\/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-? in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to

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



Interplay of pro- and anti-inflammatory cytokines to determine lipid accretion in adipocytes.  


Objective:Obesity is associated with an increase in various pro-inflammatory and anti-inflammatory cytokines, but the interplay of these cytokines is incompletely understood. We conducted experiments to test a broader hypothesis that a dynamic interplay of pro-inflammatory and anti-inflammatory cytokines controls lipid storage in adipocytes.Design:Three experiments were designed to test the overall hypothesis that proinflammatory cytokine (for example, tumor necrosis factor-? (TNF-?) inhibits anti-inflammatory cytokine (for example, adiponectin) activity in an attempt to limit excess lipid accumulation in adipocytes.Results:Experiment one showed that in pro-inflammatory animal models (ap2-P65, ob/ob and high-fat diet-induced obese mice), the increase in TNF-? expression was associated with a decrease in adiponectin expression. Experiment two showed that in 3T3-L1 adipocytes, TNF-? significantly reduced lipid accumulation and glucose uptake induced by adiponectin, and increased lipolysis. Experiment three showed that in 3T3-L1 adipocytes, TNF-? reduced mRNA and protein expression of adiponectin. Adiponectin gene transcription and mRNA stability were both reduced by TNF-?. The expression of peroxisome proliferator-activated receptor gamma, an activator of adiponectin gene promoter, was reduced by TNF-?. The inhibitory activity of TNF-? was blocked by the chemical inhibitors of NF-?B and super suppressor I?B?.Conclusions:TNF-? opposes the action of adiponectin in the regulation of lipid metabolism, and inhibits adiponectin expression at transcriptional and post-transcriptional levels. The results suggest that pro-inflammatory cytokine inhibit anti-inflammatory cytokine in adipocytes to reduce lipid storage. This suggests a potential role of anti-inflammatory cytokines in the control of adipose tissue expansion.International Journal of Obesity advance online publication, 5 February 2013; doi:10.1038/ijo.2013.9. PMID:23381555

Wang, Y; Wang, H; Hegde, V; Dubuisson, O; Gao, Z; Dhurandhar, N V; Ye, J



Anti-inflammatory effects of Scoparia dulcis L. and betulinic acid.  


The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on ?-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-?), interleukin-1? (IL-1?) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after ?-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-? and IL1-? in the ?-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-? and IL1-? in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract. PMID:21905284

Tsai, Jen-Chieh; Peng, Wen-Huang; Chiu, Tai-Hui; Lai, Shang-Chih; Lee, Chao-Ying



Identification of anti-inflammatory constituents in Hypericum perforatum and Hypericum gentianoides extracts using RAW 264.7 mouse macrophages.  


Hypericum perforatum (St. John's wort) is an herb widely used as supplement for mild to moderate depression. Our prior studies established synergistic anti-inflammatory activity associated with 4 bioactive compounds in a fraction of a H. perforatum ethanol extract. Whether these 4 compounds also contributed to the ethanol extract activity was addressed in the research reported here. Despite the popularity of H. perforatum, other Hypericum species with different phytochemical profiles could have their anti-inflammatory potentials attributed to these or other compounds. In the current study, ethanol extracts of different Hypericum species were compared for their inhibitory effect on LPS-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among these extracts, those made from H. perforatum and H. gentianoides demonstrated stronger overall efficacy. LC-MS analysis established the 4 compounds were present in the H. perforatum extract and pseudohypericin in all active fractions. The 4 compounds accounted for a significant part of the extract's inhibitory activity on PGE2, NO, tumor necrosis factor-? (TNF-?), and interleukin-1? (IL-1?) in RAW 264.7 as well as peritoneal macrophages. Pseudohypericin was the most important contributor of the anti-inflammatory potential among the 4 compounds. The lipophilic fractions of H. gentianoides extract, which did not contain the previously identified active constituents, decreased PGE2 and NO potently. These fractions were rich in acylphloroglucinols, including uliginosin A that accounted for a proportion of the anti-inflammatory activity observed with the active fractions. Overall, the current study established that a different group of major anti-inflammatory constituents were present in H. gentianoides, while showing that the previously identified 4 compound combination was important for H. perforatum's anti-inflammatory potential. PMID:21855951

Huang, Nan; Rizshsky, Ludmila; Hauck, Cathy; Nikolau, Basil J; Murphy, Patricia A; Birt, Diane F



A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia.  


Selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRI; SNRI) are the first choice pharmacological treatment options for major depression. It has long been assumed that the primary therapeutic mechanism of action of these drugs involves the modulation of monoaminergic systems. However, contemporary investigations have revealed that depression is linked with inflammation, and that SSRI/SNRIs possess significant anti-inflammatory actions. While these anti-inflammatory properties initially only related to work undertaken on cells of the peripheral immune system, it has recently become apparent that these drugs also exert anti-inflammatory effects on microglia, the principal cells within the CNS that regulate and respond to inflammatory factors. The aim of the current study was to compare SSRI/SNRIs in terms of their anti-inflammatory potency, and to determine the specific mechanisms through which these effects are mediated. Accordingly, the current study evaluated the ability of five different SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram) and one SNRI (venlafaxine) to suppress microglial responses to an inflammatory stimulus. Specifically, we examined their ability to alter tumour necrosis factor-? (TNF-?) and nitric oxide (NO) production after 4 and 24 h stimulation with lipopolysaccharide. Our results indicated that the SSRIs potently inhibited microglial TNF-? and NO production. We then investigated whether these effects might involve either ?-adrenoceptor or cAMP signalling. Using the protein kinase A inhibitor Rp-CAMPs, we found evidence to suggest that cAMP signalling is involved in regulating the anti-inflammatory response. These findings suggest that antidepressants may owe at least some of their therapeutic effectiveness to their anti-inflammatory properties. PMID:22251606

Tynan, Ross J; Weidenhofer, Judith; Hinwood, Madeleine; Cairns, Murray J; Day, Trevor A; Walker, Frederick R



The Anti-inflammatory Effects of Water Extract from Cordyceps militaris in Murine Macrophage  

PubMed Central

The aim of this study was to determine the in vitro anti-inflammatory effect of hot water extract from Cordyceps militaris fruiting bodies (CMWE) on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production, tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) release in RAW 264.7 cells. The treatment of macrophages with various concentrations of hot CMWE significantly reduced LPS-induced production as well as NO, TNF-? and IL-6 secretion in a concentration-dependent manner. These results suggest that CMWE have potent inhibitory effects on the production of these inflammatory mediators.

Jo, Wol Soon; Choi, Yoo Jin; Kim, Hyoun Ji; Lee, Jae Yun; Nam, Byung Hyouk; Lee, Jae Dong; Lee, Sang Wha; Seo, Su Yeong



New anti-inflammatory ergostane-type ecdysteroids from the sclerotium of Polyporus umbellatus.  


Bioassay-guided fractionation of the ethyl acetate extract from the sclerotium of Polyporus umbellatus resulted in the isolation of three new ergostane-type ecdysteroids, named polyporoid A (1), B (2), and C (3), together with five known ecdysteroids. The structures of the new compounds were determined on the basis of extensive spectroscopic data (IR, MS, (1)H and (13)C NMR, and 2D NMR) analyses. All compounds (1-8) exhibited potent anti-inflammatory activity in the test of TPA-induced inflammation (1 microg/ear) in mice, with ID(50) values in the range of 0.117-0.682 microM/ear. PMID:18439824

Sun, Yi; Yasukawa, Ken



Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis  

Microsoft Academic Search

Background  The phytosterol guggulsterone is a potent anti-inflammatory mediator with less side effects than classic steroids. This study\\u000a assesses the impact of guggulsterone on tissue factor (TF) expression and thrombus formation.\\u000a \\u000a \\u000a \\u000a Methods and results  Guggulsterone inhibited TNF-?-induced endothelial TF protein expression and surface activity in a concentration-dependent\\u000a manner; in contrast, dexamethasone did not affect TNF-?-induced TF expression. Guggulsterone enhanced endothelial tissue factor

Catherine Gebhard; Simon F. Stämpfli; Caroline E. Gebhard; Alexander Akhmedov; Alexander Breitenstein; Giovanni G. Camici; Erik W. Holy; Thomas F. Lüscher; Felix C. Tanner



Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones.  


A variety of novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with a variety of amines, the starting material dithiocarbamate was synthesized from methylanthranilate. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. While the test compounds exhibited significant activity, the compounds A1, A2, A3 and A4 shown more potent analgesic activity, and the compound A4 shown more potent anti-inflammatory activity than the reference diclofenac sodium. PMID:15133239

Alagarsamy, Veerachamy; Rajesh, Ramadoss; Ramaseshu, Meena; Vijaykumar, Sukumaran; Ramseshu, Kona Venkat; Duraianandakumar, Thirumoorthy



Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-phenyl-3-substituted quinazolin-4(3H) ones.  


A series of novel 2-phenyl-3-substituted quinazolin-4(3H)-ones have been synthesized by treating methyl-N-(2-phenyl quinazolin-3-yl-4(3H)-one) dithiocarbamate with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds A1, A2 and A3 shown more potent analgesic activity, and the compound A3 shown more potent anti-inflammatory activity than the reference standard diclofenac sodium. PMID:12419954

Alagarsamy, Veerachamy; Salomon, Viswas Raja; Vanikavitha, Gnanavel; Paluchamy, Veeran; Chandran, Muniyandi Ravi; Sujin, Augustin Arnald; Thangathiruppathy, Arunachalam; Amuthalakshmi, Sivaperuman; Revathi, Rajappan



Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-butyl-3-substituted quinazolin-4-(3H)-ones.  


A variety of novel 2-butyl-3-substituted quinazolin-4-(3H)-ones have been synthesized by reacting (2-butyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with a variety of amines; the starting material dithiocarbamate was synthesized from anthranilic acid. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. While the test compounds exhibited significant activity, compounds A1, A2, A3 and A4 showed more potent analgesic activity and compound A4 showed more potent anti-inflammatory activity than the reference diclofenac sodium. PMID:15930752

Alagarsamy, Veerachamy; Rajasolomon, Viswas; Meena, Ramseshu; Ramseshu, Kona Venkat



Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance  

Microsoft Academic Search

The anti-inflammatory, analgesic and antipyretic properties of the new non-steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of animal models and compared with the properties of piroxicam, diclofenac, indomethacin and several other NSAIDs.

G. Engelhardt; D. Homma; K. Schlegel; R. Utzlnann; C. Schnitzler



Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.  


The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100?mg/kg, 300?mg/kg, and 500?mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models. PMID:22761611

Kaushik, Dhirender; Kumar, Ajay; Kaushik, Pawan; Rana, A C



Modeling Natural Anti-Inflammatory Compounds by Molecular Topology  

PubMed Central

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.

Galvez-Llompart, Maria; Zanni, Riccardo; Garcia-Domenech, Ramon



Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.  

PubMed Central

The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100?mg/kg, 300?mg/kg, and 500?mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models.

Kaushik, Dhirender; Kumar, Ajay; Kaushik, Pawan; Rana, A. C.



Anti-inflammatory activities of triterpenoid saponins from Polygala japonica.  


Bioassay-guided investigation was performed to identify the active constituents from a methanol extract of Polygala japonica, a folk medicinal plant widely used in China to treat inflammatory diseases. The n-BuOH and EtOAc fractions of the P. japonica methanol extract, which show significant anti-inflammatory activity in in vivo test, were further subjected to column chromatography to afford six triterpene glycosides, marked here as saponins 1-6. All compounds were evaluated for their anti-inflammatory activity in the carageenan-induced mouse paw edema test, and saponins 1, 4 and 5 showed significantly anti-inflammatory effects on both phases of carageenan-induced acute paw edema in mice. Saponin 5 was also found to significantly inhibit the production of inflammatory mediators - nitric oxide (NO) in LPS-stimulated RAW264.7 macrophages, with no obvious effects on macrophage viability. PMID:17951039

Wang, H; Gao, J; Kou, J; Zhu, D; Yu, B



Immune-stimulatory and anti-inflammatory activities of Curcuma longa extract and its polysaccharide fraction  

PubMed Central

Background: While curcuminoids have been reported to possess diverse biological activities, the anti-inflammatory activity of polar extracts (devoid of curcuminoids) of Curcuma longa (C. longa) has seldom been studied. In this study, we have investigated immune-stimulatory and anti-inflammatory activities of an aqueous based extract of C. longa (NR-INF-02) and its fractions in presence and absence of mitogens. Materials and Methods: Effects of NR-INF-02 (Turmacin™, Natural Remedies Pvt. Ltd., Bangalore, India) on proliferation, nitric oxide (NO), monocyte chemotactic protein-1 (MCP-1), interleukins (ILs) and prostaglandin (PGE2) levels of mouse splenocytes and mouse macrophage (RAW264.7) cells were determined. Results: NR-INF-02 increased splenocytes number in presence and absence of lipopolysaccharide (LPS) or concanavalin A. Treatment of NR-INF-02 showed a significant increase of NO, IL-2, IL-6, IL-10, IL-12, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and MCP-1 production in unstimulated mouse splenocytes and mouse macrophages. Interestingly, NR-INF-02 showed potent inhibitory effect towards release of PGE2 and IL-12 levels in LPS stimulated mouse splenocytes. Further, NR-INF-02 was fractionated into polysaccharide fraction (F1) and mother liquor (F2) to study their immune-modulatory effects. F1 was found to be more potent than F2 toward inhibiting PGE2 and IL-12 in LPS stimulated splenocytes. Conclusion: Present findings revealed the novel anti-inflammatory property of NR-INF-02 and its polysaccharide fraction by inhibiting the secretion of IL-12 and PGE2 in vitro.

Chandrasekaran, Chinampudur V.; Sundarajan, Kannan; Edwin, Jothie R.; Gururaja, Giligar M.; Mundkinajeddu, Deepak; Agarwal, Amit



Inflammatory Regulation Effect and Action Mechanism of Anti-Inflammatory Effective Parts of Housefly (Musca domestica) Larvae on Atherosclerosis  

PubMed Central

The protein-enriched extracts of housefly larvae were segregated by gel-filtration chromatography (GFC) and then anti-inflammatory activity screening in RAW264.7 (induced by LPS) was carried out. After acquire the anti-inflammatory effective parts, its anti-atherosclerotic properties in vivo were then evaluated. Results showed that the anti-inflammatory effective parts of housefly larvae were low-molecular-weight parts. After treated with the effective parts oral gavaged for 4 weeks, the atherosclerotic lesions of the mouse were significantly decreased. The inflammatory and lipid parameters were also reduced (except HDL which was increased). Western blot analysis demonstrated that the effective parts exerted potent inhibitory effect on expression of p65 in nucleus and cytoplasm. The results of immunofluorescence microscopy analysis also showed that the expressions of p65 both in cytoplasm and nucleus were significantly reduced. The hypothesis that the anti-inflammatory effective parts of housefly larvae possessed anti-atherosclerosis activity in mouse and the possible mechanism could be associated with the inhibition of expression and nuclear transfer of NF-?B p65 could be derived.

Chu, Fu Jiang; Jin, Xiao Bao; Xu, Yin Ye; Ma, Yan; Li, Xiao Bo; Lu, Xue Mei; Liu, Wen Bin; Zhu, Jia Yong



Anti-inflammatory properties of drugs from saffron crocus.  


The medicinal uses of saffron (Crocus sativus Linnaeus) have a long history beginning in Asian countries since the Late Bronze Age. Recent studies have validated its potential to lower the risk of several diseases. Some metabolites derived from saffron stigmas exert numerous therapeutic effects due to hypolipidemic, antitussive, antioxidant, antidiabetic activities and many others. Water and ethanol extracts of Crocus sativus L. are cardioprotective and counteract neurodegenerative disorders. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. Botany, worldwide spreading of cultivars, biochemical pathways, active constituents and chemical detection methods are reviewed. Therapeutic uses of saffron principles with particular regard to those exhibiting antioxidant and thus anti-inflammatory features are discussed. To date, very few adverse health effects of saffron have been demonstrated. At high doses (more than 5 g/die day), it should be avoided in pregnancy owing to its uterine stimulation activity. PMID:22934747

Poma, Anna; Fontecchio, Gabriella; Carlucci, Giuseppe; Chichiriccò, Giuseppe



Synthesis and anti-inflammatory activity evaluation of some novel 6-alkoxy(phenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine derivatives.  


Starting from phthalic anhydride, several new 6-alkoxy(phenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine derivatives were synthesized as potent anti-inflammatory agent. The study showed that the compounds 6h (6-(2-chlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine) and 6s (6-(4-aminophenoxy)-[1,2,4] triazolo[3,4-a]phthalazine-3-amine) exhibited the highest anti-inflammatory activity (81% and 83% inhibition, respectively, at 0.5 h after i.p. administration) which were slightly more potent than the reference drug Ibuprofen (61%). Furthermore, the peak activity of 6h and 6s was observed at the 3 h after p.o. administration, and they exhibited stronger anti-inflammatory activity than Ibuprofen at the dose of 50 mg/kg at the peak time. PMID:20813431

Sun, Xian-Yu; Hu, Chuan; Deng, Xian-Qing; Wei, Cheng-Xi; Sun, Zhi-Gang; Quan, Zhe-Shan



Cyclooxygenase2-selective Nonsteroidal Anti-Inflammatory Drugs Inhibit Hepatocyte Growth Factor\\/Scatter Factor-induced Angiogenesis  

Microsoft Academic Search

Epidemiological studies have indicated a reduced risk of malignancies with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), although the exact mechanisms are debated. NSAIDs inhibit angiogenesis, which is a key step for tumor growth. Hepatocyte growth factor\\/scatter factor (HGF\\/SF), a potent and independent angiogenic factor, has been impli- cated in tumorigenesis, but limited knowledge exists on the potential targets for

Shiladitya Sengupta; Lynda A. Sellers; Tereza Cindrova; Jeremy Skepper; Ermanno Gherardi; Ram Sasisekharan; Tai-Ping D. Fan



Bee venom injection produces a peripheral anti-inflammatory effect by activation of a nitric oxide-dependent spinocoeruleus pathway  

Microsoft Academic Search

Our recent data, obtained using a zymosan-induced inflammatory air pouch model in mice, have demonstrated that subcutaneous bee venom (BV) injection into the hind limb selectively activates the contralateral brain stem locus coeruleus (LC) and then via a descending noradrenergic pathway and subsequent adrenal medullary catecholamine release induces a potent anti-inflammatory effect. While the efferent limb of this BV-induced neuroimmune

Seo-Yeon Yoon; Young-Bae Kwon; Hyun-Woo Kim; Dae-Hyun Roh; Hyoung-Sig Seo; Ho-Jae Han; Hye-Jung Lee; Alvin J. Beitz; Jang-Hern Lee



The anti-inflammatory properties of rose-hip.  


The anti-inflammatory properties of rose-hip are described in this short report. Rose-hip extract reduced chemotaxis of peripheral blood neutrophils and monocytes of healthy subjects in vitro. Daily intake of rose-hip powder for four weeks by healthy volunteers and patients suffering from osteoarthritis, resulted in reduced serum C-reactive protein (CRP) levels and reduced chemotaxis of peripheral blood neutrophils. The results indicate that rose-hip possesses anti-inflammatory properties and might be used as a replacement or supplement for conventional drug therapies in patients with osteoarthritis. PMID:17657447

Winther, K; Rein, E; Kharazmi, A



Synthesis and anti-inflammatory activity of three nitro chalcones.  


The aim of this study was to synthesize three nitro substituted chalcones and to evaluate their anti-inflammatory activity in the model of carrageenan induced edema in rats. The nitro chalcone were prepared by aldol condensation using of mechanical agitation and environmentally friendly solvents with 72-73% yields in approximately 2h. The three structures were evaluated on biological activity at dose of 200mg/kg and they showed anti-inflammatory protective effect by both oral and intraperitoneal administration, this effect was time dependent. PMID:24012185

Gómez-Rivera, Abraham; Aguilar-Mariscal, Hidemí; Romero-Ceronio, Nancy; Roa-de la Fuente, Luis F; Lobato-García, Carlos E



Anti-inflammatory activity of some copper(II) complexes.  


Anti-inflammatory activity of some copper(II) neutral complexes and complexated salts on different animal models of inflammation has been investigated. In a preliminary screening 5 complexes were selected for a more extensive study based on their capacity inhibiting the rat hind paw edema induced by carrageenin. These selected complexes showed inhibitory action on acute and subacute inflammation with an activity degree higher than that of indometacin. They were also effective inhibitors of primary and secondary lesions in the adjuvant-induced arthritis, with an activity similar to phenylbutazone. These complexes had no topical anti-inflammatory effect. PMID:2242084

Frechilla, D; Lasheras, B; Ucelay, M; Parrondo, E; Craciunescu, G; Cenarruzabeitia, E



Anti-inflammatory new coumarin from the Ammi majus L  

PubMed Central

Investigation of the aerial parts of the Egyptian medicinal plant Ammi majus L. led to isolation of new coumarin, 6-hydroxy-7-methoxy-4 methyl coumarin (2) and 6-hydroxy-7-methoxy coumarin (3); this is the first time they have been isolated from this plant. The structures of the compounds (2 &3) were elucidated by spectroscopic data interpretation and showed anti-inflammatory and anti-viral activity. Graphical abstract An efficient, one-new coumarin (2) was isolated from the aerial parts of the A. Majus L. was evaluated for their anti-viral and anti-inflammatory activities.



Anti-inflammatory activity of some Saudi Arabian medicinal plants.  


Five plants which have been used for the treatment of rheumatism, arthritis and gout in the traditional medicine of Saudi Arabia, were evaluated for their anti-inflammatory properties. Of these the ethanolic extract of Capparis decidua and the aqueous extract of Capparis spinosa were found to possess significant anti-inflammatory activity against carrageenan induced oedema in rats. These two plants were also tested for their antipyretic and analgesic activity. C. decidua was found to possess significant antipyretic effect. Both of them are devoid of analgesic activity. PMID:3485894

Ageel, A M; Parmar, N S; Mossa, J S; Al-Yahya, M A; Al-Said, M S; Tariq, M



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


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. PMID:20149612

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



Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3.  


Uncontrolled inflammation is now considered to be a link between many widely occurring diseases. Thus, controlling the innate inflammatory response and its local chemical mediators has been receiving increasing attention. We recently identified a novel family of eicosapentaenoic acid (EPA)-derived mediators produced by eosinophils, denoted as resolvin E3 (RvE3), that possess potent anti-inflammatory actions both in vitro and in vivo. Carbons at 17 and 18 positions are asymmetric and thus the molecule has a total of four potential stereoisomers. Here, we assigned the stereochemistry of the conjugated double bonds and chirality of alcohols present in two natural isomers of RvE3 with four different stereoisomers prepared by total organic synthesis. The complete structures of two natural isomers of RvE3 were determined to be 17R,18S- and 17R,18R-dihydroxy-5Z,8Z,11Z,13E,15E-EPA, respectively. These natural isomers prepared by total organic synthesis displayed a potent anti-inflammatory action by limiting neutrophil infiltrations both in vitro and in vivo. The unnatural stereoisomers were much less active compared with the natural isomers, demonstrating the stereoselective action of RvE3. PMID:23293324

Isobe, Yosuke; Arita, Makoto; Iwamoto, Ryo; Urabe, Daisuke; Todoroki, Hidenori; Masuda, Koji; Inoue, Masayuki; Arai, Hiroyuki



Famotidine for healing and maintenance in nonsteroidal anti- inflammatory drug-associated gastroduodenal ulceration  

Microsoft Academic Search

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulceration. How to manage patients with NSAID-associated ulcers is a common clinical dilemma. High-dose famotidine in the healing and maintenance of NSAID-associated gastroduodenal ulceration was therefore evaluated. METHODS: One hundred four patients with rheumatoid or osteoarthritis who had gastroduodenal ulceration received famotidine, 40 mg twice daily. Sixteen patients

N Hudson; AS Taha; RI Russell; P Trye; J Cottrell; SG Mann; AJ Swanell; CJ Hawkey



Non-steroidal anti-inflammatory drugs for athletes: An update  

Microsoft Academic Search

Sports medicine physicians often treat athletes in pain with non-steroidal anti-inflammatory drugs (NSAIDs). However, there is a lack of high-quality evidence to guide NSAID use. Their adverse effects have clinical relevance, and their possible negative consequences on the long-term healing process are slowly becoming more obvious. This article provides some practical management guidelines for the use of NSAIDs, developed to

J.-L. Ziltener; S. Leal; P.-E. Fournier



In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin A.  


Urolithin A is a major metabolite produced by rats and humans after consumption of pomegranate juice or pure ellagitannin geraniin. In this study, we investigated the anti-inflammatory effect of urolithin A on carrageenan-induced paw edema in mice. The volume of paw edema was reduced at 1h after oral administration of urolithin A. In addition, plasma in treated mice exhibited significant oxygen radical antioxidant capacity (ORAC) scores with high plasma levels of the unconjugated form at 1h after oral administration of urolithin A. These results indicate strong associations among plasma urolithin A levels, the plasma ORAC scores, and anti-inflammatory effects and may help explain a mechanism by which ellagitannins confer protection against inflammatory diseases. PMID:21843938

Ishimoto, Hidekazu; Shibata, Mari; Myojin, Yuki; Ito, Hideyuki; Sugimoto, Yukio; Tai, Akihiro; Hatano, Tsutomu



Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites  

PubMed Central

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation.

Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.



The Use of Nonsteroidal Anti-Inflammatory Drugs in Sports.  

ERIC Educational Resources Information Center

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)

Calabrese, Leonard H.; Rooney, Theodore W.



Type I Interferons as Anti-Inflammatory Mediators  

NSDL National Science Digital Library

The type I interferons (IFNs), IFN-α and IFN-β, are cytokines that have antiviral, antiproliferative, and immunomodulatory activities. Data are now emerging that suggest that type I IFNs are also important mediators of anti-inflammatory responses. These findings, largely driven by studies to explain the beneficial effects of IFN-β in the treatment of multiple sclerosis, an autoimmune disease of the central nervous system, offer a number of mechanisms for the anti-inflammatory properties of type I IFNs. Type I IFNs, through their ability to induce the immunosuppressive cytokine interleukin-10 (IL-10), mediate the inhibition of proinflammatory gene products. In addition, type I IFNs induce other immunosuppressive mediators such as suppressor of cytokine signaling–1 (SOCS-1) and tristetrapolin (TTP), which act by divergent mechanisms to restore homeostasis to the immune system. Furthermore, type I IFNs mediate anti-inflammatory and protective effects in a variety of autoimmune disease models such as experimental colitis, experimental allergic encephalomyelitis, experimental arthritis, and neonatal inflammation. Here, we discuss the molecular basis for the anti-inflammatory properties of type I IFNs and their therapeutic potential in autoimmune and inflammatory diseases.

Etty N. Benveniste (University of Alabama at Birmingham;Department of Cell Biology REV); Hongwei Qin (University of Alabama at Birmingham;Department of Cell Biology REV)



Plant phenylpropanoids as emerging anti-inflammatory agents.  


Plant-derived phenylpropanoids (PPPs) compose the largest group of secondary metabolites produced by higher plants, mainly, for the protection against biotic or abiotic stresses such as infections, wounding, UV irradiation, exposure to ozone, pollutants, and herbivores. PPPs are parent molecules for biosynthesis of numerous structurally and functionally diverse plant polyphenols (simple phenolic acids and esters, glycosylated derivatives of primary PPPs, flavonoids, isoflavonoids, stilbenes, coumarins, curcuminoids, lignans, etc.), which play multiple essential roles in plant physiology. During the last few decades, extensive research has been dedicated to natural and biotechnologically produced PPPs for medicinal use as antioxidants, UV screens, anticancer, antiviral, anti-inflammatory, wound healing, and antibacterial agents. In the present review, the metabolic pathways of phenylpropanoid biosynthesis in plants and their re-construction in biotechnologically engineered systems are described. Chemical physical peculiarities of PPPs defining their antioxidant, metal chelating, and UV-protecting effects as a molecular basis for their anti-inflammatory properties are discussed as well. We focused also on the discovery of PPPs-based anti-inflammatory agents since distinct PPPs were found to modulate molecular pathways underlying inflammatory responses in human cells triggered by different pro-inflammatory stimuli in vitro and to inhibit inflammation in various tissues in vivo. The problem of low bioavailability, fast metabolism, and potential toxicity/sensitization as limiting factors for the development of PPPs-based anti-inflammatory drugs is also highlighted. PMID:21762105

Korkina, L; Kostyuk, V; De Luca, C; Pastore, S



Inhibition of basophil histamine release by anti-inflammatory steroids  

Microsoft Academic Search

The release of histamine from human leukocytes is a useful in vitro model for studying allergic disease1. Many of the drugs used in the treatment of allergy and asthma (for example, isoprenaline and theophylline) are effective inhibitors of in vitro histamine release2. However, the anti-inflammatory steroids have not been found to inhibit the in vitro release of histamine from mast

Robert P. Schleimer; Elizabeth Gillespie



Anti-inflammatory properties of desipramine and fluoxetine  

Microsoft Academic Search

BACKGROUND: Antidepressants are heavily prescribed drugs and have been shown to affect inflammatory signals. We examined whether these have anti-inflammatory properties in animal models of septic shock and allergic asthma. We also analysed whether antidepressants act directly on peripheral cell types that participate in the inflammatory response in these diseases. METHODS: The antidepressants desipramine and fluoxetine were compared in vivo

Caroline Roumestan; Alain Michel; Florence Bichon; Karine Portet; Maëlle Detoc; Corinne Henriquet; Dany Jaffuel; Marc Mathieu



Transdermal nitroglycerin prevents nonsteroidal anti-inflammatory drug gastropathy  

Microsoft Academic Search

The application of a transdermal nitroglycerin patch (2–30 ?g\\/3 h\\/rat) protected, in a dose-dependent manner, the rat gastric mucosa against damage induced by the nonsteroidal anti-inflammatory agent indomethacin (20 mg\\/kg s.c.).

Ma. Dolores Barrachina; Sara Calatayud; Amparo Canet; Regina Bello; Francisco Díaz de Rojas; Paul H. Guth; Juan V. Esplugues



Anti-inflammatory cytokines and risk of type 2 diabetes.  


Proinflammatory processes have been investigated extensively in the development of type 2 diabetes, but our knowledge on anti-inflammatory proteins is rather limited. This article summarizes studies that investigated associations between circulating levels of anti-inflammatory cytokines and incident type 2 diabetes preferably in prospective epidemiological studies. Adiponectin is the only known anti-inflammatory protein whose circulating levels are decreased before type 2 diabetes. In contrast, concentrations of interleukin-1 receptor antagonist (IL-1RA), transforming growth factor-?1 (TGF-?1) and growth differentiation factor-15 (GDF-15) are increased and indicate the presence of a compensatory, but eventually futile, counter-regulation of proinflammatory stimuli. Importantly, a proof-of-principle study using recombinant IL-1RA to improve metabolic control in patients with type 2 diabetes demonstrated that a more pronounced upregulation of this protein than that found in the natural course of diabetes development may have clinical relevance. Other interesting candidates like omentin (which shows similar associations with metabolic parameters as adiponectin), interleukin-10 (IL-10) and secreted frizzled-related protein-5 (Sfrp5) are currently less well studied with sometimes conflicting results regarding their association with type 2 diabetes. Thus, further research is required to better understand the causal role of proinflammatory cytokines, hypoadiponectinaemia and the upregulation of anti-inflammatory proteins before the onset of type 2 diabetes. PMID:24003920

Herder, C; Carstensen, M; Ouwens, D M



Anti-inflammatory pathways as a host evasion mechanism for pathogens.  


Lipoxins play a key role in controlling potent pro-inflammatory responses triggered by infection with pathogens, such as Toxoplasma gondii and Mycobacterium tuberculosis. In order to contain microbial dissemination, infected hosts must mount a powerful immune response to prevent mortality. The onset of the chronic phase of infection is characterized by continuous cell-mediated immunity. Such potent responses are kept under tight control by a class of anti-inflammatory eicosanoids, the lipoxins. Here, we review such immune-containment strategies from the host's perspective, to keep pro-inflammatory responses under control during chronic disease, as well as from the perspective of the pathogen, which pirates the host's lipoxygenase machinery to its own advantage as a probable immune-escape mechanism. PMID:15982863

Aliberti, Julio; Bafica, Andre


Quinones bearing non-steroidal anti-inflammatory fragments as multitarget ligands for Alzheimer's disease.  


The anti-amyloid properties shared by several quinones inspired the design of a new series of hybrids derived from the multi-target drug candidate memoquin (1). The hybrids consist of a central benzoquinone core and a fragment taken from non-steroidal anti-inflammatory drugs, connected through polyamine linkers. The new hybrids retain the potent anti-aggregating activity of the parent 1, while exhibiting micromolar AChE inhibitory activities. Remarkably, 2, 4, (R)-6 and (S)-6 were A? aggregation inhibitors even more potent than 1. The balanced amyloid/cholinesterase inhibitory profile is an added value that makes the present series of compounds promising leads against Alzheimer's disease. PMID:24140444

Prati, Federica; Bartolini, Manuela; Simoni, Elena; De Simone, Angela; Pinto, Antonella; Andrisano, Vincenza; Bolognesi, Maria Laura



Innovative formulations for the controlled and site-specific delivery of anti-inflammatory drugs.  


Pharmaceutical technology has introduced a promising pathway in the future of medicinein particular nanotechnological innovations have provided the opportunity to design and develop efficient drug delivery systems able to target and treat several diseases, including those mediated by inflammation. The engineering of drug delivery systems can be used to target tissues involved in the pathology under treatment, to avoid early drug biological environmental degradation and to modulate drug pharmacokinetics. Glucocorticoids and non-steroidal anti-inflammatory drugs are the most commonly prescribed drug categories worldwide for the treatment of disorders associated with inflammation. Although glucocorticoids can be highly effective in treating inflammation, their systemic application is limited due to the high incidence of serious adverse effects, mainly in long-term treatment. Non-steroidal anti-inflammatory drugs are a heterogeneous group of compounds and most of them have unfavorable pharmacokinetics and pharmacodynamics, leading to adverse effects, such as gastrointestinal disorders. Therefore, the need for drug delivery systems for long term administration of anti-inflammatory drugs witha well-controlled release profile is evident. The aim of this review is to assess innovative colloidal drugs carriers, in particular liposomes and nanoparticles, with special focus on site-specific delivery for particularly problematic tissues such as the gastrointestinal tract, joints and eyes. PMID:23489201

Serpe, L; Canaparo, R; Foglietta, F; Zara, G P



Viscum album Exerts Anti-Inflammatory Effect by Selectively Inhibiting Cytokine-Induced Expression of Cyclooxygenase-2  

PubMed Central

Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1? and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1?-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

Hegde, Pushpa; Maddur, Mohan S.; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srini V.



Mechanisms of the anti-inflammatory actions of the angiotensin type 1 receptor antagonist losartan in experimental models of arthritis.  


Angiotensin (Ang) II and its AT1 receptors have been implicated in the pathogenesis of rheumatoid arthritis. Activation of the counter-regulatory Ang-(1-7)-Mas receptor axis may contribute to some of the effects of AT? receptor blockers (ARBs). In this study, we have used losartan, an ARB, to investigate the role of and the mechanisms by which AT? receptors participated in two experimental models of arthritis: antigen-induced arthritis (AIA) in mice and adjuvant-induced arthritis (AdIA) in rats. Treatment with losartan decreased neutrophil recruitment, hypernociception and the production of TNF-?, IL-1? and chemokine (C-X-C motif) ligand 1 in mice subjected to AIA. Histopathological analysis showed significant reduction of tissue injury and inflammation and decreased proteoglycan loss. In addition to decreasing cytokine production, losartan directly reduced leukocyte rolling and adhesion. Anti-inflammatory effects of losartan were not associated to Mas receptor activation and/or Ang-(1-7) production. Anti-inflammatory effects were reproduced in rats subjected to AdIA. This study shows that ARBs have potent anti-inflammatory effects in animal models of arthritis. Mechanistically, reduction of leukocyte accumulation and of joint damage was associated with local inhibition of cytokine production and direct inhibition of leukocyte-endothelium interactions. The anti-inflammatory actions of losartan were accompanied by functional improvement of the joint, as seen by reduced joint hypernociception. These findings support the use of ARBs for the treatment of human arthritis and provide potential mechanisms for the anti-inflammatory actions of these compounds. PMID:23727291

Silveira, Kátia D; Coelho, Fernanda M; Vieira, Angélica T; Barroso, Lívia C; Queiroz-Junior, Celso M; Costa, Vívian V; Sousa, Larissa F C; Oliveira, Marilene L; Bader, Michael; Silva, Tarcíla A; Santos, Robson A S; Silva, Ana Cristina Simões E; Teixeira, Mauro M



Exogenous ghrelin modulates release of pro- and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways  

PubMed Central

Ghrelin, an orexigenic 28 amino-acid peptide, has been studied primarily in relation to the control of appetite and fat metabolism. In addition to these well-known functions, ghrelin, and its target receptors, growth hormone secretagogue receptors (GHS-Rs), have been localized to neutrophils, lymphocytes and macrophages suggesting that ghrelin may be involved in immune modulation. To assess the therapeutic role of ghrelin in production of pro-inflammatory and anti-inflammatory cytokines, the effects of exogenous ghrelin administration on the regulation of cytokine release in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages were analyzed. Ghrelin and GHS-Rs are expressed in murine macrophages. In addition, exogenous ghrelin inhibited the production of pro-inflammatory cytokines IL-1? & TNF-? in LPS-stimulated murine macrophages in a dose dependent and time-dependent fashion. Exogenous ghrelin pretreatment resulted in a decrease in LPS-induced NF?B activation and was presumably the reason for this ghrelin-mediated effect. In contrast to these findings, exogenous ghrelin significantly augmented the release of the anti-inflammatory cytokine IL-10 in a dose dependent and time-dependent fashion from LPS-stimulated murine macrophages. Ghrelin administration enhanced activation of p38 MAPK, which is known to control the release of IL-10 in macrophages independent of the NF?B pathway. These effects of ghrelin on both pro- and anti-inflammatory cytokines were offset when a specific GHS-R receptor antagonist was added to the culture media. In conclusion, these data suggest that ghrelin has potent anti-inflammatory properties through modulation of secretion of both pro- and anti-inflammatory cytokines from LPS-stimulated macrophages through distinct signaling cascades. Therapeutic utility of ghrelin to control, modulate or treat pathologic inflammatory conditions like endotoxemic shock and ulcerative colitis requires further investigation.

Waseem, Talat; Duxbury, Mark; Ito, Hiromichi; Ashley, Stanley W.; Robinson, Malcolm K.



644. Gene Delivery for Chronic Pain Control: Micrcroencapsulated Plasmid DNA Encoding the Anti-Inflammatory Cytokine Gene, Interleukin10 (IL10)  

Microsoft Academic Search

Chronic pain control is a major unresolved clinical problem. Spinal cord astrocytes & microglia are critically involved in the creation & maintenance of diverse enhanced pain states via the release of proinflammatory cytokines. Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, suppresses proinflammatory cytokine production & activity. We have previously shown that administration of IL-10 protein directly or via a viral vector

Erin D. Milligan; Melissa J. Mahoney; Stephen J. Langer; Travis Hughes; Evan M. Sloane; John Mahoney; Brian Jekich; Pedro E. Cruz; Terence R. Flotte; Steve F. Maier; Kirk W. Johnson; Leslie A. Leinwand; Raymond A. Chavez; Linda R. Watkins



Valuation of anti-inflammatory and antinociceptive activities of Erica species native to Turkey.  


Erica L. species (Ericaceae) have been popularly used as antirheumatic, diuretic, astringent and treatment of urinary infections. In order to evaluate this information, anti-inflammatory and antinociceptive activities of different extracts prepared with methanol, chloroform, ethyl acetate, n-butanol and water from the aerial parts of Erica arborea L., Erica manipuliflora Salisb., Erica bocquetii (Pe?men) P.F. Stevens and Erica sicula Guss. subsp. libanotica (C.&W. Barbey) P.F. Stevens (Ericaceae) of Turkish origin were investigated by using in vivo methods. For the anti-inflammatory activity, carrageenan-induced hind paw edema model, PGE(2)-induced hind paw edema model, and 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema model and for the antinociceptive activity p-benzoquinone-induced writhing test in mice were employed. The ethyl acetate extracts of Erica arborea (EAE), Erica bocquetii (EBE) and Erica manipuliflora (EME) exhibited notable inhibition against carrageenan-induced (24.1-32.3%, 23.8-36.1%, 29.2-35.1%, respectively) and PGE(2)-induced (21.2-37.7%, 6.8-29.7%, and 6.2-34.1%, respectively) hind paw edema as well as TPA-induced mouse ear edema models in mice, while the ethyl acetate extract of Erica sicula subsp. libanotica (ESE) (10.7-29.7%) displayed potent anti-inflammatory activity only on the PGE(2)-induced hind paw edema model. However, the remaining extracts were found to be inactive against inflammatory models. Same extracts, i.e., EAE, EBE and EME were also found to exhibit remarkable antinociceptive activity in p-benzoquinone-induced abdominal constriction test at a dose of 100mg/kg (46.5%, 27.7% and 36.3%, respectively). PMID:18164152

Akkol, Esra Küpeli; Ye?ilada, Erdem; Güvenç, Aysegül



Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids.  


A variety of novel aromatic and heterocyclic aromatic curcuminoids were synthesised, characterised and their anti-inflammatory activities (AIA) determined in vivo. Some of these compounds also were tested for inflammatory mediator production. The AIA of the main representatives of these compounds were assessed by oral administration to female Wistar rats using (a) acute carrageenan-induced paw oedema, (b) chronic adjuvant arthritis (therapeutic mode), and (c) anti-pyretic activity assessed in the yeast pyrexia. Gastric ulceration was determined in pre-inflamed rats. Natural curcumin showed modest aspirin-like anti-inflammatory activity which was enhanced when co-administered with the PGE(1) analogue misoprostol as a synergist. In contrast, four novel curcuminoids (RK-97, RK-103, RK-104 and RK-106) in which the bis-methoxy-phenyl group of curcumin was replaced with bis-dimethoxybutenolidyl-(ascorbate), bis-naphthyl, and bis-furanyl derivatives, respectively, had potent activity in the anti-arthritic assay with little gastric or systemic toxicity, compared with the vehicle-treated controls. Of the curcuminoids the furan RK-106 was the only compound to inhibit production of TNF? and IL-1? in a monocytic cell-line THP-1 in vitro. The inactivity of RK-106 on the production of PGE(2) may be related to its absence of gastrotoxicity. None of the curcuminoids exhibited anti-pyretic activity and this may also be related to its insensitivity to PGE(2). Thus, these novel curcuminoids, such as RK-106, may warrant the development of new low gastro-toxic anti-inflammatory agents with selective inhibitory activity of cytokine inflammatory mediators. PMID:22172598

Khan, M Akram; El-Khatib, Riyad; Rainsford, K D; Whitehouse, M W



Antinociceptive, anti-inflammatory and antiulcerogenic activities of ethanol root extract of Strophanthus hispidus DC (Apocynaceae).  


Abstract Background: Strophanthus hispidus DC (Apocynaceae) is a medicinal plant widely used in traditional African medicine in the treatment of rheumatic afflictions, ulcer, conjunctivitis, leprosy and skin diseases. This study sought to investigate the antinociceptive, anti-inflammatory and antiulcer properties of the ethanol root extract of S. hispidus. Methods: Antinociceptive activity was evaluated using acetic acid-induced writhing and formalin tests in mice. The carrageenan- and egg albumin-induced rat paw edema tests were used to investigate the anti-inflammatory actions, whereas the antiulcer activity was investigated using ethanol-, HCl- and pyloric ligation-induced gastric ulcer models in rats. Results: S. hispidus [100-800 mg/kg orally (po)] produced significant (p<0.05) inhibition of writhing reflex with peak effect of 74.13% inhibition observed at 800 mg/kg. Similarly, S. hispidus significantly (p<0.05) attenuated formalin-induced early and late phase of nociception with peak effect of 61.84% and 89.43%, respectively, at 200 mg/kg. S. hispidus (25-800 mg/kg po) caused significant (p<0.05) inhibition of edema development in the carrageenan and egg albumin models with peak effect (93.40% and 90.10% inhibition of edema formation) observed at 50 mg/kg. With respect to antiulcer activity, S. hispidus (100-800 mg/kg) showed potent antiulcer activity with respective peak effects of 96% (ethanol-induced), 99% (HCl-induced) and 70.60% inhibition of ulcer. Conclusions: The findings in this study suggest that the ethanol root extract of S. hispidus possesses antinociceptive, anti-inflammatory and antiulcerogenic activities. This justifies the use of the extract in folklore medicine for the treatment of ulcer and inflammatory disorders. PMID:23729560

Ishola, Ismail O; Awodele, Olufunsho; Oreagba, Ibrahim A; Murtala, Abdulahi A; Chijioke, Micah C



The antioxidant and anti-inflammatory effects of phenolic compounds isolated from the root of Rhodiola sachalinensis A. BOR.  


Isolation of compounds from the root of Rhodiola sachalinensis (RRS) yielded tyrosol (1), salidroside (2), multiflorin B (3), kaempferol-3,4'-di-O-?-D-glucopyranoside (4), afzelin (5), kaempferol (6), rhodionin (7), and rhodiosin (8). Quantification of these compounds was performed by high-performance liquid chromatography (HPLC). To investigate the antioxidant and anti-inflammatory effects of the compounds, DPPH radical scavenging, NBT superoxide scavenging and nitric oxide production inhibitory activities were examined in LPS-stimulated Raw 264.7 cells. We suggest that the major active components of RRS are herbacetin glycosides, exhibiting antioxidant activity, and kaempferol, exhibiting anti-inflammatory activity. PMID:23018923

Choe, Kang In; Kwon, Joo Hee; Park, Kwan Hee; Oh, Myeong Hwan; Kim, Manh Heun; Kim, Han Hyuk; Cho, Su Hyun; Chung, Eun Kyung; Ha, Sung Yi; Lee, Min Won



Screening of Bioactive Compounds from Moutan Cortex and Their Anti-Inflammatory Activities in Rat Synoviocytes  

PubMed Central

Moutan Cortex, a widely used traditional Chinese medicine for the treatment of various diseases, is the root bark of Paeonia suffruticosa Andrews (Paeoniaceae). Most of the pharmacological investigations of Moutan Cortex have been addressed to its central nervous system activities, anti-oxidative and sedative actions. Otherwise, there are few reports about the active compounds with anti-inflammatory activity of Moutan Cortex. The aim of the present study was to screen and identify bioactive compounds with anti-inflammatory effect from Moutan Cortex. With the aid of preparative high performance liquid chromatography (HPLC) technique, ethyl acetate and ethanol extract of Moutan Cortex were isolated into twenty-two fractions. Bioactivities of these fractions were evaluated by measuring expression of tumor necrosis factor-? (TNF-?) in rat synoviocytes subjected to interleukin-1? (IL-1?). Eight compounds were isolated from six active fractions and identified by HPLC/MSn. Purified compounds, paeoniflorin, paeonol and pentagalloylglucose resulted in dose-dependent inhibition of TNF-? synthesis and IL-6 production in synoviocytes treated with proinflammatory mediator. These results suggested that paeonol, paeoniflorin, glycosides and pentagalloylglucose contribute to the anti-inflammatory effect of Moutan Cortex.

Wu, Mengjie



Pharmacological study of a new anti-inflammatory steroid, tixocortol pivalate (JO 1016).  


Some pharmacological activities of pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol pivalate, JO 1016 Pivalone), a new steroidal anti-inflammatory compound, are described. The anti-inflammatory activity of tixocortol pivalate has been clearly demonstrated in various tests using adrenalectomised and intact animals. Of particular interest is the dissociation of its local and systemic activities. Comparison with hydrocortisone acetate indicates a similar or greater anti-inflammatory activity, by either the local or topical routes, but tixocortol pivalate is between 60 and 300 times less active than hydrocortisone acetate after oral or subcutaneous administration. Glucocorticoid activity was only detected at very high oral doses of tixocortol pivalate and the highest tested subcutaneous dose (300 mg/kg) failed to induce significant activity. Hydrocortisone acetate exerted glucocorticoid effects at much lower doses. It is possible therefore the local or topical use of tixocortol pivalate in therapy may not cause the unwanted side effects of many of the corticosteroids in current use. PMID:6784734

Davies, J E; Kellet, D N; Staniforth, M W; Torossian, R; Grouhel, A



Cerebroprotective potential of resveratrol through anti-oxidant and anti-inflammatory mechanisms in rats.  


Oxidative stress and inflammation are two important pathological mechanisms involved in cerebral ischemia and reperfusion injury. In pathological conditions such as cerebral infarction, the free radical production is greater than that of elimination by endogenous anti-oxidant system, by this undesirable effect brain is highly injured. Resveratrol is reported to have anti-oxidant and anti-inflammatory, athero-protective activities. Therefore, the aim of the present study is to evaluate the therapeutic potential of resveratrol against cerebral infarction induced by ischemia and reperfusion injury in Wistar rats. Bi-common carotid occlusion followed by 4 h reperfusion model was used to induce cerebral infarction. Percent infarction, oxidative stress markers (malondialdehyde, catalase, superoxide dismutase) and inflammatory markers (myeloperoxidase, TNF-?, IL-6, ICAM-1 and IL-10) were measured. TNF-?, IL-6, IL-10, and intracellular adhesive molecule-I (ICAM-1) levels were quantified by enzyme-linked immunosorbent assay (ELISA). Resveratrol produced significant dose-dependent reduction in percent cerebral infarct volume. At resveratrol 20 mg/kg dose, there was a significant reduction in oxidative stress and inflammatory markers like malondialdehyde, TNF-?, IL-6, myeloperoxidase and ICAM-I and in contrast there was a significant increase in anti-oxidants and anti-inflammatory markers like superoxide dismutase, catalase and IL-10 levels. Resveratrol showed significant cerebroprotective action mediated by anti-oxidant and anti-inflammatory mechanisms. PMID:23371441

Orsu, Prabhakar; Murthy, B V S N; Akula, Annapurna



The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis  

PubMed Central

Background It has been generally well accepted that chronic inflammation is a necessary component of lung fibrosis but this concept has recently been challenged. Methods Using biochemical, histological, immunohistochemistry, and cellular analyses, we compared the lung responses (inflammation and fibrosis) to fibrogenic silica particles (2.5 and 25 mg/g lung) in Sprague-Dawley rats and NMRI mice. Results Rats treated with silica particles developed chronic and progressive inflammation accompanied by an overproduction of TNF-? as well as an intense lung fibrosis. Dexamethasone or pioglitazone limited the amplitude of the lung fibrotic reaction to silica in rats, supporting the paradigm that inflammation drives lung fibrosis. In striking contrast, in mice, silica induced only a limited and transient inflammation without TNF-? overproduction. However, mice developed lung fibrosis of a similar intensity than rats. The fibrotic response in mice was accompanied by a high expression of the anti-inflammatory and fibrotic cytokine IL-10 by silica-activated lung macrophages. In mice, IL-10 was induced only by fibrotic particles and significantly expressed in the lung of silica-sensitive but not silica-resistant strains of mice. Anti-inflammatory treatments did not control lung fibrosis in mice. Conclusion These results indicate that, beside chronic lung inflammation, a pronounced anti-inflammatory reaction may also contribute to the extension of silica-induced lung fibrosis and represents an alternative pathway leading to lung fibrosis.

Barbarin, Virginie; Nihoul, Aurelie; Misson, Pierre; Arras, Mohammed; Delos, Monique; Leclercq, Isabelle; Lison, Dominique; Huaux, Francois



MFG-E8 released by apoptotic endothelial cells triggers anti-inflammatory macrophage reprogramming.  


Apoptotic endothelial cells are an important component of the "response to injury" process. Several atherosclerosis risk factors such as hyperglycemia and oxidized low-density lipoproteins, and immune injuries, such as antibodies and complement, induce endothelial cell apoptosis. While endothelial cell apoptosis is known to affect neighboring vascular wall cell biology, its consequences on macrophage reprogramming are ill defined. In this study, we report that apoptosis of human and mouse endothelial cells triggers the release of milk fat globule-epidermal growth factor 8 (MFG-E8) and reprograms macrophages into an anti-inflammatory cells. We demonstrated that MFG-E8 is released by apoptotic endothelial cells in a caspase-3-dependent manner. When macrophages were exposed to conditioned media from serum-starved apoptotic endothelial cells, they adopt a high anti-inflammatory, low pro-inflammatory cytokine/chemokine secreting phenotype that is lost if MFG-E8 is absent from the media. Macrophage treatment with recombinant MFG-E8 recapitulates the effect of conditioned media. Finally, we showed that MFG-E8-mediated reprogramming of macrophages occurs through increased phosphorylation of signal transducer and activator of transcription-3 (STAT-3). Taken together, our study suggests a key role of MFG-E8 release from apoptotic endothelial cells in macrophage reprogramming and demonstrates the importance of the apoptotic microenvironment in anti-inflammatory macrophage responses. PMID:22558449

Brissette, Marie-Joëlle; Lepage, Stéphanie; Lamonde, Anne-Sophie; Sirois, Isabelle; Groleau, Jessika; Laurin, Louis-Philippe; Cailhier, Jean-François



Screening of bioactive compounds from moutan cortex and their anti-inflammatory activities in rat synoviocytes.  


Moutan Cortex, a widely used traditional Chinese medicine for the treatment of various diseases, is the root bark of Paeonia suffruticosa Andrews (Paeoniaceae). Most of the pharmacological investigations of Moutan Cortex have been addressed to its central nervous system activities, anti-oxidative and sedative actions. Otherwise, there are few reports about the active compounds with anti-inflammatory activity of Moutan Cortex. The aim of the present study was to screen and identify bioactive compounds with anti-inflammatory effect from Moutan Cortex. With the aid of preparative high performance liquid chromatography (HPLC) technique, ethyl acetate and ethanol extract of Moutan Cortex were isolated into twenty-two fractions. Bioactivities of these fractions were evaluated by measuring expression of tumor necrosis factor-alpha (TNF-alpha) in rat synoviocytes subjected to interleukin-1beta (IL-1beta). Eight compounds were isolated from six active fractions and identified by HPLC/MS(n). Purified compounds, paeoniflorin, paeonol and pentagalloylglucose resulted in dose-dependent inhibition of TNF-alpha synthesis and IL-6 production in synoviocytes treated with proinflammatory mediator. These results suggested that paeonol, paeoniflorin, glycosides and pentagalloylglucose contribute to the anti-inflammatory effect of Moutan Cortex. PMID:18955220

Wu, Mengjie; Gu, Zhiyuan




Center for Biologics Evaluation and Research (CBER)

Text Version... studies lasting up to 3 years, to decrease the risk of symptomatic ulcers and ulcer ... on recurrent ulcer bleeding and endoscopic ulcers in high-risk ... More results from


Anti-inflammatory and antinociceptive effects of cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis.  


The anti-inflammatory and antinociceptive activities of cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis, were studied. The effects of cordymin on cytokine levels and total antioxidant activity were analysed. The antinociceptive effects of cordymin in vivo and in vitro were also determined. Cordymin treatment decreased the levels of tumour necrosis factor alpha, interleukin 1 beta and total antioxidant status. Cordymin inhibited the acetic acid-induced abdominal constrictions in mice in a dose-dependent manner. In the hot-plate test, results showed that cordymin significantly inhibited the reaction time to thermal stimuli at 30, 60 and 90 min. In neurolysin inhibition assay, cordymin showed strong activities against neurolysin (IC(50)?= 0.1 µM). Our results show that cordymin is a potent anti-inflammatory and analgesic medicine. PMID:22348255

Qian, Gui-min; Pan, Guo-Feng; Guo, Jian-You



Bioassay-guided isolation of iridoid glucosides with antinociceptive and anti-inflammatory activities from Veronica anagallis-aquatica L.  


Extracts obtained from the herbs of various Veronica species are used as folk remedy worldwide for the treatment of various inflammatory ailments including rheumatism. In vivo anti-inflammatory and antinociceptive activities of Veronica anagallis-aquatica L. aerial parts were investigated. Methanolic extract of the plant was shown to possess significant inhibitory activity against carrageenan-induced hind paw edema model and of p-benzoquinone-induced writhings in mice. Through bioassay-guided fractionation and isolation procedures eight compounds, aquaticoside A (1), aquaticoside B (2), aquaticoside C (3), veronicoside (4), catalposide (5), verproside (6), verminoside (7) and martynoside (8) were isolated and their structures were elucidated by spectral techniques. Catapol derivative iridoid glucosides, verproside (6) and catalposide (5), were found to possess potent antinociceptive and anti-inflammatory activities, per os without inducing any apparent acute toxicity as well as gastric damage. Results of the present study supported the utilization of the plant in Turkish folk medicine. PMID:16019176

Küpeli, Esra; Harput, U Sebnem; Varel, Mehtap; Yesilada, Erdem; Saracoglu, Iclal



Objective Assessment of Topical Anti-Inflammatory Drug Activity on Experimentally Induced Nickel Contact Dermatitis: Comparison between Visual Scoring, Colorimetry, Laser Doppler Velocimetry and Transepidermal Water Loss  

Microsoft Academic Search

Four topical anti-inflammatory drugs were investigated for their effect on allergic contact dermatitis. Nickel dermatitis was chosen for its high incidence in European healthy volunteers. Experimental lesions were treated twice daily with two steroids, two non-steroidal anti-inflammatory drugs and a blank base for 4.5 days without occlusion. The influence of treatments was assessed by daily visual grading and one site

Catherine Queille-Roussel; Luc Duteil; Jean-Michel Padilla; Michel Poncet; Janusz Czernielewski



[Anti-inflammatory actions of proteases, bromelain, trypsin and their mixed preparation (author's transl)].  


Anti-inflammatory actions of proteases, bromelain (BR), trypsin (TR) and their mixed preparation (KT) were studied mainly in rabbits using various experimental test methods. Inhibitory action of edema formation induced by carrageenin was observed to be dose dependent with oral administrations of KT. This inhibitory action of KT was more remarkable than actions of BR and TR, suggesting a possible synergism between the latter two. Such action was also observed with non-steroidal anti-rheumatic drugs, phenylbutazone (PB), indomethacin and acetylsalicylic acid. Oral administration of KT exerted definite inhibition or a tendency toward inhibition against paw edema induced by dextran, histamine or egg albumin or skin edema induced by anti-rabbit serum and thermal stimulation. Furthermore, inhibition of vascular permeability increase induced by histamine and bradykinin as well as a tendency toward inhibition against protein exudation in CMC-pouch method were observed. On the other hand, contrary to PB, potent inhibitory action was not manifested in the persistent proliferative inflammation models, the granuloma formation induced formalin soaked filter paper and cotton pellet and the mustard edema. Therefore, it can be deduced that the inhibitory action of KT against edema formation may be dependent mainly on the inhibitory action of vascular permeability increase and the anti-inflammatory action may be specific for acute exudative inflammation. PMID:395051

Ito, C; Yamaguchi, K; Shibutani, Y; Suzuki, K; Yamazaki, Y; Komachi, H; Ohnishi, H; Fujimura, H



Anti-proliferative, anti-inflammatory and antioxidant effects of curcumin analogue A2.  


In the present study, we determined the anti-proliferative, anti-inflammatory and antioxidant effects of a curcumin analogue, 2,6-bis(3,4-dihydroxybenzylidene) cyclohexanone (designated as A2). In vitro studies showed that A2 had a stronger inhibitory effect on the growth of mouse macrophage RAW 264.7 cells than curcumin. A2 also showed a stronger inhibitory effect than curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in NF-?B activation and IL-1? expression as well as in aldose reductase activity. A2 was a stronger antioxidant than curcumin as determined by inhibition of lipid peroxidation, inhibition of 1,1-diphenyl-2-picryl-hydrazyl free radical formation, and inhibition of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical formation. In vivo studies indicated that A2 was more potent than curcumin for inhibiting TPA-induced ear edema and TPA-induced increases in IL-1?. In addition, oral administration of A2 at a dose of 2,000 mg/kg body weight did not cause acute toxicity in mice. Taken together, the results of our study indicate that the curcumin analogue A2 has stronger anti-proliferative, anti-inflammatory and antioxidant activities than curcumin. PMID:23888334

Du, Zhi-Yun; Wei, Xingchuan; Huang, Mou-Tuan; Zheng, Xi; Liu, Yue; Conney, Allan H; Zhang, Kun



Convergence of nitric oxide and lipid signaling: anti-inflammatory nitro-fatty acids.  


The signaling mediators nitric oxide ( NO) and oxidized lipids, once viewed to transduce metabolic and inflammatory information via discrete and independent pathways, are now appreciated as interdependent regulators of immune response and metabolic homeostasis. The interactions between these two classes of mediators result in reciprocal control of mediator synthesis that is strongly influenced by the local chemical environment. The relationship between the two pathways extends beyond coregulation of NO and eicosanoid formation to converge via the nitration of unsaturated fatty acids to yield nitro derivatives (NO(2)-FA). These pluripotent signaling molecules are generated in vivo as an adaptive response to oxidative inflammatory conditions and manifest predominantly anti-inflammatory signaling reactions. These actions of NO(2)-FA are diverse, with these species serving as a potential chemical reserve of NO, reacting with cellular nucleophiles to posttranslationally modify protein structure, function, and localization. In this regard these species act as potent endogenous ligands for peroxisome proliferator-activated receptor gamma. Functional consequences of these signaling mechanisms have been shown in multiple model systems, including the inhibition of platelet and neutrophil functions, induction of heme oxygenase-1, inhibition of LPS-induced cytokine release in monocytes, increased insulin sensitivity and glucose uptake in adipocytes, and relaxation of preconstricted rat aortic segments. These observations have propelled further in vitro and in vivo studies of mechanisms of NO(2)-FA signaling and metabolism, highlighting the therapeutic potential of this class of molecules as anti-inflammatory drug candidates. PMID:19200454

Baker, Paul R S; Schopfer, Francisco J; O'Donnell, Valerie B; Freeman, Bruce A



Anti-inflammatory activity of Yanshu spraying agent in animal models  

PubMed Central

Acute pharyngitis is characterized by an inflammation of the mucous membranes in the pharynx. Yanshu spraying agent was prepared according to the traditional Chinese formulation for the treatment of acute pharyngitis. The present study aimed to investigate the anti-inflammatory effect of Yanshu in xylene-induced ear edema in mice and carrageenan-induced paw edema in rats by measuring the degree of edema in the animal models. The histopathology and the levels of prostaglandin E2 (PGE2) and cycloxygenase-2 (COX-2) in the hind paws of the carrageenan-treated rats were also analyzed. The results showed that Yanshu significantly reduced ear edema in the mice and paw edema in the rats. Furthermore, treatment with Yanshu also reduced the number of inflammatory cells in tissue and decreased the production of PGE2 and COX-2. These results suggest that Yanshu possesses potent anti-inflammatory activity mediated by the inhibition of COX-2 expression which, in turn, downregulates the inflammatory mediator PGE2.




Anti inflammatory activity of Myrica nagi Linn. Bark  

PubMed Central

The present study evaluated the anti inflammatory activity of ethyl acetate and aqueous extracts of bark of M. nagi using carrageenan and histamine induced rat paw edema. Adult Wistar albino rats were subjected to carrageenan and histamine induced rat paw edema tests. In carrageenan induced rat paw edema the effects of ethyl acetate and aqueous extract at 100 and 200 mg/kg showed % inhibition of edema 27% and 22% respectively than the standard drug aspirin (28%). These ethyl acetate and aqueous extract extracts also showed % inhibition of edema 25% and 18% respectively than the standard drug (27%) when rats challenged with histamine induced rat paw edema. Future research should focus on the identification and the anti inflammatory activity of the constituents from this plant.

Patel, Tejaa; Dudhpejiya, Ashvin; Sheath, Navin



Constituents from Vigna vexillata and Their Anti-Inflammatory Activity  

PubMed Central

The seeds of Vigna genus are important food resources and there have already been many reports regarding their bioactivities. In our preliminary bioassay, the chloroform layer of methanol extracts of V. vexillata demonstrated significant anti-inflammatory bioactivity. Therefore, the present research is aimed to purify and identify the anti-inflammatory principles of V. vexillata. One new sterol (1) and two new isoflavones (2,3) were reported from the natural sources for the first time and their chemical structures were determined by the spectroscopic and mass spectrometric analyses. In addition, 37 known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. Among the isolates, daidzein (23), abscisic acid (25), and quercetin (40) displayed the most significant inhibition of superoxide anion generation and elastase release.

Leu, Yann-Lii; Hwang, Tsong-Long; Kuo, Ping-Chung; Liou, Kun-Pei; Huang, Bow-Shin; Chen, Guo-Feng



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


Inflammation is a serious medical problem that causes suffering in many common diseases such as rheumatoid arthritis and asthma. Despite the fact that the clinical signs of inflammation--rubor, tumor, calor and dolor--have been known for almost two thousand years, our knowledge of the molecular pathways that mediate inflammation is still limited. Today's anti-inflammatory drugs are non-specific and have many undesirable side effects. The discovery of chemokines as small specific regulatory proteins of the immune system has increased our understanding of the inflammatory process. We have reason to believe that chemokines and their receptors are going to be targets for a new kind of anti-inflammatory therapy. PMID:12024779

Schedvins, Per; Hjelmström, Peter



Antioxidant activity of anti-inflammatory plant extracts  

Microsoft Academic Search

The antioxidant properties of twenty medical herbs used in the traditional Mediterranean and Chinese medicine were studied. Extracts from Forsythia suspensa, Helichrysum italicum, Scrophularia auriculata, Inula viscosa, Coptis chinensis, Poria cocos and Scutellaria baicalensis had previously shown anti-inflammatory activity in different experimental models. Using free radical-generating systems H. italicum, I. viscosa and F. suspensa protected against enzymatic and non-enzymatic lipid

G. R. Schinella; H. A. Tournier; J. M. Prieto; P. Mordujovich de Buschiazzo; J. L. R??os



Nonsteroidal anti-inflammatory drug-induced hepatoxicity.  


Nonsteroidal anti-inflammatory drugs are among the most prescribed medications worldwide. After antibiotics and anticonvulsants they are considered the most common medications associated with drug-induced liver injury mainly through an idiosyncratic form of hepatotoxicity. In rare cases severe hepatotoxicity has been described with significant morbidity and mortality. Genetic risk factors have been reported with diclofenac and lumiracoxib. Postmarketing surveillance and monitoring is crucial to identify severe cases of hepatotoxicity. PMID:24099022

Unzueta, Alberto; Vargas, Hugo E



Immunosuppressive and anti-inflammatory activities of sinomenine.  


Sinomenine (SN), a pure compound extracted from the Sinomenium acutum plant, has been found to inhibit T- and B-lymphocyte activation, proliferation and function and to interfere with the differentiation, recruitment and function of several other cell types, such as dendritic cells (DC). SN has demonstrated its potential anti-inflammatory role for treating immune-related disorders in experimental animal models and in some clinical applications. This review will summarize its potential effects, mechanisms and applications. PMID:21109035

Wang, Quanxing; Li, Xiao-Kang



Biochemical pharmacology of biflavonoids: Implications for anti-inflammatory action  

Microsoft Academic Search

Biflavonoids belong to a subclass of the plant flavonoid family. Distribution of biflavonoids in the plant kingdom is limited\\u000a to several species. Previously, some pharmacological activities of biflavonoids were described such as inhibition of histamine\\u000a release from mast cells and inhibition of lymphocyte proliferation, suggesting the anti-inflammatory\\/antiallergic potential\\u000a of the biflavonoids. Furthermore, several natural biflavonoids including ochnaflavone and ginkgetin inhibit

Hyun Pyo Kim; Kun Ho Son; Hyeun Wook Chang; Sam Sik Kang



Anti-inflammatory cyclohexenyl chalcone derivatives in Boesenbergia pandurata.  


The cyclohexenyl chalcone derivative [(-)-hydroxypanduratin A], together with the previously known panduratin A, sakuranetin, pinostrobin, pinocembrin, and dihydro-5,6-dehydrokawain were isolated from the chloroform extract of the red rhizome variety of Boesenbergia pandurata (Robx.) Schltr. [currently known as Boesenbergia rotunda (L.) Mansf., Kulturpfl.]. Their structures were assigned on the basis of their spectroscopic data. (-)-Hydroxypanduratin A and (-)-panduratin A showed significant topical anti-inflammatory activity in the assay of TPA-induced ear edema in rats. PMID:11809452

Tuchinda, Patoomratana; Reutrakul, Vichai; Claeson, Per; Pongprayoon, Ubonwan; Sematong, Tuanta; Santisuk, Thawatchai; Taylor, Walter C



Anti-inflammatory activities of triterpenoid saponins from Polygala japonica  

Microsoft Academic Search

Bioassay-guided investigation was performed to identify the active constituents from a methanol extract of Polygala japonica, a folk medicinal plant widely used in China to treat inflammatory diseases. The n-BuOH and EtOAc fractions of the P. japonica methanol extract, which show significant anti-inflammatory activity in in vivo test, were further subjected to column chromatography to afford six triterpene glycosides, marked

H. Wang; J. Gao; J. Kou; D. Zhu; B. Yu



Aspririn and nonsteroidal anti-inflammatory drug hypersensitivity  

Microsoft Academic Search

Acetylsalicylic acid (ASA) or aspirin and nonsteroidal anti-inflammatory drug (NSAID) sensitivities encompass a diverse group\\u000a of both pharmacological and hypersensitivity reactions. Conventionally, hypersensitivities include aspirin-exacerbated respiratory\\u000a disease (AERD), ASA-induced urticaria, and anaphylaxis. With an increasing prevalence of coronary artery disease in an aging\\u000a population, aspirin continues to play a significant role in cardiac prophylaxis in a large patient population. Invariably,

James S. W. Kong; Suzanne S. Teuber; M. Eric Gershwin



Anti-Inflammatory Effects of Thyme Essential Oil in Mice  

Microsoft Academic Search

Juhás Š., D. Buj?áková, P. Rehák, Š. ?ikoš, S. Czikková, J. Veselá, G. I?ková, J. Koppel: Anti-Inflammatory Effects of Thyme Essential Oil in Mice. Acta Vet. Brno 2008, 77: 327-334. Plant essential oils are plant secondary metabolites possessing various pharmacological properties, primarily anti-oxidative, antimicrobial or immunomodulatory ones. The aim of this work was to study the effects of thyme essential

Š. Juhás; D. Buj?áková; P. Rehák; Š. ?ikoš; S. Czikková; J. Veselá; G. I?ková; J. Koppel



Clinical Management of Nonsteroidal Anti-inflammatory Drug Hypersensitivity  

PubMed Central

Hypersensitivity diseases caused by nonsteroidal anti-inflammatory agents are relatively common in the population. This article summarizes the present understanding on the various allergic and nonallergic clinical pictures produced through hypersensitivity to these drugs using the pathogenic classification of hypersensitivity reactions recently proposed by the Nomenclature Committee of the World Allergy Organization to guide clinicians in the diagnosis and management of patients with these conditions.



Anti-inflammatory and immunosuppressive compounds from Tripterygium wilfordii  

Microsoft Academic Search

The extract of Tripterygium wilfordii Hook F. (TwHF), which showed anti-inflammatory and immunosuppressive activities in human clinical trials for rheumatoid arthritis, was subjected to the activity-guided fractionation and spectroscopic characterization of bioactives. A tetrahydrofuran lignan, tripterygiol (1), and eight known compounds, all capable of suppressing pro-inflammatory gene expression were identified. Most of the pharmacological activity of the extract can be

Jun Ma; Moul Dey; Hui Yang; Alexander Poulev; Reneta Pouleva; Ruth Dorn; Peter E. Lipsky; Edward J. Kennelly; Ilya Raskin



Toxicity of antirheumatic and anti-inflammatory drugs in children  

Microsoft Academic Search

The aim of the study was to describe the longterm toxicity of antirheumatic and anti-inflammatory drugs in a paediatric rheumatology clinic population. One hundred and seventeen children were studied on first admission to a paediatric rheumatology clinic and after a mean of 8.6±0.4 years of follow-up. Medical records from the intermediate period were reviewed. The patients had 155 exposures to

B. Flatø; O. Vinje; Ø. Førre



Analgesic, diuretic, and anti-inflammatory principle from Scoparia dulcis.  


Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant analgesic (p < 0.001) and anti-inflammatory activity (p < 0.01) in animals. A sedative action of scoparinol was demonstrated by a marked potentiation of pentobarbital-induced sedation with a significant effect on both onset and duration of sleep (p < 0.05). Measurement of urine volume after administration of scoparinol indicated its significant diuretic action. PMID:11534346

Ahmed, M; Shikha, H A; Sadhu, S K; Rahman, M T; Datta, B K



Antinociceptive and anti-inflammatory activity of Sida rhomboidea leaves  

Microsoft Academic Search

Various organic extracts of Sida rhomboidea leaves were studied for antinociceptive and anti- inflammatory activity at a dose of 200 mg\\/kg. Ethyl acetate extract has shown significant (P<0.01) antinociceptive activity. Percentage inhibition of edema by butanolic extract (33.05, P<0.001) is comparable to that of phenylbutazone, 100 mg\\/kg inhibition (38.83%). Phytochemical screening of the extracts indicated the presence of alkaloids, steroids

S Venkatesh; Y. Siva Rami Reddy; B Suresh; B. Madhava Reddy; M Ramesh



Anti-Inflammatory Drugs in the 21st Century  

Microsoft Academic Search

Historically, anti-inflammatory drugs had their originsin the serendipitous discovery of certain plants and their extracts\\u000a being applied for the relief of pain, fever and inflammation. When salicylates were discovered in the mid-19th century to\\u000a be the active components of Willow Spp., thisenabled these compounds to be synthesized and from this,acetyl-salicylic acid or Aspirin trademark was developed.Likewise,\\u000a the chemical advances of

K. D. Rainsford


Metallothionein as an Anti-Inflammatory Mediator  

PubMed Central

The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT) is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions.

Inoue, Ken-ichiro; Takano, Hirohisa; Shimada, Akinori; Satoh, Masahiko



Isolation, purification and characterisation of lunasin from defatted soybean flour and in vitro evaluation of its anti-inflammatory activity  

Microsoft Academic Search

Lunasin is a chemopreventive peptide present in soybean and other plant sources. The high cost involved in obtaining synthetic lunasin limits its application in chemopreventive and nutritional interventions. The objective of this study was to isolate, purify and characterise lunasin from defatted soybean flour and determine its in vitro anti-inflammatory activity using RAW 264.7 macrophages. Isolation and purification was achieved

V. P. Dia; W. Wang; V. L. Oh; B. O. de Lumen; E. Gonzalez de Mejia



Synthesis and anti-inflammatory activity of celecoxib like compounds.  


Nine novel 4-[3-(4-Dimethylamino-phenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]-benzenesulfonamides (2a-i) were synthesized and evaluated for their anti-inflammatory and antiproliferative activities. These compounds (2a-i) showed moderate to strong anti-inflammatory activity in carrageenan rat paw oedema test. Compounds 2b, 2d and 2g showing comparable anti-inflammatory activity to that of reference drug celecoxib were evaluated for their ulcerogenic and analgesic activities. The effect of 2b, 2d and 2g on the content of NO, TNF-? and PGE2 in exudates from rat paw stimulated by carrageenan was also evaluated. The compound 2c showed considerable antitumor activities against all 60 human tumor cell lines with effective GI50 (MG-MID) value of 3.63 µM. It exhibited maximum activity against melanoma (LOX IMVI and SK-MEL-5) cancer cell lines with GI50 value less than 2 ?M. PMID:22957719

Ovais, Syed; Yaseen, Shafiya; Bashir, Rafia; Rathore, Pooja; Samim, Mohammed; Singh, Surender; Nair, Vinod; Javed, Kalim



Porphyrins as new endogenous anti-inflammatory agents.  


A series of porphyrins, tetrapyrrole natural organic compounds, are evaluated here as endogenous anti-inflammatory agents. They directly inhibit the activity of Fyn, a non-receptor Src-family tyrosine kinase, triggering anti-inflammatory events associated with down-regulation of T-cell receptor signal transduction, leading to inhibition of tumor necrosis factor alpha (TNF-?) production. This is one of the major pro-inflammatory cytokines, associated with diseases such as diabetes, tumorigenesis, rheumatoid arthritis, and inflammatory bowel disease. Porphyrins, as a chemical class, inhibited Fyn kinase activity in a non-competitive, linear-mixed fashion. In cell-based in vitro experiments on polymorphonuclear cells, porphyrins inhibited TNF-? cytokine production, T-cell proliferation, and the generation of free radicals in the oxidative burst, in a concentration-related manner. In vivo, lipopolysaccharide-induced TNF-? production in mice was inhibited by several of the porphyrins. These findings may be very important for the overall understanding of the role(s) of porphyrins in inflammation and their possible application as new anti-inflammatory agents. PMID:22687816

Jeli?, Dubravko; Tati?, Iva; Trzun, Marija; Hrva?i?, Boška; Brajša, Karmen; Verbanac, Donatella; Tomaškovi?, Marija; ?uli?, Ognjen; Antolovi?, Roberto; Glojnari?, Ines; Weygand-?uraševi?, Ivana; Vladimir-Kneževi?, Sanda; Mildner, Boris



Anti-Inflammatory Activity and Composition of Senecio salignus Kunth  

PubMed Central

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

Perez Gonzalez, Cuauhtemoc; Serrano Vega, Roberto; Gonzalez-Chavez, Marco; Zavala Sanchez, Miguel Angel; Perez Gutierrez, Salud



Analgesic and anti-inflammatory activity of Argyreia speciosa root  

PubMed Central

Objective: To study analgesic and anti-inflammatory activities of a methanolic extract (ME) of Argyreia speciosa (AS) root powder. Materials and Methods: The study was carried out using male albino mice (20-25 gm) and male wistar rats (100-150gm). The ME was prepared using soxhlet extraction process. The effect of ME of A. speciosa was investigated for analgesic activity using acetic acid-induced abdominal constriction, tail immersion method and hot plate method. The anti-inflammatory activity of ME of AS roots was studied using carrageenan-induced rat paw edema. Result: The ME of A. speciosa root was used in pain and inflammation models. The analgesic activity of AS at the dose of (30,100, and 300 mg/kg p.o) showed significant (P<0.01) decrease in acetic acid-induced writhing, whereas ME of A. speciosa at the dose of (100, 300 mg/kg p.o) showed significant (P<0.01) increase in latency to tail flick in tail immersion method and elevated mean basal reaction time in hot plate method. The ME of the A. speciosa at doses (30, 100, and 300mg/kg) showed significant (P < 0.01) inhibition of carrageenan induced hind paw edema in rats. Conclusion: The ME of A. speciosa showed significant analgesic and anti-inflammatory activity in mice and rat.

Bachhav, R.S.; Gulecha, V.S.; Upasani, C.D.



UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect  

PubMed Central

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.

Couteau, Celine; Chauvet, Catherine; Paparis, Eva; Coiffard, Laurence



Synthesis and biological evaluation of novel sinomenine derivatives as anti-inflammatory agents.  


Sinomenine (1) is clinically available for the treatment of rheumatoid arthritis (RA), however, its efficacy is quite weak. In the present study, a library of novel sinomenine-based homodimers and monomers through variable-length linkers were designed and synthesized, and their bioactivities were evaluated using RAW264.7 cells and mice. Among the compounds, 2f and 3b possessed much more potent inhibitory effects on the production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) than 1. Preliminary mechanism investigation revealed that 3b inhibited nuclear factor-?B (NF-?B) signaling pathway specifically, 2f suppressed both NF-?B and mitogen-activated protein kinase (MAPK) cascades. Moreover, 3b and 2f significantly alleviated the lipopolysaccharide (LPS)-induced mortality. These two compounds might serve as valuable candidates for anti-inflammatory drug discovery. PMID:22325804

Teng, Peng; Liu, Hai-Liang; Zhang, Lei; Feng, Li-Li; Huai, Yue; Deng, Zhang-Shuang; Sun, Yang; Xu, Qiang; Li, Jian-Xin



Diterpenoids and triterpenoids with potential anti-inflammatory activity from the leaves of Aglaia odorata.  


Chemical investigation of the leaves of the oriental medicinal plant Aglaia odorata resulted in the isolation of five compounds: two dolabellane diterpenoids, two dammarane triterpenoids and a protostane triterpenoid, along with twenty known compounds. Their structures were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR spectroscopic data with those reported in the literature. The anti-inflammatory activities of all compounds were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Eleven compounds possessed potent nitric oxide inhibitory activity with IC(50) values ranging from 2.1 to 14.2 ?M, these being better than that of the positive control, indomethacin (IC(50)=14.5 ?M). In addition, three compounds exhibited significant activity against PGE(2) release with IC(50) values of 2.6, 16.1 and 23.0 ?M. PMID:22321385

Yodsaoue, Orapun; Sonprasit, Jarinthon; Karalai, Chatchanok; Ponglimanont, Chanita; Tewtrakul, Supinya; Chantrapromma, Suchada



[The application of Harpagophytum procumbens extract in anti-inflammatory preparations applied on skin produced on acrylic acid polymers base].  


An attempt was made to use dry standardized extract from Harpagophytum procumbens of confirmed anti-inflammatory activity in formulations applied on skin. To obtain synergy in the area of analgesic and anti-inflammatory activity formulations were produced containing plant extract and nonsteroidal anti-inflammatory drug (ketoprofen). All the preparations were prepared on the base of acrylic acid polymers (Carbopol Ultrez 10, Carbopol 980). The formulations were subjected to complementary physicochemical investigations. Viscosity parameters (structural viscosity, yield stress, thixotrophy) were determined with cone-plate digital rheometer. Potentiometric method was used to measure pH of the produced hydrogels. The test for ketoprofen pharmaceutical availability through a semipermeable membrane to acceptor fluid was performed in vitro. The rate of the process of release was tested by determining the quantity of the therapeutic agent diffusing into acceptor fluid at defined time intervals by spectrophotometric method. The effect of Harpagophytum procumbens extract components on ketoprofen diffusion was estimated. Viscosity tests revealed that all the formulations are viscoelastic systems having yield stress. All model formulations were tested 24h after production and after 6-month storage. All the formulations demonstrate rheological stability and high pharmaceutical availability of ketoprofen. The suggested formulations can be an alternative for market preparations applied on skin of anti-inflammatory and analgesic activity. PMID:19873929

Piechota-Urba?ska, Magdalena; Ko?odziejska, Justyna; Berner-Strzelczyk, Aneta



Design, synthesis and evaluation of some novel pyrazoline derivatives as potential anti-inflammatory and antitumor agents.  


A new series of pyrazoline derivatives was designed and synthesized with the objective of developing agents with anti-inflammatory activity together with chemoprevention of hepatobiliary malignancies. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced granuloma bioassay, using celecoxib as a reference drug. Ulcerogenic effect and acute toxicity profiles (ALD50) for the most active compounds were also determined. Compound 5c was proved to display anti-inflammatory activity better than celecoxib. Compounds 4b, 5d, 5c and 8 were found to be safer than indomethacin with respect to ulcerogenic effect and were well tolerated by the experimental animals with high safety margin (ALD50 >300 mg/Kg). Moreover, histopathological examination was carried out to detect the anti-inflammatory effect of the tested compounds on the livers of carrageenan-injected rats. On the other hand, compounds 4b, 4c, 4d, 5b, 5c, 5d, 6a, 6b, 6c, 6d, 8 and 9 were selected by the NCI to be evaluated for their anticancer activities but none has passed to the 5-dose assay. In addition, the ligand-receptor interactions of the most active compounds with COX-2 were investigated by performing docking studies using Molecular Operating Environment (MOE) version 2008.10. PMID:23585301

Elbayaa, R Y; Badr, M H; Khalil, A A; Abdelhadi, M



Anti-inflammatory activities of Aller-7, a novel polyherbal formulation for allergic rhinitis.  


Allergic rhinitis is an immunological disorder and an inflammatory response of nasal mucosal membranes. Allergic rhinitis, a state of hypersensitivity, occurs when the body overreacts to a substance such as pollens or dust. A novel, safe polyherbal formulation (Aller-7/NR-A2) has been developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. Since inflammation is an integral mechanistic component of allergy, the present study aimed to determine the anti-inflammatory activity of Aller-7 in various in vivo models. The efficacy of Aller-7 was investigated in compound 48/80-induced paw edema both in Balb/c mice and Swiss Albino mice, carrageenan-induced paw edema in Wistar Albino rats and Freund's adjuvant-induced arthritis in Wistar Albino rats. The trypsin inhibitory activity of Aller-7 was also determined and compared with ovomucoid. At a dose of 250 mg/kg, Aller-7 demonstrated 62.55% inhibition against compound 48/80-induced paw edema in Balb/c mice, while under the same conditions prednisolone at an oral dose of 14 mg/kg exhibited 44.7% inhibition. Aller-7 significantly inhibited compound 48/80-induced paw edema at all three doses of 175, 225 or 275 mg/kg in Swiss Albino mice, while the most potent effect was observed at 225 mg/kg. Aller-7 (120 mg/kg, p.o.) demonstrated 31.3% inhibition against carrageenan-induced acute inflammation in Wistar Albino rats, while ibuprofen (50 mg/kg, p.o.) exerted 68.1% inhibition. Aller-7 also exhibited a dose-dependent (150-350 mg/kg) anti-inflammatory effect against Freund's adjuvant-induced arthritis in Wistar Albino rats and an approximately 63% inhibitory effect was observed at a dose of 350 mg/kg. The trypsin inhibitory activity of Aller-7 was determined, using ovomucoid as a positive control. Ovomucoid and Aller-7 demonstrated IC50 concentrations at 1.5 and 9.0 microg/ml, respectively. These results demonstrate that this novel polyherbal formulation is a potent anti-inflammatory agent that can ameliorate the symptoms of allergic rhinitis. PMID:15573692

Pratibha, N; Saxena, V S; Amit, A; D'Souza, P; Bagchi, M; Bagchi, D



Anti-inflammatory effect of pigment epithelium-derived factor in DBA/2J mice  

PubMed Central

Purpose Glaucoma is the second leading cause of blindness. The ultimate cause of vision loss in glaucoma is thought to be retinal ganglion cell (RGC) death. Neuroprotection of RGC is therefore an important goal of glaucoma therapy. Several lines of evidence suggest that pigment epithelium derived factor (PEDF) is a potent anti-angiogenic, neuroprotective, and anti-inflammatory factor for neurons. In this study, we examined the potential role of PEDF in protection of RGC in the DBA/2J mouse, an animal model of inherited glaucoma. Methods DBA/2J mice at two months of age were transfected intravitreally with adeno-associated virus (AAV)-PEDF or AAV-green fluorescent protein (AAV-GFP). RGC and nerve fiber layer protection were evaluated in retinal cross sections. Biochemical alterations in the retinas of DBA/2J mice in response to intravitreal transfection of PEDF were also examined by reverse transcriptase PCR (RT–PCR) and western blot. Cellular localization of PEDF and glial fibrillary acidic protein (GFAP) was determined by immunohistochemistry. Visual acuity was determined by optomotor testing. Results PEDF protein levels in the retina and optic nerves of DBA/2J mice declined with age. The expression of tumor necrosis factor (TNF), GFAP, and interleukin-18 (IL-18) increased with age in the retina and optic nerve of DBA/2J mice. Intravitreal PEDF transfection in DBS/2J mice reduced loss of RGC and nerve fiber layer, delayed vision loss, and reduced TNF, IL-18, and GFAP expression in the retina and optic nerve. Conclusions Transduced PEDF potently and efficaciously reduces RGC loss and vision decline in DBA/2J mice, possibly via the reduction of TNF and IL-18, and downregulation of GFAP. The anti-inflammatory effect of PEDF represents a novel approach to the prevention of glaucomatous RGC death.

Zhou, Xiaohong; Li, Feng; Kong, Li; Chodosh, James



Cholesterol Efflux Potential and Anti-inflammatory Properties of HDL following Treatment with Niacin or Anacetrapib  

PubMed Central

Objective This study examines the effects of treatments with niacin or anacetrapib (an inhibitor of cholesteryl ester transfer protein (CETP)) on the ability of HDL to promote net cholesterol efflux and reduce Toll-like receptor-mediated inflammation in macrophages. Methods and Results 18 subjects received niacin 2g daily for 4 weeks, 20 subjects received anacetrapib 300mg daily for 8 weeks and 2 groups of 4 and 5 subjects, respectively received placebo. HDL samples were isolated by PEG precipitation or ultracentrifugation, tested for ability to promote cholesterol efflux in cholesterol-loaded THP-1 or mouse peritoneal macrophages, or used to pre-treat macrophages followed by LPS exposure. HDL cholesterol levels were increased by 30% in response to niacin and by ~100% in response to anacetrapib. Niacin treatment increased HDL-mediated net cholesterol efflux from foam cells primarily by increasing HDL concentration, whereas anacetrapib treatment increased cholesterol efflux both by increasing HDL concentration and by causing increased efflux at matched HDL concentrations. The increased efflux potential of anacetrapib-HDL was more prominent at higher HDL cholesterol concentrations (> 12?g/ml), associated with an increased content of lecithin:cholesterol acyltransferase (LCAT) and apolipoprotein E (apoE) and completely dependent on expression of ATP binding cassette transporters, ABCA1 and ABCG1. Potent anti-inflammatory effects of HDL were observed at low HDL concentrations (3–20 ?g/ml) and were partly dependent on expression of ABCA1 and ABCG1. All HDL preparations showed similar anti-inflammatory effects, proportionate to HDL cholesterol concentration. Conclusions Niacin treatment caused a moderate increase in the ability of HDL to promote net cholesterol efflux while inhibition of CETP via anacetrapib led to a more dramatic increase in association with enhanced particle functionality at higher HDL concentrations. All HDLs exhibited potent ability to suppress macrophage TLR4-mediated inflammatory responses, in a process partly dependent on cholesterol efflux via ABCA1 and ABCG1.

Yvan-Charvet, Laurent; Kling, Jelena; Pagler, Tamara; Li, Hongna; Hubbard, Brian; Fisher, Tim; Sparrow, Carl P.; Taggart, Andrew K.; Tall, Alan R.



Evaluation of Salicornia herbacea as a potential antioxidant and anti-inflammatory agent.  


In this study, the antioxidant and anti-inflammatory activities of Salicornia herbacea were evaluated. The crude CH(2)Cl(2)/methanol extract of S. herbacea showed 52% and 86% scavenging activities of the authentic ONOO(-) and ONOO(-) from 3-morpholinosydnomimine (SIN-1) at a concentration of 50 microg/mL, respectively, and was subjected to a further fractionation with n-hexane, 85% aqueous methanol, n-butanol, and water. Additional purification of the n-butanol fraction revealed that the most potent scavenging activity led to the isolation of isorhamnetin 3-O-beta-d-glucopyranoside as the active principle. The structure of isorhamnetin 3-O-beta-d-glucopyranoside was elucidated by extensive two-dimensional nuclear magnetic resonance experiments such as (1)H correlation spectroscopy nuclear Overhauser effect spectroscopy, heteronuclear single quantum correlation, and heteronuclear multiple-bond correlation as well as by comparison with the published spectral data. Isorhamnetin 3-O-beta-d-glucopyranoside exhibited dose-dependent scavenging activities of the authentic ONOO(-) and ONOO(-) from SIN-1. The electron spin resonance spin-trap techniques confirmed that reactive oxygen species, including the hydroxyl, superoxide, carbon-centered, and 1,1-diphenyl-2-picrylhydrazyl radicals, were actively quenched by addition of isorhamnetin 3-O-beta-d-glucopyranoside. In addition, isorhamnetin 3-O-beta-d-glucopyranoside suppressed the lipopolysaccharide-induced nitric oxide production and the expression of cytokines such as inducible nitric oxide synthase, tumor necrosis factor-alpha, and interleukin-1beta in Raw 264.7 cells. Findings from this study should underscore the nutraceutical value of S. herbacea-derived isorhamnetin 3-O-beta-d-glucopyranoside as a potent antioxidative and anti-inflammatory agent via alleviation of radical-induced toxicities and pro-inflammatory responses. PMID:19627218

Kim, You Ah; Kong, Chang-Suk; Um, Young Ran; Lim, Sun-Young; Yea, Sung Su; Seo, Youngwan



Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-? gene by the same.  


In view of the folklore use of green leaves to treat inflammation, the anti-inflammatory property of chlorophylls and their degradation products were studied. Chlorophyll a and pheophytin a (magnesium-free chlorophyll a) from fresh leaves showed potent anti-inflammatory activity against carrageenan-induced paw edema in mice and formalin-induced paw edema in rats. Chlorophyll a inhibited bacterial lipopolysaccharide-induced TNF-? (a pro-inflammatory cytokine) gene expression in HEK293 cells, but it did not influence the expression of inducible nitric acid synthase and cyclooxygenase-2 genes. Chlorophyll b only marginally inhibited both inflammation and TNF-? gene expression. But both chlorophyll a and chlorophyll b showed the same level of marginal inhibition on 12-O-tetradecanoyl-phorbol-13-acetate-induced NF-?B activation. Chlorophylls and pheophytins showed in vitro anti-oxidant activity. The study shows that chlorophyll a and its degradation products are valuable and abundantly available anti-inflammatory agents and promising for the development of phytomedicine or conventional medicine to treat inflammation and related diseases. PMID:22038065

Subramoniam, Appian; Asha, Velikkakathu V; Nair, Sadasivan Ajikumaran; Sasidharan, Sreejith P; Sureshkumar, Parameswaran K; Rajendran, Krishnan Nair; Karunagaran, Devarajan; Ramalingam, Krishnan



Application of the solvent extraction technique to investigation of the anti-inflammatory activity of adlay bran.  


The current study utilised a bioassay-directed chemical analysis scheme to screen the anti-inflammatory activity of fractions and compounds from adlay bran (AB). Liquid-liquid extraction couple with liquid chromatography-mass spectrometry (LC-MS) was applied to the isolation, analysis and identification of active components in AB samples. Ethanol extracts of AB (ABE) and ethyl acetate extracts AB (ABEa) were obtained and further partitioned with different solvents. The results showed that among all 16 kinds of fractions from ABE and ABEa, ABEa-Ea-B (80% Ea/n-hexane sub-fraction from ABE-Ea) had the most potent inhibitory effects on NO production, iNOS and COX-2 expressions, and proinflammatory IL-6 and TNF-? secretion in lipopolysaccharide-activated RAW264.7 cells system. Mechanistic data from luciferase reporter-gene assay revealed that the anti-inflammatory action of ABEa-Ea-B may be associated with inhibition of NF-kB transcriptional activity. Notably, tangeretin, nobiletin, and p-hydroxybenzoic acid were found to be the main active compounds for the anti-inflammatory properties in ABEa-Ea-B. PMID:24128500

Huang, Din-Wen; Wu, Chi-Hao; Shih, Chun-Kuang; Liu, Chia-Yu; Shih, Ping-Hsiao; Shieh, Tzong-Ming; Lin, Ching-I; Chiang, Wenchang; Hsia, Shih-Min



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


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)-1? and exposed to dynamic tensile strain, respectively. The gene expression of IL-1?, 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-1? 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-1? 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. PMID:21225299

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



Anti-inflammatory and antinociceptive activities of Homalium letestui.  


Abstract Context. Homalium letestui Pellegr (Flacourtiaceae) is used in various decoctions traditionally by the Ibibios of the Niger Delta of Nigeria to treat stomach ulcer, malaria and other inflammatory diseases, as well as an aphrodisiac. Objective: To investigate the anti-inflammatory and antinociceptive activities of the stem extract of the plant. Materials and methods: The ethanol stem extract (500, 750, 1000?mg/kg, i.p.) of H. letestui was investigated for anti-inflammatory activity using carrageenan, egg albumin-induced and xylene-induced ear edema models and analgesic activity using acetic acid-induced writhing, formalin-induced paw licking and thermal-induced pain models. The ethanol extract was administered to the animals orally, 30?min to 1?h depending on the model, before induction of inflammation/pain. The LD50 was also determined. GC-MS analysis of dichloromethane fraction was carried out. Results: The extract caused a significant (p?anti-inflammatory and analgesic properties which may in part be mediated through the chemical constituents of the plant as revealed by the GC-MS. PMID:23862982

Okokon, Jude E; Okokon, Patience J; Dar Farooq, Ahsana; Choudhary, Mohammed Iqbal



Muscle-strengthening drugs and anti-inflammatory drugs  

US Patent & Trademark Office Database

A muscle-strengthening, anti-inflammatory, antiasthmatic, antidiarrheal or an antidepressant method, or a method for the treatment of diminution of vision, hepatitis, inflammatory intestinal syndrome, functional enteropathy, functional hepatopathy, functional nephropathy, dementia, climacteric symptoms, senile dementia and/or Alzheimer disease, said method comprising: administering to skin a composition comprising (a) at least one member selected from the group consisting of isoflavones and isoflavone glycosides, (b) curcumin, and (c) cholic acid or at least one member selected from the group consisting of scymnol and scymnol esters.



Anti-inflammatory and immunosuppressive drugs and reproduction  

PubMed Central

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

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



Calcium Fructoborate—Potential Anti-inflammatory Agent  

Microsoft Academic Search

Calcium fructoborate is a boron-based nutritional supplement. Its chemical structure is similar to one of the natural forms\\u000a of boron such as bis-manitol, bis-sorbitol, bis-fructose, and bis-sucrose borate complexes found in edible plants. In vitro studies revealed that calcium fructoborate is a superoxide ion\\u000a scavenger and anti-inflammatory agent. It may influence macrophage production of inflammatory mediators, can be beneficial\\u000a for

Romulus Ion Scorei; Petre Rotaru


Nitro-fatty acids: novel anti-inflammatory lipid mediators.  


Nitro-fatty acids are formed and detected in human plasma, cell membranes, and tissue, modulating metabolic as well as inflammatory signaling pathways. Here we discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, redirecting arachidonic acid metabolism and signaling. We also analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases. PMID:24068188

Rubbo, H



Nonsteroidal Anti-Inflammatory Drugs for Retinal Disease  

PubMed Central

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in ophthalmology for pain and photophobia after photorefractive surgery and to reduce miosis, inflammation, and cystoid macular edema following cataract surgery. In recent years, the US Food and Drug Administration has approved new topical NSAIDs and previously approved NSAIDs have been reformulated. These changes may allow for greater drug penetration into the retina and thereby offer additional therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on the scientific rationale and clinical use of NSAIDs for retinal disease.

Schoenberger, Scott D.; Kim, Stephen J.



Natural anti-inflammatory agents for pain relief  

PubMed Central

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

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



Anti-inflammatory guaiane-type sesquiterpenes from the fruits of Pittosporum undulatum.  


Two unprecedented guaiane-type sesquiterpene glycosides (undulatumosides A and B) were isolated by bioassay-guided fractionation from the MeOH extract of Pittosporum undulatum fruits, along with six known compounds, including the guaiane isomers 5-guaien-11-ol and 4-guaien-11-ol. The structures of the compounds were established as 4-guaiene-11-O-?-d-(3'-angeloxy-6'-deoxy)-glucopyranoside and 1(5)-guaiene-11-O-?-d-(3'-angeloxy-6'-deoxy)-glucopyranoside by spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY), and HR-mass spectrometry. P. undulatum is a highly invasive weed that often outcompetes other plants, yet its fruits have become a traditional anti-inflammatory medicine in Azores. Therefore, aiming to investigate the claimed properties, the in vitro anti-inflammatory activity of guaiane-type sesquiterpenes was evaluated by analyzing their inhibitory effects on chemical mediators released by the LPS activated RAW 264.7 murine macrophages cell line. In addition, the cytotoxicity of these compounds was also evaluated in this cell line. Undulatumoside A, 5-guaien-11-ol and 4-guaien-11-ol displayed anti-inflammatory activity with IC50 values of 16.4, 8.1 and 7.2?M, respectively, comparable to that of the positive control, indomethacin (IC50=18.2?M), with no cytotoxic effects (IC50?198?M). Furthermore, the same set of compounds was also assessed for anti-proliferative activity in lung large cell carcinoma COR-L23 and amelanotic melanoma C32 cells. PMID:23899690

Mendes, Sofia A C; Mansoor, Tayyab A; Rodrigues, Ana; Armas, Jácome Bruges; Ferreira, Maria-José U



Modified acidic nonsteroidal anti-inflammatory drugs as dual inhibitors of mPGES-1 and 5-LOX.  


mPGES-1 is a promising target for development of new anti-inflammatory drugs. We aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs by replacing the carboxylic acid functionality by sulfonamide moieties. Compounds were also tested for 5-LOX inhibition. The most potent mPGES-1 inhibitor was lonazolac derivative 22 (IC?? = 0.16 ?M), while the best 5-LOX inhibition was attained by indomethacin derivative 17 (IC?? = 0.9 ?M). Inhibition of COX-1 activity was completely removed. PMID:22992107

Elkady, Mahmoud; Nieß, Raimund; Schaible, Anja M; Bauer, Julia; Luderer, Susann; Ambrosi, Giulia; Werz, Oliver; Laufer, Stefan A



Discovery and structure-activity relationships of 6-(benzoylamino)benzoxaboroles as orally active anti-inflammatory agents.  


Structure-activity relationships of 6-(benzoylamino)benzoxaborole analogs were investigated for the inhibition of TNF-?, IL-1?, and IL-6 from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compound 1q showed potent activity against all three cytokines with IC50 values between 0.19 and 0.50?M, inhibited LPS-induced TNF-? and IL-6 elevation in mice and improved collagen-induced arthritis in mice. Compound 1q (AN4161) is considered to be a promising lead for novel anti-inflammatory agent with an excellent pharmacokinetic profile. PMID:24075731

Akama, Tsutomu; Dong, Chen; Virtucio, Charlotte; Freund, Yvonne R; Chen, Daitao; Orr, Matthew D; Jacobs, Robert T; Zhang, Yong-Kang; Hernandez, Vincent; Liu, Yang; Wu, Anne; Bu, Wei; Liu, Liang; Jarnagin, Kurt; Plattner, Jacob J



The metabolic effects of inhibitors of 5-lipoxygenase and of cyclooxygenase 1 and 2 are an advancement in the efficacy and safety of anti-inflammatory therapy.  


Chronic treatment of inflammatory diseases with non-steroidal anti-inflammatory drugs is effective but not always devoid of serious side effects. In particular, the use of traditional non-steroidal aspirin-like drugs has been associated with a high incidence of gastrointestinal bleedings. The development of a new class of drugs, the selective cyclooxygenase type 2 (COX-2) inhibitors, has generated much expectation on the possibility to have safer compounds. After the initial enthusiasm of the scientific community, a re-evaluation of some large, randomized double-blind clinical studies performed with two of these compounds, has disclosed that the late serious gastrointestinal complications are not significantly reduced in comparison with non-selective inhibitors and that cardiovascular concerns might arise particularly if theses drugs are utilized in patients with underlying heart diseases. A new promising class of drugs to control inflammatory diseases is in advanced clinical development. The balanced inhibitors of 5-lipoxygenase (5-LOX) and of cyclooxygenase (both types 1 and 2) block the formation of all the enzymatically arachidonic acid-derived metabolites, both prostaglandins (like COX inhibitors) and leukotrienes (LT); these drugs have been shown to possess a very good anti-inflammatory efficacy without serious side effects. Licofelone, previously known as ML3000, is the molecule in the most advanced phase of clinical development (phase III) among this class of compounds; it is a potent, competitive, and well balanced inhibitor of 5-LOX and COX pathways. The drug has been shown to possess analgesic, anti-inflammatory, antipyretic antibronchocostrictory and antiplatelet properties at doses which are safe for the gastrointestinal tract. Moreover, the newly performed preclinical studies, here briefly reviewed, appear to indicate that the compound seems particularly suitable to protect the articular cartilage and the synovial space in degenerative joint disease and to exert a relevant antithrombotic activity. Preliminary results of clinical studies of licofelone in osteoarthritis indicate that the drug has a comparable or slightly better efficacy than that of naproxen but possesses a much better gastrointestinal safety. This latter important aspect has been also evaluated by an endoscopic study in normal volunteers randomly assigned to a 4-week treatment with licofelone, placebo or naproxen. The results indicate that no ulcers occurred in either licofelone group or the placebo group, while ulcers with unequivocal depth were present in 20% of the naproxen-treated subjects. PMID:14518558

Celotti, Fabio; Durand, Thierry



Anti-Inflammatory Polymeric Coatings for Implantable Biomaterials and Devices  

PubMed Central

Synthetic polymer coatings are used extensively in modern medical devices and implants because of their material versatility and processability. These coatings are designed for specific applications by controlling composition and physical and chemical properties, and they can be formed into a variety of complex structures and shapes. However, implantation of these materials into the body elicits a strong inflammatory host response that significantly limits the integration and biological performance of devices. Biomaterial-mediated inflammation is a complex reaction involving protein adsorption, leukocyte recruitment and activation, secretion of inflammatory mediators, and fibrous encapsulation of the implant. Significant research efforts have focused on modifying material properties using various anti-inflammatory polymeric surface coatings to generate more biocompatible implants. This minireview provides a brief background on the events of biomaterial-mediated inflammation and highlights various approaches used for modifying material surfaces to modulate inflammatory responses. These include both passive and active strategies, such as nonfouling surface treatments and delivery of anti-inflammatory agents, respectively. Novel approaches will be needed to extend the in vivo lifetime and performance of devices and reduce the need for multiple implantation surgeries.

Bridges, Amanda W.; Garcia, Andres J.



Anti-inflammatory activity of Seabuckthorn (Hippophae rhamnoides) leaves.  


Immunomodulatory activity of Seabuckthorn (SBT) leaf extract was evaluated in adjuvant induced arthritis (AIA) rat model. Inflammation was induced by injecting Complete Freund's Adjuvant (CFA) in the right hind paw of rats. SBT extract was administered intraperitoneally to treat the inflammation. The extent of inflammation and treatment response was evaluated by clinical analysis, scintigraphic visualization using technitium-99m-glutathione (Tc99m-GSH) and lymphocyte proliferation. Serial evaluation was carried out on days 1, 7, 14, 21 and 28 after creation of inflammation. The Tc99m-GSH uptake in the inflamed leg was compared with the normal contralateral leg of the same animal. The measurements were done by obtaining scintigraphic images using gamma camera and an online computer. Both qualitative and quantitative evaluation of radiotracer accumulation was considered to evaluate the anti-inflammatory response. The lymphocyte proliferation study revealed cellular immunosuppression during the early phase of the disease. Administration of SBT extract on the same day or 5 days prior to inflammatory insult into the joint, significantly reduced the inflammation as compared to the untreated animals in a dose dependent manner. These observations suggest that the SBT leaf extract has a significant anti-inflammatory activity and has the potential for the treatment of arthritis. PMID:16102517

Ganju, Lilly; Padwad, Yogendra; Singh, Richa; Karan, Dev; Chanda, Sudipta; Chopra, Mohinder Kumar; Bhatnagar, Parul; Kashyap, Ravi; Sawhney, Ramesh Chandra



The anti-inflammatory properties of cocoa flavanols.  


Signs of chronic or acute inflammation have been demonstrated in most cardiovascular diseases of multifactorial pathogenesis, including atherosclerosis and chronic heart failure. The triggers and mechanisms leading to inflammation may vary between clinical conditions but they share many common mediators, including specific patterns of eicosanoid and cytokine production. Certain cocoa-based products can be rich in a subclass of flavonoids known as flavanols, some of which have been found in model systems to possess potential anti-inflammatory activity relevant to cardiovascular health. Indeed, experimental evidence demonstrates that some cocoa-derived flavanols can reduce the production and effect of pro-inflammatory mediators either directly or by acting on signaling pathways. However, it should be noted that the evidence for any beneficial effects of cocoa flavanols in providing a meaningful anti-inflammatory action has been gathered predominantly from in vitro experiments. Therefore, additional research in well-designed human clinical experiments, using cocoa properly characterized in terms of flavanol content, would be a welcome addition to the evidence base to determine unambiguously if this benefit does indeed exist. If so, then flavanol-rich cocoa could be a potential candidate for the treatment, or possibly prevention, of the broad array of chronic diseases that are linked to dysfunctional inflammatory responses. PMID:16794453

Selmi, Carlo; Mao, Tin K; Keen, Carl L; Schmitz, Harold H; Eric Gershwin, M



Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta.  


Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for analgesic, antipyretic and anti-inflammatory properties in mice and rats, in order to complete its activity profile, after the confirmation of the existence of a central depressant activity particularly expressed by a strong sedative effect, associated with anxiolytic effects. This study leads us to the conclusion that this plant extract exerts central analgesic properties. Such a dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, from the doses of 20 and 25 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. An antipyretic activity was obtained at the sedative doses of 100 and 400 mg/kg, on the yeast-induced hyperthermia. Finally, significant and dose-dependent anti-inflammatory effects were observed on an acute inflammatory process (carrageenan-induced edema test in rats) from the dose of 100 mg/kg. On the other hand, plant extract remained inactive on chronic processes such as Freund's adjuvant-induced rheumatoid arthritis, after a chronic treatment during fourteen days at the daily dose of 200 or 400 mg/kg; however, if inefficacy was observed on rat backpaws edema and on loss of weight, the aqueous extract reduced the inflammatory hyperalgia. PMID:1896520

Lanhers, M C; Fleurentin, J; Dorfman, P; Mortier, F; Pelt, J M



Anti-inflammatory activities of hypocretenolides from Leontodon hispidus.  


Hypocretenolides, a small group of sesquiterpene lactones with an unusual ring structure, are constituents of a small number of species from the Lactuceae tribe (Asteraceae). Three biogenetically closely related 14-hypocretenolides from Leontodon hispidus L. were investigated for a putative anti-inflammatory activity. 14-Hydroxyhypocretenolide-beta-D-glucoside-4'-14"-hydroxyhypocr etenoate significantly exhibited in vivo anti-inflammatory activity in the croton oil-induced mouse ear edema. To obtain first information regarding the molecular targets which might be affected by this constituent, two in vitro bioassays were performed: (i) DNA binding activity of the transcription factor NF-kappa B was evaluated by electrophoretic mobility shift assay (EMSA) using TNF-alpha-activated Jurkat T cells and (ii) nitrite accumulation in cell culture supernatants of LPS-activated RAW 264.7 macrophages was determined as a parameter for inducible nitric oxide synthase (iNOS)-dependent nitric oxide release. In order to gain information about structure-activity relationships, additionally the aglycone 14-hydroxyhypocretenolide and its D-glycoside were investigated in these in vitro systems. 14-Hydroxyhypocretenolide-beta-D-glucoside-4'-14"-hydroxyhypocr etenoate as well as its aglycone exhibited activity in both test systems, whereas the D-glucoside was not or only weakly active. PMID:10630109

Zidorn, C; Dirsch, V M; Rüngeler, P; Sosa, S; Della Loggia, R; Merfort, I; Pahl, H L; Vollmar, A M; Stuppner, H



Anti-inflammatory properties of exenatide in human pancreatic islets.  


Exenatide is an analog of the incretin hormone glucagon-like peptide (GLP-1) that is used for the treatment of T2D for their metabolic effects. In addition to its insulinotropic effects, exenatide increases functional islet mass and improves their survival. Improved outcomes have been reported in recent clinical islet transplantation trials for the treatment of type 1 diabetes. The purpose of this study was to investigate whether exenatide has anti-inflammatory properties in human islets. Exenatide treatment improved islet function, significantly reduced content of inflammation-related molecules (tissue factor, IFN-?, IL-17, IL-1?, and IL-2) and caspase 3 activation, whereas increased phosphorylation of ERK1/2, STAT3, and Akt in vitro. Immunostaining showed expression of GLP-1R in ?-cells but not in ?-cells. IL-1? colocalized with GLP-1R in ?-cells. Induction of serine proteinase inhibitor 9 (PI-9) was detected after exposure of human islets to exenatide in vitro and after transplantation into immunodeficient mice. GLP-1 induced PI-9 expression in vitro but to a lower extent than exenatide. This effect was partially blocked by the antagonist exendin-9 in vitro. As assessed by immunostaining PI-9 is mostly expressed in ?-cells but not in ?-cells. In conclusion, we describe anti-inflammatory and cytoprotective properties of exenatide in human islets. Exenatide-mediated PI-9 expression, the only known granzyme B inhibitor, unveils potential immunoregulatory properties. PMID:21669040

Cechin, S R; Pérez-Álvarez, I; Fenjves, E; Molano, R D; Pileggi, A; Berggren, P-O; Ricordi, C; Pastori, R L



Potential anti-inflammatory actions of the elmiric (lipoamino) acids  

PubMed Central

A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells was the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ2 with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them.

Burstein, Sumner H.; Adams, Jeffrey K.; Bradshaw, Heather B.; Fraioli, Cristian; Rossetti, Ronald G.; Salmonsen, Rebecca A.; Shaw, John W.; Walker, J. Michael; Zipkin, Robert E.; Zurier, Robert B.



?-Mangostin: Anti-Inflammatory Activity and Metabolism by Human Cells  

PubMed Central

Information about the anti-inflammatory activity and metabolism of ?-mangostin (?-MG), the most abundant xanthone in mangosteen fruit, in human cells is limited. On the basis of available literature, we hypothesized that ?-MG will inhibit the secretion of pro-inflammatory mediators by control and activated macrophage-like THP-1, hepatic HepG2, enterocyte-like Caco-2, and colon HT-29 human cell lines, as well as primary human monocyte-derived macrophages (MDM), and that such activity would be influenced by the extent of metabolism of the xanthone. ?-MG attenuated TNF-? and IL-8 secretion by the various cell lines but increased TNF-? output by both quiescent and LPS-treated MDM. The relative amounts of free and phase II metabolites of ?-MG and other xanthones present in media 24 h after addition of ?-MG was shown to vary by cell type and inflammatory insult. Increased transport of xanthones and their metabolites across Caco-2 cell monolayers suggests enhanced absorption during an inflammatory episode. The anti-inflammatory activities of xanthones and their metabolites in different tissues merit consideration.

Gutierrez-Orozco, Fabiola; Chitchumroonchokchai, Chureeporn; Lesinski, Gregory B.; Suksamrarn, Sunit; Failla, Mark L.



Anti-inflammatory agents of the carbamoylmethyl ester class: synthesis, characterization, and pharmacological evaluation.  


In this study, target compounds 5-12 were synthesized via acid amine coupling of ibuprofen and naproxen with methyl ester derivatives of amino acids, namely, l-proline, sarcosine, l-tyrosine, and l-glutamic acid. When tested for anti-inflammatory activity using the acute carrageenan-induced hind paw method in rats, compounds 5-12 showed significantly greater anti-inflammatory activity, in the range of 40.64%-87.82%, compared with a placebo control group (P < 0.001). Among the newly synthesized compounds 5-12, naproxen derivatives 9-12 with anti-inflammatory activity ranging between 66.99% and 87.82% showed significantly higher (P < 0.05) potency than ibuprofen derivatives 5-8 with inhibition in the range of 22.03%-52.91% and control groups of ibuprofen (76.34%) or naproxen (75.59%, P < 0.05). Moreover, derivatives 9-12 derived from naproxen, in particular compounds 9 and 10 which achieved 83.91% and 87.82% inhibition of inflammation, respectively, showed significantly (P < 0.05) higher potency than naproxen derivatives 11 and 12. Notably, among naproxen derivatives 9-12, the gastric ulcerogenicity for 9 (ulcer index 11.73) and 10 (ulcer index 12.30) was found to be significantly lower (P < 0.05) than that of the active ibuprofen and naproxen control groups with ulcer indices of 22.87 and 24.13, respectively. On the other hand, naproxen derivatives 9-11 showed significant inhibition (P < 0.05) of prostaglandin E2 synthesis when compared with the active control group receiving indomethacin, suggesting a correlation between the observed low ulcerogenicity and effect on prostaglandin E2 synthesis for compounds 9 and 10. However, significant inhibition of prostaglandin E2 observed for naproxen derivative 11 (107.51) did not correlate with its observed ulcer index (16.84). Our overall findings for carbamoylmethyl ester derivatives named 5-12 clearly suggest that the compounds showing potent antiinflammatory effect. PMID:23576876

Sadek, Bassem; Hamruoni, Amar Mansuor; Adem, Abdu



Imbricaric Acid and Perlatolic Acid: Multi-Targeting Anti-Inflammatory Depsides from Cetrelia monachorum.  


In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E2 synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E2 synthase-1 (IC50 = 1.9 and 0.4 µM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC50 = 5.3 and 1.8 µM, resp.) and on purified enzyme (IC50 = 3.5 and 0.4 µM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC50 values of 2.0 and 7.0 µM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy. PMID:24130812

Oettl, Sarah K; Gerstmeier, Jana; Khan, Shafaat Y; Wiechmann, Katja; Bauer, Julia; Atanasov, Atanas G; Malainer, Clemens; Awad, Ezzat M; Uhrin, Pavel; Heiss, Elke H; Waltenberger, Birgit; Remias, Daniel; Breuss, Johannes M; Boustie, Joel; Dirsch, Verena M; Stuppner, Hermann; Werz, Oliver; Rollinger, Judith M



Imbricaric Acid and Perlatolic Acid: Multi-Targeting Anti-Inflammatory Depsides from Cetrelia monachorum  

PubMed Central

In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E2 synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E2 synthase-1 (IC50 = 1.9 and 0.4 µM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC50 = 5.3 and 1.8 µM, resp.) and on purified enzyme (IC50 = 3.5 and 0.4 µM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC50 values of 2.0 and 7.0 µM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy.

Oettl, Sarah K.; Gerstmeier, Jana; Khan, Shafaat Y.; Wiechmann, Katja; Bauer, Julia; Atanasov, Atanas G.; Malainer, Clemens; Awad, Ezzat M.; Uhrin, Pavel; Heiss, Elke H.; Waltenberger, Birgit; Remias, Daniel; Breuss, Johannes M.; Boustie, Joel; Dirsch, Verena M.; Stuppner, Hermann; Werz, Oliver; Rollinger, Judith M.



Copper complexes of non-steroidal anti-inflammatory drugs: an opportunity yet to be realized  

Microsoft Academic Search

The proposed curative properties of Cu-based non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous Cu(II) complexes of NSAIDs with enhanced anti-inflammatory activity and reduced gastrointestinal (GI) toxicity compared with their uncomplexed parent drug. These low toxicity Cu drugs have yet to reach an extended human market, but are of enormous interest, because many of today's anti-inflammatory drug

Jane E. Weder; Carolyn T. Dillon; Trevor W. Hambley; Brendan J. Kennedy; Peter A. Lay; J. Ray Biffin; Hubert L. Regtop; Neal M. Davies



Anti-inflammatory and anti-itch activity of sertaconazole nitrate  

Microsoft Academic Search

Cutaneous fungal infections are frequently associated with an inflammatory component including irritated skin, itching and stinging\\/burning. Therapeutic anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The

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



Anti inflammatory activity of an isolated flavonoid fraction from Celosia argentea Linn  

Microsoft Academic Search

The flavonoid fraction from alcoholic extract of the leaves of Celosia argentea L (Amaranthaceae) was investigated for anti-inflammatory activity in animal models. Results of the study revealed that flavonoid possesses significant anti-inflammatory properties when investigated by employing carrageenan induced rat paw edema and cotton pellet induced chronic inflammatory models. The study showed significant dose dependent anti-inflammatory activities in both the

S. Bhujbal; S. Chitlange; Anupama A. Suralkar; B. Shinde; Manohar J. Patil


Synthesis and pharmacological evaluation of some 3-(4-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents.  


A variety of 3-(4-methyl phenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-methyl phenyl)-3H-quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(4-methyl phenyl)-3H-quinazolin-4-one was synthesized from 4-methyl aniline. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic index activities. While the test compounds exhibited significant activity, compounds Al, A2, and A3 showed more potent analgesic activity and the compound A3 showed more potent anti-inflammatory activity when compared to the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to aspirin. PMID:17206609

Alagarsamy, Veerachamy; Shankar, Durairaj; Murugan, Muthuvel; Siddiqui, Anees Ahmed; Rajesh, Ramadoss



Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content.  


Cat's claw is an herbal medicine from the Amazon that is used widely to treat inflammatory disorders. The purpose of this study was to characterize the antioxidative and antiinflammatory properties of cat's claw, Uncaria tomentosa (UT) and Uncaria guianensis (UG). Alkaloids and flavanols were determined using reversed-phase HPLC; scavenging of 1,1-diphenyl-2-picrilhydrazyl (DPPH), hydroxyl radicals, and lipid peroxidation by spectrophotometry; and TNFalpha production by ELISA. Anti-inflammatory activity was assessed in vitro by inhibition of TNFalpha and nitrite production from RAW 264.7 cells exposed to LPS (50 ng/ml) and in vivo using the indomethacin-induced gastritis model. Apoptosis was assessed using the TUNEL technique and TNFalpha mRNA by in situ RT-PCR. In each of the antioxidant assays tested, UG was more potent than UT (P < 0.01). The total oxindole and pentacyclic alkaloid content of UT was 35-fold > UG. The IC50 value for inhibition of TNFalpha production was significantly (P < 0.01) higher for UT (14.1 ng/ml) vs UG (9.5 ng/ml), yet at concentrations that were considerable lower than that required for antioxidant activity. Non-alkaloid HPLC fractions from UT decreased LPS-induced TNFalpha and nitrite production in RAW 264.7 cells (P < 0.01) at a concentration range comparable to the parent botanical. Oral pretreatment for 3 d with UT protected against indomethacin-induced gastritis, and prevented TNFalpha mRNA expression and apoptosis. These results indicate that while both species of cat's claw provide effective antioxidant and anti-inflammatory activities, U. guianensis is more potent. In conclusion, the presence of oxindole or pentacyclic alkaloids did not influence the antioxidant and anti-inflammatory properties of cat's claw. PMID:12120814

Sandoval, M; Okuhama, N N; Zhang, X J; Condezo, L A; Lao, J; Angeles', F M; Musah, R A; Bobrowski, P; Miller, M J S



Mechanisms for anti-inflammatory effects of 1-[15(S)-hydroxyeicosapentaenoyl] lysophosphatidylcholine, administered intraperitoneally, in zymosan A-induced peritonitis  

PubMed Central

BACKGROUND AND PURPOSE Lysophosphatidylcholines (lysoPCs) with polyunsaturated acyl chains are known to exert anti-inflammatory actions. 15-Lipoxygeanation is crucial for anti-inflammatory action of polyunsaturated acylated lysoPCs. Here, the anti-inflammatory actions of 1-(15-hydroxyeicosapentaenoyl)-lysoPC (15-HEPE-lysoPC) and its derivatives were examined in a mechanistic analysis. EXPERIMENTAL APPROACH Anti-inflammatory actions of 15-HEPE-lysoPC in zymosan A-induced peritonitis of mice were examined by measuring plasma leakage and leucocyte infiltration, and determining levels of lipid mediators or cytokines. KEY RESULTS When each lysoPC, administered i.v., was assessed for its ability to suppress zymosan A-induced plasma leakage, 15-HEPE-lysoPC was found to be more potent than 1-(15-hydroperoxyeicosapentaenoyl)-lysoPC or 1-eicosapentaenoyl-lysoPC. Separately, i.p. administration of 15-HEPE-lysoPC markedly inhibited plasma leakage, in contrast to 15-HEPE, which had only a small effect. 15-HEPE-lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation of LTC4 and LTB4, 5-lipoxygenation products, as well as the levels of pro-inflammatory cytokines. The time-course study indicated that 15-HEPE-lysoPC might participate in both the early inflammatory phase and resolution phase. Additionally, 15-HEPE-lysoPC administration caused a partial suppression of LTC4-induced plasma leakage and LTB4-induced leucocyte infiltration. In the metabolism study, peritoneal exudate was shown to contain lysoPC-hydrolysing activity, crucial for anti-inflammatory activity, and a system capable of generating lipoxin A from 15-hydroxy eicosanoid precursor. CONCLUSIONS AND IMPLICATIONS 15-HEPE-lysoPC, a precursor for 15-HEPE in target cells, induced anti-inflammatory actions by inhibiting the formation of pro-inflammatory leukotrienes and cytokines, and by enhancing the formation of lipoxin A. 15-HEPE-lysoPC might be one of many potent anti-inflammatory lipids in vivo.

Hung, Nguyen Dang; Kim, Mee Ree; Sok, Dai-Eun



Anti-inflammatory and antifibrotic effects of methyl palmitate  

SciTech Connect

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

El-Demerdash, Ebtehal, E-mail:



Study of the anti-inflammatory and analgesic effects of novel rigid benzofuran-3, 4-dihydroxy chalcone by formalin, hot-plate and carrageenan tests in mice.  


It is reported that dihydroxy chalcones have analgesic and anti-inflammatory effects. Study of the structure activity relationship (SAR) shows that benzofuran-3-one derivatives may be more effective in this respect. In this study, a new (Z)-2-(3,4-dihydroxybenzylidene)-5-methoxybenzofuran-3(2H)-one (compound 5) was synthesized and its analgesic and anti-inflammatory effects were evaluated by formalin, carrageenan and hot-Plate methods in mice. The results showed that, compound 5 induced significant antinociceptive and anti-inflammatory effect (P<0.01). Maximum analgesia (42.6%) was obtained at dose of 25 mg/kg in the first phase of formalin test. The effect of compound 5 was higher (87.7%) in chronic phase of inflammation induced by formalin (P<0.01). Administration of 25 mg/kg of compound 5 inhibited the inflammation induced by carrageenan, 32.8% and 41.7%, 1 and 3 hour after carrageenan injection, respectively. In addition, this dose of compound 5, induces significant analgesia (20.2%) in hot plate test 45 minutes after injection (P<0.01). Therefore it seems that compound 5 has potential for discovery of a compound with potent anti-inflammatory and analgesic effects and its scaffold could be use for further structural modifications. PMID:19783518

Heidari, Mahmoud Reza; Foroumadi, Alireza; Noroozi, Hojat; Samzadeh-Kermani, Ali; Azimzadeh, Behzad Sarvar



Comparison of the effects of antioxidant non-steroidal anti-inflammatory drugs against myeloperoxidase and hypochlorous acid luminol-enhanced chemiluminescence  

Microsoft Academic Search

The interaction of myeloperoxidase (MPO) with H2O2 and Cl? provides a potent antimicrobial\\/cytotoxic system for polymorphonuclear leukocytes (PMNs). MPO-related cytotoxicity may be associated with the formation of toxic oxidant MPO intermediates, HOCl, or both. MPO itself is able to oxidize drugs and cellular components. Non-steroidal anti-inflammatory drugs (NSAIDs) able to act as antioxidant free radical scavengers have recently been shown

Gary Pekoe; Knox Van Dyke; Henry Mengoli; David Peden; Denis English



Anti-oxidant and anti-inflammatory activities of Inonotus obliquus and germinated brown rice extracts.  


Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on germinated brown rice (GBR) in the present study and the antioxidant and anti-inflammatory activities of the IO grown on germinated brown rice (IOGBR) extracts were evaluated extensively and compared with those for IO and GBR. IOGBR showed highest antioxidant activities with scavenging total intracellular ROS and MDA levels as well as increasing the antioxidant enzymes activity in the H?O?-stimulated mice liver. It also exhibited best inflammatory activities by suppressing the proinflammatory mediators such as NO, PGE?, iNOS, COX-2, TNF-?, IL-1?, and IL-6 in an LPS-stimulated RAW 264.7 cell line. This study provides a comparative approach to find out an excellent natural source of antioxidants and anti-inflammatory agent as a dietary supplement. PMID:23917116

Debnath, Trishna; Park, Sa Ra; Kim, Da Hye; Jo, Jeong Eun; Lim, Beong Ou



Anti-inflammatory properties of azelnidipine, a dihydropyridine-based calcium channel blocker.  


Accumulating evidence suggests that inflammation as well as oxidative stress play essential roles in atherogenesis, progression of atherosclerosis, and plaque instability and rupture. Recent studies on available anti-hypertensive agents have focused on their anti-atherosclerotic effects over and above their blood pressure lowering action. These studies have included investigations on several types of calcium channel blockers, with several investigations indicating that a dihydropiridine-based calcium channel blocker, azelnidipine, developed in Japan, has unique anti-oxidative properties. An anti-inflammatory effect of azelnidipine has, however, yet to be established and therefore we carried out a series of in vivo and in vitro studies to investigate this possibility. This was achieved by measuring inflammatory and oxidative stress markers in 16 high risk hypertensive patients administered 16mg/day of azelnidipine. After 4 weeks of treatment, serum levels of hsCRP, IL-6, and IL-8 and urinary 8-OHdG were decreased significantly, despite blood pressure remaining unchanged. Cultures of human mononuclear leukocytes collected from six healthy volunteers showed 100 nM of azelnidipine caused significant inhibition of formyl-methyonyl leucyl phenylalanine (fMLP)-induced production of IL-8. Taken together, these results suggest that azelnidipine has anti-inflammatory effects independent of its anti-hypertensive action. As leukocytes do not possess voltage-operated calcium channels, the effect of azelnidipine in these cells appears to occur independently of an L-type calcium channel antagonizing effect. PMID:20374186

Komoda, Hiroshi; Inoue, Teruo; Node, Koichi



Cannabinoid-based drugs as anti-inflammatory therapeutics.  


In the nineteenth century, marijuana was prescribed by physicians for maladies ranging from eating disorders to rabies. However, as newer, more effective drugs were discovered and as the potential for abuse of marijuana was recognized, its use as a therapeutic became restricted, and only recently has its therapeutic potential been re-evaluated. Recent studies in animal models and in humans have produced promising results for the treatment of various disorders - such as obesity, cancer, and spasticity and tremor due to neuropathology - with drugs based on marijuana-derived cannabinoids. Moreover, as I discuss here, a wealth of information also indicates that these drugs have immunosuppressive and anti-inflammatory properties; therefore, on the basis of this mode of action, the therapeutic usefulness of these drugs in chronic inflammatory diseases is now being reassessed. PMID:15864274

Klein, Thomas W



Novel Activity of an Anti-Inflammatory Cytokine  

PubMed Central

IL-10 is an anti-inflammatory cytokine that suppresses synthesis of proinflammatory cytokines and their receptors. Here we tested the possibility that TNF?-induced hormone resistance in myoblasts might be overcome by IL-10. We found that IL-10 restores myogenesis by suppressing the ability of exogenous TNF? to inhibit IGF-I-induced myogenin. This protection occurs without decreasing global activity of TNF receptors since IL-10 does not impair TNF?-induced IL-6 synthesis or ERK1/2 phosphorylation. Instead, IL-10 acts to prevent TNF?-induced phosphorylation of JNK. These findings demonstrate that IL-10 serves a previously unrecognized protective role in muscle progenitors by overcoming TNF?-induced resistance to IGF-I.

Strle, Klemen; McCusker, Robert H.; Tran, Lynn; King, Alexandra; Johnson, Rodney W.; Freund, Gregory G.; Dantzer, Robert; Kelley, Keith W.



Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy  

PubMed Central

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in the world. NSAID-induced lower gastrointestinal (GI) complications are increasing while upper GI complications are decreasing. Lower GI events accounted for 40% of all serious GI events in patients on NSAIDs. Capsule endoscopy and device assisted enteroscopy are available for detection of small intestinal lesions. Capsule endoscopy studies have demonstrated that NSAIDs use in healthy volunteers raised the incidence (55% to 75%) of intestinal damage. It appears that selective cyclooxygenase-2 inhibitors (coxibs) improved upper and lower GI safety based on results of clinical trials. Selective coxibs are still capable of triggering GI adverse events and cardiovascular toxicity issues were the main focus of concerns. Unfortunately, definite strategies are not available to prevent or heal NSAID-induced intestinal injuries. Thus, there is still a strong clinical need for effective drugs with improved safety profiles than the existing NSAIDs.

Lim, Yun Jeong



Anti-inflammatory therapy for obstructive sleep apnea in children  

PubMed Central

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

Friedman, Bat-Chen; Goldman, Ran D.



Anti-inflammatory agents from plants: progress and potential.  


The identification of substances that can promote the resolution of inflammation in a way that is homeostatic, modulatory, efficient, and well-tolerated by the body is of fundamental importance. Traditional medicines have long provided front-line pharmacotherapy for many millions of people worldwide. Medicinal extracts are a rich source of therapeutic leads for the pharmaceutical industry. The use of medicinal plant therapies to treat chronic illness, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on the rise.The aim of this review is to present recent progress in clinical anti-inflammatory studies of plant extracts and compound leads such as green tea polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among others, against chronic inflammatory diseases, mainly RA and IBD. In this context, the present paper also highlights the most promising experimental data on those plant extracts and pure compounds active in animal models of the aforementioned diseases. PMID:22414101

Recio, M C; Andujar, I; Rios, J L



Topical delivery of nonsteroidal anti-inflammatory drugs for osteoarthritis.  


Osteoarthritis (OA) is one of the most commonly reported chronic pain syndromes experienced in the United States. Treatment guidelines for OA recommend acetaminophen for first-line pharmacotherapy for these patients; however, this strategy is rarely effective as monotherapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the next step in therapy and have accumulated a large body of data to support their efficacy for OA. Unfortunately, this class of agents is not without the potential for significant adverse effects. In an effort to capture the efficacy of NSAIDs while decreasing their side effect burden, many clinicians are turning to the topical administration of these agents. Localized pain and smaller, superficial joints may be especially amenable to the topical administration of NSAIDs. Numerous commercially available topical NSAID formulations have been shown to be efficacious in patients with OA. This review focuses on the topical delivery of NSAIDs for the treatment of OA. PMID:22448937

Herndon, Christopher M



Go Green: The Anti-Inflammatory Effects of Biliverdin Reductase  

PubMed Central

Biliverdin (BV) has emerged as a cytoprotective and important anti-inflammatory molecule. Conversion of BV to bilirubin (BR) is catalyzed by biliverdin reductase (BVR) and is required for the downstream signaling and nuclear localization of BVR. Recent data by others and us make clear that BVR is a critical regulator of innate immune responses resulting from acute insult and injury and moreover, that a lack of BVR results in an enhanced proinflammatory phenotype. In macrophages, BVR is regulated by its substrate BV which leads to activation of the PI3K–Akt-IL-10 axis and inhibition of TLR4 expression via direct binding of BVR to the TLR4 promoter. In this review, we will summarize recent findings on the role of BVR and the bile pigments in inflammation in context with its activity as an enzyme, receptor, and transcriptional regulator.

Wegiel, Barbara; Otterbein, Leo E.



[Anti-inflammatory modulators in traumatic brain injury].  


Traumatic brain injury leads to primary and secondary brain injuries. Primary brain injury results from mechanical forces applied to the head at the time of impact. Secondary brain injury occurs at some time after the primary impact. Numerous pathophysiological mechanisms have been postulated to explain the progressive tissue damage produced by secondary injuries. The endogenous neuroinflammatory response after traumatic brain injury contributes to the development of blood-brain barrier breakdown, cerebral oedema and neuronal cell death and this has led to various pharmacological therapies to try to limit this type of damage. Studies employing glutamate receptor antagonist for cerebral protection have yielded promising results in laboratory animals but failed to produce clinically significant improvements. The present review will summarize the mechanisms of post traumatic cerebral inflammation with a special focus on the anti-inflammatory drug targets. PMID:16675184

Lescot, T; Marchand-Verrecchia, C; Puybasset, L



Anti-inflammatory strategies to enhance islet engraftment and survival.  


Early innate inflammatory reaction strongly affects islet engraftment and survival after intrahepatic transplantation. This early immune response is triggered by ischemia-reperfusion injury and instant blood mediated inflammatory reaction (IBMIR) occurring hours and days after islet infusion. Evidence in both mouse model and in human counterpart suggest the involvement of coagulation, complement system, and proinflammatory chemokines/cytokines. Identification and targeting of pathway(s), playing a role as "master regulator(s)" in post-transplant detrimental inflammatory events, is now mandatory to improve islet transplantation success. This review will focus on inflammatory pathway(s) differentially modulated by islet isolation and mainly associated with the early post-transplant events. Moreover, we will take into account anti-inflammatory strategies that have been tested at 2 levels: on the graft, ex vivo, during islet culture (i.e., donor) and/or on the graft site, in vivo, early after islet infusion (i.e., recipient). PMID:23912763

Citro, Antonio; Cantarelli, Elisa; Piemonti, Lorenzo



The role of anti-inflammatory treatment in psychiatric disorders.  


Anti-inflammatory treatment could be expected to show positive effects in the subgroup of psychiatric patients who show signs of inflammation, i.e. an increase in proinflammatory cytokines and PGE2. Cyclooxygenase-2 (COX-2) not only reduces the levels of proinflammatory cytokines, but also affects glutamatergic neurotransmission and tryptophan/kynurenine metabolism. In the meantime, several studies have been performed with the COX-2 inhibitor celecoxib in schizophrenia; the studies found a therapeutic effect, mainly in the early stages of the disorder. We were able to demonstrate a statistically significant therapeutic effect of celecoxib on depressive symptoms in a study in patients with major depression (MD). Another study in fifty patients with MD also showed a statistically significant better outcome with celecoxib. This paper will discuss immune-based therapeutic approaches in both schizophrenia and depression. PMID:24048400

Müller, Norbert



The anti-inflammatory mechanisms of Hsp70  

PubMed Central

Immune responses to heat shock proteins (Hsp) develop in virtually all inflammatory diseases; however, the significance of such responses is only now becoming clear. In experimental disease models, Hsp administration can prevent or arrest inflammatory damage, and in initial clinical trials in patients with chronic inflammatory diseases, Hsp peptides have been shown to promote the production of anti-inflammatory cytokines, indicating immunoregulatory potential of Hsp. Therefore, the presence of immune responses to Hsp in inflammatory diseases can be seen as an attempt of the immune system to correct the inflammatory condition. Hsp70 can modulate inflammatory responses in models of arthritis, colitis and graft rejection, and the mechanisms underlying this effect are now being elucidated. Incubation with microbial Hsp70 was seen to induce tolerogenic dendritic cells (DCs) and to promote a suppressive phenotype in myeloid-derived suppressor cells and monocytes. These DC could induce regulatory T cells (Tregs), independently of the antigens they presented. Some Hsp70 family members are associated with autophagy, leading to a preferential uploading of Hsp70 peptides in MHC class II molecules of stressed cells. Henceforth, conserved Hsp70 peptides may be presented in these situations and constitute targets of Tregs, contributing to downregulation of inflammation. Finally, an interfering effect in multiple intracellular inflammatory signaling pathways is also known for Hsp70. Altogether it seems attractive to use Hsp70, or its derivative peptides, for modulation of inflammation. This is a physiological immunotherapy approach, without the immediate necessity of defining disease-specific auto-antigens. In this article, we present the evidence on anti-inflammatory effects of Hsp70 and discuss the need for experiments that will be crucial for the further exploration of the immunosuppressive potential of this protein.

Borges, Thiago J.; Wieten, Lotte; van Herwijnen, Martijn J. C.; Broere, Femke; van der Zee, Ruurd; Bonorino, Cristina; van Eden, Willem



Anti-inflammatory treatment induced regenerative oligodendrogenesis in parkinsonian mice.  


ABSTRACT: INTRODUCTION: The adult mammalian brain retains niches for neural stem cells (NSCs), which can generate glial and neuronal components of the brain tissue. However, it is barely established how chronic neuroinflammation, as it occurs in neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, affects adult neurogenesis and, therefore, modulates the brain's potential for self-regeneration. METHODS: Neural stem cell culture techniques, intraventricular tumor necrosis factor (TNF)-? infusion and the 6-hydroxydopamine mouse model were used to investigate the influence of neuroinflammation on adult neurogenesis in the Parkinson's disease background. Microscopic methods and behavioral tests were used to analyze samples. RESULTS: Here, we demonstrate that differences in the chronicity of TNF-? application to cultured NSCs result in opposed effects on their proliferation. However, chronic TNF-? treatment, mimicking Parkinson's disease associated neuroinflammation, shows detrimental effects on neural progenitor cell activity. Inversely, pharmacological inhibition of neuroinflammation in a 6-hydroxydopamine mouse model led to increased neural progenitor cell proliferation in the subventricular zone and neuroblast migration into the lesioned striatum. Four months after surgery, we measured improved Parkinson's disease-associated behavior, which was correlated with long-term anti-inflammatory treatment. But surprisingly, instead of newly generated striatal neurons, oligodendrogenesis in the striatum of treated mice was enhanced. CONCLUSIONS: We conclude that anti-inflammatory treatment, in a 6-hydroxydopamine mouse model for Parkinson's disease, leads to activation of adult neural stem cells. These adult neural stem cells generate striatal oligodendrocytes. The higher numbers of newborn oligodendrocytes possibly contribute to axonal stability and function in this mouse model of Parkinson's disease and thereby attenuate dysfunctions of basalganglian motor-control. PMID:22892385

Worlitzer, Maik Ma; Bunk, Eva C; Hemmer, Kathrin; Schwamborn, Jens C



1,5-Diphenylpent-3-en-1-ynes and methyl naphthalene carboxylates from Lawsonia inermis and their anti-inflammatory activity.  


Lawsonia inermis (Lythraceae) known as henna is one of the most popular and ancient plants used in cosmetics and hair dying. It is cultivated for its leaves but other parts such as seeds, flowers, stem bark and roots are also used in traditional medicine for millennia. Henna tattoo paste also proved to be beneficial for wound healing and in several skin diseases suggesting potent anti-inflammatory activity. To evaluate henna anti-inflammatory activity, 31 compounds, including three 1,5-diphenylpent-3-en-1-yne derivatives, lawsochylin A-C and three methyl naphthalene carboxylates, lawsonaphthoate A-C, were isolated from the stems and leaves of henna utilizing a bioassay-guided fractionation. The structures of the compounds were elucidated by spectroscopic data. Two compounds, lawsochylin A and lawsonaphthoate A showed potent anti-inflammatory activity by inhibition of superoxide anion generation (IC(50)=1.80 and 1.90 ?g/ml) and elastase release (IC(50)=1.58 and 3.17 ?g/ml) of human neutrophils in response to fMLP or cytochalasin B. Moreover, the known compounds, luteolin, apigenin, 4S-4-hydroxy-?-tetralone, and 2-butoxysuccinic acid, also showed potent inhibition of superoxide anion generation (IC(50)=0.75-1.78 ?g/ml) and elastase release (IC(50)=1.62-3.61 ?g/ml). PMID:23351982

Liou, Jing-Ru; El-Shazly, Mohamed; Du, Ying-Chi; Tseng, Chao-Neng; Hwang, Tsong-Long; Chuang, Yueh-Lin; Hsu, Yu-Ming; Hsieh, Pei-Wen; Wu, Chin-Chun; Chen, Shu-Li; Hou, Ming-Feng; Chang, Fang-Rong; Wu, Yang-Chang



Identification of anti-inflammatory targets for Huntington's disease using a brain slice-based screening assay  

PubMed Central

Huntington’s disease (HD) is a late-onset, neurodegenerative disease for which there are currently no cures nor disease-modifying treatments. Here we report the identification of several potential anti-inflammatory targets for HD using an ex vivo model of HD that involves the acute transfection of human mutant huntingtin-based constructs into rat brain slices. This model recapitulates key components of the human disease, including the formation of intracellular huntingtin protein (HTT)-containing inclusions and the progressive neurodegeneration of striatal neurons—both occurring within the native tissue context of these neurons. Using this "high-throughput biology" screening platform, we conducted a hypothesis-neutral screen of a collection of drug-like compounds which identified several anti-inflammatory targets that provided neuroprotection against HTT fragment-induced neurodegeneration. The nature of these targets provide further support for non-cell autonomous mechanisms mediating significant aspects of neuropathogenesis induced by mutant HTT fragment proteins.

Reinhart, Peter H.; Kaltenbach, Linda S.; Essrich, Christian; Dunn, Denise E.; Eudailey, Joshua A.; DeMarco, C. Todd; Turmel, Gregory J.; Whaley, Jennifer C.; Wood, Andrew; Cho, Seongeon; Lo, Donald C.



Synthesis of Diarylpyrazoles Containing a Phenylsulphone or Carbonitrile Moiety and their Chalcones as Possible Anti-Inflammatory Agents  

PubMed Central

A series of chalcone-based diarylpyrazoles containing a phenylsulphone or carbonitrile moiety was synthesized. Thus, 3-acetylpyrazoles 6a–c and 10a–c were used as useful substrates in facile synthesis of functional pyrazoles 7a–f and 11a–f, respectively. The anti-inflammatory activity and ulcerogenic effect were evaluated and some of the obtained products possessed a significant anti-inflammatory activity. 1-[1-(3-Methylphenyl)-5-phenyl-4-(phenylsulfonyl)-1H-pyrazol-3-yl]ethanone (6b) showed a high activity when compared with indomethacin as reference drug with lower gastrointestinal (GI) profile. Furthermore, molecular docking studies were performed in order to rationalize the obtained biological results.

Nassar, Ekhlass; Abdel-Aziz, Hatem A.; Ibrahim, Hany S.; Mansour, Ahmed M.



Synthesis and anti-inflammatory activities investigation of sinomenine derivatives on ring C  

Microsoft Academic Search

Eighteen sinomenine derivatives on ring C were prepared, and their anti-inflammatory activities were also investigated. Most of these derivatives showed mild to moderate activities. Compounds 4a, 4c and 5b showed better anti-inflammatory activity. So further modification of the ring C in sinomenine should be worthwhile.

Qiang Tang; Juan Luo; Qianli Zhu; Yin Li; Shufan Yin



Anti-inflammatory profile of dehydrocostic acid, a novel sesquiterpene acid with a pharmacophoric conjugated diene  

Microsoft Academic Search

Sesquiterpene acids are natural products that, in contrast with the thoroughly studied sesquiterpene lactones, have received little pharmacological attention. A good source of this class of compounds is Inula viscosa (Asteraceae), a plant with documented anti-inflammatory effects. The present paper gives the results of our investigations on the biochemical mechanisms involved in the anti-inflammatory activity of one such compound, dehydrocostic

V. Hernández; S. Máñez; M. C. Recio; R. M. Giner; J. L. Ríos



Hypericum in Infection: Identification of Anti-viral and Anti-inflammatory Constituents  

Technology Transfer Automated Retrieval System (TEKTRAN)

The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum and Prunella supplements for human-health benefit, focusing on anti-viral, anti-inflammatory and anti-pain effects. This paper reports on ongoing anti-viral and anti-inflammatory studies on Hypericu...


Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice  

Technology Transfer Automated Retrieval System (TEKTRAN)

Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesiz...


Use of Inhaled Anti-inflammatory Medication in Children With Asthma in Managed Care Settings  

Microsoft Academic Search

Background: Many factors affect use of inhaled therapy in asthma. Relatively little is known about current pat- terns of use of anti-inflammatory medication in chil- dren with asthma and whether variations occur with age and use of bronchodilator medication. Objective: To study the factors associated with dis- pensing of anti-inflammatory (controller) asthma medi- cation to children in 3 managed care

Robert J. Adams; Anne Fuhlbrigge; Jonathan A. Finkelstein; Paula Lozano; James M. Livingston; Kevin B. Weiss; Scott T. Weiss


Analgesic, anticonvulsant and anti-inflammatory activities of some synthesized benzodiazipine, triazolopyrimidine and bis-imide derivatives.  


A series of diazipine, pyrimidine, fused triazolopyrimidine and imide derivatives were newly synthesized using 4-phenyl-but-3-en-2-one 1 as a starting material and compounds 2 and 9 are intermediates. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds were interestingly less toxic than the reference drug. The pharmacological screening showed that many of these obtained compounds have good analgesic, anticonvulsant and anti-inflammatory activities comparable to Valdecoxib, Carbamazepine and Predensilone as reference drugs. Regarding the protection against Carrageenan induced edema, five compounds were found more potent than Prednisolone. On the other hand, in searching for COX-2 inhibitor, the inhibition of plasma PGE2 for the compounds were determined and four compounds were found more potent than Prednisolone. The detailed synthesis, spectroscopic data, pharmacological screening and acute toxicity LD(50) for the synthesized compounds were reported. PMID:19682771

Said, Said A; Amr, Abd el-Galil E; Sabry, Nermien M; Abdalla, Mohamed M



Antitumor Agents. 271. Total Synthesis and Evaluation of Brazilein and Analogs as Anti-inflammatory and Cytotoxic Agents  

PubMed Central

The first total synthesis of the naturally occurring tetracyclic homoisoflavonoid brazilein (1) and 14 new analogs (1a–n) is reported. Target compounds and intermediates were assayed for anti-inflammatory effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB, and for cytotoxic activity against nasopharyngeal (KB), vincristine-resistant nasopharyngeal (KBvin), lung (A549) and prostate (DU-145) human cancer cell lines. The most active compound 1b showed potent effects on superoxide anion generation and elastase release with IC50 values of 1.2 and 1.9 µM, respectively, and was 65 times more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in the latter assay. Additionally, 1b exhibited broad spectrum in vitro anticancer activity with IC50 values of 6–11 µM against the four tested cancer cell lines.

Yen, Chiao-Ting; Nakagawa-Goto, Kyoko; Hwang, Tsong-Long; Wu, Pei-Chi; Morris-Natschke, Susan L.; Lai, Wan-Chun; Bastow, Kenneth F.; Chang, Fang-Rong; Wu, Yang-Chang; Lee, Kuo-Hsiung



Anti-inflammatory and antioxidant activity of Ficus carica Linn. leaves.  


Ficus carica Linn. (Moraceae) is commonly known as edible fig. The leaves, roots, fruits and latex of the plant are medicinally used in different diseases. The leaves are claimed to be effective in various inflammatory conditions like painful or swollen piles, insect sting and bites. However, there has been no report on anti-inflammatory and antioxidant activity of F. carica leaves. Therefore the aim of this study was to evaluate the anti-inflammatory and antioxidant activity of F. carica leaves. Our study validated the traditional claim with pharmacological data. Anti-inflammatory and antioxidant activity of the drug could be due to the presence of steroids and flavanoids, respectively, which are reported to be present in the drug. Furthermore, the anti-inflammatory activity of the drug could be due to its free radical scavenging activity. Further work is also required to isolate and characterise the active constituents responsible for the anti-inflammatory activities. PMID:21644169

Ali, B; Mujeeb, M; Aeri, V; Mir, S R; Faiyazuddin, M; Shakeel, F



Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content  

PubMed Central

Background The main aim of this study is to evaluate the antioxidant and anti-inflammatory properties of forty four traditional Chinese medicinal herbal extracts and to examine these activities in relation to their antioxidant content. Methods The antioxidant activities were investigated using DPPH radical scavenging method and yeast model. The anti-inflammatory properties of the herbal extracts were evaluated by measuring their ability to inhibit the production of nitric oxide and TNF-? in RAW 264.7 macrophages activated by LPS and IFN- ?, respectively. The cytotoxic effects of the herbal extracts were determined by Alomar Blue assay by measuring cell viability. In order to understand the variation of antioxidant activities of herbal extracts with their antioxidant contents, the total phenolics, total flavonoids and trace metal (Mg, Mn, Cu, Zn, Se and Mo) quantities were estimated and a correlation analysis was carried out. Results Results of this study show that significant levels of phenolics, flavonoids and trace metal contents were found in Ligustrum lucidum, Paeonia suffuticosa, Salvia miltiorrhiza, Sanguisorba officinalis, Spatholobus suberectus, Tussilago farfara and Uncaria rhyncophylla, which correlated well with their antioxidant and anti-inflammatory activities. Some of the plants displayed high antioxidant and anti-inflammatory activities but contained low levels of phenolics and flavonoids. Interestingly, these plants contained significant levels of trace metals (such as Zn, Mg and Se) which are likely to be responsible for their activities. Conclusions The results indicate that the phenolics, flavonoids and trace metals play an important role in the antioxidant activities of medicinal plants. Many of the plants studied here have been identified as potential sources of new antioxidant compounds.



Anti-inflammatory effect of ethanolic extract from Myagropsis myagroides on murine macrophages and mouse ear edema  

PubMed Central

Background This study aims to investigate anti-inflammatory effect of ethanolic extract of Myagropsis myagroides (EMM) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and the phorbol 12-myristate 13-acetate (PMA)-induced ear edema in mice, and to clarify its underlying molecular mechanisms. Methods The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blotting. Nuclear translocation and transcriptional activation of nuclear factor-?B (NF-?B) were determined by immunocytochemistry and reporter gene assay, respectively. PMA-induced mouse ear edema was used as the animal model of inflammation. Anti-inflammatory compounds in EMM were isolated using high-performance liquid chromatography and identified by nuclear magnetic resonance. Results EMM significantly inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a dose-dependent manner and suppressed the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. EMM strongly suppressed nuclear translocation of NF-?B by preventing degradation of inhibitor of ?B-? as well as by inhibiting phosphorylation of Akt and MAPKs. EMM reduced ear edema in PMA-induced mice. One of the anti-inflammatory compounds in EMM was identified as 6,6’-bieckol. Conclusions These results suggest that the anti-inflammatory properties of EMM are associated with the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the inhibition of NF-?B pathway in LPS-stimulated macrophages.



Liquid chromatography/tandem mass spectrometry study of anti-inflammatory activity of plantain (Plantago L.) species.  


To evaluate anti-inflammatory activity of selected Plantago species (P. lanceolata L. and P. major L.) an optimized in vitro test for determination of cyclooxygenase-1 (COX-1) and 12-lipoxygenase (12-LOX) inhibition potency was undertaken. By using intact cell system (platelets) as a source of COX-1 and 12-LOX enzymes and highly sensitive and specific LC-MS/MS technique for detection of main arachidonic acid metabolites formed by COX-1 and 12-LOX, this test provides efficient method for evaluation of anti-inflammatory potential of plant extracts and isolated compounds. Our results validated the well-known COX-1 inhibitory activity of P. lanceolata and P. major methanol extracts (concentration required for 50% inhibition (IC(50)) was 2.00 and 0.65 mg/ml, respectively). Furthermore, 12-LOX inhibitory activity of examined extracts was reported for the first time (IC(50)=0.75 and 1.73 mg/ml for P. lanceolata and P. major, respectively). Although renowned inhibitors, such as acetylsalicylic acid and quercetin showed higher activity, this study verifies P. lanceolata and P. major as considerable anti-inflammatory agents. PMID:20219312

Beara, Ivana N; Orci?, Dejan Z; Lesjak, Marija M; Mimica-Duki?, Neda M; Pekovi?, Biljana A; Popovi?, Mira R



Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives  

PubMed Central

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.

Beg, Sarwar; Swain, Suryakanta; Hasan, Hameed; Barkat, M Abul; Hussain, Md Sarfaraz



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


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. PMID:22688643

Mor, Adam; Aizman, Elizabeta; Kloog, Yoel



A comparative anti-inflammatory activity of raw and processed Kupeelu (Strychnos nux-vomica Linn.) seeds on albino rats  

PubMed Central

Seeds of Kupeelu (Strychnos nux-vomica Linn.), a known poisonous drug, is used extensively in various Ayurvedic formulations with great therapeutic significance. Ayurveda recommends the administration of Kupeelu only after passing through specific purificatory procedures in different media like cow's urine (Go mutra), cow's milk (Go dugdha), cow's ghee (Go ghrita), Kanji (thin gruel) etc. Strychnos nux vomica seeds are extensively advocated for nervous debility, paralysis, and weakness of limbs, sexual weakness, dyspepsia, and dysentery and in rheumatism where it can be assumed that besides other properties, Kupeelu may have some sort of anti-inflammatory activity too. In the present study, the powder of raw and processed Kupeelu seeds (processed / purified with Kanji i.e sour gruel) as test drugs were assessed for anti-inflammatory activity by employing Carrageenan and Formaldehyde induced hind paw oedema in Wistar strain albino rats at a dose of 22.5 mg/kg body weight orally. This study reveals that both raw and purified Kupeelu showed presence of highly significant anti-inflammatory activity against formaldehyde induced hind paw oedema, but did not have similar activity against Carrageenan induced hind paw oedema.

Mitra, Swarnendu; Kumar, Vijay; Ashok, BK; Acharya, R N; Ravishankar, B



Macrophage migration inhibitory factor (MIF) tautomerase inhibitors as potential novel anti-inflammatory agents: current developments.  


Macrophage migration inhibitory factor (MIF), the pro-inflammatory cytokine, first described in 1966, plays an essential role in both, innate and adaptive immune response. It has been implicated in tumour growth and angiogenesis and it exerts an antagonistic action against glucocorticoid immunosuppressive effect. Its perplexing enzymatic tautomerase activity has attracted considerable interest in the last decade. It has been suggested, that a multitude of autoimmune/inflammatory/neoplastic disease states might benefit from therapeutic measures, targeting MIF. Hence, small molecule inhibitors of MIF are relentlessly sought as potential anti-inflammatory (antitumour) agents, while a true in vivo substrate for MIF still remains unidentified. One of the first studied MIF inhibitor group was the D-dopachrome family, and its carboxyderivatives have shown good inhibitory effect, as well as the fluorosubstituted phenylpyruvic acid class. The substance ISO-1 of isoxazoline skeleton was the first small molecular inhibitor of MIF, not related to its known substrates. N-acetyl-p-benzoquinone, an acetaminophen metabolite and its synthetic derivatives exerted submicromolar IC(50) values. An acetylenic compound, the 2-oxo-4-phenyl-3-butynoate is a potent active-site-directed irreversible inhibitor of the phenyl pyruvate tautomerase activity of MIF. Some oxygen heterocycles, coumarines and chromenes, have also drawn attention as MIF inhibitors. The alpha,beta-unsaturated carbonyl compounds constitute a large novel class of MIF inhibitors. Several potent inhibitors were found among the cinnamic acid derivatives, thealpha,beta-unsaturated cyclic ketones, and the natural curcuminoids. Some other plant derived compounds were also studied. One of the latest developments in the field is the synthesis of AVP-13546, an exceptionally potent inhibitor. The structural pattern of MIF enzyme inhibitors exhibits wide variety; compounds having quite different molecular backbones belong to the MIF inhibitor family. In this paper, the separate classes of MIF inhibitors are discussed. PMID:19275614

Garai, János; Lóránd, Tamas



Anticancer and anti-inflammatory sulfur-containing semisynthetic derivatives of sarcophine.  


Sarcophine (1), a cembranoid diterpene is known to inhibit the process of tumorigenesis. Sarcophine can be isolated in large amounts from the Red Sea soft coral Sarcophyton glaucum and hence is an ideal target for semisynthetic or biocatalytic modifications. Hydroxylated derivatives of 1 were reported to improve its anticancer activity. Despite the promising results and ready availability, there are limited attempts towards further diversifying the library of sarcophine derivatives. Hence, the current study targets the epoxide ring to generate sulfur-containing derivatives of sarcophine by reacting it with ammonium thiocyanate and Lawesson's reagent. Structure elucidation of the products was based on extensive 1D and 2D NMR and high resolution mass spectrometry, in addition to mechanistic considerations. The effect of these derivatives on highly malignant +SA mammary epithialial cell proliferation is reported. Anti-inflammatory potential of sarcophine and its derivatives is also demonstrated. PMID:16880655

Sawant, Swapnali; Youssef, Diaa; Mayer, Alejandro; Sylvester, Paul; Wali, Vikram; Arant, Mark; El Sayed, Khalid



Phenolics content and antioxidant and anti-inflammatory activities of legume fractions.  


Two faba bean (Vicia faba L.) subspecies major and minor and lentil seeds grown in Algeria were separated into cotyledons and hulls. These fractions, together with their corresponding whole seeds, were extracted with two solvents, aqueous (70%) acetone and (80%) ethanol, and evaluated for antioxidant activity in relation to their phenolic contents. Acetone selectively extracted tannins from faba beans. The hulls always exhibited high antioxidant activity, measured using the reducing power (RP), antiradical activity (DPPH) or oxygen radical absorbance capacity (ORAC) assays. Aqueous ethanol (80%) extract of lentil hulls exhibited high antioxidant and anti-inflammatory activities preferentially inhibiting 15-LOX (IC(50), 55 ?g/ml), with moderate COX-1 (IC(50), 66 ?g/ml) and COX-2 (IC(50), 119 ?g/ml) inhibitory effects on the COX pathway, whereas faba bean hull extracts exerted relatively mild LOX inhibitory activity. PMID:23411279

Boudjou, Souhila; Oomah, B Dave; Zaidi, Farid; Hosseinian, Farah



NF-?B dependent anti-inflammatory activity of chlorojanerin isolated from Saussurea heteromalla.  


Medicinal plants have shown great promise as a source of novel drug compounds for the treatment of inflammatory disorders. In our search for new entities with anti-inflammatory potential, the extracts of the whole plant of Saussurea heteromalla (family-Asteraceae), collected from Himalayas, were evaluated in the high throughput screen for TNF-? and IL-6 inhibitors. The extract blocked TNF-? and IL-6 production in LPS stimulated THP-1 cells (human acute monocyte leukemia cell line) completely at 10 and 30 ?g/ml. The plant has been found as a new source of chlorojanerin, a guaianolide type of sesquiterpene lactone. Chlorojanerin was shown to be significantly effective in inhibiting TNF-? and IL-6 production in LPS-stimulated THP-1 cells (IC(50)=2.3±0.2 ?M and 1.8±0.7 ?M respectively). The compound also blocked TNF-? and IL-6 production from LPS-stimulated human monocytes (IC(50)=1.5±0.4 and 0.7±0.2 ?M respectively) and synovial cells from a patient with rheumatoid arthritis (IC(50)<0.03 and 0.5 ?M respectively). Transcriptional profiling of the LPS stimulated THP-1 cells revealed that chlorojanerin exerted its anti-inflammatory effect by inhibiting the expression of 8 genes involved in activating the transcription factor - NF-?B. Real time analysis of these genes validated the effect of chlorojanerin on the classical downstream targets of NF-?B. Thus, this study clearly delineated 8 genes which were specifically mitigated due to the effect of chlorojanerin on NF-?B induced signaling at the mRNA level. Further, chlorojanerin at 5 ?M also inhibited the binding of NF-?B in a GFP reporter assay system by 55.5% thus validating the microarray gene expression data. This work is a step towards the isolation and characterization of lead anti-inflammatory agents from the extract of Saussurea heteromalla, which can be developed into better therapeutic molecules targeted towards some specific inflammatory diseases. PMID:22762939

Saklani, Arvind; Hegde, Bindu; Mishra, Prabha; Singh, Ruchi; Mendon, Monica; Chakrabarty, Debarshi; Kamath, Divya V; Lobo, Aurelio; Mishra, Prabhu Dutt; Dagia, Nilesh M; Padigaru, Muralidhara; Kulkarni-Almeida, Asha A



Oral azithromycin combined with topical anti-inflammatory agents in the treatment of blepharokeratoconjunctivitis in children.  


We report 3 children referred for recurrent blepharokeratoconjunctivitis, despite the application of topical antibiotic and anti-inflammatory treatments. Oral azithromycin combined with anti-inflammatory treatment was effective in controlling the disease. PMID:23360914

Choi, Daniel S; Djalilian, Ali



Nucleic acid-binding polymers as anti-inflammatory agents.  


Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids. PMID:21844380

Lee, Jaewoo; Sohn, Jang Wook; Zhang, Ying; Leong, Kam W; Pisetsky, David; Sullenger, Bruce A



Membranous Nephropathy and Nonsteroidal Anti-inflammatory Agents.  


Membranous nephropathy presents clinically as nephrotic syndrome, with subepithelial immune complex deposits seen on biopsy. Historically, in about three-quarters of membranous cases, no obvious etiologic agent or condition can be identified. More recently, serum antibodies to the phospholipase A2 receptor have been discovered in many patients with primary/idiopathic membranous nephropathy. About one-quarter of patients have membranous nephropathy as a manifestation of another systemic disorder, such as autoimmune conditions, infection, malignancy, toxin exposure, or drugs (classically gold or penicillamine). In this report, we present a case of recurrent nephrotic syndrome with biopsy-proven membranous nephropathy closely associated with use of the nonsteroidal anti-inflammatory drugs (NSAIDs) naproxen and piroxicam. Characterization of the immunoglobulin G (IgG) subclass profile of the deposits showed abundant IgG1, weak IgG4, and positive staining for phospholipase A2 receptor. This case serves to highlight membranous nephropathy as an under-recognized renal complication of NSAID use. Other kidney effects of NSAIDs, such as hemodynamic compromise, interstitial nephritis, and minimal change disease, are more broadly recognized. PMID:23773370

Nawaz, Fareha A; Larsen, Christopher P; Troxell, Megan L



Renal effects of nonsteroidal anti-inflammatory drugs.  


All nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase, and consequently renal functions dependent upon prostaglandin synthesis can be affected. Fortunately, renal function in normal individuals is relatively independent of the PG system, and thus the NSAIDs don't usually produce any renal dysfunction. However, in some circumstances, inhibition of PG dependent renal functions can produce clinically significant effects. When the kidney is in a salt retaining state or when there is renal vascular damage, NSAIDs can reduce renal blood flow and glomerular filtration rate producing acute renal failure that is reversible upon discontinuation of the drug. NSAIDs can also: 1) reduce sodium excretion and blunt the diuretic effect of loop diuretics, thus producing or exacerbating edema, 2) inhibit PG dependent renin secretion occasionally resulting in hyperkalemia, 3) enhance the antidiuretic effects of vasopressin and 4) reduce the antihypertensive efficacy of several drugs. Evidence that any NSAID "spares" renal cyclooxygenase is controversial, and no NSAID is devoid of clinical problems. Syndromes that are less obviously related to inhibition of renal PG synthesis are acute interstitial nephritis with or without the nephrotic syndrome, renal papillary necrosis, and chronic interstitial nephritis. Recently a unique syndrome of flank pain and mild reversible renal dysfunction has been described in healthy individuals receiving suprofen, a uricosuric NSAID. This syndrome may be due to uric acid crystal deposition in the renal tubules and has resulted in the removal of suprofen from the US market. PMID:3142236

Nies, A S



Anti-inflammatory lanostanoids and lactone derivatives from Antrodia camphorata.  


Four new lanostanoids, ethyl lucidenate A (1), ethyl lucidenate F (2), 15-O-acetylganolucidate A (3), and 3,11,15,23-tetraoxo-27?-lanosta-8,16-dien-26-oic acid (4), and two new lactone derivatives, 5-hydroxy-5-(methoxymethyl)-4-methylfuran-2(5H)-one (5) and 3-(4-methoxy-2-oxo-2H-pyran-6-yl)propanoic acid (6), together with four known compounds, 11?-hydroxy-3,7-dioxolanost-8,24(E)-dien-26- oic acid (7), 3,7,11-trioxo-5?-lanosta-8,24(E)-dien-26-oic acid (8), methyl 3,7,11,12,15,23-hexaoxo-5?-lanost-8-en-26-oate (9), and ethyl 3,7,11,12,15,23-hexaoxo-5?-lanost-8-en-26-oate (10), were characterized from Antrodia camphorata. The structures of these new compounds were determined by analysis of their spectroscopic data, including 1D and 2D NMR experiments. Ten components were evaluated for anti-inflammatory activity by examining their effect on LPS-iNOS-dependent NO production in murine macrophage (RAW 264.7) cells. Among them, compounds 1, 3, 7, 8, 9, and 10 significantly suppressed the NO concentration in LPS-treated RAW 264.7 cells with IC50 values ? 10 ?M. PMID:23517145

Liaw, Chih-Chuang; Chen, Yu-Chang; Huang, Guan-Jhong; Tsai, Yao-Ching; Chien, Shih-Chang; Wu, Jyh-Horng; Wang, Sheng-Yang; Chao, Louis Kuoping; Sung, Ping-Jyun; Huang, Hui-Chi; Kuo, Yueh-Hsiung



Anti-Inflammatory Components from the Root of Solanum erianthum  

PubMed Central

Two new norsesquiterpenoids, solanerianones A and B (1–2), together with nine known compounds, including four sesquiterpenoids, (?)-solavetivone (3), (+)-anhydro-?-rotunol (4), solafuranone (5), lycifuranone A (6); one alkaloid, N-trans-feruloyltyramine (7); one fatty acid, palmitic acid (8); one phenylalkanoid, acetovanillone (9), and two steroids, ?-sitosterol (10) and stigmasterol (11) were isolated from the n-hexane-soluble part of the roots of Solanum erianthum. Their structures were elucidated on the basis of physical and spectroscopic data analyses. The anti-inflammatory activity of these isolates was monitored by nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells. The cytotoxicity towards human lung squamous carcinoma (CH27), human hepatocellular carcinoma (Hep 3B), human oral squamous carcinoma (HSC-3) and human melanoma (M21) cell lines was also screened by using an MTT assay. Of the compounds tested, 3 exhibited the strongest NO inhibition with the average maximum inhibition (Emax) at 100 ?M and median inhibitory concentration (IC50) values of 98.23% ± 0.08% and 65.54 ± 0.18 ?M, respectively. None of compounds (1–9) was found to possess cytotoxic activity against human cancer cell lines at concentrations up to 30 ?M.

Chen, Yu-Chang; Lee, Hong-Zin; Chen, Hsin-Chun; Wen, Chi-Luan; Kuo, Yueh-Hsiung; Wang, Guei-Jane



Anti-inflammatory phenanthrene derivatives from stems of Dendrobium denneanum.  


Cultivated Dendrobium denneanum has been substituted for other endangered Dendrobium species in recent years, but there have been few studies regarding either its chemical constituents or pharmacological effects. In this study, three phenanthrene glycosides, three 9,10-dihydrophenanthrenes, two 9,10-dihydrophenanthrenes glycosides, and four known phenanthrene derivatives, were isolated from the stems of D. denneanum. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Ten compounds were found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells with IC50 values of 0.7-41.5?M, and exhibited no cytotoxicity in RAW264.7, HeLa, or HepG2 cells. Additionally, it was found that 2,5-dihydroxy-4-methoxy-phenanthrene 2-O-?-d-glucopyranoside, and 5-methoxy-2,4,7,9S-tetrahydroxy-9,10-dihydrophenanthrene suppressed LPS-induced expression of inducible NO synthase (iNOS) inhibited phosphorylation of p38, JNK as well as mitogen-activated protein kinase (MAPK), and inhibitory kappa B-? (I?B?). This indicated that both compounds exert anti-inflammatory effects by inhibiting MAPKs and nuclear factor ?B (NF-?B) pathways. PMID:24042064

Lin, Yuan; Wang, Fei; Yang, Li-Juan; Chun, Ze; Bao, Jin-Ku; Zhang, Guo-Lin



Anti-inflammatory and immunomodulatory activities of rifamycin SV.  


There have been several reports showing convincing evidence for non-bactericidal activities of the rifamycin antibiotics. In particular, the parent compound rifamycin SV has been employed in a limited number of cases to treat rheumatoid arthritis. Moreover, rifamycin SV and its derivative rifaximin have been found to be effective in experimental animal models of gut inflammation. The efficacy of rifamycin SV and rifaximin in these settings has been attributed partially to indirect non-bactericidal activities. To better clarify the mechanisms by which these two antibiotics exert their non-bactericidal effects, their activities were compared in in vitro cellular models of immunomodulation and inflammation. Both antibiotics were found to inhibit cytokine and chemokine synthesis from lipopolysaccharide-activated THP-1 monocytes and macrophages. It was also demonstrated, for the first time, that rifamycin SV exerts anti-inflammatory activities in HT-29 colonic epithelial cells. Moreover, rifamycin SV is also very effective in downregulating secretion of inflammatory cytokines from human CD4 T-cells. In general, both antibiotics show similar activities on all four cell types tested. However, rifamycin SV is less cytotoxic than rifaximin when tested in these cells. PMID:23756321

Rosette, Caridad; Buendia-Laysa, Fernando; Patkar, Seema; Moro, Luigi; Celasco, Giuseppe; Bozzella, Roberta; Ajani, Mauro; Gerloni, Mara



Anti-inflammatory dimethylfumarate: a potential new therapy for asthma?  


Asthma is a chronic inflammatory disease of the airways, which results from the deregulated interaction of inflammatory cells and tissue forming cells. Beside the derangement of the epithelial cell layer, the most prominent tissue pathology of the asthmatic lung is the hypertrophy and hyperplasia of the airway smooth muscle cell (ASMC) bundles, which actively contributes to airway inflammation and remodeling. ASMCs of asthma patients secrete proinflammatory chemokines CXCL10, CCL11, and RANTES which attract immune cells into the airways and may thereby initiate inflammation. None of the available asthma drugs cures the disease--only symptoms are controlled. Dimethylfumarate (DMF) is used as an anti-inflammatory drug in psoriasis and showed promising results in phase III clinical studies in multiple sclerosis patients. In regard to asthma therapy, DMF has been anecdotally reported to reduce asthma symptoms in patients with psoriasis and asthma. Here we discuss the potential use of DMF as a novel therapy in asthma on the basis of in vitro studies of its inhibitory effect on ASMC proliferation and cytokine secretion in ASMCs. PMID:23606796

Seidel, Petra; Roth, Michael



Nucleic acid-binding polymers as anti-inflammatory agents  

PubMed Central

Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids.

Lee, Jaewoo; Sohn, Jang Wook; Zhang, Ying; Leong, Kam W.; Pisetsky, David; Sullenger, Bruce A.



Anti-inflammatory effects of the Mediterranean diet: the experience of the PREDIMED study.  


Several epidemiological and clinical studies have evaluated the effects of a Mediterranean diet (Med-Diet) on total cardiovascular mortality, and all concluded that adherence to the traditional Med-Diet is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In a pilot study of the PREvencion con DIeta MEDiterranea (PREDIMED) trial, we analysed the short-term effects of two Med-Diet interventions, one supplemented with virgin olive oil and another with nuts, on vascular risk factors in 772 subjects at high risk for CVD, and in a second study we evaluated the effects of these interventions on cellular and serum inflammatory biomarkers in 106 high-risk subjects. Compared to a low-fat diet, the Med-Diet produced favourable changes in all risk factors. Thus, participants in both Med-Diet groups reduced blood pressure, improved lipid profile and diminished insulin resistance compared to those allocated a low-fat diet. In addition, the Med-Diet supplemented with virgin olive oil or nuts showed an anti-inflammatory effect reducing serum C-reactive protein, IL-6 and endothelial and monocytary adhesion molecules and chemokines, whereas these parameters increased after the low-fat diet intervention. In conclusion, Med-Diets down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high cardiovascular risk. These results support the recommendation of the Med-Diet as a useful tool against CVD. PMID:20515519

Estruch, Ramon



Synthesis, analgesic and anti-inflammatory activities of some novel 2,3-disubstituted quinazolin-4(3H)-ones.  


A series of novel 2-benzylamino-3-substituted quinazolin-4(3H)-ones have been synthesized by treating 3-amino-2-benzylamino quinazolin-4(3H)-one, with different aldehydes and ketones. The starting material 3-amino-2-benzylamino quinazolin-4(3H)-one was synthesized by nucleophilic substitution of thiomethyl group of 3-amino-2-methylthio quinazolin-4(3H)-one by benzylamine. The title compounds were investigated for analgesic and anti-inflammatory activities. All the test compounds exhibited significant analgesic activity, whereas the compound III is equipotent with diclofenac sodium. The compounds I, II and III showed more potent anti-inflammatory activity than diclofenac sodium. PMID:12673044

Alagarsamy, Veerachamy; Muthukumar, Veluchamy; Pavalarani, Nagendran; Vasanthanathan, Poongavanam; Revathi, Rajappan



Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax  

PubMed Central

Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium vivax isolates ex vivo, 10 of which had multiple dhfr mutations associated with Pyr resistance. Despite high-grade resistance to Pyr (median 50% inhibitory concentration [IC50], 13,345 nM), these parasites were all highly susceptible to MTX (median IC50, 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation.

Imwong, Mallika; Suwanarusk, Rossarin; Nzila, Alexis; Leimanis, Mara L.; Sriprawat, Kanlaya; Kaewpongsri, Supaporn; Phyo, Aung Pyae; Snounou, Georges; Nosten, Francois; Renia, Laurent



Non-steroidal anti-inflammatory drugs for athletes: an update.  


Sports medicine physicians often treat athletes in pain with non-steroidal anti-inflammatory drugs (NSAIDs). However, there is a lack of high-quality evidence to guide NSAID use. Their adverse effects have clinical relevance, and their possible negative consequences on the long-term healing process are slowly becoming more obvious. This article provides some practical management guidelines for the use of NSAIDs, developed to help sports medicine physicians deal with frequent sports-related injuries. We do not recommend their use for muscle injuries, bone fractures (also stress fractures) or chronic tendinopathy. In all cases, if chosen, NSAID treatments should always be kept as short as possible and should take into account the specific type of injury, the level of dysfunction and pain. PMID:20363203

Ziltener, J-L; Leal, S; Fournier, P-E



Anti-Inflammatory Activity of TS-13, ARE-Inducing Phenol Antioxidant.  


The protective effect of water-soluble TS-13 monophenol inducing the antioxidant-responsive element (ARE) system was studied on the models of acute inflammation. Intragastric administration of TS-13 to rats significantly reduced the severity of acute aseptic inflammation induced by intravenous injection of zymosan particles: granulocyte blood count and volume density of infiltrates in the liver decreased on day 3, spontaneous production of activated oxygen metabolites and respiratory burst in blood granulocytes decreased on days 2 and 3. A single dose of TS-13 improved survival of mice with endotoxin shock induced by intraperitoneal injection of E. coli LPS. These results confirmed high anti-inflammatory activity of TS-13. PMID:24137605

Menshchikova, E B; Tkachev, V O; Zenkov, N K; Lemza, A E; Sharkova, T V; Kandalintseva, N V



Characterizing the Metabolic Fingerprint and Anti-inflammatory Activity of Hypericum gentianoides  

PubMed Central

In this paper we characterize the metabolic fingerprint and first reported anti-inflammatory activity of Hypericum gentianoides. H. gentianoides has a history of medical use by Native Americans, but it has been studied very little for biological activity. High-performance liquid chromatography (HPLC) and liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) analyses of a methanol extract show that H. gentianoides contains a family of over nine related compounds that have retention times, mass spectra, and a distinctive UV absorption spectra characteristic of certain acyl-phloroglucinols. These metabolites are abundant relative to other secondary products present in H. gentianoides, accounting for approximately 0.2 g per gram of dry plant tissue. H. gentianoides methanol extracts and a specific semipreparative HPLC fraction from these extracts containing the putative acyl-phloroglucinols reduce prostaglandin E2 synthesis in mammalian macrophages.

Hillwig, Matthew L.; Hammer, Kimberly D. P.; Birt, Diane F.; Wurtele, Eve Syrkin



Monoterpenoid indole alkaloids from Alstonia yunnanensis and their cytotoxic and anti-inflammatory activities.  


The 80% ethanol extract of Alstonia yunnanensis afforded five new monoterpenoid indole alkaloids: 11-hydroxy-6,7-epoxy-8-oxo-vincadifformine (1), 14-chloro-15-hydroxy- vincadifformine (2), perakine N(4)-oxide (3), raucaffrinoline N(4)-oxide (4), and vinorine N(1),N(4)-dioxide (5), together with three known compounds: 11-methoxy-6,7-epoxy-8-oxo- vincadifformine (6), vinorine N(4)-oxide (7) and vinorine (8). The structures of the isolated compounds were established based on 1D and 2D (1H-1H-COSY, HMQC, HMBC, and ROESY) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic potential against seven tumor cell lines and anti-inflammatory activities. Compounds 3, 4 and 7 exhibited weak cytotoxicity against the tested cell lines and selective inhibition of Cox-2 (> 85%). PMID:23159924

Cao, Peng; Liang, Yong; Gao, Xu; Li, Xiao-Ming; Song, Zhen-Quan; Liang, Guobiao



Phytochemical Analysis and Anti-inflammatory Potential of Hyphaene thebaica L. Fruit.  


Metabolite profiling and biological activity are reported from organic and aqueous extracts of the fruit from the desert palm Hyphaene thebaica. Phenolics and oxylipids profiles were determined using UPLC-PDA-TOF (ultra performance-photodiode array-time of flight) high-resolution mass spectrometry in order to obtain the molecular formula and exact mass Under optimized conditions, 17 compounds were simultaneously identified and quantified including 2 cinnamic acid derivatives, 5 flavonoids, 6 fatty acids, 2 sphingolipids, a lignan, and a stilbene. Sugars composition in the fruit was characterized and quantified by (1) H-NMR (nuclear magnetic resonance) with sucrose detected as the major component in fruit at a level of 219 mg/g. Fruit organic extracts anti-inflammatory potential was assessed in vitro by cyclooxygenase-1 enzyme inhibition. PMID:24025087

Farag, Mohamed A; Paré, Paul W



Anti-inflammatory procyanidins and triterpenes in 109 apple varieties.  


We evaluated the potential of apple to reduce inflammation. Phenolic compounds and triterpenes were analyzed in 109 apple cultivars. Total phenolics ranged from 29 to 7882 ?g g(-1) of fresh weight (FW) in the flesh and from 733 to 4868 ?g g(-1) FW in the skin, with flavanols including epicatechin and procyanidins as major components. Ursolic (44.7 to 3522 ?g g(-1) FW) and oleanolic (47.2 to 838 ?g g(-1) FW) acids dominated the skin triterpene profile. Five chemically contrasting cultivars were fractionated and their immune-modulating activity measured using two cell-based assays targeting key points in the inflammation process. Cultivars exhibiting high contents of procyanidins were the most potent at inhibiting NF-?B while triterpene-rich fractions reduced the promoter activity of the gene of TNF?. This study provides new insights into how apple genetic diversity could be used to alleviate inflammation. PMID:23013475

Andre, Christelle M; Greenwood, Jeffrey M; Walker, Edward G; Rassam, Maysoon; Sullivan, Michael; Evers, Danièle; Perry, Nigel B; Laing, William A



Evaluation of the anti-inflammatory activity of luteolin in experimental animal models.  


Luteolin, a flavonoid abundant in plants worldwide, demonstrates a spectrum of biological activities. This study is aimed at evaluating its inhibiting effects on inflammatory responses in vivo. We investigated the anti-inflammatory activity of luteolin in acute and chronic models in mice. We found that oral administration of luteolin (10 and 50 mg/kg) efficiently suppressed paw edema when induced by injecting carrageenan, and a similar tendency was also observed in the cotton pellet granuloma test. In the air pouch test, luteolin markedly reduced the number of infiltrated leukocytes and the elevated level of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) in the exudate. The results derived from the whole blood assay for cyclooxygenase (COX) and from the reverse transcription-polymerase chain reaction (RT-PCR) assay indicate that luteolin may be a potent selective inhibitor of cyclooxygenase-2 (COX-2) and that the inhibition is attributable to its down-regulation of the mRNA expression of COX-2 in inflammatory responses. PMID:17354164

Ziyan, Li; Yongmei, Zhou; Nan, Zhang; Ning, Tang; Baolin, Liu



Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice.  


Licorice, the roots and rhizomes of several Glycyrrhiza species (Leguminosae), is an important natural sweetening agent and a widely used herbal medicine. In this work, six flavonoids, 5-(1,1-dimethylallyl)-3,4,4'-trihydroxy-2-methoxychalcone (1), licochalcone B (2), licochalcone A (3), echinatin (4), glycycoumarin (5) and glyurallin B (6), were isolated from the extracts of licorice (Glycyrrhiza inflata and Glycyrrhiza uralensis). Their structures were elucidated using various spectroscopic methods. To our knowledge, compound 1 was isolated from natural plants for the first time. All the isolates were tested by antioxidant and anti-inflammatory assays. Compounds 2, 4 and 5 showed strong scavenging activity toward the ABTS(+) radical, and compounds 1, 2, 3, 5 and 6 exhibited potent inhibition of lipid peroxidation in rat liver microsomes compared with the reference controls. Compounds 1-4 dose-dependently inhibited LPS induced reactive oxygen species (ROS) production in RAW 264.7 cells. Furthermore, compounds 1-5 were demonstrated to inhibit the production of nitric oxide (NO), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) in LPS-induced macrophage cells. Moreover, the contents of the six compounds, in different Glycyrrhiza species, were quantified by HPLC-MS. PMID:23790887

Fu, Yu; Chen, Jun; Li, Yan-Jing; Zheng, Yun-Feng; Li, Ping



Novel analgesic/anti-inflammatory agents: diarylpyrrole acetic esters endowed with nitric oxide releasing properties.  


The design of compounds that are able to inhibit cyclooxygenase (COX) and to release nitric oxide (NO) should give rise to drugs endowed with an overall safer profile for the gastrointestinal and cardiovascular systems. Herein we report a new class of pyrrole-derived nitrooxy esters (11a-j), cyclooxygenase-2 (COX-2) selective inhibitors endowed with NO releasing properties, with the goal of generating new molecules able to both strongly inhibit this isoform and reduce the related adverse side effects. Taking into account the metabolic conversion of nitrooxy esters into corresponding alcohols, we also studied derivatives 12a-j. All compounds proved to be very potent and selective COX-2 inhibitors; nitrooxy derivatives displayed interesting ex vivo NO-dependent vasorelaxing properties. Compounds 11c, 11d, 12c, and 12d were selected for further in vivo studies that highlited good anti-inflammatory and antinociceptive activities. Finally, two selected compounds (11c and 12c) tested in human whole blood (HWB) assay proved to be preferential inhibitors of COX-2. PMID:21992176

Biava, Mariangela; Porretta, Giulio Cesare; Poce, Giovanna; Battilocchio, Claudio; Alfonso, Salvatore; Rovini, Michele; Valenti, Salvatore; Giorgi, Gianluca; Calderone, Vincenzo; Martelli, Alma; Testai, Lara; Sautebin, Lidia; Rossi, Antonietta; Papa, Giuseppina; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Giordani, Antonio; Anzellotti, Paola; Bruno, Annalisa; Patrignani, Paola; Anzini, Maurizio



Tristetraprolin is required for full anti-inflammatory response of murine macrophages to IL-10 1  

PubMed Central

IL-10 is essential for inhibiting chronic and acute inflammation by decreasing the amounts of proinflammatory cytokines made by activated macrophages. IL-10 controls pro-inflammatory cytokine and chemokine production indirectly via the transcription factor Stat3. One of the most physiologically significant IL-10 targets is tumor necrosis factor-alpha (TNFalpha), a potent pro-inflammatory mediator that is the target for multiple anti-TNFalpha clinical strategies in Crohn’s Disease and rheumatoid arthritis. The anti-inflammatory effects of IL-10 seem to be mediated by several incompletely understood transcriptional and posttranscriptional mechanisms. Here we show that in LPS-activated bone marrow-derived murine macrophages, IL-10 reduces the mRNA and protein levels of TNFalpha and IL-1alpha in part through the RNA destabilizing factor tristetraprolin (TTP). TTP is known for its central role in destabilizing mRNA molecules containing class II AU-rich elements in 3? untranslated regions. We found that IL-10 initiates a Stat3-dependent increase of TTP expression accompanied by a delayed decrease of p38MAPK activity. The reduction of p38MAPK activity releases TTP from the p38MAPK-mediated inhibition thereby resulting in diminished mRNA and protein levels of proinflammatory cytokines. These findings establish that TTP is required for full responses of bone marrow-derived murine macrophages to IL-10.

Schaljo, Barbara; Kratochvill, Franz; Gratz, Nina; Sadzak, Iwona; Sauer, Ines; Hammer, Michael; Vogl, Claus; Strobl, Birgit; Muller, Mathias; Blackshear, Perry J.; Poli, Valeria; Lang, Roland; Murray, Peter J.; Kovarik, Pavel



Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms  

PubMed Central

Ethyl pyruvate (EP) is protective in experimental models of many illnesses. This study investigates whether EP can protect against neonatal hypoxic-ischemic (H-I) brain injury. Pre-treatment with EP significantly reduced brain damage at 7 days post-H-I, with 50 mg/kg EP achieving over 50% recovery in tissue loss compared to vehicle-treated animals. Delayed treatment with EP until 30 min after H-I was still neuroprotective. EP-afforded brain protection, together with neurological function improvement, was observed up to 2 months after H-I. We further demonstrated an inhibitory effect of EP on cell death, both in an in vivo model of H-I and in in vitro neuronal cultures subjected to OGD, by reducing calpain activation and calcium dysregulation. Moreover, EP exerted an anti-inflammatory effect in microglia by inhibiting NF-?B activation and subsequent release of inflammatory mediators. Taken together, our results suggest that EP confers potent neuroprotection against neonatal H-I brain injury via its anti-cell death and anti-inflammatory actions. EP is a potential novel therapeutic agent for neonatal H-I brain injury.

Shen, Hongxia; Hu, Xiaoming; Liu, Can; Wang, Suping; Zhang, Wenting; Gao, Hui; Stetler, R. Anne; Gao, Yanqin; Chen, Jun



Cyclodextrin-Complexed Curcumin Exhibits Anti-inflammatory and Antiproliferative Activities Superior to Those of Curcumin Through Higher Cellular Uptake  

PubMed Central

Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel cyclodextrin complex of curcumin (CDC) and examined here this compound for anti-inflammatory and antiproliferative effects. Using the electrophoretic gel shift mobility assay, we found that CDC was more active than free curcumin in inhibiting TNF-induced activation of the inflammatory transcription factor NF-?B and in suppressing gene products regulated by NF-?B, including those involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). CDC was also more active than free curcumin in inducing the death receptors DR4 and DR5. Annexin V staining, cleavage of caspase-3 and PARP, and DNA fragmentation showed that CDC was more potent than free curcumin in inducing apoptosis of leukemic cells. Antiproliferative assays also demonstrated that CDC was more active than free curcumin in suppressing proliferation of various cancer cell lines. The cyclodextrin vehicle had no effect in these assays. Compared with free curcumin, CDC had a greater cellular uptake and longer half-life in the cells. Overall we demonstrated that CDC had superior attributes compared with free curcumin for cellular uptake and for antiproliferative and anti-inflammatory activities.

Yadav, Vivek R.; Prasad, Sahdeo; Kannappan, Ramaswamy; Ravindran, Jayaraj; Chaturvedi, Madan M; Vaahtera, Lauri; Parkkinen, Jaakko; Aggarwal, Bharat B.



Sulphurous thermal water increases the release of the anti-inflammatory cytokine IL-10 and modulates antioxidant enzyme activity.  


The beneficial effects of hot springs have been known for centuries and treatments with sulphurous thermal waters are recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects of the therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements. Here, the effects of an S-based compound (NaSH) and of a specific sulphurous thermal water characterized by additional ions such as sodium chloride, bromine and iodine (STW) were investigated in terms of cytokine release and anti-oxidant enzyme activity in primary human monocytes and in saliva from 50 airway disease patients subjected to thermal treatments. In vitro, NaSH efficiently blocked the induction of pro-inflammatory cytokines and counterbalanced the formation of ROS. Despite STW not recapitulating these results, possibly due to the low concentration of S-based compounds reached at the minimum non-toxic dilution, we found that it enhanced the release of IL-10, a potent anti-inflammatory cytokine. Notably, higher levels of IL-10 were also observed in patients? saliva following STW treatment and this increase correlated positively with salivary catalase activity (r2 = 0.19, *p less than 0.01). To our knowledge, these results represent the first evidence suggesting that S-based compounds and STW may prove useful in facing chronic inflammatory and age-related illness due to combined anti-inflammatory and anti-oxidant properties. PMID:24067460

Prandelli, C; Parola, C; Buizza, L; Delbarba, A; Marziano, M; Salvi, V; Zacchi, V; Memo, M; Sozzani, S; Calza, S; Uberti, D; Bosisio, D


Lactarius rufus (1?3),(1?6)-?-D-glucans: structure, antinociceptive and anti-inflammatory effects.  


Medicinal health benefits uses of edible as well as non-edible mushrooms have been long recognized. The pharmacological potential of mushrooms, especially antitumor, immunostimulatory and anti-inflammatory activities has been documented. Wild ectomycorrhizal mushroom, Lactarius rufus had the anti-inflammatory and antinociceptive potential of their polysaccharides evaluated using the formalin model. Two structurally different (1?3),(1?6)-linked ?-D-glucans were isolated from fruiting bodies. Soluble (FSHW) ?-D-glucan 1-30 mg kg(-1) produced potent inhibition of inflammatory pain caused by formalin when compared with the insoluble one (IHW), suggesting that solubility and/or branching degree could alter the activity of ?-glucans. Their structures were determined using mono- and bi-dimensional NMR spectroscopy, methylation analysis, and controlled Smith degradation. They were ?-D-glucans, with a main chain of (1?3)-linked Glcp residues, substituted at O-6 by single-unit Glcp side chains (IHW), on average to every fourth residue of the backbone, or by mono- and few oligosaccharide side chains for soluble ?-glucan. PMID:23544521

Ruthes, Andrea Caroline; Carbonero, Elaine R; Córdova, Marina Machado; Baggio, Cristiane Hatsuko; Santos, Adair Roberto Soares; Sassaki, Guilherme Lanzi; Cipriani, Thales Ricardo; Gorin, Philip Albert James; Iacomini, Marcello



Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia.  


Interleukin-1 receptor antagonist (IL-1ra) is an important anti-inflammatory cytokine that blocks all known actions of IL-1 and markedly protects against experimentally induced ischemic, excitotoxic, and traumatic brain insults. Cannabinoids (CBs) also exert potent anti-inflammatory and neuroprotective effects, but the mechanisms of their actions are unknown. Here we tested the hypothesis that the actions of CBs are mediated by endogenous IL-1ra. We report for the first time that both CB1 and CB2 receptors modulate release of endogenous IL-1ra from primary cultured glial cells. Activation of CB1 or CB2 receptors increased lipopolysaccharide-induced IL-1ra release, and specific CB1 or CB2 antagonists blocked lipopolysaccharide-induced production of IL-1ra from glial cells. Comparison of neuronal cultures from wild-type mice and mice lacking IL-1ra (knock-out) indicates that endogenous IL-1ra is essential for the neuro-protective effects of CBs against excessive activation of glutamate receptors (excitotoxicity) in response to S-AMPA or NMDA. Similarly, analysis of mixed glial cultures from IL-1ra knock-out mice indicates that endogenous IL-1ra is required for the CB-induced inhibition of nitric oxide production in response to bacterial lipopolysaccharide. These data suggest a novel neuroprotective mechanism of action for CBs in response to inflammatory or excitotoxic insults that is mediated by both CB1 and CB2 receptor-dependent pathways. PMID:12878687

Molina-Holgado, Francisco; Pinteaux, Emmanuel; Moore, Jonathan D; Molina-Holgado, Eduardo; Guaza, Carmen; Gibson, Rosemary M; Rothwell, Nancy J



Anti-Inflammatory, Antioxidant, Anti-Angiogenic and Skin Whitening Activities of Phryma leptostachya var. asiatica Hara Extract  

PubMed Central

This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine.

Jung, Hyun-Joo; Cho, Young-Wook; Lim, Hye-Won; Choi, Hojin; Ji, Dam-Jung; Lim, Chang-Jin



Synthesis of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents.  


Thirteen new 2-pyrazoline derivatives bearing benzenesulfonamide moiety (2a-m) were synthesized by condensing appropriate chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride and tested for anticancer and anti-inflammatory actions. According to the protocol of the National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay compounds 2b, 2c, 2e, 2f and 2g exhibited considerable antitumor activities against the entire tested tumor cell lines and showed effective growth inhibition GI(50) (MG-MID) values of 2.63, 2.57, 6.61, 3.31 and 2.57?M, respectively, beside a cyclostatic activity TGI (MG-MID) 9.54, 8.51, 24.0, 19.9 and 8.71?M, respectively. Two compounds 2g and 2k showed more potent anti-inflammatory activity than celecoxib at 5h in carrageenan-induced rat paw edema bioassay. These compounds (2g and 2k) proved to have superior gastrointestinal safety profiles as compared to celecoxib, when tested for their ulcerogenic effects. Compounds 2g and 2k showed no inhibition against the enzymatic activity of bovine COX-2 (in vitro). PMID:21664130

Bashir, Rafia; Ovais, Syed; Yaseen, Shafiya; Hamid, Hinna; Alam, M S; Samim, Mohammad; Singh, Surender; Javed, Kalim



Synthesis and pharmacological investigation of 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones as analgesic and anti-inflammatory agents.  


In the present work, design, synthesis, and pharmacological evaluation of the analgesic, anti-inflammatory, and ulcerogenic-index activities of new 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones, structurally planed by exploiting a clear concept of bio-isosterism, are reported. All compounds exhibited significant analgesic and anti-inflammatory activity. Compounds A1, A3 showed higher analgesic activity and more potent anti-inflammatory activity than that of the reference compound diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to that of acetylsalicylic acid. PMID:17610301

Alagarsamy, V; Solomon, V Raja; Deepa, G; Parthiban, P; Anjana, G V



In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an apoA-1 mimetic peptide  

PubMed Central

Features of end-stage renal disease such as oxidative stress, inflammation, hypertension, and dyslipidemia are associated with accelerated atherosclerosis and increased risk of death from cardiovascular disease. By inhibiting the formation and increasing the disposal of oxidized lipids, HDL exerts potent antioxidant and anti-inflammatory actions. Given that apolipoproteinA-1 can limit atherosclerosis, we hypothesized that an apolipoproteinA-1 mimetic peptide, 4F, may reduce the proinflammatory properties of LDL and enhance the anti-inflammatory properties of HDL in uremic plasma. To test this, plasma from each of 12 stable hemodialysis patients and age-matched control subjects was incubated with 4F or vehicle. The isolated HDL and LDL fractions were added to cultured human aortic endothelial cells to quantify monocyte chemotactic activity, thus measuring their pro- or anti-inflammatory index. The LDL from the hemodialysis patients was more pro-inflammatory and their HDL was less anti-inflammatory than those of the control subjects. Pre-incubation of the plasma from the hemodialysis patients with 4F decreased LDL pro-inflammatory activity and enhanced HDL anti-inflammatory activity. Whether 4F or other apolipoproteinA-1 mimetic peptides will have any therapeutic benefit in end-stage renal disease will have to be examined directly in clinical studies.

Vaziri, Nosratola D; Moradi, Hamid; Pahl, Madeleine V; Fogelman, Alan M; Navab, Mohamad



Synthesis and Evaluation of Benzophenone-N-ethyl Morpholine Ethers as Anti-inflammatory Agents  

PubMed Central

The synthesis of hydroxy benzophenones and benzophenone-N-ethyl morpholine ethers and the results of anti-inflammatory activity in vivo are described. The structures of the compounds were elucidated by IR, 1H-NMR, mass spectroscopy and the elementary analysis. The anti-inflammatory activity of the synthesized compounds were determined by carrageenan-induced hind paw oedema test in rats. Most of the tested compounds exhibited anti-inflammatory activity and some of them were more active than standard drugs. In addition ulcerogenic and cyclooxygenase activities are also described.

Khanum, Shaukath A.; Begum, Bushra A.; Girish, V.; Khanum, Noor Fatima



Anti-inflammatory activity of root bark and stem bark of Shyonaka  

PubMed Central

Background: Shyonaka (Oroxylum indicum Vent.; Bignoniaceae) root bark is one of the ingredients of dashamoola (a group of 10 roots), and is used for its anti-inflammatory and analgesic action in a number of compound formulations in Ayurveda. Aim: Ayurvedic Pharmacopoeia of India (API) recommends using the stem bark instead of root bark. Material and Methods: An attempt has been made to study the anti-inflammatory activity of both root bark and stem bark kashaya (decoction) experimentally. Conclusion Results showed significant anti-inflammatory activity of root bark and stem bark decoction.

Doshi, Krunal; Ilanchezhian, R; Acharya, Rabinarayan; Patel, B. R.; Ravishankar, B.



The role of non-steroidal anti-inflammatory drugs in acute liver injury  

Microsoft Academic Search

OBJECTIVE--To investigate the association between use of non-steroidal anti-inflammatory drugs and serious, acute non-infectious liver injury. DESIGN--Retrospective cohort study, cross over design. SETTING--Health records from provincial database in Saskatchewan, Canada, 1982-6. SUBJECTS--228,392 adults who contributed 645,456 person years. All were either using or had used non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES--Number and type of prescriptions for non-steroidal anti-inflammatory drugs. Admission

L. A. García Rodríguez; S. Pérez Gutthann; A. M. Walker; L. Lueck



Lymphoblastosis inhibition and plaque-forming cell response of several anti-inflammatory steroids in mice  

Microsoft Academic Search

Anti-inflammatory glucocorticoid (GC) derivatives have been clinically used in immune-malfunctional diseases for their immunosuppressive\\u000a activity. However, there is still a lack of knowledge on the relationship between anti-inflammatory and immuno-suppressive\\u000a activities. In order to compare immunosuppressive activities with the known anti-inflammatory activities of the GC derivatives,\\u000a eight clinically used GC derivatives including hydrocortisone, prednisolone, 6?-methyl prednisolone, triamcinolone, dexamethasone,\\u000a betamethasone, triamcinolone

Hong Pil Choi; Kilhyoun Kim; Hyun Pyo Kim



HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons  

PubMed Central

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1?. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1?-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

Zhang, Jianying; Middleton, Kellie K.; Fu, Freddie H.; Im, Hee-Jeong; Wang, James H-C.



HGF mediates the anti-inflammatory effects of PRP on injured tendons.  


Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1?. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1?-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. PMID:23840657

Zhang, Jianying; Middleton, Kellie K; Fu, Freddie H; Im, Hee-Jeong; Wang, James H-C



A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.  


Control of systemic iron homeostasis is interconnected with the inflammatory response through the key iron regulator, the antimicrobial peptide hepcidin. We have previously shown that mice with iron deficiency anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficient-high hepcidin Tmprss6 KO mice. The transcriptional response associated with chronic hepcidin overexpression due to genetic inactivation of Tmprss6 is unknown. By using whole genome transcription profiling of the liver and analysis of spleen immune-related genes we identified several functional pathways differentially expressed in Tmprss6 KO mice, compared to IDA animals and thus irrespective of the iron status. In the effort of defining genes potentially targets of Tmprss6 we analyzed liver gene expression changes according to the genotype and independently of treatment. Tmprss6 inactivation causes down-regulation of liver pathways connected to immune and inflammatory response as well as spleen genes related to macrophage activation and inflammatory cytokines production. The anti-inflammatory status of Tmprss6 KO animals was confirmed by the down-regulation of pathways related to immunity, stress response and intracellular signaling in both liver and spleen after LPS treatment. Opposite to Tmprss6 KO mice, Hfe(-/-) mice are characterized by iron overload with inappropriately low hepcidin levels. Liver expression profiling of Hfe(-/-) deficient versus iron loaded mice show the opposite expression of some of the genes modulated by the loss of Tmprss6. Altogether our results confirm the anti-inflammatory status of Tmprss6 KO mice and identify new potential target pathways/genes of Tmprss6. PMID:23922777

Riba, Michela; Rausa, Marco; Sorosina, Melissa; Cittaro, Davide; Garcia Manteiga, Jose Manuel; Nai, Antonella; Pagani, Alessia; Martinelli-Boneschi, Filippo; Stupka, Elia; Camaschella, Clara; Silvestri, Laura



Anti-inflammatory effect of licofelone against various inflammatory challenges.  


We investigated the pharmacological profile of licofelone [6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizine-5-acetic acid] against different inflammogens. The anti-inflammatory and anti-hyperalgesic effect of licofelone (2, 30 and 100 mg/kg, p.o.) against all the challenges was statistically significant (P < 0.05) when compared with control and indomethacin (10 mg/kg, p.o.). The ED(50) value of 19.1 mg/kg (onset by 2 h, duration: short), 13.0 mg/kg and 16.8 mg/kg (onset by 1 h, duration: long) was observed for licofelone against carrageenan-, arachidonic acid- and bradykinin-induced paw oedema, respectively. Similarly, licofelone showed ED(50) value of 47.6 mg/kg (onset by 1 h, duration: long), 92.2 mg/kg (onset by 1 h, duration: medium), and 78.6 mg/kg (onset by 2 h, duration: medium) against carrageenan-, arachidonic acid- and bradykinin-induced mechanical hyperalgesia, respectively. The rank order of potency based on percent inhibition and percent reversal against inflammation and mechanical hyperalgesia, respectively, was found to be licofelone > indomethacin. Moreover, licofelone (10-100 mg/kg, p.o.) significantly (P < 0.05) and dose-dependently prevented the Freund's adjuvant-induced increased vascularity in mice (vascularity index; 10 mg/kg: 0.059 +/- 0.015; 20 mg/kg: 0.048 +/- 0.004; 30 mg/kg: 0.039 +/- 0.012; 100 mg/kg: 0.025 +/- 0.015 vs. control: 0.0285 +/- 0.003). Furthermore, the results suggested that dual inhibitors of cyclooxygenase and lipoxygenase like licofelone provide an effective control of inflammation and hyperalgesia against acute inflammation/hyperalgesia in rats and mice. PMID:16448396

Singh, Vijay Pal; Patil, Chandrashekhar S; Kulkarni, Shrinivas K



Licofelone--a novel analgesic and anti-inflammatory agent.  


Dual inhibitors that block both cyclooxygenase (COX) and lipoxygenase (LOX) metabolic pathways of arachidonic acid are expected to possess clinical advantages over the selective inhibitors of COX enzyme. One of the most promising compounds belonging to this category is licofelone ([2,2 -dimethyl -6-(4-chloropheny-7-phenyl-2,3-dihydro-1H-pyrrazoline-5-yl] acetic acid). Originally discovered by Merckle GmbH and developed by EuroAllaince, licofelone (IC(50) COX=0.21 microM, IC(50) 5-LOX=0.18 microM) possesses significant analgesic, anti-inflammatory, and antiasthmatic effects at doses that cause no gastrointestinal (GI) side effects. The pharmacodynamic profile of licofelone has been assessed and compared with widely used NSAIDs in different animal models. The ED(50) value of licofelone is reported to be 11.22-27.07 mg/kg, po and 39.5-55-8 mg/kg, po against carrageenan-induced paw oedema and Randal Selitto hyperalgesic assay in rats, respectively. Licofelone showed analgesic effect (ED(50) = 31.33 mg/kg) against acetic acid-induced writhing in mice. Licofelone has long duration of action and more effective than indomethacin and zileuton with ED(50) values of 2.92 mg/kg, po and 36.77 mg/kg, po, in the mechanical hyperalgesia and cold allodynia testing, respectively, against rat model of incisional pain. Licofelone significantly ameliorated indomethacin-induced gastric ulceration, neutrophil adhesion in mesentery, and lipid peroxides in rat gastric mucosa. Also, licofelone reversed the altered vascular permeability, morphological changes, and prevented NSAIDs-related increase in leukotriene levels in gastric mucosa. The preclinical studies have shown that licofelone not only has convincing pharmacodynamic effect but also it is well tolerated. It is currently under clinical evaluation in osteoarthritis (OA), the most common form of arthritis. The present review describes pharmacological and clinical development of licofelone as a dual inhibitor. PMID:17305568

Kulkarni, S K; Singh, Vijay Pal



Cardiovascular Risk Comparisons of Non-Steroidal Anti-Inflammatory Agents in the TRICARE Population.  

National Technical Information Service (NTIS)

This report examines differences in risk of myocardial infarction and stroke (cardiovascular events) between the cyclooxygenase-2 (COX-2) inhibitors Rofecoxib, Celecoxib, and Valdecoxib, and the traditional nonsteroidal anti-inflammatory agents (NSAIDs) N...

K. L. Lefebvre



Experimental evaluation of analgesic and anti-inflammatory potential of Oyster mushroom Pleurotus florida  

PubMed Central

Background: Edible mushrooms have been used as flavorful foods and as health nutritional supplements for several centuries. A number of bioactive molecules have been identified in numerous mushroom species Objective: To evaluate the analgesic and anti-inflammatory potential of Oyster Mushroom Pleurotus florida using various experimental models in Wistar rats. Materials and Methods: Acute toxicity studies were performed whereby dose of 250 mg/ kg and 500 mg/kg was selected for present study, Analgesic activity was determined using hot plate method, tail flick method, acetic acid induced writhing and formalin induced pain in rats, while carrageenan was used to induce inflammation and anti-inflammatory studies were performed. Results: HEE showed significant (P < 0.01) analgesic and anti-inflammatory response against all experimental models. Conclusion: These studies conclude that Pleurotus florida possesses analgesic and anti- inflammatory potential which might be due to presence of myochemicals like flavonoids, phenolics and polysaccharides.

Ganeshpurkar, Aditya; Rai, Gopal



Investigation the antinociceptive, antipyretic and anti- inflammatory activities of Curcuma aeruginosa Roxb. extracts in experimental animals  

Microsoft Academic Search

Reanmongkol, W., Subhadhirasakul, S., Khaisombat, N., Fuengnawakit, P., Jantasila, S. and Khamjun, A. Investigation the antinociceptive, antipyretic and anti-inflammatory activities of Curcuma aeruginosa Roxb. extracts in experimental animals

Wantana Reanmongkol; Sanan Subhadhirasakul; Narinee Khaisombat; Parichat Fuengnawakit; Saranya Jantasila; Arunee Khamjun



A concise access to a new class of selective anti-inflammatory steroid derivatives  

Microsoft Academic Search

The 17?-thiomethyl-16?,17?-ketal motif of a new class of selective anti-inflammatory androstane derivatives useful in the treatment of asthma is readily constructed by a new radical degradation of the corticosteroid side chain.

Béatrice Quiclet-Sire; Samir Z. Zard



Stereochemical Purification of an Anti-Inflammatory Drug in an Enzyme Membrane Reactor.  

National Technical Information Service (NTIS)

The objective of the project is to examine the technical and economic feasibility of membrane bioreactor processes for the enzymatic resolution of optical isomers of anti-inflammatory pharmaceuticals. The research encompassed enzyme screening and characte...

S. L. Matson



Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1.  


Sepsis, a serious unbalanced hyperinflammatory condition, is a tremendous burden for healthcare systems, with a high mortality and limited treatment. Increasing evidences indicated that some active components derived from natural foods have potent anti-inflammatory properties. Here we show that mangiferin (MF), a natural glucosyl xanthone found in both mango and papaya, attenuates cecal ligation and puncture-induced mortality and acute lung injury (ALI), as indicated by reduced systemic and pulmonary inflammatory responses. Moreover, pretreatment with MF inhibits sepsis-activated mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells signaling, resulting in inhibiting production of proinflammatory mediators. Notably, MF dose-dependently up-regulates the expression and activity of heme oxygenase (HO)-1 in the lung of septic mice. Further, these beneficial effects of MF on the septic lung injury were eliminated by ZnPP IX, a specific HO-1 inhibitor. Our results suggest that MF attenuates sepsis by up-regulation of HO-1 that protects against sepsis-induced ALI through inhibiting inflammatory signaling and proinflammatory mediators. Thereby, MF may be effective in treating sepsis with ALI. PMID:23266284

Gong, Xia; Zhang, Li; Jiang, Rong; Ye, Mengliang; Yin, Xinru; Wan, Jingyuan



Biological evaluation of isoegomaketone isolated from Perilla frutescens and its synthetic derivatives as anti-inflammatory agents.  


The anti-inflammatory activities of a prepared isoegomaketone 3a and its derivatives 3b-3f were evaluated in RAW 264.7 cells. Among these, the compound 3d was displayed the most potent inhibitory activities against production of nitric oxide, monocyte chemoattractant protein-1 and interleukin-6. Based on these results, the abilities of compounds 3a-3f to modulate NF-?B and AP-1-mediated gene transcription using a luciferase reporter assay were investigated. The transcriptional activities of NF-?B and AP-1 decreased when pretreated with 3a-3f. Interestingly, at 10 ?M, compound 3d markedly suppressed the lipopolysaccharide-induced NF-?B and activator protein-1 DNA binding activities. Some preliminary structure-activity relationships were proposed that may provide a direction for further study. PMID:21910048

Park, Yong Dae; Jin, Chang Hyun; Choi, Dae Seong; Byun, Myung-Woo; Jeong, Il Yun



Design and synthesis of novel deoxybenzoin derivatives as FabH inhibitors and anti-inflammatory agents.  


Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. The synthesis and biological evaluation halide-deoxybenzoins derivatives are described in this Letter. Potent FabH inhibitory and selective anti-Gram-negative bacteria activities were observed in deoxybenzoin derivatives. Furthermore, compound 19 was able to reduce the ECE-induced IL-8 production in gastric mucosal cells significantly. Based on the biological data and molecular docking, compound 19 is a potential FabH inhibitor and anti-inflammatory agent deserving further research. PMID:20153183

Li, Huan-Qiu; Luo, Yin; Lv, Peng-Cheng; Shi, Lei; Liu, Chang-Hong; Zhu, Hai-Liang



Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages.  


Oxidative stress and inflammation are two of the most critical factors implicated in carcinogenesis and other degenerative disorders. We have investigated how lunasin, a known anti-cancer seed peptide, affect these factors. This peptide inhibits linoleic acid oxidation and acts as 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenger. Furthermore, using LPS-stimulated RAW 264.7 macrophages, we have demonstrated that lunasin reduces, in a significant dose-dependent manner, the production of reactive oxygen species (ROS) by LPS-induced macrophages. Lunasin also inhibits the release of pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukine-6 [IL-6]). On the basis of these potent antioxidant and anti-inflammatory properties, we propose lunasin not only as a cancer preventive and therapeutic agent but also as an agent against other inflammatory-related disorders. PMID:19836349

Hernández-Ledesma, Blanca; Hsieh, Chia-Chien; de Lumen, Ben O



Synthesis and pharmacological evaluation of 2-substituted benzo[b]thiophenes as anti-inflammatory and analgesic agents.  


An efficient method for trapping isocyanate 4, generated from the Curtius rearrangement, with ethyl alcohol to afford the carbamate 5 is reported. 5-Nitrobenzo[b]thiophene-2-carboxylic acid 1 is converted to the corresponding hydrazide 2 by the reaction with hydrazine hydrate and then to the azide 3 with nitrous acid, followed by thermal rearrangement, cooling, and trapping in one pot reaction. The carbamate 5 is treated with hydrazine hydrate to afford the desired, Zileuton analogue, 4-(5-nitrobenzo[b]thiophene-2-yl)semicarbazide 6. Also the reactivity of hydrazide 2 towards some carboxyaldehydes and phenylisothiocyanate afforded the corresponding carbohydrazides 7, 8 and phenylthiosemicarbazide 9, respectively. Compounds 9, 2 and 6, respectively, were more potent as anti-inflammatory and anti-nociceptive agents. PMID:18433939

Fakhr, Issa M I; Radwan, Mohamed A A; el-Batran, Seham; Abd el-Salam, Omar M E; el-Shenawy, Siham M



Inhibition of chronic skin inflammation by topical anti-inflammatory flavonoid preparation, ato formula ®  

Microsoft Academic Search

Flavonoids are known as natural anti-inflammatory agents. In this investigation, an anti-inflammatory potential of new topical\\u000a preparation (SK Ato Formula®) containing flavonoid mixtures fromScutellaria baicalensis Georgi roots andGinkgo biloba L. leaves with an extract ofGentiana scabra Bunge roots was evaluated in an animal model of chronic skin inflammation. Multiple 12-O-tetradecanoylphorbol-13-acetate treatments for 7 consecutive days on ICR mouse ear provoked

Hyun Lim; Kun Ho Son; Hyeun Wook Chang; Sam Sik Kang; Hyun Pyo Kim



Anti-inflammatory activity of the major constituents of Lonicera japonica  

Microsoft Academic Search

Previously, we reported that then-butanol fraction ofLonicera japonica showed anti-inflammatrory activity in mice and rats. Several constituents such as loniceroside A and B, flavonoids and iridoids\\u000a were isolated from this fraction. In this investigation, the anti-inflammatory activity of the major constituents ofL. japonica was studied. Loniceroside A, lonicerin and loganin showed anti-inflammatory activity comparable to aspirin.

Song Jin Lee; Eun Joo Shin; Kun Ho Son; Hyeun Wook Chang; Sam Sik Kang; Hyun Pyo Kim



Anti-Inflammatory Activity of Immunoglobulin G Resulting from Fc Sialylation  

Microsoft Academic Search

Immunoglobulin G (IgG) mediates pro- and anti-inflammatory activities through the engagement of its Fc fragment (Fc) with distinct Fcgamma receptors (FcgammaRs). One class of Fc-FcgammaR interactions generates pro-inflammatory effects of immune complexes and cytotoxic antibodies. In contrast, therapeutic intravenous gamma globulin and its Fc fragments are anti-inflammatory. We show here that these distinct properties of the IgG Fc result from

Yoshikatsu Kaneko; Falk Nimmerjahn; Jeffrey V. Ravetch



Theoretical Analysis of the Reactive Sites of Non-steroidal Anti-inflammatory Drugs  

Microsoft Academic Search

Motivation. Inflammation is a disease condition in which body tissues are affected by heat, redness, swelling and pain. The therapeutic effects of non-steroid anti-inflammatory drugs (NSAIDs) are well known regarding different diseases. Although there remain a number of other potential sites of action for anti-inflammatory agents, the mode of action of the NSAIDs is attributed primarily to the inhibition of

Nora Okulik; Alicia H. Jubert; Roque Sáenz Peña



Anti-inflammatory activity of Jatropha curcas roots in mice and rats  

Microsoft Academic Search

Anti-inflammatory activity of topical application of Jatropha curcas L. root powder in paste form in TPA-induced ear inflammation was confirmed in albino mice and the successive solvent extraction of these roots was carried out by ether and methanol. The methanol extract exhibited systemic and significant anti-inflammatory activity in acute carrageenan-induced rat paw edema. It also showed activity against formalin-induced rat

A. M Mujumdar; A. V Misar



Effect of anti-inflammatory drugs on partitioning characteristics of propranolol and oxprenolol.  


The influence of a range of nine anti-inflammatory drugs on the octan-1-ol aqueous phosphate buffer pH 7.4 apparent partition coefficients of propranolol and oxprenolol has been examined. All produced a change in the apparent partition coefficient which can be explained in terms of partitioning of hydrophobic ion-pairs formed between the ionic anti-inflammatory compound and the protonated cationic drug. PMID:6141266

Parkin, J E



Analgesic and anti-inflammatory properties of aqueous extract from leaves of Solanum torvum (Solanaceae).  


Solanum torvum is used in Cameroonian traditional medicine for the management of pain and inflammation. The present work assesses the pain-killing and anti-inflammatory properties of the aqueous extracts of Solanum torvum leaves. Acetic acid- and pressure- induced pains were reduced by this extract while carrageenan-induced inflammation was inhibited at various doses of the extract. The extract therefore has both analgesic and anti-inflammatory properties. PMID:20162098

Ndebia, E J; Kamgang, R; Nkeh-ChungagAnye, B N



Anti-inflammatory effects of a triterpenoid isolated from Wilbrandia ebracteata Cogn  

Microsoft Academic Search

Wilbrandia ebracteata (WE), a Brazilian medicinal plant used in folk medicine for the treatment of rheumatic diseases, displays anti-inflammatory properties and constitutes a rich source of cucurbitacins and cucurbitacin-related compounds. The current study investigated the potential anti-inflammatory properties of Dihydrocucurbitacin B (DHCB), a cucurbitacin-derived compound isolated from roots of WE, in some in vivo and in vitro experimental models. Intraperitoneal

Jarbas Mota Siqueira; Rodrigo Rebelo Peters; Andressa Córneo Gazola; Patrícia Baier Krepsky; Mareni Rocha Farias; Giles Alexander Rae; Artur José de Brum-Fernandes; Rosa Maria Ribeiro-do-Valle



A novel approach to the discovery of non-systemic anti-inflammatory steroids; Antedrug  

Microsoft Academic Search

Therapeutic use of anti-inflammatory steroids is limited due primarily to their systemic suppressive effects on pituitary\\u000a function and the immune system. To overcome the clinical limitation, a new approach toward the discovery of non-systemic anti-inflammatory\\u000a steroids is based upon the antedrug concept introduced by this laboratory. The new concept describes locally active agents\\u000a which are designed to undergo a predictable

Henry J. Lee; Dong-Hoon Ko



Effect of Anti-inflammatory Medications on Neuropathological Findings in Alzheimer Disease  

Microsoft Academic Search

Background: There has been no analysis of brain tis- sue from longitudinally observed, cognitively tested pa- tients to validate whether anti-inflammatory medica- tions protect against the pathological changes of Alzheimer disease. Objective: To investigate the role of anti-inflammatory medications in alleviating the pathological features of Alz- heimer disease. Design and Main Outcome Measures: A 5-year post- mortem tissue collection was

Glenda M. Halliday; Claire E. Shepherd; Heather McCann; Wayne G. J. Reid; David A. Grayson; G. Anthony Broe; Jillian J. Kril



Anti-inflammatory activity of the topical preparation of Valeriana wallichii and Achyranthes aspera leaves.  


In vivo and in vitro screening of anti inflammatory activity of Valeriana wallichii and Achyranthes aspera leaves crude extract was performed, using standardized procedures. Methanolic crude extract topical formulation (cream) of Valeriana wallichii and Achyranthes aspera leaves (Family Valerianaceae and Amaranthaceae respectively), were screened for their anti-inflammatory activity, through "Carrageenan induced hind paw edema" test, for their effect on the acute and chronic phase inflammation models in male Wistar rats. Methanolic extract and its fractions were also evaluated for their in vitro anti-inflammatory activity using lipoxygenase inhibition assay. Leaves of Valeriana wallichii showed significant (P<0.001), dose dependant anti inflammatory activity, comparable with that of the standard, in animal model. The ethyl acetate fraction of Valeriana wallichii also showed considerable (IC 50=73 ± 0.36) in vitro anti-inflammatory activity as compared to standard (6.11 ± 0.02). Similarly Achyranthes aspera leaves showed relatively weak (p>0.05) in vivo anti-inflammatory activity. However, its activity was comparable with that of standard at 10% concentration after 5 hrs of carrageenan injection. This activity was present in ethyl acetate fraction during in vitro screening (IC 50=76 ± 0.14) as compared to that of standard (IC 50=6.11 ± 0.02). The combined in vitro and in vivo Anti-inflammatory screening shows that the ethyl acetate fraction of the crude extract of Valeriana wallichii and Achyranthes aspera can be used for the isolation of new Anti-inflammatory lead compounds. PMID:23625416

Khuda, Fazli; Iqbal, Zafar; Khan, Ayub; Zakiullah; Nasir, Fazli; Shah, Yasar



Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr  

Microsoft Academic Search

The present study reports the potential antinociceptive, anti-inflammatory and hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert) Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition than aspirin in acetic-acid induced abdominal stretching at 1.0mg\\/kg dose. Lycorine also showed antinociceptive activity at 1.0mg\\/kg dose in tail-flick test. The anti-inflammatory activity

G. Saltan Çito?lu; Ö. Bahad?r Ac?kara; B. Sever Y?lmaz; H. Özbek


Comparative study of anti-inflammatory and ulcerogenic activities of different cyclo-oxygenase inhibitors  

Microsoft Academic Search

The aim of the present work was to study the in vivo anti-inflammatory activity of six NSAIDs, ibuprofen, diclofenac, nimesulide, meloxicam, celecoxib and rofecoxib, using the\\u000a rat air-pouch model of inflammation to characterize the ability of these drugs to induce gastric damage and PGE2 inhibition. Selective compounds were observed to have no ulcerogenic properties at anti-inflammatory doses; however, these\\u000a drugs

Alessandra Gambero; Tagliane Liza Becker; Andréa Silva Zago; Andréa Fermino de Oliveira; José Pedrazzoli



Anti-Inflammatory and Antinociceptive Effects of Mitragyna speciosa Korth Methanolic Extract  

Microsoft Academic Search

Objectives: To determine the anti-inflammatory and antinociceptive activities of Mitragyna speciosa Korth methanol extract in rodents. Materials and Methods: Anti-inflammatory activity was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma tests in rats. Antinociceptive activity was measured using the writhing test and the hot plate test in mice, and the formalin test in rats. All drugs and extracts were

W. M. Shaik Mossadeq; M. R. Sulaiman; T. A. Tengku Mohamad; H. S. Chiong; Z. A. Zakaria; M. L. Jabit; M. T. H. Baharuldin; D. A. Israf



Non-steroidal anti-inflammatory drugs in sports medicine: guidelines for practical but sensible use  

Microsoft Academic Search

Introduction:Non-steroidal anti-inflammatory drugs (NSAID) are commonly used in sports medicine. NSAID have known anti-inflammatory, analgesic, antipyretic and antithrombotic effects, although their in-vivo effects in treating musculoskeletal injuries in humans remain largely unknown. NSAID analgesic action is not significantly greater than paracetamol for musculoskeletal injury but they have a higher risk profile, with side-effects including asthma exacerbation, gastrointestinal and renal side-effects,

J. A. Paoloni; C. Milne; J. Orchard



Novel anti-inflammatory plant labdanes: Comparison of in vitro properties with aspirin and indomethacin  

Microsoft Academic Search

Two purified plant products were obtained from anti-inflammatory extracts of the Spanish herbSideritis javalambrensis: ent-13-epi-12?-acetoxy-manoyl oxide (=“manoyl oxide F1”) andent-8?-hydroxy-labda-13 (16), 14-dien (=“labdane F2”). They were evaluated for possible anti-inflammatory actionsin vitro, and were compared with aspirin, sodium salicylate and indomethacin. Neither of the natural products affected superoxide generation or scavenging and they did not affect granular enzyme secretion from

Beatriz de las Heras; Angel Villar; José M. Vivas; J. R. S. Hoult



Screening for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala koidz  

Microsoft Academic Search

The aim of this study was to screen for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala Koidz. The rhizomes of Atractylodes macrocephala were treated with supercritical CO2 fluid and the extract was separated by normal-phase and reverse-phase column chromatography. The separated samples were screened with white blood cell membrane (WBCM) chromatography (WBCM-C). The anti-inflammatory effects of these

Cui-Qin Li; Lang-Chong He; Hai-Yan Dong; Ju-Qing Jin



Ion exchange chromatographic separation and isolation of oligosaccharides of intact low-molecular-weight heparin for the determination of their anticoagulant and anti-inflammatory properties.  


It is well known that enoxaparin, a widely used anticoagulant and low-molecular-weight heparin containing a large number of oligosaccharides, possesses anti-inflammatory activity. Whilst enoxaparin has shown promising results in various inflammatory disorders, some of its oligosaccharides have anti-inflammatory properties and others increase the risk of bleeding due to their anticoagulant effects. The aim of this study was to develop an effective ion exchange chromatographic (IC) technique which allows the separation, isolation and, consequently, the identification of different oligosaccharides of enoxaparin with or without anticoagulant activity. The developed method utilises a semi-preparative CarboPac PA100 (9?×?250 mm) ion exchange column with sodium chloride gradient elution and UV detection at 232 nm. The method successfully resolved enoxaparin into more than 30 different peaks. IC-derived oligosaccharides with high, moderate, low or no anticoagulant activity were identified using an anti-factor Xa assay. The anti-inflammatory activity of selected oligosaccharides was investigated using the Griess assay. Using this technique, the oligosaccharides of enoxaparin with low or no anticoagulant activity, whilst exhibiting significant anti-inflammatory activity, could be fractionated. This technique can provide a platform to identify the oligosaccharides which are devoid of significant anticoagulant activity and are responsible for the therapeutic effects of enoxaparin that have been observed in various inflammatory conditions. PMID:23712644

Shastri, Madhur D; Johns, Cameron; Hutchinson, Joseph P; Khandagale, Manish; Patel, Rahul P



Antimicrobial, Antiparasitic, Anti-Inflammatory, and Cytotoxic Activities of Lopezia racemosa  

PubMed Central

The present study investigates the potential benefits of the Mexican medicinal plant Lopezia racemosa (Onagraceae). Extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Extracts and fractions were tested against a panel of nine bacterial and four fungal species. The antiparasitic activity was tested against Leishmania donovani, whereas the anti-inflammatory activity of the compounds was determined by measuring the secretion of interleukin-6 from human-derived macrophages. The same macrophage cell line was used to investigate the cytotoxicity of the compounds. Various extracts and fractions showed antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. The hexanic fraction HF 11-14b was the most interesting fraction with antimicrobial, and anti-inflammatory activities. The benefit of L. racemosa as a traditional medicinal plant was confirmed as shown by its antibacterial, antifungal and anti-inflammatory activities. To the best of our knowledge, this is the first study reporting the biological activities of L. racemosa, including antiparasitic and anti-inflammatory activities.

Cruz Paredes, Carla; Bolivar Balbas, Paulina; Juarez, Zaida Nelly; Sanchez Arreola, Eugenio; Hernandez, Luis Ricardo



Modulation of anti-inflammatory response in lipopolysaccharide stimulated human THP-1 cell line and mouse model at gene expression level with indigenous putative probiotic lactobacilli.  


The anti-inflammatory potential of eight indigenous probiotic Lactobacillus isolates was evaluated in vitro in terms of modulating the expression of tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6) in human acute monocytic leukemia (THP-1) cells under inflammatory conditions. Amongst these, Lactobacillus plantarum Lp91 was the most potent anti-inflammatory strain as it evoked a significant (P < 0.001) down-regulation of TNF-? by -1.45-fold relative to the control in THP-1 cells. However, in terms of IL-6 expression, all the strains could up-regulate its expression considerably at different levels. Hence, based on in vitro expression of TNF-?, Lp91 was selected for in vivo study in lipopolysaccharide (LPS)-induced mouse model to look at the expression of TNF-?, IL-6, monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and E-selectin in mouse aorta. In LPS challenged (2 h) mice group fed with Lp91 for 10 days, TNF-?, IL-6, MCP-1, VCAM-1, ICAM-1 and E-selectin expressions were significantly down-regulated by 3.10-, 10.02-, 4.22-, -3.14-, 2.28- and 5.71-fold relative to control conditions. In conclusion, Lp91 could serve as a candidate probiotic strain to explore it as a possible biotherapeutic anti-inflammatory agent against inflammatory diseases including cardiovascular disease. PMID:23728791

Aparna Sudhakaran, V; Panwar, Harsh; Chauhan, Ritu; Duary, Raj Kumar; Rathore, Rahul Kumar; Batish, Virender Kumar; Grover, Sunita



Evaluation of the new anti-inflammatory compound ethyl salicylate 2-O-?-D-glucoside and its possible mechanism of action.  


Ethyl salicylate 2-O-?-d-glucoside (ESG) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, it has been used for the treatments of rheumatoid arthritis, swelling and pain. The aim of this study was to evaluate the anti-inflammatory effects of ESG and explore the anti-inflammatory mechanisms. We found that ESG had potent anti-inflammatory effects on the lipopolysaccharide (LPS)-activated murine macrophages RAW264.7. ESG exerted a dose-dependent inhibition of the LPS-stimulated release of the pro-inflammatory cytokines TNF-? and IL-1?. Moreover, it significantly inhibited LPS-stimulated the production of NO and PGE2 by repressing the expression of iNOS and COX protein respectively. Western blot analysis showed that ESG prominently inhibited LPS-induced activation of NF-?B in RAW264.7 cells by blocking phosphorylation of inhibitor I?B? and p65. Consistent with these results, we found that ESG prevented the nuclear translocation of NF-?B induced by LPS. Our study suggests that ESG may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the NF-?B signal pathway. PMID:23219581

Xin, Wenyu; Huang, Chao; Zhang, Xue; Zhang, Guidong; Ma, Xiaowei; Sun, Lan; Wang, Chao; Zhang, Dongming; Zhang, Tiantai; Du, Guanhua



Analgesic and Anti-Inflammatory Properties of Extracts from the Bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae) in Mice and Rats  

PubMed Central

The aqueous and methanol extracts from the dry bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae)—evaluated orally at the doses of 300 and 600?mg/kg against pain induced by acetic acid, formalin, pressure and against inflammation induced by carrageenan, histamine, serotonin and formalin in mice and rats, showed a dose dependant inhibition of pain and inflammation with a maximum effect of 56.38%, 73.06% and 42.79% produced by the aqueous extract, respectively on pain induced by acetic acid, formalin and pressure while the methanol extract at the same dose respectively inhibited these models of pain by 62.70%, 84.54% and 47.70%. The oral administration of aqueous and methanol extracts caused significant anti-inflammatory activity on paw oedema induced by histamine, serotonin and formalin. The present results show that the bulbils of Dioscorea bulbifera var sativa possess potent analgesic and anti-inflammatory activities. These activities may results from the inhibition of inflammatory mediators such as histamine, serotonin and prostaglandins. Thus, the analgesic activity of the bulbils of Dioscorea bulbifera may be at least partially linked to its anti-inflammatory activity.

Mbiantcha, M.; Kamanyi, A.; Teponno, R. B.; Tapondjou, A. L.; Watcho, P.; Nguelefack, T. B.



Anti-inflammatory properties of clovamide and Theobroma cacao phenolic extracts in human monocytes: evaluation of respiratory burst, cytokine release, NF-?B activation, and PPAR? modulation.  


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-?B 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-?B activation; the two cocoa extracts were less effective. In all tests, clovamide was the most potent compound and also enhanced peroxisome