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Sample records for highly potent anti-inflammatory

  1. Discovery of a highly potent anti-inflammatory epoxyisoprostane-derived lactone.

    PubMed

    Egger, Julian; Bretscher, Peter; Freigang, Stefan; Kopf, Manfred; Carreira, Erick M

    2014-12-17

    Epoxyisoprostanes EI (1) and EC (2) are effective inhibitors of the secretion of proinflammatory cytokines IL-6 and IL-12. In detailed studies toward the investigation of the molecular mode of action of these structures, a highly potent lactone (3) derived from 1 was identified. The known isoprostanoids 1 and 2 are most likely precursors of 3, the product of facile intramolecular reaction between the epoxide with the carboxylic acid in 2. PMID:25474746

  2. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

    PubMed

    Haj, Christeene G; Sumariwalla, Percy F; Hanuš, Lumír; Kogan, Natalya M; Yektin, Zhana; Mechoulam, Raphael; Feldmann, Mark; Gallily, Ruth

    2015-10-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to ?(9)-tetrahydrocannabinol (?(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-?, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive ?(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a ?(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-? production by macrophages); in vivo it led to suppression of production of TNF-? and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause ?(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. PMID:26272937

  3. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    PubMed Central

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-01-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155?nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies. PMID:26584637

  4. Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.

    PubMed

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Tziona, Paraskevi; Kourounakis, Panos N; Rekka, Eleni A

    2015-11-15

    Novel esters of non steroidal anti-inflammatory drugs, ?-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders. PMID:26494261

  5. CHF6001 I: a novel highly potent and selective phosphodiesterase 4 inhibitor with robust anti-inflammatory activity and suitable for topical pulmonary administration.

    PubMed

    Moretto, Nadia; Caruso, Paola; Bosco, Raffaella; Marchini, Gessica; Pastore, Fiorella; Armani, Elisabetta; Amari, Gabriele; Rizzi, Andrea; Ghidini, Eleonora; De Fanti, Renato; Capaldi, Carmelida; Carzaniga, Laura; Hirsch, Emilio; Buccellati, Carola; Sala, Angelo; Carnini, Chiara; Patacchini, Riccardo; Delcanale, Maurizio; Civelli, Maurizio; Villetti, Gino; Facchinetti, Fabrizio

    2015-03-01

    This study examined the pharmacologic characterization of CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a novel phosphodiesterase (PDE)4 inhibitor designed for treating pulmonary inflammatory diseases via inhaled administration. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity (IC50 = 0.026 ± 0.006 nM). CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (i.e., >40) and displayed >20,000-fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively inhibited (subnanomolar IC50 values) the release of tumor necrosis factor-? from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). Moreover, CHF6001 potently inhibited the activation of oxidative burst in neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon-? from CD4(+) T cells. In all these functional assays, CHF6001 was more potent than previously described PDE4 inhibitors, including roflumilast, UK-500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide]. When administered intratracheally to rats as a micronized dry powder, CHF6001 inhibited liposaccharide-induced pulmonary neutrophilia (ED50 = 0.205 ?mol/kg) and leukocyte infiltration (ED50 = 0.188 ?mol/kg) with an efficacy comparable to a high dose of budesonide (1 ?mol/kg i.p.). In sum, CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including asthma and chronic obstructive pulmonary disease. PMID:25576075

  6. Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents.

    PubMed

    Zheng, Suqing; Santosh Laxmi, Y R; David, Emilie; Dinkova-Kostova, Albena T; Shiavoni, Katherine H; Ren, Yanqing; Zheng, Ying; Trevino, Isaac; Bumeister, Ronald; Ojima, Iwao; Wigley, W Christian; Bliska, James B; Mierke, Dale F; Honda, Tadashi

    2012-05-24

    Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-? and IL-1? with potencies that are higher than those of bardoxolone methyl and TBE-31. PMID:22533790

  7. Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs

    PubMed Central

    Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

    2014-01-01

    Background Volatile oils obtained from lemon grass [Cymbopogon citratus (DC.) Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims In the present study, lemon grass essential oil (LGEO) was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis revealed two major components: geranial (42.2%), and neral (31.5%). The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs) (35–90 mm). IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally) significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg), which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for the treatment of fungal infections and skin inflammation that should be explored in future studies. PMID:25242268

  8. A Novel Anti-Inflammatory Effect for High Density Lipoprotein

    PubMed Central

    Cameron, Scott J.; Morrell, Craig N.; Bao, Clare; Swaim, AnneMarie F.; Rodriguez, Annabelle; Lowenstein, Charles J.

    2015-01-01

    High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis. PMID:26680360

  9. Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties.

    PubMed

    Ximenes, José Christian Machado; de Oliveira Gonçalves, Danilo; Siqueira, Rafaelly Maria Pinheiro; Neves, Kelly Rose Tavares; Santos Cerqueira, Gilberto; Correia, Alyne Oliveira; Félix, Francisco Hélder Cavalcante; Leal, Luzia Kalyne Almeida Moreira; de Castro Brito, Gerly Anne; da Graça Naffah-Mazzacorati, Maria; Viana, Glauce Socorro de Barros

    2013-07-01

    Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. It has a wide activity spectrum, reflecting on mechanisms of action that are not fully understood. The objectives of this work were to study the effects of VA on acute models of nociception and inflammation in rodents. VA (0.5, 1, 10, 25, and 50 mg/kg, p.o.) effects were evaluated on the carrageenan-induced paw edema, carrageenan-induced peritonitis, and plantar tests in rats, as well as by the formalin test in mice. The HE staining and immunohistochemistry assay for TNF-? in carrageenan-induced edema, from paws of untreated and VA-treated rats, were also carried out. VA decreased paw edema after carrageenan, and maximum effects were seen with doses equal to or higher than 10 mg/kg. VA also preserved the tissue architecture as assessed by the HE staining. Immunohistochemical studies revealed that VA significantly reduced TNF-? immunostaining in carrageenan-inflamed rat paws. In addition, the anti-inflammatory action of VA was potentiated by pentoxifylline (a phosphodiesterase inhibitor, known to inhibit TNF-? production), but not by sodium butyrate or by suberoylanilide hydroxamic acid (SAHA), nonspecific and specific inhibitors, respectively, of histone deacetylase. However, the decrease in the number of positive TNF-? cells in the rat paw was drastically potentiated in the VA + SAHA associated group. VA also reduced leukocytes and myeloperoxidase (MPO) releases to the peritoneal exudate, in the carrageenan-induced peritonitis. Although in the formalin test, VA inhibited both phases, the inhibition was mainly on the second phase. Furthermore, VA significantly increased the reaction time to thermal stimuli, as assessed by the plantar test. VA is a multi-target drug, presenting potent antinociceptive and anti-inflammatory properties at a lower dose range. These effects are partly dependent upon its inhibitory action on TNF-?-related pathways. However, the participation of the HDAC inhibition with the VA anti-inflammatory action cannot be ruled out. Inflammatory processes are associated with free radical damage and oxidative stress, and their blockade by VA could also explain the present results. PMID:23584602

  10. Design and synthesis of aloe-emodin derivatives as potent anti-tyrosinase, antibacterial and anti-inflammatory agents.

    PubMed

    Liu, Jinbing; Wu, Fengyan; Chen, Changhong

    2015-11-15

    Twenty aloe-emodin derivatives were designed, synthesized, and their biological activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, compounds with thiosemicarbazide moiety showed more potent inhibitory effects than the other compounds. The structure-activity relationships (SARs) were preliminarily discussed. The inhibition mechanism of selected compounds 1 and 13 were investigated. The results showed compound 1 was reversible inhibitor, however, compound 13 was irreversible. Kinetic analysis indicated that compound 1 was competitive tyrosinase inhibitor. Furthermore, the antibacterial activities and anti-inflammatory activities of some selected compounds were also screened. The results showed that compound 3 exhibited more potent antibacterial activity than the aloe-emodin, compounds 5 and 6 possessed more potent anti-inflammatory activities than the diacerein. PMID:26471089

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

    PubMed Central

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

    2010-01-01

    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. PMID:20161797

  12. One-Step Synthesis of Chiral Oxindole-type Analogues with Potent Anti-inflammatory and Analgesic Activities

    PubMed Central

    Sun, Yulong; Liu, Jia; Jiang, Xianxing; Sun, Tao; Liu, Luping; Zhang, Xiaoyuan; Ding, Shaoli; Li, Jingyi; Zhuang, Yan; Wang, Yiqing; Wang, Rui

    2015-01-01

    Here we report a facile approach to synthesize highly optically active oxindole-type analogues with both high yield and enantioselectivity. This single-step synthesis strategy represents a substantial improvement upon existing methods that are often involved with multi-step routes and have suboptimal atomic economy. One such compound, namely Q4c, showed remarkable in vivo anti-inflammatory activity with efficiency approaching to that of a steroidal compound dexamethasone. Moreover, Q4c alleviated pain in mouse models with comparable activity to morphine. Further investigation suggested that nitric oxide signaling pathway is involved in the anti-inflammatory and analgesic activities of Q4c. Notably, this is the first time that chiral oxindole-type analogues have been identified to be both anti-inflammatory and analgesic, and our study also paved the way for future development of oxindoles as drug candidates in this field. PMID:26324065

  13. Synthesis of rhodamine-labelled dieckol: its unique intracellular localization and potent anti-inflammatory activity.

    PubMed

    Kwak, Jong Hwan; He, Yanxia; Yoon, Byungkwon; Koo, Seyoung; Yang, Zhigang; Kang, Eun Ju; Lee, Bong Ho; Han, Seung-Yun; Yoo, Yung Choon; Lee, Kyung Bok; Kim, Jong Seung

    2014-11-01

    Rhodamine-labelled dieckol (1) synthesized through a click reaction was found to be localized in the endoplasmic reticulum (ER) of RAW 264.7 cells. Anti-inflammatory activity of compound was considerably greater than that of dieckol itself. PMID:25034407

  14. A Short Peptide That Mimics the Binding Domain of TGF-?1 Presents Potent Anti-Inflammatory Activity

    PubMed Central

    Vaz, Emília R.; Fujimura, Patrícia T.; Araujo, Galber R.; da Silva, Carlos A. T.; Silva, Rangel L.; Cunha, Thiago M.; Lopes-Ferreira, Mônica; Lima, Carla; Ferreira, Márcio J.; Cunha-Junior, Jair P.; Taketomi, Ernesto A.; Goulart, Luiz R.; Ueira-Vieira, Carlos

    2015-01-01

    The transforming growth factor beta 1 (TGF-?1) is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-?1-mediated immune dysfunction may lead to pathological conditions, such as inflammation. Chronic inflammatory process is characterized by a continuous release of pro-inflammatory cytokines, and the inhibition or the blockage of these cytokines signaling pathways are considered a target treatment. In this context, despite the high numbers of TGF-?-targeted pathways, the inducible regulatory T cells (iTreg) to control inflammation seems to be a promising approach. Our aim was to develop novel peptides through phage display (PhD) technology that could mimic TGF-?1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-?1 recombinant as a competitor during elution step. We have selected a peptide that seems to play an important role on cellular differentiation and modulation of TNF-? and IL-10 cytokines. The synthetic pm26TGF-?1 peptide tested in PBMC significantly down-modulated TNF-? and up-regulated IL-10 responses, leading to regulatory T cells (Treg) phenotype differentiation. Furthermore, the synthetic peptide was able to decrease leukocytes rolling in BALB/C mice and neutrophils migration during inflammatory process in C57BL/6 mice. These data suggest that this peptide may be useful for the treatment of inflammatory diseases, especially because it displays potent anti-inflammatory properties and do not exhibit neutrophils’ chemoattraction. PMID:26312490

  15. Berteroin Present in Cruciferous Vegetables Exerts Potent Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin

    PubMed Central

    Jung, Yoo Jin; Jung, Jae In; Cho, Han Jin; Choi, Myung-Sook; Sung, Mi-Kyung; Yu, Rina; Kang, Young-Hee; Park, Jung Han Yoon

    2014-01-01

    Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of ?B? (I?B?) and nuclear factor-?B p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor ? activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent. PMID:25393510

  16. Berteroin present in cruciferous vegetables exerts potent anti-inflammatory properties in murine macrophages and mouse skin.

    PubMed

    Jung, Yoo Jin; Jung, Jae In; Cho, Han Jin; Choi, Myung-Sook; Sung, Mi-Kyung; Yu, Rina; Kang, Young-Hee; Park, Jung Han Yoon

    2014-01-01

    Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of ?B? (I?B?) and nuclear factor-?B p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor ? activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent. PMID:25393510

  17. Potent Anti-Inflammatory Activity of Carbohydrate Polymer with Oxide of Zinc

    PubMed Central

    Moreno-Eutimio, Mario Adan; Nieto-Velázquez, Nayeli Goreti; Espinosa-Monroy, Lorena; Torres-Ramos, Yessica; Montoya-Estrada, Araceli; Cueto, Jorge; Hicks, Juan Jose; Acosta-Altamirano, Gustavo

    2014-01-01

    Pebisut is a biological adhesive composed of naturally occurring carbohydrates combined with zinc oxide (ZnO) initially used as a coadjutant for healing of anastomoses. Likewise some works demonstrated that carbohydrate complexes exerts anti-inflammatory activity and it is widely known that ZnO modulate inflammation. However, the direct effects of Pebisut on isolated cells and acute inflammatory responses remained to be investigated. The present study evaluated anti-inflammatory effect of Pebisut using lipopolysaccharide (LPS) stimulated human mononuclear cells, chemotaxis, and cell infiltration in vivo in a murine model of peritonitis. Our data show that human cells treated with different dilutions of Pebisut release less IL-6, IL-1?, and IL-8 after LPS stimuli compared with the control treated cells. In addition, Pebisut lacked chemotactic activity in human mononuclear cells but was able to reduce chemotaxis towards CCL2, CCL5, and CXCL12 that are representative mononuclear cells chemoattractants. Finally, in a murine model of peritonitis, we found less number of macrophages (F4/80+) and T lymphocytes (CD3+) in peritoneal lavages from animals treated with Pebisut. Our results suggest that Pebisut has anti-inflammatory activity, which might have a beneficial effect during anastomoses healing or wounds associated with excessive inflammation. PMID:24757670

  18. Potent anti-inflammatory activity of pheophytin a derived from edible green alga, Enteromorpha prolifera (Sujiao-nori).

    PubMed

    Okai, Y; Higashi-Okai, K

    1997-06-01

    Recently, a chlorophyll-related compound, pheophytin a, has been identified from an edible green alga, Enteromorpha prolifera (Sujiao-nori in Japanese) as a potent suppressive substance against genotoxin-induced umu C gene expression in a tester bacteria (Okai and Higashi-Okai, 1997, J. Sci. Food Agricul. 71, 531-535). In the present study, anti-inflammatory effects of pheophytin a from Enteromorpha prolifera have been analyzed using in vitro and in vivo experiments. 1. Pheophytin a suppressed the production of superoxide anion (O2-) in mouse macrophages induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) using the cytochrome C reduction method. 2. Pheophytin a caused a suppressive effect against formyl-Met-Leu-Phe, (FMLP)-induced chemotaxis of human polymorphonuclear leukocytes (PMNs) in Boyden's chamber experiment. 3. Pheophytin a exhibited a significant suppression against TPA-induced inflammatory reaction such as edema formation in BALB/c mouse ear. These results suggest that pheophytin a from Enteromorpha prolifera has a potent anti-inflammatory activity. PMID:9467755

  19. New Coumarin Derivatives as Potent Selective COX-2 Inhibitors: Synthesis, Anti-Inflammatory, QSAR, and Molecular Modeling Studies.

    PubMed

    Dawood, Dina H; Batran, Rasha Z; Farghaly, Thoraya A; Khedr, Mohammed A; Abdulla, Mohamed M

    2015-12-01

    Two new series of coumarin derivatives incorporating thiazoline and thiazolidinone moieties were designed, synthesized, and investigated in vivo for their anti-inflammatory activities using the carrageenan-induced rat paw edema model and in vitro for their inhibitory activities against the human cyclooxygenase (COX)-1 and COX-2 isoforms. Most of the synthesized compounds demonstrated exceptionally high in vivo anti-inflammatory activity and displayed superior GI safety profiles (0-7% ulceration) as compared to indomethacin. All the bioactive compounds showed in vitro high affinity and selectivity toward the COX-2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78??M. The ethyl thiosemicarbazone 2b, thiazoline derivatives 3a, 3b, 5b, 6a, and 7f, and the thiazolidinone compounds 8b and 9a showed the highest in vivo and in vitro anti-inflammatory activities with remarkable COX-2 selectivity. Quantitative structure-activity relationship study (QSAR) was done and resulted in a highly predictive power R(2) (0.908). A molecular docking study revealed a relationship between the docking affinity and the biological results. PMID:26462142

  20. Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents.

    PubMed

    Ali, Yakub; Alam, Mohammad Sarwar; Hamid, Hinna; Husain, Asif; Bano, Sameena; Dhulap, Abhijeet; Kharbanda, Chetna; Nazreen, Syed; Haider, Saqlain

    2015-03-01

    Nineteen novel piperine based triazoles have been synthesized using click chemistry approach and were tested for in vivo anti-inflammatory activity. The most active compounds were evaluated for in vitro TNF-? expression. Compounds 3g and 3f were found to show significant in vivo inhibition of inflammation, 80.40% and 76.71%, respectively after 5 h in comparison to piperine (54.72%) and the standard drug indomethacin (77.02%) without causing any damage to the stomach. Compounds 3g and 3f suppressed TNF-? level by 73.73% and 70.64%, respectively and protein expression of COX-2, NF-?B and TNF-? more than indomethacin. Moreover, the compound 3g was found to show significant analgesic activity of 54.09% which was comparable with the indomethacin (57.43%). PMID:25596479

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

    PubMed Central

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

    2012-01-01

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

  2. Anti-allergic and anti-inflammatory properties of a potent histamine H1 receptor antagonist, desloratadine citrate disodium injection, and its anti-inflammatory mechanism on EA.hy926 endothelial cells.

    PubMed

    Jie, Qiong; Kodithuwakku, Nandani Darshika; Yuan, Xin; He, Guangwei; Chen, Meiling; Xu, Shuhong; Wu, Yulin

    2015-05-01

    The present study, demonstrates that, desloratadine citrate disodium injection (DLC) possesses antihistaminic, anti-allergic and anti-inflammatory properties and elucidates its molecular mechanisms of anti-inflammatory properties. In vitro antihistamine activity of DLC was determined in guinea pig isolated tissues. In vivo antihistamine effects were evaluated after following intravenous administration of DLC in mice with histamine- induced paw edema and in rats with increased capillary permeability. Anti-allergic effects were assessed through passive cutaneous anaphylactic (PCA) reactions in sensitized rodents and ovalbumin-induced allergic rhinitis in rats. Anti-inflammatory properties and molecular mechanisms of DLC were determined on histamine- and lipopolysaccharide (LPS)-induced EA.hy926 endothelial cells. DLC exhibited significant and reversible inhibition of histamine-induced contractions of isolated guinea pig ileum with pA2 value of 8.88. Histamine-induced paw edema and increased capillary permeability were notably inhibited by DLC intravenous administration. In the model of PCA reactions, DLC showed significant activity in a dose-dependent nd potently inhibited both the early-phase and late-phase allergic reaction of ovalbumin-induced allergic rhinitis in rats. DLC alleviated the rhinitis symptoms and inhibited inflammatory cell infiltration, IL-4 and protein leakage in nasal lavage fluid (NLF). In EA.hy926 cells, DLC significantly inhibited the histamine- and LPS- induced IL-6 and IL-8 production and P-selectin and intercellular cell adhesion molecule-1 (ICAM-1) expression. Moreover, DLC reduced translocation of nuclear factor-kappaB (NF-?B) to the nucleus in activated EA.hy926 cells. These results provide evidence that DLC possesses potent antihistaminic, anti-allergic and, anti-inflammatory properties via suppressing IL-6, IL-8, P-selectin and ICAM-1 expression. PMID:25704613

  3. Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism.

    PubMed

    Wei, Lin; Gao, Jiuxiang; Zhang, Shumin; Wu, Sijin; Xie, Zeping; Ling, Guiying; Kuang, Yi-Qun; Yang, Yongliang; Yu, Haining; Wang, Yipeng

    2015-07-01

    Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic ?-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-?, IL-1?, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics. PMID:26013823

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

    PubMed

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

    2013-01-15

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

  5. Anti-inflammatory activity of cinnamon (C. zeylanicum and C. cassia) extracts - identification of E-cinnamaldehyde and o-methoxy cinnamaldehyde as the most potent bioactive compounds.

    PubMed

    Gunawardena, Dhanushka; Karunaweera, Niloo; Lee, Samiuela; van Der Kooy, Frank; Harman, David G; Raju, Ritesh; Bennett, Louise; Gyengesi, Erika; Sucher, Nikolaus J; Münch, Gerald

    2015-03-01

    Chronic inflammation is a contributing factor in many age-related diseases. In a previous study, we have shown that Sri Lankan cinnamon (C. zeylanicum) was one of the most potent anti-inflammatory foods out of 115 foods tested. However, knowledge about the exact nature of the anti-inflammatory compounds and their distribution in the two major cinnamon species used for human consumption is limited. The aim of this investigation was to determine the anti-inflammatory activity of C. zeylanicum and C. cassia and elucidate their main phytochemical compounds. When extracts were tested in LPS and IFN-? activated RAW 264.7 macrophages, most of the anti-inflammatory activity, measured by down-regulation of nitric oxide and TNF-? production, was observed in the organic extracts. The most abundant compounds in these extracts were E-cinnamaldehyde and o-methoxycinnamaldehyde. The highest concentration of E-cinnamaldehyde was found in the DCM extract of C. zeylanicum or C. cassia (31 and 34 mg g(-1) of cinnamon, respectively). When these and other constituents were tested for their anti-inflammatory activity in RAW 264.7 and J774A.1 macrophages, the most potent compounds were E-cinnamaldehyde and o-methoxycinnamaldehyde, which exhibited IC?? values for NO with RAW 264.7 cells of 55 ± 9 ?M (7.3 ± 1.2 ?g mL(-1)) and 35 ± 9 ?M (5.7 ± 1.5 ?g mL(-1)), respectively; and IC?? values for TNF-? of 63 ± 9 ?M (8.3 ± 1.2 ?g mL(-1)) and 78 ± 16 ?M (12.6 ± 2.6 ?g mL(-1)), respectively. If therapeutic concentrations can be achieved in target tissues, cinnamon and its components may be useful in the treatment of age-related inflammatory conditions. PMID:25629927

  6. Potent anti-inflammatory effects of the narrow spectrum kinase inhibitor RV1088 on rheumatoid arthritis synovial membrane cells

    PubMed Central

    To, Wing S; Aungier, Susan R; Cartwright, Alison J; Ito, Kazuhiro; Midwood, Kim S

    2015-01-01

    Background and Purpose To investigate whether a narrow spectrum kinase inhibitor RV1088, which simultaneously targets specific MAPKs, Src and spleen tyrosine kinase (Syk), is more effective at inhibiting inflammatory signalling in rheumatoid arthritis (RA) than single kinase inhibitors (SKIs). Experimental Approach elisas were used to determine the efficacy of RV1088, clinically relevant SKIs and the pharmaceutical Humira on pro-inflammatory cytokine production by activated RA synovial fibroblasts, primary human monocytes and macrophages, as well as spontaneous cytokine synthesis by synovial membrane cells from RA patients. In human macrophages, RNAi knockdown of individual kinases was used to reveal the effect of inhibition of kinase expression on cytokine synthesis. Key Results RV1088 reduced TNF-?, IL-6 and IL-8 production in all individual activated cell types with low, nM, IC50s. SKIs, and combinations of SKIs, were significantly less effective than RV1088. RNAi of specific kinases in macrophages also caused only modest inhibition of pro-inflammatory cytokine production. RV1088 was also significantly more effective at inhibiting IL-6 and IL-8 production by monocytes and RA synovial fibroblasts compared with Humira. Finally, RV1088 was the only inhibitor that was effective in reducing TNF-?, IL-6 and IL-8 synthesis in RA synovial membrane cells with low nM IC50s. Conclusions and Implications This study demonstrates potent anti-inflammatory effect of RV1088, highlighting that distinct signalling pathways drive TNF-?, IL-6 and IL-8 production in the different cell types found in RA joints. As such, targeting numerous signalling pathways simultaneously using RV1088 could offer a more powerful method of reducing inflammation in RA than targeting individual kinases. PMID:25891413

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

    PubMed

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

    2013-01-01

    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

  8. Ethanol Extract of Peanut Sprout Exhibits a Potent Anti-Inflammatory Activity in Both an Oxazolone-Induced Contact Dermatitis Mouse Model and Compound 48/80-Treated HaCaT Cells

    PubMed Central

    Choi, Da-In; Choi, Jee-Young; Kim, Young Jee; Lee, Jee-Bum; Kim, Sun-Ouck; Shin, Hyong-Taek

    2015-01-01

    Background We developed an ethanol extract of peanut sprouts (EPS), a peanut sprout-derived natural product, which contains a high level of trans-resveratrol (176.75 µg/ml) and was shown to have potent antioxidant activity. Objective We evaluated the potential anti-inflammatory activity of EPS by measuring its antioxidant potential in skin. Methods The anti-inflammatory activity of EPS was tested using two models of skin inflammation: oxazolone (OX)-induced contact dermatitis in mice and compound 48/80-treated HaCaT cells. As biomarkers of skin inflammation, cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) levels were measured. Results OX-induced contact dermatitis was suppressed markedly in mice that were treated with an ointment containing 5% EPS as evidenced by a decrease in the extent of scaling and thickening (p<0.05) and supported by a histological study. COX-2 (messenger RNA [mRNA] and protein) and NGF (mRNA) levels, which were upregulated in the skin of OX-treated mice, were suppressed markedly in the skin of OX+EPS-treated mice. Consistent with this, compound 48/80-induced expression of COX-2 (mRNA and protein) and NGF (mRNA) in HaCaT cells were suppressed by EPS treatment in a dose-dependent manner. As an inhibitor of NF-?B, I?B protein levels were dose-dependently upregulated by EPS. Fluorescence-activated cell sorting (FACS) analysis revealed that EPS scavenged compound 48/80-induced reactive oxygen species (ROS) in HaCaT cells. Conclusion EPS exerts a potent anti-inflammatory activity via its anti-oxidant activity in both mouse skin and compound 48/80-treated HaCaT cells in vitro. Compound 48/80-treated HaCaT cells are a useful new in vitro model of skin inflammation. PMID:25834352

  9. Antioxidant and anti-inflammatory effects of Marrubium alysson extracts in high cholesterol-fed rabbits

    PubMed Central

    Essawy, Soha S.; Abo-elmatty, Dina M.; Ghazy, Nabila M.; Badr, Jihan M.; Sterner, Olov

    2013-01-01

    The antioxidant and anti-inflammatory effects of hexane (HEXA), chloroform (CHLORO), ethyl acetate (EA) and total alcoholic (T. ALCOH) extracts of Marrubium alysson in hypercholesterolemic-fed rabbits were evaluated. Hypercholesterolemia was induced in male rabbits by high cholesterol diet (HCD) (350 mg/kg) for 8 weeks. Hypercholesterolemic rabbits were allocated into groups, treated with simvastatin (SIM 5 mg/kg), different extracts of M. alysson at two doses of 250, 500 mg/kg. A normal control group and an HCD control one were used for comparison. Lipid profile, as well as oxidized low density lipoprotein-cholesterol (ox-LDL-C), myeloperoxidase activity (MPO) and superoxide anion production (O2•?), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were also evaluated. In addition, histological examination of ascending aorta was performed. We found dyslipidemia associated with significant increases in ox-LDL-C 123.5 ± 9.8 nmol MDA/mg non-HDL, MPO activity 0.08 ± 0.05 U/100 mg tissue and O2•? production 3.5 ± 0.3 nmol cytochrome C reduced/min/g tissue × 10?4 in hypercholerterolemic rabbits. In addition, there was a significant increase in CRP 6.6 ± 0.49 ?mol/L and MCP-1 190.9 ± 6.4 pg/ml and its mRNA expression in HCD. Intima appeared thick with thick plaques surrounding the intima and luminal narrowing. SIM, EA and HEXA extracts of M. alysson had lipid lowering effect, decrease in ox-LDL-C, MPO, O2•?, CRP and MCP-1 mRNA expression with improvement of the pathological picture. M. alysson enhanced the stability of plaque, had lipid lowering, anti-inflammatory and antioxidant activities. PMID:25473336

  10. Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities.

    PubMed

    Jiao, Heng; Shang, Xiaohui; Dong, Qi; Wang, Shuang; Liu, Xiaoyu; Zheng, Heng; Lu, Xiaoling

    2015-09-01

    As a source of potent anti-inflammatory traditional medicines, the quantitative chromatographic fingerprints of sea urchin shell polysaccharides were well established via pre-column derivatization high performance liquid chromatography (HPLC) analysis. Based on the quantitative results, the content of fucose and glucose could be used as preliminary distinguishing indicators among three sea urchin shell species. Besides, the anti-inflammatory activities of the polysaccharides from sea urchin shells and their gonads were also determined. The gonad polysaccharide of Anthocidaris crassispina showed the most potent anti-inflammatory activity among all samples tested. PMID:26389925

  11. Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities

    PubMed Central

    Jiao, Heng; Shang, Xiaohui; Dong, Qi; Wang, Shuang; Liu, Xiaoyu; Zheng, Heng; Lu, Xiaoling

    2015-01-01

    As a source of potent anti-inflammatory traditional medicines, the quantitative chromatographic fingerprints of sea urchin shell polysaccharides were well established via pre-column derivatization high performance liquid chromatography (HPLC) analysis. Based on the quantitative results, the content of fucose and glucose could be used as preliminary distinguishing indicators among three sea urchin shell species. Besides, the anti-inflammatory activities of the polysaccharides from sea urchin shells and their gonads were also determined. The gonad polysaccharide of Anthocidaris crassispina showed the most potent anti-inflammatory activity among all samples tested. PMID:26389925

  12. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics.

    PubMed

    Luz, John Gately; Antonysamy, Stephen; Kuklish, Steven L; Condon, Bradley; Lee, Matthew R; Allison, Dagart; Yu, Xiao-Peng; Chandrasekhar, Srinivasan; Backer, Ryan; Zhang, Aiping; Russell, Marijane; Chang, Shawn S; Harvey, Anita; Sloan, Ashley V; Fisher, Matthew J

    2015-06-11

    Microsomal prostaglandin E synthase 1 (mPGES-1) is an ?-helical homotrimeric integral membrane inducible enzyme that catalyzes the formation of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). Inhibition of mPGES-1 has been proposed as a therapeutic strategy for the treatment of pain, inflammation, and some cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the potential circumvention of cardiovascular risks associated with anti-inflammatory cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway downstream of PGH2 synthesis and avoiding suppression of antithrombotic prostacyclin production. We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to understand their structure-activity relationships and provide a framework for the rational design of improved molecules. In addition, we developed a light-scattering-based thermal stability assay to identify molecules for crystallographic studies. PMID:25961169

  13. Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study

    PubMed Central

    Di Caprio, Roberta; Di Costanzo, Luisa; Monfrecola, Giuseppe

    2015-01-01

    Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200?mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40?mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-?, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-?, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled. PMID:25977597

  14. Synthesis of N-benzenesulfonamide-1H-pyrazoles bearing arylsulfonyl moiety: novel celecoxib analogs as potent anti-inflammatory agents.

    PubMed

    Abdel-Aziz, Hatem A; Al-Rashood, Khalid A; ElTahir, Kamal Eldin H; Suddek, Ghada M

    2014-06-10

    The reaction of arylsulfones 11a-d with hydrazonoyl chloride derivative 13 furnished celecoxib analogs 4-(3-acetyl-5-aryl-4-(arylsulfonyl)-1H-pyrazol-1-yl)benzenesulfonamides 15a-d, respectively. Oximes 16a, b and hydrazones 17a, b were prepared by reacting sulfones 11a, b with hydroxyl amine and phenyl hydrazine, respectively. The anti-inflammatory activity of the synthesized compounds showed that, 5-(4-bromophenyl)-4-(phenylsulfonyl)pyrazole 15c and 5-(4-bromophenyl)-4-(4-tolylsulfonyl)pyrazole 15d exhibited excellent anti-inflammatory activity with ED50 = 68 ± 2.2 and 51 ± 0.7 ?M/kg, respectively, higher than that of celecoxib (ED50 = 86 ± 1.1 ?M/kg) after 3 h with acceptable ulcer index. In addition, the LD50 of 15c and 15d is 7.1 mM/kg for each, and 9.8 mM/kg for celecoxib. Compound 15d appeared selectivity index (COX-2/COX-1) almost the half of celecoxib while 15c is non-selective for COX-2. Compound 15c with ED50 = 80 ± 2.8 ?M/kg showed a significant analgesic activity when compared with celecoxib (ED50 = 70 ± 3.9 ?M/kg) after 2 h whereas 15b (ED50 = 50 ± 1.2 ?M/kg) and 15d (ED50 = 69 ± 2.7 ?M/kg) seemed to be more potent than celecoxib (ED50 = 156 ± 4.8 ?M/kg) but with a shorter duration (0.5 h). PMID:24794773

  15. Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence.

    PubMed

    Gapeyev, A B; Mikhailik, E N; Chemeris, N K

    2008-04-01

    Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency and power dependence of anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was found. Single whole-body exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h after zymosan injection reduced both the footpad edema and local hyperthermia on average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other frequencies from the frequency range of 37.5-70 GHz were less effective or not effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2), the effect had bell-shaped dependence on exposure duration with a maximum at 20-40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the effect dependence on exposure duration to a linear one. Combined action of cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial additive effect of decrease in footpad edema. Combined action of antihistamine clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that arachidonic acid metabolites and histamine are involved in realization of anti-inflammatory effects of low-intensity EHF EMR. PMID:18044738

  16. PGH1, the Precursor for the Anti-Inflammatory Prostaglandins of the 1-series, Is a Potent Activator of the Pro-Inflammatory Receptor CRTH2/DP2

    PubMed Central

    Schröder, Ralf; Xue, Luzheng; Konya, Viktoria; Martini, Lene; Kampitsch, Nora; Whistler, Jennifer L.; Ulven, Trond; Heinemann, Akos; Pettipher, Roy; Kostenis, Evi

    2012-01-01

    Prostaglandin H1 (PGH1) is the cyclo-oxygenase metabolite of dihomo-?-linolenic acid (DGLA) and the precursor for the 1-series of prostaglandins which are often viewed as “anti-inflammatory”. Herein we present evidence that PGH1 is a potent activator of the pro-inflammatory PGD2 receptor CRTH2, an attractive therapeutic target to treat allergic diseases such as asthma and atopic dermatitis. Non-invasive, real time dynamic mass redistribution analysis of living human CRTH2 transfectants and Ca2+ flux studies reveal that PGH1 activates CRTH2 as PGH2, PGD2 or PGD1 do. The PGH1 precursor DGLA and the other PGH1 metabolites did not display such effect. PGH1 specifically internalizes CRTH2 in stable CRTH2 transfectants as assessed by antibody feeding assays. Physiological relevance of CRTH2 ligation by PGH1 is demonstrated in several primary human hematopoietic lineages, which endogenously express CRTH2: PGH1 mediates migration of and Ca2+ flux in Th2 lymphocytes, shape change of eosinophils, and their adhesion to human pulmonary microvascular endothelial cells under physiological flow conditions. All these effects are abrogated in the presence of the CRTH2 specific antagonist TM30089. Together, our results identify PGH1 as an important lipid intermediate and novel CRTH2 agonist which may trigger CRTH2 activation in vivo in the absence of functional prostaglandin D synthase. PMID:22442685

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

    PubMed Central

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

    2012-01-01

    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

  18. Potent Elastase Inhibitors from Cyanobacteria: Structural Basis and Mechanisms Mediating Cytoprotective and Anti-inflammatory Effects in Bronchial Epithelial Cells

    PubMed Central

    Salvador, Lilibeth A.; Taori, Kanchan; Biggs, Jason S.; Jakoncic, Jean; Ostrov, David A.; Paul, Valerie J.; Luesch, Hendrik

    2013-01-01

    We discovered new structural diversity to a prevalent, yet medicinally underappreciated, cyanobacterial protease inhibitor scaffold and undertook comprehensive protease profiling to reveal potent and selective elastase inhibition. SAR and X-ray cocrystal structure analysis allowed a detailed assessment of critical and tunable structural elements. To realize the therapeutic potential of these cyclodepsipeptides, we probed the cellular effects of a novel and representative family member, symplostatin 5 (1), which attenuated the downstream cellular effects of elastase in an epithelial lung airway model system, alleviating clinical hallmarks of chronic pulmonary diseases such as cell death, cell detachment and inflammation. This compound attenuated the effects of elastase on receptor activation, proteolytic processing of the adhesion protein ICAM-1, NF-?B activation and transcriptomic changes, including the expression of pro-inflammatory cytokines IL1A, IL1B and IL8. Compound 1 exhibited activity comparable to the clinically-approved elastase inhibitor sivelestat in short-term assays and demonstrated superior sustained activity in longer-term assays. PMID:23350733

  19. Beta caryophyllene and caryophyllene oxide, isolated from Aegle marmelos, as the potent anti-inflammatory agents against lymphoma and neuroblastoma cells.

    PubMed

    Sain, Soumyadeep; Naoghare, Pravin K; Devi, S Saravana; Daiwile, Atul; Krishnamurthi, K; Arrigo, P; Chakrabarti, T

    2014-03-01

    Aegle marmelos (Indian Bael) is a tree which belongs to the family of Rutaceae. It holds a prominent position in both Indian medicine and Indian culture. We have screened various fractions of Aegle marmelos extracts for their anticancer properties using in vitro cell models. Gas chromatography-Mass spectrometry (GC-MS) was employed to analyze the biomolecules present in the Aegle marmelos extract. Jurkat and human neuroblastoma (IMR-32) cells were treated with different concentrations of the fractionated Aegle marmelos extracts. Flow cytometric analysis revealed that optimal concentration (50 µg/ml) of beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract can induce apoptosis in Jurkat cell line. cDNA expression profiling of pro-apoptotic and anti-apoptotic genes was carried out using real time PCR (RT-PCR). Down-regulation of anti-apoptotic genes (bcl-2, mdm2, cox2 and cmyb) and up-regulation of pro-apoptotic genes (bax, bak1, caspase-8, caspase-9 and ATM) in Jurkat and IMR-32 cells treated with the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract revealed the insights of the downstream apoptotic mechanism. Furthermore, in-silico approach was employed to understand the upstream target involved in the induction of apoptosis by the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract. Herein, we report that beta caryophyllene and caryophyllene oxide isolated from Aegle marmelos can act as potent anti-inflammatory agents and modulators of a newly established therapeutic target, 15-lipoxygenase (15-LOX). Beta caryophyllene and caryophyllene oxide can induce apoptosis in lymphoma and neuroblastoma cells via modulation of 15-LOX (up-stream target) followed by the down-regulation of anti-apoptotic and up-regulation of pro-apoptotic genes. PMID:24484210

  20. A high performance liquid chromatography with ultraviolet method for Eschweilera nana leaves and their anti-inflammatory and antioxidant activities

    PubMed Central

    Outuki, Priscila M.; Lazzeri, Nides S.; de Francisco, Lizziane M. B.; Bersani-Amado, Ciomar A.; Ferreira, Izabel C. P.; Cardoso, Mara Lane C.

    2015-01-01

    Background: Eschweilera nana Miers is a tree widely distributed in Cerrado, Brazil. Objective: In this study, we aimed to describe its phytochemical properties and antioxidant and topical anti-inflammatory effects for the first time, as well validate an high performance liquid chromatography with ultraviolet/visible (HPLC-UV-Vis) method for the separation and quantification of the main components (hyperoside and rutin) in the hydroalcoholic extract of E. nana leaves. Materials and Methods: Structural identification of compounds in E. nana extract was performed by analysis of spectral data by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance and/or ESI/EM. The HPLC-UV-Vis method was validated according International Conference on Harmonization (ICH) parameters. The 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) method were used for determination of in vitro antioxidant activities and the croton oil-induced inflammation for evaluation of in vivo anti-inflammatory effects. Results: Hyperoside, rutin, ?-amirin, ?-amirin, ?-sitosterol, and stigmasterol were identified in the hydroalcoholic extract of E. nana leaves. HPLC-UV-Vis was validated according to ICH parameters. Furthermore, in vitro and in vivo assays demonstrated that the hydroalcoholic extract and methanol fraction showed significant antioxidant and topical anti-inflammatory effects, as they were able to reduce ear edema induced by croton-oil application. Conclusions: This research showed the first phytochemical study of E. nana extract and their biological activities may be associated with the presence of flavonoids in the extracts. PMID:26246741

  1. Mechanisms of LtxA (Leukotoxin), a Potent New Anti-Inflammatory Agent for the Treatment of Alopecia Areata.

    PubMed

    Kachlany, Scott C

    2015-11-01

    Alopecia areata is an autoimmune condition where activated, pro-inflammatory white blood cells (WBCs) attack the hair follicles, resulting in hair loss. Migration of these activated WBCs from the blood stream and into the follicle tissue requires interaction between the integrin, lymphocyte function-associated antigen-1 (LFA-1) on WBCs, and ICAM-1 on vascular endothelial cells. High levels of active LFA-1 are uniquely expressed on WBCs that are involved in autoimmune and inflammatory conditions. The natural biologic agent LtxA (Leukothera) preferentially targets and depletes disease activated and malignant WBCs by binding to active LFA-1. The experimental drug has demonstrated significant therapeutic efficacy against autoimmune/inflammatory conditions such as psoriasis and allergic asthma in mouse models for these diseases. In addition, when injected into rodents, rhesus macaques, and dogs, LtxA was demonstrated to be physiologically active, biologically specific, and extremely well-tolerated. LFA-1 is an attractive target for therapy because it is only normally present on WBCs and has been shown to be activated and overexpressed on WBCs that are responsible for autoimmune/inflammatory conditions. PMID:26551939

  2. [Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].

    PubMed

    Gapeev, A B; Lushnikov, K V; Shumilina, Iu V; Chemeris, N K

    2006-01-01

    The anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the action of the known anti-inflammatory drug sodium diclofenac and the antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local inflammatory reaction was induced by intraplantar injection of zymosan into the left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected intraperitoneally 30 min after the initiation of inflammation. The animals were whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of inflammation. The inflammatory reaction was assessed over 3 - 8 h after the initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the average by 26% as compared to the control. Hyperthermia of the inflamed paw decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by about 20%, which was comparable with the effect of a single therapeutic dose of diclofenac (3 - 5 mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2 mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The combined action of clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that both arachidonic acid metabolites and histamine are involved in the realization of anti-inflammatory effects of low-intensity PMID:17175917

  3. Extraction Optimization for Obtaining Artemisia capillaris Extract with High Anti-Inflammatory Activity in RAW 264.7 Macrophage Cells

    PubMed Central

    Jang, Mi; Jeong, Seung-Weon; Kim, Bum-Keun; Kim, Jong-Chan

    2015-01-01

    Plant extracts have been used as herbal medicines to treat a wide variety of human diseases. We used response surface methodology (RSM) to optimize the Artemisia capillaris Thunb. extraction parameters (extraction temperature, extraction time, and ethanol concentration) for obtaining an extract with high anti-inflammatory activity at the cellular level. The optimum ranges for the extraction parameters were predicted by superimposing 4-dimensional response surface plots of the lipopolysaccharide- (LPS-) induced PGE2 and NO production and by cytotoxicity of A. capillaris Thunb. extracts. The ranges of extraction conditions used for determining the optimal conditions were extraction temperatures of 57–65°C, ethanol concentrations of 45–57%, and extraction times of 5.5–6.8?h. On the basis of the results, a model with a central composite design was considered to be accurate and reliable for predicting the anti-inflammation activity of extracts at the cellular level. These approaches can provide a logical starting point for developing novel anti-inflammatory substances from natural products and will be helpful for the full utilization of A. capillaris Thunb. The crude extract obtained can be used in some A. capillaris Thunb.-related health care products. PMID:26075271

  4. Enhanced Anti-inflammatory Effects of ?-irradiated Pig Placenta Extracts

    PubMed Central

    Kim, Youn Kyu; Kim, Chang-Kyu; Oh, Yu-Kyung

    2015-01-01

    Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with ?-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-?, IL-1?, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, ?-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-?, IL-1?, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that ?-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines.

  5. Potent Anti-Inflammatory Activity of Pyrenocine A Isolated from the Marine-Derived Fungus Penicillium paxilli Ma(G)K

    PubMed Central

    Toledo, Thaís Regina; Dejani, Naiara N.; Monnazzi, Luis Gustavo Silva; Kossuga, Miriam H.; Berlinck, Roberto G. S.; Sette, Lara D.; Medeiros, Alexandra I.

    2014-01-01

    Very little is known about the immunomodulatory potential of secondary metabolites isolated from marine microorganisms. In the present study, we characterized pyrenocine A, which is produced by the marine-derived fungus Penicillium paxilli Ma(G)K and possesses anti-inflammatory activity. Pyrenocine A was able to suppress, both pretreatment and posttreatment, the LPS-induced activation of macrophages via the inhibition of nitrite production and the synthesis of inflammatory cytokines and PGE2. Pyrenocine A also exhibited anti-inflammatory effects on the expression of receptors directly related to cell migration (Mac-1) as well as costimulatory molecules involved in lymphocyte activation (B7.1). Nitrite production was inhibited by pyrenocine A in macrophages stimulated with CpG but not Poly I:C, suggesting that pyrenocine A acts through the MyD88-dependent intracellular signaling pathway. Moreover, pyrenocine A is also able to inhibit the expression of genes related to NF?B-mediated signal transduction on macrophages stimulated by LPS. Our results indicate that pyrenocine A has promissory anti-inflammatory properties and additional experiments are necessary to confirm this finding in vivo model. PMID:24574582

  6. Linear, Mannitol-Based Poly(anhydride-esters) with High Ibuprofen Loading and Anti-Inflammatory Activity.

    PubMed

    Stebbins, Nicholas D; Yu, Weiling; Uhrich, Kathryn E

    2015-11-01

    Sugar alcohols, such as mannitol and xylitol, are biocompatible polyols that have been used to make highly cross-linked polyester elastomers and dendrimers for tissue engineering and drug delivery. However, research that utilizes the secondary hydroxyl groups as sites for pendant bioactive attachment and subsequent polymerization is limited. This work is the first report of a linear, completely biodegradable polymer with a sugar alcohol backbone and chemically incorporated pendant bioactives that exhibits sustained bioactive release and high bioactive loading (?70%). With four pendant esters per repeat unit, this poly(anhydride-ester) has high loading and biodegrades into three biocompatible products: bioactive, sugar alcohol, and alkyl-based diacid. Ibuprofen serves as a representative bioactive, whereas mannitol is a representative polyol. Polymerization was achieved through reaction with (trimethylsilyl)ethoxyacetylene. Drug release via polymer degradation was quantified by high performance liquid chromatography. Additionally, a cytocompatibility study with fibroblast cells was performed to elucidate the polymer's suitability for in vivo use and a cyclooxygenase-2 (COX-2) assay was performed on the degradation media to ensure that released ibuprofen retained its anti-inflammatory activity. This work enables the future development of novel, biodegradable polymers exhibiting two key features: (i) polymer backbones with easily modified pendant groups, such as targeting moieties, and (ii) high drug loading using a multitude of bioactive classes. PMID:26450447

  7. Similar Anti-Inflammatory Acute Responses from Moderate-Intensity Continuous and High-Intensity Intermittent Exercise

    PubMed Central

    Cabral-Santos, Carolina; Gerosa-Neto, José; Inoue, Daniela Sayuri; Panissa, Valéria Leme Gonçalves; Gobbo, Luís Alberto; Zagatto, Alessandro Moura; Campos, Eduardo Zapaterra; Lira, Fábio Santos

    2015-01-01

    The purpose of this study was to compare the effect of high-intensity intermittent exercise (HIIE) versus volume matched steady state exercise (SSE) on inflammatory and metabolic responses. Eight physically active male subjects completed two experimental sessions, a 5-km run on a treadmill either continuously (70% vVO2max) or intermittently (1:1 min at vVO2max). Blood samples were collected at rest, immediately, 30 and 60 minutes after the exercise session. Blood was analyzed for glucose, non-ester fatty acid (NEFA), uric acid, lactate, cortisol, and cytokines (IL-6, IL-10 and TNF-?) levels. The lactate levels exhibited higher values immediately post-exercise than at rest (HIIE 1.34 ± 0.24 to 7.11 ± 2.85, and SSE 1.35 ± 0.14 to 4.06±1.60 mmol·L-1, p < 0.05), but HIIE promoted higher values than SSE (p < 0.05); the NEFA levels were higher immediately post-exercise than at rest only in the SSE condition (0.71 ± 0.04 to 0.82±0.09 mEq/L, respectively, p < 0.05), yet, SSE promoted higher values than HIIE immediately after exercise (HIIE 0.72±0.03 vs SSE 0.82±0.09 mEq·L-1, p < 0.05). Glucose and uric acid levels did not show changes under the different conditions (p > 0.05). Cortisol, IL-6, IL-10 and TNF-? levels showed time-dependent changes under the different conditions (p < 0.05), however, the area under the curve of TNF-? in the SSE were higher than HIIE (p < 0.05), and the area under the curve of IL-6 in the HIIE showed higher values than SSE (p < 0.05). In addition, both exercise conditions promote increased IL-10 levels and IL-10/TNF-? ratio (p < 0.05). In conclusion, our results demonstrated that both exercise protocols, when volume is matched, promote similar inflammatory responses, leading to an anti-inflammatory status; however, the metabolic responses are different. Key points Metabolic contribution of both exercise, HIIE and SSE, was different. Both protocols leading to an anti-inflammatory status. HIIE induce a higher energy expenditure take into account total session duration. PMID:26664283

  8. A versatile high throughput screening system for the simultaneous identification of anti-inflammatory and neuroprotective compounds.

    PubMed

    Hansen, Elizabeth; Krautwald, Martina; Maczurek, Annette E; Stuchbury, Grant; Fromm, Phillip; Steele, Megan; Schulz, Oliver; Garcia, Obdulio Benavente; Castillo, Julian; Körner, Heinrich; Münch, Gerald

    2010-01-01

    In many chronic neurodegenerative diseases including Frontotemporal Dementia and Alzheimer's disease (AD), microglial activation is suggested to be involved in pathogenesis or disease progression. Activated microglia secrete a variety of cytokines, including interleukin-1beta, interleukin-6, and tumor necrosis factor as well as reactive oxygen and nitrogen species (ROS/RNS). ROS and RNS contribute to alterations in neuronal glucose uptake, inhibition of mitochondrial enzymes, a decrease in mitochondrial membrane potential, impaired axonal transport, and synaptic signaling. In addition, ROS act as signaling molecules in pro-inflammatory redox-active signal transduction pathways. To establish a high throughput screening system for anti-inflammatory and neuroprotective compounds, we have constructed an "Enhanced Green Fluorescent protein" (EGFP) expressing neuronal cell line and set up a murine microglia/neuron co-culture system with these EGFP expressing neuronal cells. We show that microglia activation leads to neuronal cell death, which can be conveniently measured by loss of neuronal EGFP fluorescence. Moreover, we used this system to test selected polyphenolic compounds for their ability to downregulate inflammatory markers and to protect neurons against microglial insult. We suggest that this system might allow accelerated drug discovery for the treatment of inflammation-mediated neurodegenerative diseases. PMID:20110593

  9. Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo

    PubMed Central

    Aerts, J.; Vandenbroucke, R. E.; Dera, R.; Balusu, S.; Van Wonterghem, E.; Moons, L.; Libert, C.; Dehaen, W.; Arckens, L.

    2015-01-01

    A hydroxypyrone-based matrix metalloproteinase (MMP) inhibitor was synthesized and assayed for its inhibitory capacity towards a panel of ten different MMPs. The compound exhibited selective inhibition towards MMP-12. The effects of inhibition of MMP-12 on endotoxemia and inflammation-induced blood-cerebrospinal fluid barrier (BCSFB) disruption were assessed both in vitro and in vivo. Similar to MMP-12 deficient mice, inhibitor-treated mice displayed significantly lower lipopolysaccharide- (LPS-) induced lethality compared to vehicle treated controls. Following LPS injection Mmp-12 mRNA expression was massively upregulated in choroid plexus tissue and a concomitant increase in BCSFB permeability was observed, which was restricted in inhibitor-treated mice. Moreover, an LPS-induced decrease in tight junction permeability of primary choroid plexus epithelial cells was attenuated by inhibitor application in vitro. Taken together, this hydroxypyrone-based inhibitor is selective towards MMP-12 and displays anti-inflammatory activity in vitro and in vivo. PMID:26351407

  10. Low volume-high intensity interval exercise elicits antioxidant and anti-inflammatory effects in humans.

    PubMed

    Wadley, Alex J; Chen, Yu-Wen; Lip, Gregory Y H; Fisher, James P; Aldred, Sarah

    2016-01-01

    The purpose of the present study was to compare acute changes in oxidative stress and inflammation in response to steady state and low volume, high intensity interval exercise (LV-HIIE). Untrained healthy males (n = 10, mean ± s: age 22 ± 3 years; VO2MAX 42.7 ± 5.0 ml · kg(-1) · min(-1)) undertook three exercise bouts: a bout of LV-HIIE (10 × 1 min 90% VO2MAX intervals) and two energy-matched steady-state cycling bouts at a moderate (60% VO2MAX; 27 min, MOD) and high (80% VO2MAX; 20 min, HIGH) intensity on separate days. Markers of oxidative stress, inflammation and physiological stress were assessed before, at the end of exercise and 30 min post-exercise (post+30). At the end of all exercise bouts, significant changes in lipid hydroperoxides (LOOH) and protein carbonyls (PCs) (LOOH (nM): MOD +0.36; HIGH +3.09; LV-HIIE +5.51 and PC (nmol · mg(-1) protein): MOD -0.24; HIGH -0.11; LV-HIIE -0.37) were observed. Total antioxidant capacity (TAC) increased post+30, relative to the end of all exercise bouts (TAC (µM): MOD +189; HIGH +135; LV-HIIE +102). Interleukin (IL)-6 and IL-10 increased post+30 in HIGH and LV-HIIE only (P < 0.05). HIGH caused the greatest lymphocytosis, adrenaline and cardiovascular response (P < 0.05). At a reduced energy cost and physiological stress, LV-HIIE elicited similar cytokine and oxidative stress responses to HIGH. PMID:25915178

  11. Anti-inflammatory sesquiterpene pyridine alkaloids from Tripterygium wilfordii.

    PubMed

    Gao, Chang; Huang, Xiao-Xiao; Bai, Ming; Wu, Jie; Li, Jian-You; Liu, Qing-Bo; Li, Ling-Zhi; Song, Shao-Jiang

    2015-09-01

    During a screening procedure involving higher plants to find novel candidates for use as anti-inflammatory agents, Tripterygium wilfordii Hook. f. was shown to exhibit considerable inhibitory activity. Five new sesquiterpene pyridine alkaloids, tripterygiumines S-W (1-4,15), along with 14 known dihydroagarofuran derivatives, were isolated from the roots of the T. wilfordii Hook. f. Their structures were established by extensive use of spectroscopic techniques, including 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. All compounds were evaluated for their anti-inflammatory activity by measuring the nitric oxide production by the LPS-induced murine macrophage cell line RAW264.7. It was found that 1, 5, and 19 possessed potent nitric oxide inhibitory activity with IC50 values ranging from 2.99 to 28.80 ?M, without any effect on the cell viability of RAW264.7 cells. Accordingly, compounds 1, 5, and 19, especially 5, were identified as promising candidates for further scientific investigation of their potential use as anti-inflammatory agents. PMID:26071072

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

    PubMed Central

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

    2014-01-01

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

  13. Anti-inflammatory effect of water-soluble complex of 1'-acetoxychavicol acetate with highly branched ?-1,3-glucan on contact dermatitis.

    PubMed

    Li, Jiawei; Aizawa, Yui; Hiramoto, Keiichi; Kasahara, Emiko; Tsuruta, Daisuke; Suzuki, Toshio; Ikeda, Atsushi; Azuma, Hideki; Nagasaki, Takeshi

    2015-02-01

    The anti-inflammatory effect on contact dermatitis of the water solubilized 1'-Acetoxychavicol Acetate (ACA) by complexation with ?-1,3-glucan isolated form Aureobasidium pullulans black yeast is reported. It is well-known that ACA possesses a function to inhibit the activation of NF-?B by which genes encoding proinflammatory cytokines, chemokines, and growth factors are regulated. However, because ACA is quite insoluble in water, its usefulness has been extremely limited. On the other hand, a triple-helical polysaccharide ?-1,3-glucan can include hydrophobic compounds into intrastrand hydrophobic cavity and solubilize poorly water-soluble compounds. In this study, solubilization of ACA by complexation with highly branched ?-1,3-glucan was achieved. The effect of anti-inflammatory response of water-soluble ACA complex with ?-1,3-glucan was confirmed in vitro and in vivo. PMID:25661358

  14. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits

    PubMed Central

    2013-01-01

    Background Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play an important role in the early progression of it. The aim of the present study was to evaluate the effect of kaempferol on the inflammatory molecules such as E-selectin (E-sel), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in high cholesterol induced atherosclerosis rabbit models. Methods Thirty male New Zealand white (NZW) rabbits were randomly divided into five groups, control group, model group, fenofibrate (12mg/kg) group and kaempferol groups (150 mg/kg and 30 mg/kg). The rabbits were fed with a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, serum tumour-necrosis factor-alpha (TNF-?) and serum interleukin-1beta (IL-1?) were detected at the end of the sixth and tenth week. Malonaldehyde (MDA) level and superoxide dismutase (SOD) activity in serum were also determined. Lesion areas of the aorta were measured with morphometry analysis after ten weeks. Gene expression of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas was determined by RT-PCR (reverse transcription-polymerase chain reaction). Immunohistochemical staining was employed to measure protein expression of E-sel, ICAM-1, VCAM-1 and MCP-1. Results Model rabbits fed with ten weeks of high-cholesterol diet developed significant progression of atherosclerosis. Compared with the control, levels of blood lipids, TNF-?, IL-1? and MDA increased markedly in serum of model rabbits, while SOD levels decreased. Gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in atherosclerotic aortas increased remarkably in model group. However, comparing to the model rabbits, levels of TNF-?, IL-1? and MDA decreased significantly and serum SOD activity increased, gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas decreased significantly with the treatment of kaempferol. Conclusion Kaempferol shows anti-atherosclerotic effect by modulating the gene and protein expression of inflammatory molecules. PMID:23895132

  15. Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits.

    PubMed

    El-Sheakh, Ahmed R; Ghoneim, Hamdy A; Suddek, Ghada M; Ammar, El-Sayed M

    2015-12-01

    Flavocoxid is a mixed extract containing baicalin and catechin, and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. In the present study, an experimental rabbit model of hypercholesterolemia was developed and the effects of flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-cholesterol-diet (HCD)-fed group, HCD plus flavocoxid (20 mg/kg/day), or HCD plus atorvastatin (10 mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs, LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both tumor necrosis factor-alpha (TNF-?) and nuclear factor (NF)-?B. Rabbits in flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and LDL-C did not significantly affected by flavocoxid treatment. Additionally, flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to acetylcholine and decreased the elevated I/M ratio. This effect was confirmed by histopathological examination of the aorta. Moreover, flavocoxid effectively suppresses the release of inflammatory markers. In conclusion, these findings demonstrated that flavocoxid would be useful in preventing oxidative stress, inflammation, and vascular dysfunction induced by HCD. PMID:26341793

  16. Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties.

    PubMed

    Gordon, Scott M; McKenzie, Benjamin; Kemeh, Georgina; Sampson, Maureen; Perl, Shira; Young, Neal S; Fessler, Michael B; Remaley, Alan T

    2015-12-01

    Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to low density lipoprotein cholesterol (LDL-C) lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n = 10) with normal LDL-C (<130 mg/dL), who were treated with rosuvastatin (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, large high density lipoprotein (HDL-L), and small HDL (HDL-S) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the rosuvastatin treatment was an increase in ?-1-antirypsin (A1AT) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7-fold increase in HDL-L associated A1AT. Molecular modeling predictions indicated that the hydrophobic reactive center loop of A1AT, the functional domain responsible for its protease inhibitor activity, is likely involved in lipid binding and association with HDL was found to protect A1AT against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of A1AT with HDL enhances its antiprotease activity, preventing elastase induced production of tumor necrosis factor ?. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between A1AT and HDL. The up-regulation of A1AT on HDL enhances its anti-inflammatory functionality, which may contribute to the non-lipid lowering beneficial effects of statins. PMID:26483418

  17. Anti-Inflammatory Iridoids of Botanical Origin

    PubMed Central

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

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

  18. PXS-4681A, a potent and selective mechanism-based inhibitor of SSAO/VAP-1 with anti-inflammatory effects in vivo.

    PubMed

    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

    2013-11-01

    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

  19. Evaluation of Caesalpinia bonducella flower extract for anti-inflammatory action in rats and its high performance thin layer chromatography chemical fingerprinting

    PubMed Central

    Arunadevi, Rathinam; Murugammal, Shanmugam; Kumar, Dinesh; Tandan, Surendra Kumar

    2015-01-01

    Objective: The study is aimed to evaluate anti-inflammatory activity of Caesalpinia bonducella Fleming (Caesalpiniaceae) flower extract (CBFE) and to study its effect on radiographic outcome in adjuvant induced arthritis and authentication by high performance thin layer chromatography (HPTLC) chemical fingerprinting. Materials and Methods: CBFE was administered orally (30, 100, and 300 mg/kg b.wt.) and tested for its anti-inflammatory activity in carrageenan-induced inflammation, cotton pellet induced chronic granulomatous inflammation and autacoids-induced inflammation. Effect on radiographic outcome was tested in adjuvant-induced arthritis. CBFE was HPTLC fingerprinted in suitable solvent system. Result: In carrageenan-induced inflammation, CBFE produced significant inhibition in edema volume at all the doses (30, 100 and 300 mg/kg b.wt.) and percentage of inhibition was 28.68, 31.00, and 22.48, respectively as compared to control at 5 h of its administration. In cotton pellet granuloma assay, CBFE significantly decreased the granuloma weight at 300 mg/kg dose level by 22.53%. CBFE (300 mg/kg) caused significant inhibition by 37.5, 44.44, and 35.29% edema volume, at ½, 1 and 3 h after 5-hydroxytryptamine injection, respectively. Radiographic score of animals treated with 300 mg/kg CBFE was significantly decreased when compared to arthritic control animals. Conclusion: The extract was found to possess significant anti-inflammatory activity. CBFE treatment improved the bony architecture in adjuvant-induced arthritis in rats. The developed HPTLC fingerprint would be helpful in the authentication of C. bonducella flower extract. PMID:26729956

  20. Lactoferrin : an anti?inflammatory molecule released by apoptotic cells to inhibit granulocyte migration 

    E-print Network

    Bournazou, Irini

    2010-11-24

    Apoptosis is a physiological form of cell death. It is a highly evolutionarily conserved process that is non-inflammatory or anti-inflammatory in nature. This anti-inflammatory nature of apoptosis is evident by the ...

  1. Anti-inflammatory activity and qualitative analysis of different extracts of Maytenus obscura (A. Rich.) Cuf. by high performance thin layer chromatography method

    PubMed Central

    Alajmi, Mohamed F.; Alam, Perwez

    2014-01-01

    Objective To perform aqueous ethanol soluble fraction (AESF) and dichloromethane extract of aerial parts of Maytenus obscura (A. Rich.) Cuf. using high performance thin layer chromatography (HPTLC) and to test anti-inflammatory activity of these extracts. Methods HPTLC studies were carried out using CAMAG HPTLC system equipped with Linomat IV applicator, TLC scanner 3, Reprostar 3, CAMAG ADC 2 and WIN CATS-4 software were used. The anti-inflammatory activity was tested by injecting different groups of rats (6 each) with formalin in hind paw and measuring the edema volume before and 1 h later formalin injection. Control group received saline i.p. The extracts treatment was injected i.p. in doses of 100 and 200 mg/kg 1 h before formalin administration. Indomethacin (30 mg/kg) was used as standard. Results The results of preliminary phytochemical studies confirmed the presence of protein, lipid, carbohydrate, phenol, flavonoid, saponin, triterpenoid, alkaloid and anthraquinone in both extracts. Chromatography was performed on glass-backed silica gel 60 F254 HPTLC plates with the green solvents toluene: ethyacetate: glacial acetic acid (5:3:0.2, v/v/v) as mobile phase. HPTLC finger printing of AESF revealed major eight peaks with Rf values in the range of 0.28 to 0.80 and the dichloromethane revealed major 11 peaks with Rf values in the range of 0.12 to 0.76. The purity of sample was confirmed by comparing the absorption spectra at start, middle and end position of the band. Treatment of rats (i.p.) with AESF and dichloromethane in doses of 100 and 200 mg/kg inhibited singnificantly (P<0.05, n=6) formalin-induced inflammation by 50%, 55.9%, 45.5%, and 51.4%, respectively. Conclusions HPTLC finger printing of AESF and dichloromethane of Maytenus obscura revealed eight major spots for alcoholic extracts and nine major spots for dichloromethane extracts. These HPTLC profiles may be of great usefulness in the quality control of herbal products containing these extracts. The anti-inflammatory activity of both extracts also revealed the medicinal importance of these extracts. The plant can be further explored for the isolation of phytoconstituents having anti-inflammatory activity. PMID:25182287

  2. First evidence for the anti-inflammatory activity of fucoxanthin in high-fat-diet-induced obesity in mice and the antioxidant functions in PC12 cells.

    PubMed

    Tan, Cong-ping; Hou, Yun-hua

    2014-04-01

    Obesity, characterized as a state of low-level inflammation, is a powerful determinant influencing the development of insulin resistance and progression to type 2 diabetes. The purpose of the present study was to investigate the anti-inflammatory activity of fucoxanthin in experimental high-fat-diet-induced obesity in mice and antioxidant activity in PC12 cells under oxidative stress situation. The anti-inflammatory potential of fucoxanthin in the regulation of maleic dialdehyde (MDA), polymorphonuclear cells (PMNs), interleukin-1? (IL-1?), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-?), and cyclooxygenase-2 (COX-2) was determined by ELISA. Fucoxanthin significantly inhibited obesity-induced upregulation of the production of IL-1?, TNF-?, iNOS, and COX-2. Moreover, fucoxanthin suppressed MDA and infiltration of PMNs. The protective effects were associated with lack of hypertrophy and crown-like structures in mammary gland. At the same time, fucoxanthin showed an advantage of antioxidant activity in PC12 cells under oxidative stress situation. These results suggest that supplementation of fucoxanthin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications. PMID:24146106

  3. Structural Insights into the Interaction Between a Potent Anti-Inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1

    SciTech Connect

    Kuo, Nai-Wei; Gao, Yong; Schill, Megan S.; Isern, Nancy G.; Dupureur, Cynthia M.; Liwang, Patricia J.

    2014-01-30

    Chemokines play important roles in the immune system, not only recruiting leukocytes to the site of infection and inflammation but also guiding cell homing and cell development. The soluble poxvirusencoded protein vCCI, a CC chemokine inhibitor, can bind to human CC chemokines tightly to impair the host immune defense. This protein has no known homologs in eukaryotes, and may represent a potent method to stop inflammation. Previously, our structure of the vCCI:MIP-1? complex indicated that vCCI uses negatively charged residues in ?-sheet II to interact with positively charged residues in the MIP-1?N-terminus, 20’s region and 40’s loop. However, the interactions between vCCI and other CC chemokines have not yet been fully explored. Here, we used NMR and fluorescence anisotropy to study the interaction between vCCI and eotaxin-1 (CCL11), another CC chemokine that is an important factor in the asthma response. NMR results reveal that the binding pattern is very similar to the vCCI:MIP-1?complex, and suggest that electrostatic interactions provide a major contribution to binding. Fluorescence anisotropy results on variants of eotaxin-1 further confirm the critical roles of the charged residues in eotaxin. Compared to wild-type eotaxin, single, double, or triple mutations at these critical charged residues weaken the binding. One exception is the K47A mutation that exhibits increased affinity for vCCI, which can be explained structurally. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1, MIP-1? and RANTES, were determined as 1.09 nM, 1.16 nM, and 0.22 nM, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and different CC chemokines.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22364136

  5. Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial

    PubMed Central

    Kåss, Anita; Hollan, Ivana; Fagerland, Morten Wang; Gulseth, Hans Christian; Torjesen, Peter Abusdal; Førre, Øystein Torleiv

    2015-01-01

    Objectives Gonadotropin-releasing hormone (GnRH) and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA) onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels. Methods We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99). Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1–2; 3mg days 3–5) or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed. Results The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP), improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0?010). By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP?3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism ‘Good-responses’ (19% vs. 0%, P = 0.026). Tumor necrosis factor-?, interleukin-1?, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15. Adverse event rates were similar between groups. Conclusions GnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in RA. Trial Registration ClinicalTrials.gov NCT00667758 PMID:26460564

  6. Synthesis of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives as potent anti-inflammatory agents and inhibitors of monocyte-to-macrophage transformation.

    PubMed

    Gannarapu, Malla Reddy; Vasamsetti, Sathish Babu; Punna, Nagender; Royya, Naresh Kumar; Pamulaparthy, Shanthan Rao; Nanubolu, Jagadeesh Babu; Kotamraju, Srigiridhar; Banda, Narsaiah

    2014-03-21

    A series of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives 7a-h and 9a-h were synthesized starting from sodium salt of saccharin 1 in series of steps. Final compounds 7a-h and 9a-h were evaluated for the anti-inflammatory activity and their ability to inhibit monocyte-to-macrophage transformation. Compounds 7e, 9b, 9e and 9h showed impressive anti-inflammatory activities (TNF-?, IL-8 and MCP-1) at micro molar concentration which was found to be better than positive control i.e., piroxicam. Compound 9e marginally and compound 9h significantly inhibited PMA-induced MMP-9 gelatinase activity. Also compounds 9e and 9h greatly inhibited the PMA-induced monocyte-to-macrophage transformation, a pre-requisite step in the formation of atheroma. PMID:24531227

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

    PubMed

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

    2012-06-01

    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

  8. De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities

    PubMed Central

    Ahn, Mija; Hwang, Eunha; Sohn, Hoik; Park, Hyo-Nam; Lee, Eunjung; Seo, Ji-Hyung; Cheong, Chaejoon; Nam, Ky-Youb; Hyun, Jae-Kyung; Jeong, Ki-Woong; Kim, Yangmee; Shin, Song Yub; Bang, Jeong Kyu

    2013-01-01

    Background Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability. Methodology/Principal Findings In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(?)- and N(?)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. Conclusion/Significance The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics. PMID:24302996

  9. Anti-inflammatory effects of novel sinomenine derivatives.

    PubMed

    Zhao, Zijian; Xiao, Jing; Wang, Jiancheng; Dong, Wanrong; Peng, Zhihong; An, Delie

    2015-12-01

    Sinomenine is an isoquinoline-type alkaloid found in Sinomenium acutum (Thunb.) Rehd. et Wils and S. acutum (Thunb.) Rehd. et Wils var. cinereum Rehd. et Wils. When used as a medicine, this compound exhibits anti-inflammatory properties; however, sinomenine's use as a medication is limited by side effects, a short half-life, and low efficacy. Owing to these limits, attempts have been made to synthesize sinomenine derivatives with enhanced efficacy. In this study, the anti-inflammatory effects of novel sinomenine derivatives (S1a-S1f) were examined on the basis of lipopolysaccharide-induced inflammatory factor expression in Raw264.7 cells, dimethylbenzene-induced ear oedema, and Evan's blue leakage in mice, and carrageenan-induced paw oedema in rats. Compared with sinomenine, the derivatives significantly inhibited the expression of the inflammatory factors IL-1? and IL-6 at the transcriptional and translational levels. Topical application of 3.250mg/kg of the derivatives also alleviated ear oedema. Compared with the vehicle, the derivatives significantly inhibited carrageenan-induced rat paw oedema after 6h. Among the derivatives, S1a exhibited the most potent anti-inflammatory activity. S1a also significantly increased the sinomenine-induced inhibition of Evan's blue leakage. Thus, S1a may elicit the strongest anti-inflammatory effects of the tested compounds. Based on these results, further development of this compound may be warranted. PMID:26525983

  10. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-01

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-?) and nuclear factor kappa B (NF-?B-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-? production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-? and NO. Analog 2 has a pronounced inhibitory effect on NF-?B-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself. PMID:26051520

  11. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties.

    PubMed

    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder

    2015-12-01

    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Anti-cancer: We examined the effects of NOSH-sulindac on the growth properties of 12 human cancer cell lines of six different tissue origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH-sulindac. SOD activity was significantly lowered by sulindac but increased by NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Sulindac increased plasma TNF? whereas this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold greater than that of sulindac. NOSH-sulindac inhibited cell proliferation, induced apoptosis, and caused G2/M cell cycle block. These results demonstrate that NOSH-sulindac is gastrointestinal safe, and maintains the anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of its parent compound sulinsac, with anti-growth activity against a wide variety of human cancer cells. PMID:26298203

  12. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties

    PubMed Central

    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder

    2015-01-01

    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6 h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5 h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5 h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Anti-cancer: We examined the effects of NOSH-sulindac on the growth properties of 12 human cancer cell lines of six different tissue origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH-sulindac. SOD activity was significantly lowered by sulindac but increased by NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Sulindac increased plasma TNF? whereas this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold greater than that of sulindac. NOSH-sulindac inhibited cell proliferation, induced apoptosis, and caused G2/M cell cycle block. These results demonstrate that NOSH-sulindac is gastrointestinal safe, and maintains the anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of its parent compound sulinsac, with anti-growth activity against a wide variety of human cancer cells. PMID:26298203

  13. Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.

    PubMed

    Mostafa, Dina Mahmoud; Ammar, Nagwa Mohammed; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; Hussein, Rehab Ali; Awad, Gamal; El-Awdan, Sally Abdul-Wanees

    2015-01-01

    Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-?-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance. PMID:25895614

  14. Role of effective composition on antioxidant, anti-inflammatory, sedative-hypnotic capacities of 6 common edible Lilium varieties.

    PubMed

    Wang, Tingting; Huang, Hanhan; Zhang, Yao; Li, Xia; Li, Hongfa; Jiang, Qianqian; Gao, Wenyuan

    2015-04-01

    Nine Lilium samples (belong to 6 different cultivars with different maturity stage) were qualitatively and quantitatively analyzed of total phenolics (TP), total flavonoids (TF), total saponins (TS), total carbohydrates (TC, polysaccharides), and soluble proteins contents (SP), and the monomeric components were quantified utilizing high-performance liquid chromatography with photodiode array detector (HPLC-PAD) associated with liquid chromatography-mass spectrometry (HPLC-MS). Antioxidant activity (reducing power and DPPH radical scavenging activity), anti-inflammatory (xylene-induced mouse ear edema detumescent assay and carrageenan-induced mouse paw edema detumescent assay), and sedative-hypnotic capacities (sodium pentobarbital-induced sleep assay) were comparatively evaluated in mouse model. Additionally, correlation analysis and principal component analysis were carried out to detect clustering and elucidate relationships between components' concentrations and bioactivities to clarify the role of effective composition. Lilium bulbs in later maturity stage preliminary evidenced higher saponins content, and lower phenolic acids and flavonoids content. The result demonstrated that Lilium bulbs generally had distinct antioxidant, anti-inflammatory, and sedative-hypnotic capacities. Varieties statistically differed (P < 0.05) in chemical composition and bioactivities. Lilium varieties of Dongbei and Lanzhou presented potent sedative-hypnotic effect and anti-inflammatory activity. The antioxidant capacity was related to the phenolic acids and flavonoids contents, the anti-inflammatory and sedative-hypnotic capacities were related to the saponins content. This is first study presenting comprehensive description of common edible Lilium bulbs' chemical compositions, sedative-hypnotic, and anti-inflammatory capacities grown in China. It would informatively benefit the genetic selection and cultivated optimization of Lilium varieties to improve nutritional quality, and promote Lilium bulbs as a therapeutic functional food worldwide. PMID:25702713

  15. The anti-inflammatory effects of levocetirizine--are they clinically relevant or just an interesting additional effect?

    PubMed

    Walsh, Garry M

    2009-12-01

    Levocetirizine, the R-enantiomer of cetirizine dihydrochloride has pharmacodynamically and pharmacokinetically favourable characteristics, including rapid onset of action, high bioavailability, high affinity for and occupancy of the H1-receptor, limited distribution, minimal hepatic metabolism together with minimal untoward effects. Several well conducted randomised clinical trials have demonstrated the effectiveness of levocetirizine for the treatment of allergic rhinitis and chronic idiopathic urticaria in adults and children. In addition to the treatment for the immediate short-term manifestations of allergic disease, there appears to be a growing trend for the use of levocetirizine as long-term therapy. In addition to its being a potent antihistamine, levocetirizine has several documented anti-inflammatory effects that are observed at clinically relevant concentrations that may enhance its therapeutic benefit. This review will consider the potential or otherwise of the reported anti-inflammatory effects of levocetirizine to enhance its effectiveness in the treatment of allergic disease. PMID:20066054

  16. Problems in selection of topical anti-inflammatory corticosteroids

    PubMed Central

    Stewart, Wm. D.; Runikis, J. O.; Verma, S. C.; Wallace, S.

    1973-01-01

    Desonide, a non-fluorinated topical corticosteroid (16-alpha-hydroxyprednisolone acetonide), is compared with its fluorinated analogue, triamcinolone acetonide, as to vasoconstriction ability and epidermal penetration rate. Clinical effectiveness of desonide is further assessed by means of a double-blind paired comparison with an accepted potent fluorinated steroid, betamethasone 17-valerate. It is demonstrated that fluorination of the steroid molecule is not necessary to achieve potent topical anti-inflammatory effect. Vasoconstriction and epidermal penetration are not enhanced by fluorination in the drugs studied. PMID:4682636

  17. Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

    PubMed Central

    Bala, Suman; Sharma, Neha; Saini, Vipin

    2014-01-01

    Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. PMID:25383223

  18. Bioactive peptide from Pyropia yezoensis and its anti-inflammatory activities.

    PubMed

    Lee, Hyun-Ah; Kim, In-Hye; Nam, Taek-Jeong

    2015-12-01

    Pyropia yezoensis (P. yezoensis) is an important marine algae. Its high protein content serves as a good source of biologically active peptides. Potent inhibitory effects on the production of inflammatory mediators were observed in a bioactive peptide derived from P. yezoensis (peptide from P. yezoensis; PPY1), as demonstrated in lipopolysaccharide (LPS)?stimulated macrophages. The present study showed that peptide concentrations ranging from 250 to 1,000 ng/ml had no significant cytotoxicity in the cell viability assay when applied to the RAW 264.7 cells for 24 h. PPY1 completely inhibited LPS?stimulated nitric oxide (NO) release in a dose?dependent manner. Fluorescence intensity, corresponding to intracellular reactive oxygen species (ROS) produced by 10 ng/ml LPS?stimulated cells, significantly shifted, indicating that the peptide reduced the level of ROS. Furthermore, PPY1 exerted potent inhibitory activity to reduce the release of pro?inflammatory cytokines (inducible NO synthase, cyclooxygenase?2, interleukin?1? and tumor necrosis factor??) in LPS?stimulated macrophages in a dose?dependent manner. These results also showed that the anti?inflammatory activity of PPY1 was associated with downregulation of extracellular signal?regulated kinase, protein 38, and c?jun NH2?terminal kinase phosphorylation in the mitogen?activated protein kinase pathways. In conclusion, PPY1 can have a significant role as an anti?inflammatory agent, with a potential for use in marine products. PMID:26497591

  19. Anti-inflammatory and pro-resolving properties of benzo-lipoxin A4 analogs

    PubMed Central

    Sun, Yee-Ping; Tjonahen, Eric; Keledjian, Raquel; Zhu, Min; Yang, Rong; Recchiuti, Antonio; Pillai, Padmini S; Petasis, Nicos A.; Serhan, Charles N.

    2009-01-01

    SUMMARY Lipoxins (LXs) are potent endogenous counter-regulatory lipid mediators that dampen acute inflammation and promote its resolution. Here, we present our investigation of a new class of thermally and metabolically stable benzo-LXA4 analogs that are potently anti-inflammatory and easier to synthesize. Replacement of the tetraene unit of native LXA4 with a benzo-fused ring system not only increases the thermal stability but also enables highly convergent and efficient syntheses of these analogs. In addition, they resist rapid catalysis and inactivation by eicosanoid oxidoreductase. Like native LXs, o-[9, 12]-benzo-?6-epi-LXA4, o-[9, 12]-benzo-deoxy-LXA4, m-[9, 12]-benzo-?6-epi-LXA4 and [9, 14]-benzo-?6-(R/S)-LXA4 demonstrated potent time-dependent reduction, at nanogram dosages, of PMN infiltration and pro-inflammatory cytokine generation in vivo in murine peritonitis and were organ protective in hind limb ischemia-reperfusion injury of the lung. The o-[9, 12]-benzo-?6-epi-LXA4 and m-[9, 12]-benzo-?6-epi-LXA4 were most potent in nanogram doses; both decreased PMN infiltration by ~32%, while o-[9, 12]-benzo-deoxy-LXA4 and [9, 15]-?6-(R/S)-LXA4 were less potent. The [9,12]- benzo-?6-epi-LXA4 also activated a lipoxin A4 GPCR and increased macrophage phagocytic activity. Taken together, these findings demonstrate a new generation of LXA4 stable analogs that are easy to synthesize and anti-inflammatory. These benzo-LXA4 analogs are promising tools for new therapeutic approaches as well as assessing endogenous mechanisms in anti-inflammation and resolution. PMID:19853429

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

    SciTech Connect

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

    2011-09-01

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

  1. Differentiating oxicam nonsteroidal anti-inflammatory drugs in phosphoglyceride monolayers.

    PubMed

    Czapla, Katarzyna; Korchowiec, Beata; Rogalska, Ewa

    2010-03-01

    Meloxicam, piroxicam, and tenoxicam belong to a highly potent oxicam group of nonsteroidal anti-inflammatory drugs. Whereas the structurally similar oxicams have different pharmacokinetics, treatment efficiency, and adverse effects, their common mechanism of action is the inhibition of a membrane enzyme, cyclooxygenase. Because the prerequisite for accessing the cyclooxygenase by the drugs is interaction with the membrane, the focus of the current study was a comparison of how meloxicam, piroxicam, and tenoxicam interact with lipid monolayers used as models of biological membranes. The monolayers were formed with 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol), 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-myristoyl-sn-glycero-3-phosphoethanolamine, and 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine. These systems were examined via surface pressure and surface electrical potential measurements, polarization modulation infrared reflection adsorption spectra, and Brewster angle microscopy. The three oxicams are differentiated in the monolayers; meloxicam shows the highest ability to modify membrane fluidity and surface potential, followed by piroxicam and tenoxicam. The dissimilarity of the biological activity of the oxicams may be linked to different interaction with the membrane, as revealed by the present study. PMID:20030324

  2. Structures and mechanism for the design of highly potent glucocorticoids.

    PubMed

    He, Yuanzheng; Yi, Wei; Suino-Powell, Kelly; Zhou, X Edward; Tolbert, W David; Tang, Xiaobo; Yang, Jing; Yang, Huaiyu; Shi, Jingjing; Hou, Li; Jiang, Hualiang; Melcher, Karsten; Xu, H Eric

    2014-06-01

    The evolution of glucocorticoid drugs was driven by the demand of lowering the unwanted side effects, while keeping the beneficial anti-inflammatory effects. Potency is an important aspect of this evolution as many undesirable side effects are associated with use of high-dose glucocorticoids. The side effects can be minimized by highly potent glucocorticoids that achieve the same treatment effects at lower doses. This demand propelled the continuous development of synthetic glucocorticoids with increased potencies, but the structural basis of their potencies is poorly understood. To determine the mechanisms underlying potency, we solved the X-ray structures of the glucocorticoid receptor (GR) ligand-binding domain (LBD) bound to its endogenous ligand, cortisol, which has relatively low potency, and a highly potent synthetic glucocorticoid, mometasone furoate (MF). The cortisol-bound GR LBD revealed that the flexibility of the C1-C2 single bond in the steroid A ring is primarily responsible for the low affinity of cortisol to GR. In contrast, we demonstrate that the very high potency of MF is achieved by its C-17? furoate group completely filling the ligand-binding pocket, thus providing additional anchor contacts for high-affinity binding. A single amino acid in the ligand-binding pocket, Q642, plays a discriminating role in ligand potency between MF and cortisol. Structure-based design led to synthesis of several novel glucocorticoids with much improved potency and efficacy. Together, these results reveal key structural mechanisms of glucocorticoid potency and provide a rational basis for developing novel highly potent glucocorticoids. PMID:24763108

  3. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-?B activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  4. Fructose 1,6-bisphosphate, a high-energy intermediate of glycolysis, attenuates experimental arthritis by activating anti-inflammatory adenosinergic pathway

    PubMed Central

    Veras, Flávio P.; Peres, Raphael S.; Saraiva, André L. L.; Pinto, Larissa G.; Louzada-Junior, Paulo; Cunha, Thiago M.; Paschoal, Jonas A. R.; Cunha, Fernando Q.; Alves-Filho, José C.

    2015-01-01

    Fructose 1,6-bisphosphate (FBP) is an endogenous intermediate of the glycolytic pathway. Exogenous administration of FBP has been shown to exert protective effects in a variety of ischemic injury models, which are attributed to its ability to sustain glycolysis and increase ATP production. Here, we demonstrated that a single treatment with FBP markedly attenuated arthritis, assessed by reduction of articular hyperalgesia, joint swelling, neutrophil infiltration and production of inflammatory cytokines, TNF and IL-6, while enhancing IL-10 production in two mouse models of arthritis. Our mechanistic studies showed that FBP reduces joint inflammation through the systemic generation of extracellular adenosine and subsequent activation of adenosine receptor A2a (A2aR). Moreover, we showed that FBP-induced adenosine generation requires hydrolysis of extracellular ATP through the activity of the ectonucleosides triphosphate diphosphohydrolase-1 (ENTPD1, also known as CD39) and ecto-5?-nucleotidase (E5NT, also known as CD73). In accordance, inhibition of CD39 and CD73 abolished anti-arthritic effects of FBP. Taken together, our findings provide a new insight into the molecular mechanism underlying the anti-inflammatory effect of FBP, showing that it effectively attenuates experimental arthritis by activating the anti-inflammatory adenosinergic pathway. Therefore, FBP may represent a new therapeutic strategy for treatment of rheumatoid arthritis (RA). PMID:26478088

  5. The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers.

    PubMed

    Bury, Matthew I; Fuller, Natalie J; Meisner, Jay W; Hofer, Matthias D; Webber, Matthew J; Chow, Lesley W; Prasad, Sheba; Thaker, Hatim; Yue, Xuan; Menon, Vani S; Diaz, Edward C; Stupp, Samuel I; Cheng, Earl Y; Sharma, Arun K

    2014-11-01

    Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings. PMID:25145852

  6. The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers

    PubMed Central

    Bury, Matthew I.; Fuller, Natalie J.; Meisner, Jay W.; Hofer, Matthias D.; Webber, Matthew J.; Chow, Lesley W.; Prasad, Sheba; Thaker, Hatim; Yue, Xuan; Menon, Vani S.; Diaz, Edward C.; Stupp, Samuel I.; Cheng, Earl Y.; Sharma, Arun K.

    2014-01-01

    Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings. PMID:25145852

  7. The detection and characterization of analgesics and anti-inflammatory drugs on high performance thin-layer chromatography plates using tandem mass spectrometry: application to drugs and metabolites in urine.

    PubMed

    Morden, W; Wilson, I D

    1996-01-01

    The application of tandem mass spectrometry to the analysis and identification of analgesics and non-steroidal anti-inflammatory drugs such as paracetamol, ibuprofen and indomethacin following thin-layer chromatography (TLC) is described. TLC was combined successfully with mass spectrometry and with tandem mass spectrometry using silica gel and diol-bonded silica gel high performance TLC plates. The diol-bonded phase was found to be superior for use with biological samples and enabled the identification of paracetamol, ibuprofen and salicylhippuric acid (the major metabolite of acetylsalicylic acid) in human urine extracts following normal therapeutic doses. PMID:9004530

  8. Small molecules with anti-inflammatory properties in clinical development.

    PubMed

    Hanke, Thomas; Merk, Daniel; Steinhilber, Dieter; Geisslinger, Gerd; Schubert-Zsilavecz, Manfred

    2016-01-01

    Inflammation is a crucial physiological response of our body to any kind of noxa be it an infection or tissue injury. However, this physiological process can be detrimental if dysregulated, and when the acute inflammatory response fails to resolve the cause of inflammation, there can be a switch to chronification. According to ICD 10 (WHO) over 3.000 diseases exist with the suffix "-itis" which terms an inflammatory disease. For the treatment of inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widespread drugs while glucocorticoids are among our strongest weapons against inflammation, making them emergency treatments for acute episodes of chronic inflammation. For the treatment of many inflammatory disorders, both are not satisfying. Consequently, industrial and academic research on anti-inflammatory drugs is very intensive. In this review, we evaluate current treatments and unmet needs of chronic inflammatory diseases with high prevalence (rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disease, inflammatory bowel disease, and psoriasis), and systematically review small molecules with anti-inflammatory properties presently in clinical trials for the aforementioned diseases. As the pathophysiological knowledge of diseases increased over the last decades, a more specific intervention of inflammatory pathways becomes possible. After one hundred years of NSAIDs and over fifty years of glucocorticoids, more specific drugs for anti-inflammatory therapy such as roflumilast or fingolimod are rising. The aim of this article is to critically review the literature on small anti-inflammatory molecules in clinical trials to generate an idea of what we can expect in the future. PMID:26627986

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

    PubMed Central

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

    2013-01-01

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

  10. The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema

    PubMed Central

    Hajhashemi, Valiollah; Minaiyan, Mohsen; Banafshe, Hamid Reza; Mesdaghinia, Azam; Abed, Alireza

    2015-01-01

    Objective(s): Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms. Materials and Methods: We examined the anti-inflammatory effects of intraperitoneal (IP) and intracerebroventricular (ICV) administration of venlafaxine in the rat model of carrageenan-induced paw edema. Results: Our results showed that both IP (50 and 100 mg/kg) and ICV (50 and 100 ?g/rat) injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO) activity and interleukin (IL)-1? and tumor necrosis factor (TNF)-? production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP), an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti-inflammatory effect of venlafaxine. Conclusion: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti-inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1? and TNF-? production and decreases MPO activity in the site of inflammation. PMID:26351555

  11. Identification and evaluation of anti-inflammatory compounds from Kaempferia parviflora.

    PubMed

    Horigome, Satoru; Yoshida, Izumi; Tsuda, Aiko; Harada, Teppei; Yamaguchi, Akihiro; Yamazaki, Kumiko; Inohana, Shuichi; Isagawa, Satoshi; Kibune, Nobuyuki; Satoyama, Toshiya; Katsuda, Shin-ichi; Suzuki, Shinobu; Watai, Masatoshi; Hirose, Naoto; Mitsue, Takahiro; Shirakawa, Hitoshi; Komai, Michio

    2014-01-01

    The rhizome of Kaempferia parviflora has been used in traditional Thai medicine. In this study, we identified and compared specific compounds from the hexane extract of K. parviflora with those from other Zingiberaceous plants by using gas chromatography-mass spectrometry. We identified 5,7-dimethoxyflavone (DMF), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (TMF), estimated 3,5,7-trimethoxyflavone, 5-hydroxy-7,4'-dimethoxyflavone, 3,5,7,4'-tetramethoxyflavone, and investigated their anti-inflammatory effects in rat basophilic leukemia (RBL-2H3) cells stimulated with an IgE antigen or a calcium ionophore. We found that DMF and TMF more potently inhibited antigen-induced degranulation than did nobiletin, a well-known anti-inflammatory agent. In addition, compared to RBL-2H3 cells stimulated with a calcium ionophore, those treated with DMF and TMF showed more marked inhibition of the degranulation and the production and mRNA expression of inflammatory mediators. These results suggest that DMF and TMF inhibit an early step in the high-affinity IgE receptor signaling cascade rather than intracellular calcium release and protein kinase C activation. PMID:25035989

  12. Anti-inflammatory effects of five commercially available mushroom species determined in lipopolysaccharide and interferon-? activated murine macrophages.

    PubMed

    Gunawardena, Dhanushka; Bennett, Louise; Shanmugam, Kirubakaran; King, Kerryn; Williams, Roderick; Zabaras, Dimitrios; Head, Richard; Ooi, Lezanne; Gyengesi, Erika; Münch, Gerald

    2014-04-01

    Inflammation is a well-known contributing factor to many age-related chronic diseases. One of the possible strategies to suppress inflammation is the employment of functional foods with anti-inflammatory properties. Edible mushrooms are attracting more and more attention as functional foods since they are rich in bioactive compounds, but their anti-inflammatory properties and the effect of food processing steps on this activity has not been systematically investigated. In the present study, White Button and Honey Brown (both Agaricus bisporus), Shiitake (Lentinus edodes), Enoki (Flammulina velutipes) and Oyster mushroom (Pleurotus ostreatus) preparations were tested for their anti-inflammatory activity in lipopolysaccharide (LPS) and interferon-? (IFN-?) activated murine RAW 264.7 macrophages. Potent anti-inflammatory activity (IC??<0.1 mg/ml), measured as inhibition of NO production, could be detected in all raw mushroom preparations, but only raw Oyster (IC??=0.035 mg/ml), Shiitake (IC??=0.047 mg/ml) and Enoki mushrooms (IC??=0.099 mg/ml) showed also potent inhibition of TNF-? production. When the anti-inflammatory activity was followed through two food-processing steps, which involved ultrasonication and heating, a significant portion of the anti-inflammatory activity was lost suggesting that the anti-inflammatory compounds might be susceptible to heating or prone to evaporation. PMID:24262531

  13. Sucrose esters from Physalis peruviana calyces with anti-inflammatory activity.

    PubMed

    Franco, Luis A; Ocampo, Yanet C; Gómez, Harold A; De la Puerta, Rocío; Espartero, José L; Ospina, Luis F

    2014-11-01

    Physalis peruviana is a native plant from the South American Andes and is widely used in traditional Colombian medicine of as an anti-inflammatory medicinal plant, specifically the leaves, calyces, and small stems in poultice form. Previous studies performed by our group on P. peruviana calyces showed potent anti-inflammatory activity in an enriched fraction obtained from an ether total extract. The objective of the present study was to obtain and elucidate the active compounds from this fraction and evaluate their anti-inflammatory activity in vivo and in vitro. The enriched fraction of P. peruviana was purified by several chromatographic methods to obtain an inseparable mixture of two new sucrose esters named peruviose A (1) and peruviose B (2). Structures of the new compounds were elucidated using spectroscopic methods and chemical transformations. The anti-inflammatory activity of the peruvioses mixture was evaluated using ?-carrageenan-induced paw edema in rats and lipopolysaccharide-activated peritoneal macrophages. Results showed that the peruvioses did not produce side effects on the liver and kidneys and significantly attenuated the inflammation induced by ?-carrageenan in a dosage-dependent manner, probably due to an inhibition of nitric oxide and prostaglandin E2, which was demonstrated in vitro. To our knowledge, this is the first report of the presence of sucrose esters in P. peruviana that showed a potent anti-inflammatory effect. These results suggest the potential of sucrose esters from the Physalis genus as a novel natural alternative to treat inflammatory diseases. PMID:25338213

  14. Anti-Inflammatory and Pro-Resolving Lipid Mediators

    PubMed Central

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

    2009-01-01

    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. PMID:18233953

  15. CHF6001 II: a novel phosphodiesterase 4 inhibitor, suitable for topical pulmonary administration--in vivo preclinical pharmacology profile defines a potent anti-inflammatory compound with a wide therapeutic window.

    PubMed

    Villetti, Gino; Carnini, Chiara; Battipaglia, Loredana; Preynat, Laurent; Bolzoni, Pier Tonino; Bassani, Franco; Caruso, Paola; Bergamaschi, Marco; Pisano, Anna Rita; Puviani, Veronica; Stellari, Fabio Franco; Cenacchi, Valentina; Volta, Roberta; Bertacche, Vittorio; Mileo, Valentina; Bagnacani, Valentina; Moretti, Elisa; Puccini, Paola; Catinella, Silvia; Facchinetti, Fabrizio; Sala, Angelo; Civelli, Maurizio

    2015-03-01

    CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide] is a novel phosphodiesterase 4 (PDE4) inhibitor designed for use in pulmonary diseases by inhaled administration. Intratracheal administration of CHF6001 to ovalbumin-sensitized Brown-Norway rats suppressed the antigen-induced decline of lung functions (ED50 = 0.1 µmol/kg) and antigen-induced eosinophilia (ED50 = 0.03 µmol/kg) when administered (0.09 ?mol/kg) up to 24 hours before antigen challenge, in agreement with CHF6001-sustained lung concentrations up to 72 hours after intratracheal treatment (mean residence time 26 hours). Intranasal, once daily administration of CHF6001 inhibited neutrophil infiltration observed after 11 days of tobacco smoke exposure in mice, both upon prophylactic (0.15-0.45 µmol/kg per day) or interventional (0.045-0.45 µmol/kg per day) treatment. CHF6001 was ineffective in reversing ketamine/xylazine-induced anesthesia (a surrogate of emesis in rat) up to 5 µmol/kg administered intratracheally, a dose 50- to 150-fold higher than anti-inflammatory ED50 observed in rats. When given topically to ferrets, no emesis and nausea were evident up to 10 to 20 µmol/kg, respectively, whereas the PDE4 inhibitor GSK-256066 (6-[3-(dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3-carboxamide) induced nausea at 1 µmol/kg intratracheally. A 14-day inhalation toxicology study in rats showed a no-observed-adverse-effect level dose of 4.4 µmol/kg per day for CHF6001, lower than the 0.015 ?mol/kg per day for GSK-256066. CHF6001 was found effective and extremely well tolerated upon topical administration in relevant animal models, and may represent a step forward in PDE4 inhibition for the treatment of asthma and chronic obstructive respiratory disease. PMID:25576073

  16. The anti-inflammatory effect of opioids.

    PubMed

    Gavalas, A; Victoratos, P; Yiangou, M; Hadjipetrou-Kourounakis, L; Rekka, E; Kourounakis, P

    1994-01-01

    The anti-inflammatory activity of two novel opioids PM and PO as well as of pethidine was studied. The mouse paw edema, induced by various phlogistic agents, was significantly inhibited after the administration of opioids, fact that was independent of their antioxidant properties. The anti-inflammatory action of the above opioids was not reversed by naloxone. These results suggest that a variety of complex regulatory activities may be performed by opioid agonists via naloxone-sensitive or naloxone insensitive receptors on inflammatory cells, directly or indirectly by the inhibition of cytokines and mediators involved in inflammation. PMID:7928110

  17. Photoelectron spectroscopy of non-steroidal anti-inflammatory drugs

    NASA Astrophysics Data System (ADS)

    Novak, Igor; Klasinc, Leo; Chong, Delano P.; McGlynn, Sean P.

    2013-08-01

    The electronic structures of eight non-steroidal anti-inflammatory drugs (NSAIDs) had been studied by UV photoelectron spectroscopy (UPS) and high-level Green's function (GF) calculations. Our UPS data show that the electronic structure influences the measured biological activity of NSAID, but that it is not the dominating factor. The role of electronic structure needs to be considered in conjunction with other factors like steric properties of the COX active site and orientation of relevant residues in the same site.

  18. Determination of Residual Nonsteroidal Anti-Inflammatory Drugs in Aqueous Sample Using Magnetic Nanoparticles Modified with Cetyltrimethylammonium Bromide by High Performance Liquid Chromatography

    PubMed Central

    Khoeini Sharifabadi, Malihe; Saber-Tehrani, Mohammad; Waqif Husain, Syed; Mehdinia, Ali; Aberoomand-Azar, Parviz

    2014-01-01

    A simple and sensitive solid-phase extraction method for separation and preconcentration of trace amount of four nonsteroidal anti-inflammatory drugs (naproxen, indomethacin, diclofenac, and ibuprofen) using Fe3O4 magnetic nanoparticles modified with cetyltrimethylammonium bromide has been developed. For this purpose, the surface of MNPs was modified with cetyltrimethylammonium bromide (CTAB) as a cationic surfactant. Effects of different parameters influencing the extraction efficiency of drugs including the pH, amount of salt, shaking time, eluent type, the volume of solvent, amount of adsorbent, sample volume, and the time of desorption were investigated and optimized. Methanol has been used as desorption solvent and the extracts were analysed on a reversed-phase octadecyl silica column using 0.02 M phosphate-buffer (pH = 6.02) acetonitrile (65?:?35?v/v) as the mobile phase and the effluents were measured at 202?nm with ultraviolet detector. The relative standard deviation (RSD%) of the method was investigated at three concentrations (25, 50, and 200?ng/mL) and was in the range of 3.98–9.83% (n = 6) for 50?ng/mL. The calibration curves obtained for studied drugs show reasonable linearity (R2 > 0.99) and the limit of detection (LODs) ranged between 2 and 7?ng/mL. Finally, the proposed method has been effectively employed in extraction and determination of the drugs in biological and environmental samples. PMID:24982923

  19. Structural characterization of anti-inflammatory Immunoglobulin G Fc proteins

    PubMed Central

    Ahmed, Alysia A.; Giddens, John; Pincetic, Andrew; Lomino, Joseph V.; Ravetch, Jeffrey V.; Wang, Lai-Xi; Bjorkman, Pamela J.

    2014-01-01

    Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen. Recent studies have indicated that the Fc effector domain also displays considerable heterogeneity, accounting for its complex effector functions of inflammation, modulation and immune suppression. Therapeutic anti-tumor antibodies, for example, require the pro-inflammatory properties of the IgG Fc to eliminate tumor cells, while the anti-inflammatory activity of Intravenous Immunoglobulin G (IVIG) requires specific Fc glycans for activity. In particular, the anti-inflammatory activity of IVIG is ascribed to a small population of IgGs in which the Asn297-linked complex N-glycans attached to each Fc CH2 domain include terminal ?2,6-linked sialic acids. We used chemoenzymatic glycoengineering to prepare fully di-sialylated IgG Fc and solved its crystal structure. Comparison of the structures of asialylated Fc, sialylated Fc, and F241A Fc, a mutant that displays increased glycan sialylation, suggests that increased conformational flexibility of the CH2 domain is associated with the switch from pro- to anti-inflammatory activity of the Fc. PMID:25036289

  20. Anti-inflammatory properties of new bioisosteres of indomethacin synthesized from safrole which are sulindac analogues.

    PubMed

    Pereira, E F; Pereira, N A; Lima, M E; Coelho, F A; Barreiro, E J

    1989-01-01

    The anti-inflammatory activities of new compounds (I, II, III and IV) synthesized in 30% overall yield from the abundant natural product safrole, the principal chemical constituent of the oil of sassafras (Ocotea pretiosa, Lauraceae), were determined in mice. The synthesis of these new indenyl-acetic acids (I and II) and indenyl-propionic acids (III and IV) was based on the minimal structural features of non-steroid anti-inflammatory agents of the aryl- or heteroarylcarboxylic acid group. The compounds exhibited potencies 4- to 10-fold less than that of indomethacin in inhibiting carrageenan-induced hindpaw edema. In contrast, like sulindac, all the new compounds were more potent than indomethacin in antagonizing writhing pain and increased vascular permeability caused by acetic acid. The results confirm the anticipated bioisosteric relationship between these synthetic derivatives, designed as sulindac analogues, and the classical non-steroidal anti-inflammatory agent, indomethacin. PMID:2638933

  1. An anti-inflammatory property of Candida albicans ?-glucan: Induction of high levels of interleukin-1 receptor antagonist via a Dectin-1/CR3 independent mechanism

    PubMed Central

    Smeekens, Sanne P.; Gresnigt, Mark S.; Becker, Katharina L.; Cheng, Shih-Chin; Netea, Stejara A.; Jacobs, Liesbeth; Jansen, Trees; van de Veerdonk, Frank L.; Williams, David L.; Joosten, Leo A.B.; Dinarello, Charles A.; Netea, Mihai G.

    2015-01-01

    Background Candida albicans is an opportunistic fungal pathogen that induces strong proinflammatory responses, such as IL-1? production. Much less is known about the induction of immune modulatory cytokines, such as the IL-1 receptor antagonist (IL-1Ra) that is the main natural antagonist of IL-1, by C. albicans. Methods Peripheral blood mononuclear cells (PBMC) of healthy individuals were stimulated with C. albicans and different components of the fungal cell wall. The role of pathogen recognition receptors (PRRs) for the induction of IL-1? and IL-1Ra was investigated by using specific blockers or in PBMC from Dectin-1 deficient patients. Results C. albicans induced a strong IL-1Ra response, and this induction was primarily induced by the cell-wall component ?-glucan. Blocking IL-1Ra significantly increased C. albicans ?-glucan hyphae induced IL-1? and IL-6 production. Surprisingly, blocking the ?-glucan receptor Dectin-1 or the downstream Syk or Raf-1 pathways only marginally reduced C. albicans-induced IL-1Ra production, while blocking of the complement receptor 3 (CR3), TLR2 or TLR4 had no effect. In line with this, blocking MAP kinases had little effect on Candida-induced IL-1Ra production. PBMC isolated from Dectin-1 deficient patients produced normal IL-1Ra amounts in response to C. albicans stimulation. Interestingly, the IL-1Ra synthesis induced by ?-glucan was blocked by inhibitors of the Akt/PI3 K pathway. Conclusions ?-glucan of C. albicans induces a strong IL-1Ra response, which is independent of the ?-glucan receptors dectin-1 and CR3. These data strongly argue for the existence of an unknown ?-glucan receptor that specifically induces an Akt/PI3 K-dependent anti-inflammatory IL-1Ra response upon recognition of C. albicans. PMID:25461401

  2. Relatively high levels of serum adiponectin in obese women, a potential indicator of anti-inflammatory dysfunction: Relation to sex hormone-binding globulin

    PubMed Central

    Onat, Altan; Hergenç, Gülay; Dursuno?lu, Dursun; Küçükdurmaz, Zekeriya; Bulur, Serkan; Can, Günay

    2008-01-01

    It is unclear whether serum adiponectin concentrations diminish linearly with increasing adiposity and, if not, which factors codetermine this association. These issues were investigated cross-sectionally in 1188 men and women, representative of middle-aged and elderly Turkish adults. Serum total adiponectin was assayed by ELISA. Serum adiponectin values in men, though declining significantly in transition from the bottom to the mid tertile of body mass index (BMI) and waist circumference (WC), were similar in the two respective upper tertiles. In women, serum adiponectin concentrations were not significantly different in any tertile of these indices, were significantly correlated with BMI or WC within the low tertiles and not within the two higher tertiles. In a linear regression analysis for WC (or BMI) in a subset of the sample in which serum sex hormone-binding globulin (SHBG) was available and which additionally comprised adiponectin, fasting insulin and other confounders, only insulin and, in women SHBG, were significantly associated, but not adiponectin. In linear regression analyses for covariates of adiponectin in two models comprising 12 variables, insulin and SHBG concentrations were significantly associated in both genders though not BMI. Whereas in men HDL-cholesterol and CRP were covariates of adiponectin (both p<0.01), SHBG and apolipoprotein B positively associated in women (p<0.001), independent of BMI and fasting insulin levels. Conclusions: Relationship between excess adiposity and adiponectin levels is inconsistent in Turkish adults. Independently from obesity and hyperinsulinemia, serum adiponectin discloses significant relationship with inflammatory markers and HDL only in men, not in women in whom it is influenced by SHBG, with consequent attenuation of its anti-inflammatory activities. PMID:18695734

  3. Molecular Targets of Dietary Polyphenols with Anti-inflammatory Properties

    PubMed Central

    Yoon, Joo-Heon

    2005-01-01

    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. PMID:16259055

  4. Passively Administered Pooled Human Immunoglobulins Exert IL-10 Dependent Anti-Inflammatory Effects that Protect against Fatal HSV Encephalitis

    PubMed Central

    Ramakrishna, Chandran; Newo, Alain N. S.; Shen, Yueh-Wei; Cantin, Edouard

    2011-01-01

    HSV-1 is the leading cause of sporadic encephalitis in humans. HSV infection of susceptible 129S6 mice results in fatal encephalitis (HSE) caused by massive inflammatory brainstem lesions comprising monocytes and neutrophils. During infection with pathogenic microorganisms or autoimmune disease, IgGs induce proinflammatory responses and recruit innate effector cells. In contrast, high dose intravenous immunoglobulins (IVIG) are an effective treatment for various autoimmune and inflammatory diseases because of potent anti-inflammatory effects stemming in part from sialylated IgGs (sIgG) present at 1–3% in IVIG. We investigated the ability of IVIG to prevent fatal HSE when given 24 h post infection. We discovered a novel anti-inflammatory pathway mediated by low-dose IVIG that protected 129S6 mice from fatal HSE by modulating CNS inflammation independently of HSV specific antibodies or sIgG. IVIG suppressed CNS infiltration by pathogenic CD11b+ Ly6Chigh monocytes and inhibited their spontaneous degranulation in vitro. Fc?RIIb expression was required for IVIG mediated suppression of CNS infiltration by CD45+ Ly6Clow monocytes but not for inhibiting development of Ly6Chigh monocytes. IVIG increased accumulation of T cells in the CNS, and the non-sIgG fraction induced a dramatic expansion of FoxP3+ CD4+ T regulatory cells (Tregs) and FoxP3? ICOS+ CD4+ T cells in peripheral lymphoid organs. Tregs purified from HSV infected IVIG treated, but not control, mice protected adoptively transferred mice from fatal HSE. IL-10, produced by the ICOS+ CD4+ T cells that accumulated in the CNS of IVIG treated, but not control mice, was essential for induction of protective anti-inflammatory responses. Our results significantly enhance understanding of IVIG's anti-inflammatory and immunomodulatory capabilities by revealing a novel sIgG independent anti-inflammatory pathway responsible for induction of regulatory T cells that secrete the immunosuppressive cytokine IL-10 and further reveal the therapeutic potential of IVIG for treating viral induced inflammatory diseases. PMID:21655109

  5. QSAR and docking studies on capsazepine derivatives for immunomodulatory and anti-inflammatory activity.

    PubMed

    Shukla, Aparna; Sharma, Pooja; Prakash, Om; Singh, Monika; Kalani, Komal; Khan, Feroz; Bawankule, Dnyaneshwar Umrao; Luqman, Suaib; Srivastava, Santosh Kumar

    2014-01-01

    Capsazepine, an antagonist of capsaicin, is discovered by the structure and activity relationship. In previous studies it has been found that capsazepine has potency for immunomodulation and anti-inflammatory activity and emerging as a favourable target in quest for efficacious and safe anti-inflammatory drug. Thus, a 2D quantitative structural activity relationship (QSAR) model against target tumor necrosis factor-? (TNF-?) was developed using multiple linear regression method (MLR) with good internal prediction (r2?=?0.8779) and external prediction (r2pred?=?0.5865) using Discovery Studio v3.5 (Accelrys, USA). The predicted activity was further validated by in vitro experiment. Capsazepine was tested in lipopolysaccharide (LPS) induced inflammation in peritoneal mouse macrophages. Anti-inflammatory profile of capsazepine was assessed by its potency to inhibit the production of inflammatory mediator TNF-?. The in vitro experiment indicated that capsazepine is an efficient anti-inflammatory agent. Since, the developed QSAR model showed significant correlations between chemical structure and anti-inflammatory activity, it was successfully applied in the screening of forty-four virtual derivatives of capsazepine, which finally afforded six potent derivatives, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36. To gain more insights into the molecular mechanism of action of capsazepine and its derivatives, molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were performed. The results of QSAR, molecular docking, in silico ADMET screening and in vitro experimental studies provide guideline and mechanistic scope for the identification of more potent anti-inflammatory & immunomodulatory drug. PMID:25003344

  6. QSAR and Docking Studies on Capsazepine Derivatives for Immunomodulatory and Anti-Inflammatory Activity

    PubMed Central

    Shukla, Aparna; Sharma, Pooja; Prakash, Om; Singh, Monika; Kalani, Komal; Khan, Feroz; Bawankule, Dnyaneshwar Umrao; Luqman, Suaib; Srivastava, Santosh Kumar

    2014-01-01

    Capsazepine, an antagonist of capsaicin, is discovered by the structure and activity relationship. In previous studies it has been found that capsazepine has potency for immunomodulation and anti-inflammatory activity and emerging as a favourable target in quest for efficacious and safe anti-inflammatory drug. Thus, a 2D quantitative structural activity relationship (QSAR) model against target tumor necrosis factor-? (TNF-?) was developed using multiple linear regression method (MLR) with good internal prediction (r2?=?0.8779) and external prediction (r2pred?=?0.5865) using Discovery Studio v3.5 (Accelrys, USA). The predicted activity was further validated by in vitro experiment. Capsazepine was tested in lipopolysaccharide (LPS) induced inflammation in peritoneal mouse macrophages. Anti-inflammatory profile of capsazepine was assessed by its potency to inhibit the production of inflammatory mediator TNF-?. The in vitro experiment indicated that capsazepine is an efficient anti-inflammatory agent. Since, the developed QSAR model showed significant correlations between chemical structure and anti-inflammatory activity, it was successfully applied in the screening of forty-four virtual derivatives of capsazepine, which finally afforded six potent derivatives, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36. To gain more insights into the molecular mechanism of action of capsazepine and its derivatives, molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were performed. The results of QSAR, molecular docking, in silico ADMET screening and in vitro experimental studies provide guideline and mechanistic scope for the identification of more potent anti-inflammatory & immunomodulatory drug. PMID:25003344

  7. Synthesis and Anti-Inflammatory Activity of New Alkyl-Substituted Phthalimide 1H-1,2,3-Triazole Derivatives

    PubMed Central

    Assis, Shalom Pôrto de Oliveira; da Silva, Moara Targino; de Oliveira, Ronaldo Nascimento; Lima, Vera Lúcia de Menezes

    2012-01-01

    Four new 1,2,3-triazole phthalimide derivatives with a potent anti-inflammatory activity have been synthesized in the good yields by the 1,3-dipolar cycloaddition reaction from N-(azido-alkyl)phthalimides and terminal alkynes. The anti-inflammatory activity was determined by injecting carrageenan through the plantar tissue of the right hind paw of Swiss white mice to produce inflammation. All the compounds 3a–c and 5a–c exhibited an important anti-inflammatory activity; the best activity was found for the compounds 3b and 5c, which showed to be able to decrease by 69% and 56.2% carrageenan-induced edema in mice. These compounds may also offer a future promise as a new anti-inflammatory agent. PMID:23304092

  8. Ketogenic diet exhibits anti-inflammatory properties.

    PubMed

    Dupuis, Nina; Curatolo, Niccolo; Benoist, Jean-François; Auvin, Stéphane

    2015-07-01

    The ketogenic diet (KD) is an established treatment for refractory epilepsy, including some inflammation-induced epileptic encephalopathies. In a lipopolysaccharide (LPS)-induced fever model in rats, we found that animals given the KD for 14 days showed less fever and lower proinflammatory cytokine levels than control animals. However, KD rats exhibited a decrease in circulating levels of arachidonic acid and long-chain n-3 polyunsaturated fatty acids (PUFAs), suggesting that the anti-inflammatory effect of KD was probably not due to an increase in anti-inflammatory n-3 PUFA derivatives. These properties might be of interest in some conditions such as fever-induced refractory epileptic encephalopathy in school-aged children. PMID:26011473

  9. Anti-inflammatory actions of acupuncture.

    PubMed Central

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

    2003-01-01

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

  10. Anti-Inflammatory Effect of Selected Dihydroxyflavones

    PubMed Central

    Sangeetha, K.S.Sridevi

    2015-01-01

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

  11. Anti-Inflammatory Effect of Aprotinin: A Meta-Analysis

    PubMed Central

    Brown, Jeremiah R.; Toler, Andrew W.J.; Kramer, Robert S.; Landis, R. Clive

    2009-01-01

    Abstract: It is important to define the extent, and any limitations, of potential anti-inflammatory regimens used in cardiac surgery to guide the rational combination of drugs to suppress the systemic inflammatory response. Aprotinin (Trasylol) is an anti-fibrinolytic agent with reported anti-inflammatory properties. In this study, we investigated the published data on aprotinin’s effect on acute phase protein and cytokine levels in cardiac surgery patients. Randomized placebo-controlled trials of aprotinin published between 1985 and 2007, in adult cardiac surgery using cardiopulmonary bypass, reporting tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), IL-8, and IL-10 levels were included for review. Two independent reviewers graded each paper and collected information on inflammatory markers. RevMan 4.3 statistical software was used to calculate and plot the weighted mean difference between placebo and aprotinin groups. Thirteen studies met the review criteria. None of the inflammatory markers were reduced by high-dose aprotinin treatment. Low-dose aprotinin significantly reduced IL-10 levels after protamine administration (?41.3 pg/mL; 95% CI: ?59.5, ?23.1), but this result was gone by the first post-operative day. These meta-analyses showed no significant effect of aprotinin on acute phase proteins or systemic cytokine markers of inflammation during clinical adult cardiac surgery using cardiopulmonary bypass. While recognizing that other host defense systems, such as coagulation and complement, contribute to the overall systemic inflammatory response, the evidence presented here does not support the clinical use of aprotinin as an anti-inflammatory agent on its own. PMID:19681304

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

    PubMed Central

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

    1974-01-01

    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. PMID:4152780

  13. Erdosteine: antitussive and anti-inflammatory effects.

    PubMed

    Dal Negro, Roberto W

    2008-01-01

    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

  14. Anti-inflammatory effects of isoketocharbroic acid from brown alga, Sargassum micracanthum

    PubMed Central

    Ham, Young Min; Yoon, Weon-Jong; Lee, Wook Jae; Kim, Sang-Cheol; Baik, Jong Seok; Kim, Jin Hwa; Lee, Geun Soo; Lee, Nam Ho; Hyun, Chang-Gu

    2015-01-01

    During our on-going screening program designed to isolate natural compounds from marine environments, we isolated isoketochabrolic acid (IKCA) from Sargassum micracanthum, an important brown algae distributed in Jeju Island, Korea. Furthermore, we evaluated the inhibitory effects of IKCA on nitric oxide (NO) production in lipopolysaccharide (LPS)-triggered macrophages. IKCA strongly inhibited NO production, with an IC50 value of 58.31 ?M. Subsequent studies demonstrated that IKCA potently and concentration-dependently reduced prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-?), interleukin (IL)-1?, and IL-6 cytokine production. In conclusion, to the best of our knowledge, this is the first study to show that IKCA isolated from S. micracanthum has a potent anti-inflammatory activity. Therefore, IKCA might be useful as an anti-inflammatory health supplement or functional cosmetics. PMID:26600756

  15. Anti-Inflammatory and Immunoregulatory Functions of Artemisinin and Its Derivatives

    PubMed Central

    Shi, Chenchen; Yang, Yifu

    2015-01-01

    Artemisinin and its derivatives are widely used in the world as the first-line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti-inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions. PMID:25960615

  16. Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats.

    PubMed

    Karoui, Amine; Allouche, Fatma; Deghrigue, Monia; Agrebi, Asma; Bouraoui, Abderrahman; Chabchoub, Fakher

    2014-01-01

    We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3',4':4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50-100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic-lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R3) had a pronounced effect on the anti-inflammatory activity. Studies of structure-activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N (1)-phenyl-1,7-dihydropyrazolo[3',4':4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer. PMID:24489456

  17. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

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

  18. Brucella C?G induces a dual pro- and anti-inflammatory response leading to a transient neutrophil recruitment.

    PubMed

    Degos, Clara; Gagnaire, Aurélie; Banchereau, Romain; Moriyón, Ignacio; Gorvel, Jean-Pierre

    2015-01-01

    Brucella is the causing agent of a chronic zoonosis called brucellosis. The Brucella ?-1,2 cyclic glucan (C?G) is a virulence factor, which has been described as a potent immune stimulator, albeit with no toxicity for cells and animals. We first used a genome-wide approach to characterize human myeloid dendritic cell (mDC) responses to C?G. Transcripts related to inflammation (IL-6, IL2RA, PTGS2), chemokine (CXCR7, CXCL2) and anti-inflammatory pathways (TNFAIP6, SOCS3) were highly expressed in C?G-treated mDC. In mouse GMCSF-derived DC, C?G triggered the expression of both activation (CXCL2, KC) and inhibition (SOCS3 and TNFAIP6) molecules. We then characterized the inflammatory infiltrates at the level of mouse ear when injected with C?G or LPS. C?G yielded a lower and transient recruitment of neutrophils compared to LPS. The consequence of these dual pro- and anti-inflammatory signals triggered by C?G corresponds to the induction of a controlled local inflammation. PMID:25654761

  19. Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates.

    PubMed

    Ravanan, Palaniyandi; Singh, Sanjay K; Rao, Gsr Subba; Kondaiah, Paturu

    2011-06-01

    Triterpenoids are pentacyclic secondary metabolites present in many terrestrial plants. Natural triterpenoids have been reported to exhibit anti-inflammatory and anti-carcinogenic activities. Here, we show that modifications of ring A of boswellic acid (2 cyano, 3 enone) resulted in a highly active growth inhibitory, anti-inflammatory, prodifferentiative and anti-tumour triterpenoid compound called cyano enone of methyl boswellates (CEMB). This compound showed cytotoxic activity on a number of cancer cell lines with IC?? ranging from 0.2 to 0.6 ?M. CEMB inhibits DNA synthesis and induces apoptosis in A549 cell line at 0.25 ?M and 1 ?M concentrations, respectively. CEMB induces adipogenic differentiation in 3T3-L1 cells at a concentration of 0.1 ?M. Finally, administration of CEMB intra-tumourally significantly inhibited the growth of C6 glioma tumour xenograft in immuno-compromised mice. Collectively, these results suggest that CEMB is a very potent anti-tumour compound. PMID:21654084

  20. Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: anti-inflammatory and analgesic activities.

    PubMed

    Alanazi, Amer M; El-Azab, Adel S; Al-Suwaidan, Ibrahim A; ElTahir, Kamal Eldin H; Asiri, Yousif A; Abdel-Aziz, Naglaa I; Abdel-Aziz, Alaa A-M

    2015-03-01

    A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 = 0.18, 0.24, 0.28 and 0.36 ?M; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 6a as a highly potent (IC50 = 0.18 ?M), and an extremely selective [COX-2 (SI) = 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 54.0 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His(90) (3.02 ?), Arg(513) (1.94, 2.83 ?), and Gln(192) (3.25 ?). PMID:25549551

  1. Evaluation of Anticancer, Antioxidant, and Possible Anti-inflammatory Properties of Selected Medicinal Plants Used in Indian Traditional Medication

    PubMed Central

    Shaikh, Rafik; Pund, Mahesh; Dawane, Ashwini; Iliyas, Sayyed

    2014-01-01

    The present study was carried out to evaluate the anticancer, antioxidant, and possible anti-inflammatory properties of diverse medicinal plants frequently used in Indian traditional medication. The selected botanicals such as Soymida fembrifuga (Roxb.) A. Juss. (Miliaceae), Tinospora cordifolia (Willd.) Miers. (Menispermaceae), Lavandula bipinnata (L.) O. Ktze. (Lamiaceae), and Helicteres isora L. (Sterculiaceae) extracted in different solvents were evaluated for their in vitro anticancer and antioxidant activities. The results obtained indicate that H. isora has potent cytotoxic activity toward the selected cancer cells such as HeLa-B75 (34.21 ± 0.24%), HL-60 (30.25 ± 1.36%), HEP-3B (25.36 ± 1.78%), and PN-15 (29.21 ± 0.52%). Interestingly, the selected botanicals selectively inhibited cyclooxygenase-2 (COX-2) more than (COX-1), which are the key enzymes implicated in inflammation. COX-2 inhibition was observed to be in the range of 19.66-49.52% as compared to COX-1 inhibition (3.93-19.61%). The results of the antioxidant study revealed that the selected plants were found to be effective 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging agents. High-performance thin layer chromatography (HPTLC) fingerprint of flavonoids was used as a measure of quality control of the selected plant samples. The results of the present findings strengthen the potential of the selected plants as a resource for the discovery of novel anticancer, anti-inflammatory, and antioxidant agents. PMID:25379467

  2. Anti-Inflammatory and Antinociceptive Activities of Untreated, Germinated, and Fermented Mung Bean Aqueous Extract

    PubMed Central

    Ali, Norlaily Mohd; Mohd Yusof, Hamidah; Yeap, Swee-Keong; Ho, Wan-Yong; Beh, Boon-Kee; Koh, Soo-Peng; Abdullah, Mohd Puad; Alitheen, Noorjahan Banu

    2014-01-01

    Evaluation of anti-inflammatory and antinociceptive activities of untreated mung bean (MB), germinated mung bean (GMB), and fermented mung bean (FMB) was performed on both in vitro (inhibition of inflammatory mediator, nitric oxide(NO)) and in vivo (inhibition of ear oedema and reduction of response to pain stimulus) studies. Results showed that both GMB and FMB aqueous extract exhibited potent anti-inflammatory and antinociceptive activities in a dose-dependent manner. In vitro results showed that GMB and FMB were potent inflammatory mediator (NO) inhibitors at both 2.5 and 5?mg/mL. Further in vivo studies showed that GMB and FMB aqueous extract at 1000?mg/kg can significantly reduce ear oedema in mice caused by arachidonic acid. Besides, both 200?mg/kg and 1000?mg/kg concentrations of GMB and FMB were found to exhibit potent antinociceptive effects towards hotplate induced pain. With these, it can be concluded that GMB and FMB aqueous extract exhibited potential anti-inflammatory and antinociceptive effects. PMID:25045389

  3. Chemical composition and anti-inflammatory and antioxidant activities of eight pear cultivars.

    PubMed

    Li, Xia; Zhang, Jun-Ying; Gao, Wen-Yuan; Wang, Ying; Wang, Hai-Yang; Cao, Jing-Guo; Huang, Lu-Qi

    2012-09-01

    The contents of total phenolics, total flavonoids, total anthocyanins, and total triterpenes of eight pear samples were determined, and the monomeric compounds were identified and quantitated using high-performance liquid chromatography. The in vitro antioxidant and in vivo anti-inflammatory activities of the different pear cultivars were compared. Arbutin and catechin were the dominant polyphenol compounds in the eight pear varieties, followed by chlorogenic acid, quercetin, and rutin. In addition, Xuehua pear and Nanguo pear had significantly higher total phenolics and flavonoids contents, while Dangshansu pear had the largest total triterpenes value (209.2 mg/100 g). Xuehua pear and Nanguo pear also were the highest in total anthocyanins. The pears with high total phenolics and total flavonoids contents had significantly higher antioxidant and anti-inflammatory abilities than those of other species. Anthocyanins were correlated to antioxidant capacity in pears, whereas total triterpenoids were strongly correlated to anti-inflammatory activity. PMID:22880800

  4. Anti-inflammatory action of ?-irradiated genistein in murine peritoneal macrophage

    NASA Astrophysics Data System (ADS)

    Sung, Nak-Yun; Byun, Eui-Baek; Song, Du-Sup; Jin, Yeung-Bae; Park, Jae-Nam; Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Park, Sang-Hyun; Lee, Ju-Woon; Kim, Jae-Hun

    2014-12-01

    This present study was to examine the cytotoxicity and anti-inflammatory activity of gamma (?)-irradiated genistein in murine peritoneal macrophage. Inflammation to macrophage was induced by adding the lipopolysaccharide (LPS). ?-Irradiated genistein significantly decreased the cytotoxicity to murine peritoneal macrophage in dose ranges from 5 to 10 ?M than that of non-irradiated genistein. Anti-inflammatory activity within the doses less than 2 ?M showed that ?-irradiated genistein treatment remarkably reduced the lipopolysaccharide-induced inflammation by decreasing the nitric oxide (NO) and cytokines (TNF-?, IL-6) production. In a structural analysis through the high pressure liquid chromatography (HPLC), ?-irradiated genistein showed a new peak production distinguished from main peak of genistein (non-irradiated). Therefore, increase of anti-inflammatory activity may closely mediate with structural changes induced by ? irradiation exposure. Based on the above result, ?-irradiation could be an effective tool for reduction of toxicity and increase of physiological activity of biomolecules.

  5. Corneal reepithelialization and anti-inflammatory agents.

    PubMed Central

    Srinivasan, B D

    1982-01-01

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

  6. 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

    McGettigan, Patricia; Henry, David

    2013-01-01

    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 PMID:23424288

  7. Sol-gel-derived magnetic SiO2/TiO2 nanocomposite reinforced hollow fiber-solid phase microextraction for enrichment of non-steroidal anti-inflammatory drugs from human hair prior to high performance liquid chromatography.

    PubMed

    Es'haghi, Zarrin; Esmaeili-Shahri, Effat

    2014-10-01

    Hollow fiber-solid phase micro-extraction (HF-SPME) technique containing sol-gel-derived Fe3O4/SiO2/TiO2 core-double shell nanocomposite as a novel high efficiency sorbent, coupled with high performance liquid chromatography was used to extraction and determination of six non-steroidal anti-inflammatory drugs; acetylsalicylic acid, naproxen, piroxicam, diclofenac, indomethacin and mefenamic acid, in hair samples. First, magnetite nanoparticles (Fe3O4-NPs) were synthesized by chemical co-precipitation of Fe(II) and Fe(III) ions (where the ratio of Fe(II) to Fe(III) is 1:2 and a non-oxidizing environment), in alkaline medium to produce magnetite particles. Subsequently, surface of Fe3O4-NPs was modified with SiO2 and TiO2 using layer-by-layer chemical technique. A core-shell structure of Fe3O4/SiO2/TiO2 composite was prepared by coating magnetite core particles with silica and titania layers. In the proposed method, NSAIDs were extracted by the synthesized nanocomposite and analyzed by HPLC. The parameters affecting the efficiency of magnetic nanoparticle (MNPs) assisted HF-SPME were investigated and optimized. The method validation was included and satisfying results with high pre-concentration factors (405 up to 2450) were obtained. It owes large surface area and porosity of the nano-adsorbent. Under the optimal conditions, the method detection limits (S/N=3) were in the range of 0.01-0.10?gml(-1) and the limits of quantification (S/N=10) between 0.04 and 0.30?gml(-1). Relative standard deviations were 3.09-6.61%. Eventually, the method was successfully applied to human hair after administration of NSAIDs. PMID:25464107

  8. Antioxidant, anti-inflammatory and anti-hyperglycaemic activities of heterocyclic homoprostanoid derivatives.

    PubMed

    Manohara Reddy, S A; Mudgal, Jayesh; Bansal, Punit; Vasanthraju, S G; Srinivasan, K K; Rao, C Mallikarjuna; Gopalan Kutty, N

    2011-01-01

    A series of 19 heterocyclic homoprostanoids were synthesized from easily available oleic and ricinoleic acids and evaluated for their possible antioxidant, anti-inflammatory and anti-hyperlipidaemic activities. Compounds with thioxo- and oxoimidazole ring (1) and (2) have shown potent antioxidant activity with IC(50) values 0.23±0.09 and 0.41±0.01mM comparable with standard ascorbic acid. Compound (3) with a quinoxaline ring showed maximum inhibition of BSA denaturation at 1mM concentration and comparable with standard diclofenac. Incorporation of electron withdrawing substitutions like chloro- and nitro-groups in the quinoxaline ring has resulted in an increase anti-inflammatory activity. Test compounds (3), (3a) and (3c) showed modest inhibition of DPP-IV in vitro. However, the unsubstituted quinoxaline (3) and substituted quinoxalines (3b and 3c) reduced plasma glucose levels indicating the presence of hypoglycemic activity. PMID:21146413

  9. Anti-inflammatory principles from the stem and root barks of Citrus medica.

    PubMed

    Chan, Yu-Yi; Li, Chan-Hao; Shen, Yuh-Chiang; Wu, Tian-Shung

    2010-01-01

    Bioassay-guided investigation of the anti-inflammatory principles from the stem and root barks of Citrus medica L. var. sarcodactylis SWINGLE has led to the isolation of a new coumarin, namely citrumedin-B (1) and thirty known compounds. The anti-inflammatory components were xanthyletin (2), nordentatin (3), atalantoflavon (4) and lonchocarpol A (5) which displayed potent nitric oxide (NO)-reducing activity in microglial cells. The structure of this new compound was completely elucidated using a combination of 2D NMR techniques (correlation spectroscopy (COSY), nuclear Overhauser effect spectroscopy (NOESY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond connectivity (HMBC)) and HR-electrospray ionization (ESI)-MS analyses. The known compounds were identified by comparison of their spectroscopic and physical data with those reported in the literature. These results can be inferred from the treatment of allergic response and inflammatory properties of Citrus medica L. var. sarcodactylis SWINGLE in traditional Chinese medicine. PMID:20045968

  10. Anti-leishmanial, anti-inflammatory and antimicrobial activities of phenolic derivatives from Tibouchina paratropica.

    PubMed

    Tracanna, María I; Fortuna, Antonio M; Cárdenas, Angel V Contreras; Marr, Alexandra K; McMaster, W Robert; Gómez-Velasco, Anaximandro; Sánchez-Arreola, Eugenio; Hernández, Luis Ricardo; Bach, Horacio

    2015-03-01

    A new phenolic derivative, 2,8-dihydroxy-7H-furo[2,3-f]chromen-7-one (1), together with isoquercitrin (2), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti-parasitic activity against Leishmania donovani (IC50 ?=?0.809?µg/mL). In addition, an 85% reduction in the secretion of the pro-inflammatory cytokine IL-6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1, but no effect on the anti-inflammatory IL-10 was observed. Compound 2 showed neither anti-parasitic nor anti-inflammatory properties. In addition, no cytotoxic activities were observed against the human-derived macrophage THP-1 cells. PMID:25417600

  11. Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

    PubMed Central

    Washburn, Nathaniel; Schwab, Inessa; Ortiz, Daniel; Bhatnagar, Naveen; Lansing, Jonathan C.; Medeiros, Amy; Tyler, Steven; Mekala, Divya; Cochran, Edward; Sarvaiya, Hetal; Garofalo, Kevin; Meccariello, Robin; Meador, James W.; Rutitzky, Laura; Schultes, Birgit C.; Ling, Leona; Avery, William; Nimmerjahn, Falk; Manning, Anthony M.; Kaundinya, Ganesh V.; Bosques, Carlos J.

    2015-01-01

    Despite the beneficial therapeutic effects of intravenous immunoglobulin (IVIg) in inflammatory diseases, consistent therapeutic efficacy and potency remain major limitations for patients and physicians using IVIg. These limitations have stimulated a desire to generate therapeutic alternatives that could leverage the broad mechanisms of action of IVIg while improving therapeutic consistency and potency. The identification of the important anti-inflammatory role of fragment crystallizable domain (Fc) sialylation has presented an opportunity to develop more potent Ig therapies. However, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for clinical use. Therefore, we set out to develop the first, to our knowledge, robust and scalable process for generating a well-qualified sialylated IVIg drug candidate with maximum Fc sialylation devoid of unwanted alterations to the IVIg mixture. Here, we describe a controlled enzymatic, scalable process to produce a tetra-Fc–sialylated (s4-IVIg) IVIg drug candidate and its qualification across a wide panel of analytic assays, including physicochemical, pharmacokinetic, biodistribution, and in vivo animal models of inflammation. Our in vivo characterization of this drug candidate revealed consistent, enhanced anti-inflammatory activity up to 10-fold higher than IVIg across different animal models. To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity. PMID:25733881

  12. Investigation of the anti-inflammatory effects of safranal on high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model.

    PubMed

    Hazman, Ömer; Oval?, Serhat

    2015-06-01

    In the present study, it was aimed to investigate the effects of safranal, one of the components of saffron plant, on the inflammation in the rats in which experimental type 2 diabetes and obesity were formed. Type 2 diabetes is a disease characterized by insulin resistance and ?-cell dysfunction. Therefore, in the present study, high-fat diet (HFD) and streptozotocin were used for being able to create experimental type 2 diabetes. In the first 6 weeks of the study, experimental groups were formed in five groups, after the stage of creating insulin resistance. The study groups were designed as control, HFD, HFD-Saf, DYB, and DYB-Saf groups. Safranal treatment was applied to the treatment groups for a period of 4 weeks. Throughout the study period (10 weeks), the weight gains and plasma glucose levels of the rats were determined each week and bi-weekly, respectively. At the end of the study, interferon gamma (IFN-?), interleukin (IL)-1?, IL-6, tumor necrosis factor alpha (TNF-?), TAS and TOS levels in the pancreas and plasma were measured. In addition, the insulin and leptin levels in the plasma were determined. It was ascertained that, compared to the diabetic group, safranal decreased the inflammation both in the plasma and pancreas tissue, by reducing the TNF-? and IL-1? levels in particular. In addition, safranal was also found to decrease the oxidative stress increased due to type 2 diabetes in the plasma and pancreas tissue. It was concluded that safranal might be helpful in terms of reduction of diabetic complications, by means of its effects on both oxidative stress and inflammation, and that further studies should be carried out for this purpose. PMID:25411096

  13. 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...

  14. A preoperative mixture of anesthetic jelly, dilating drops, antibiotics, and anti-inflammatories for cataract surgery.

    PubMed

    Bohigian, George M

    2006-01-01

    A technique of using a preoperative mixture of topical anesthetic jelly, mydriatics, antibiotics, and anti-inflammatories for cataract surgery is described. The goals of this technique are to improve efficiency and effectiveness and obtain optimal pupillary dilation with an intracameral antibiotic level. Using an all-in-one mixture can be highly effective and efficient for the surgical nursing staff. PMID:16749268

  15. Hemeoxygenase 1 partly mediates the anti-inflammatory effect of dieckol in lipopolysaccharide stimulated murine macrophages.

    PubMed

    Yayeh, Taddesse; Im, Eun Ju; Kwon, Tae-Hyung; Roh, Seong-Soo; Kim, Suk; Kim, Ji Hye; Hong, Seung-Bok; Cho, Jae Youl; Park, Nyun-Ho; Rhee, Man Hee

    2014-09-01

    Eisenia bicyclis is edible brown algae recognized as a rich source of bioactive derivatives mainly phlorotannins reported for their anti-oxidant properties. Of all phlorotannins identified so far, dieckol has shown the most potent effect in anti-inflammatory, radical scavenging and neuroprotective functions. However, whether dieckol up-regulates hemeoxygenase 1 (HO-1) and this mediates its anti-inflammatory effect in murine macrophages remains poorly understood. Dieckol (12.5-50 ?M) inhibited nitric oxide production and attenuated inducible nitric oxide synthase, phospho (p)-PI-3K, p-Akt, p-IKK-?/?, p-I?B-? and nuclear p-NF-?Bp65 protein expressions, and NF-?B transcriptional activity in LPS (0.1 ?g/ml) stimulated murine macrophages. On the other hand, dieckol up-regulated HO-1 which partly mediated its anti-inflammatory effect in murine macrophages. Thus, dieckol appeared to be a potential therapeutic agent against inflammation through HO-1 up-regulation. PMID:24953853

  16. Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances.

    PubMed

    Mahdizadeh, Shahla; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2015-01-01

    Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain. PMID:26101752

  17. Phytochemical study, cytotoxic, analgesic, antipyretic and anti-inflammatory activities of Strychnos nux-vomica.

    PubMed

    Eldahshan, Omayma A; Abdel-Daim, Mohamed M

    2015-10-01

    The strychnine tree (Strychnos nux-vomica L.) (S. nux-vomica) belonging to family Loganiaceae has been a very promising medication for certain disorders. Different chromatographic methods were used to isolate the phenolic compounds from the aqueous methanolic extract of the S. nux-vomica leaves. Their identification was achieved through spectroscopic techniques. Cytotoxicity, analgesic, antipyretic and anti-inflammatory activities of S. nux-vomica leaves extract were evaluated. Five phenolic compounds were isolated and identified; Kaempferol-7 glucoside 1, 7-Hydroxy coumarin 2, Quercetin-3-rhamnoside 3, Kaempferol 3-rutinoside 4, and Rutin 5. Furthermore, the cytotoxic activity of the extract was evaluated against different cancer cell lines. The extract showed potential cytotoxic activity against human epidermoid larynx carcinoma cells (Hep-2) and against breast carcinoma cell line (MCF-7). Colon carcinoma cells (HCT) were the least one affected by the extract. In addition, the extract exhibited promising analgesic, antipyretic as well as anti-inflammatory activities. It is concluded that, leaves extract of S. nux vomica possess potent cytotoxic, analgesic, antipyretic and anti-inflammatory activities. These activities could be due to the presence of phenolic compounds revealed by our phytochemical investigations. PMID:24711053

  18. Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants

    NASA Astrophysics Data System (ADS)

    Zhang, Zhiling; Nong, Jia; Zhong, Yinghui

    2015-08-01

    Objective. Infection, inflammation, and neuronal loss are common issues that seriously affect the functionality and longevity of chronically implanted neural prostheses. Minocycline hydrochloride (MH) is a broad-spectrum antibiotic and effective anti-inflammatory drug that also exhibits potent neuroprotective activities. In this study, we investigated the development of biocompatible thin film coatings capable of sustained release of MH for improving the long term performance of implanted neural electrodes. Approach. We developed a novel magnesium binding-mediated drug delivery mechanism for controlled and sustained release of MH from an ultrathin hydrophilic layer-by-layer (LbL) coating and characterized the parameters that control MH loading and release. The anti-biofilm, anti-inflammatory and neuroprotective potencies of the LbL coating and released MH were also examined. Main results. Sustained release of physiologically relevant amount of MH for 46 days was achieved from the Mg2+-based LbL coating at a thickness of 1.25 ?m. In addition, MH release from the LbL coating is pH-sensitive. The coating and released MH demonstrated strong anti-biofilm, anti-inflammatory, and neuroprotective potencies. Significance. This study reports, for the first time, the development of a bioactive coating that can target infection, inflammation, and neuroprotection simultaneously, which may facilitate the translation of neural interfaces to clinical applications.

  19. Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances

    PubMed Central

    Mahdizadeh, Shahla; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2015-01-01

    Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain. PMID:26101752

  20. Anti-inflammatory therapies for cardiovascular disease

    PubMed Central

    Ridker, Paul M.; Lüscher, Thomas F.

    2014-01-01

    Atherothrombosis is no longer considered solely a disorder of lipoprotein accumulation in the arterial wall. Rather, the initiation and progression of atherosclerotic lesions is currently understood to have major inflammatory influences that encompass components of both the innate and acquired immune systems. Promising clinical data for ‘upstream’ biomarkers of inflammation such as interleukin-6 (IL-6) as well as ‘downstream’ biomarkers such as C-reactive protein, observations regarding cholesterol crystals as an activator of the IL-1? generating inflammasome, and recent Mendelian randomization data for the IL-6 receptor support the hypothesis that inflammatory mediators of atherosclerosis may converge on the central IL-1, tumour necrosis factor (TNF-?), IL-6 signalling pathway. On this basis, emerging anti-inflammatory approaches to vascular protection can be categorized into two broad groups, those that target the central IL-6 inflammatory signalling pathway and those that do not. Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). Both approaches have the potential to benefit patients and reduce vascular events. However, care should be taken when interpreting these trials as outcomes for agents that target IL-6 signalling are unlikely to be informative for therapies that target alternative pathways, and vice versa. As the inflammatory system is redundant, compensatory, and crucial for survival, evaluation of risks as well as benefits must drive the development of agents in this class. PMID:24864079

  1. Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins.

    PubMed

    Tubaro, Aurelia; Giangaspero, Anna; Sosa, Silvio; Negri, Roberto; Grassi, Gianpaolo; Casano, Salvatore; Della Loggia, Roberto; Appendino, Giovanni

    2010-10-01

    A selection of seven phytocannabinoids representative of the major structural types of classic cannabinoids and their corresponding cannabivarins was investigated for in vivo topical anti-inflammatory activity in the Croton oil mouse ear dermatitis assay. Differences in the terpenoid moiety were far more important for anti-inflammatory activity than those at the C-3 alkyl residue, suggesting the involvement not only of cannabinoid receptors, but also of other inflammatory end-points targeted by phytocannabinoids. PMID:20450962

  2. The Anti-inflammatory Effects of Acidic Polysaccharide from Artemisia capillaris on Helicobacter pylori Infection

    PubMed Central

    Park, Jong-Min; Hahm, Ki-Baik; Kwon, Sang-Oh; Kim, Eun-Hee

    2013-01-01

    Background: Helicobacter pylori infection is associated with diverse upper gastrointestinal diseases, such as peptic and duodenal ulcers as well as gastric cancer. Longstanding period of infection impose great risk of H. pylori-related gastric disease, based on the evidence that early childhood infection is responsible for ensuing atrophic gastritis and gastric cancer related to H. pylori infection. Artemisiahas been known to be beneficial for heath for a long time. In spite of well-acknowledged cytoprotective and anti-inflammatory actions of Artemisia, the effects of the acidic polysaccharide fractions on the gastroprotection remain to be investigated. Methods: In the current study, we compared anti-inflammatory actions of the acidic polysaccharide fraction between Artemisia and Panax ginseng against H. pylori infection in vitro. The polysaccharide fractions were pretreated 1 h before H. pylori infection on normal gastric mucosal RGM-1 cells and gastric cancer MKN-28 cells. RT-PCR and Western blot was performed to check anti-inflammatory actions. Results: The expressions of inflammatory markers including COX-2, iNOS and IL-8 increased after H. pylori infection, of which levels were significantly decreased when treating with the polysaccharide fractions from Artemisia and ginseng in RGM1 and gastric cancer MKN-28 cells. In addition, the polysaccharide fractions significantly ameliorated H. pylori-induced angiogenic and invasive markers such as HIF-1? and ICAM1. Moreover, H. pylori-induced apoptosis were prevented by pretreatment with the polysaccharide fractions. The polysaccharide fraction from Artemisia showed the most protective effects among the several polysaccharide fractions used in this study. Conclusions: The polysaccharide fraction of Artemisia capillariscan is a candidate substance which can attenuate either H. pylori-induced gastritis or tumorigenesis based on potent anti-inflammatory action. PMID:25337542

  3. Physicochemical characteristics and anti-inflammatory activities of antrodan, a novel glycoprotein isolated from Antrodia cinnamomea mycelia.

    PubMed

    Chiu, Chun-Hung; Peng, Chiung-Chi; Ker, Yaw-Bee; Chen, Chin-Chu; Lee, Arwen; Chang, Wan-Lin; Chyau, Charng-Cherng; Peng, Robert Y

    2013-01-01

    Antrodia cinnamomea (AC) is a unique fungus found inhabiting the rotten wood of Cinnamomum kanehirai. A submerged liquid culture of AC has been developed and its bioproducts have been used to meet the market demand for natural fruiting bodies. AC exhibits anti-inflammatory, antitumor, antioxidant, and immunomodulatory effects. Previously, we isolated polysaccharide AC-2 from AC mycelia by means of alkali extraction with subsequent acid precipitation and found it had a pronounced anti-inflammatory effect. In this study, a novel polysaccharide named "antrodan" was obtained by further purification of AC-2 using Sepharose CL-6B column chromatography. Antrodan exhibited a molecular weight of 442 kD and contained a particularly high content of uronic acid (152.6±0.8 mg/g). The protein content was 71.0%, apparently, higher than the carbohydrate content (14.1%), and thus antrodan was characterized as a glycoprotein. Its total glucan content was 15.65%, in which ?-glucan (14.20%) was prominently higher than ?-glucan (1.45%). Its FTIR confirmed the presence of ?-linkages between sugars, and intramolecular amide bonds between sugars and amino acids. Its 1H-NMR spectrum showed that antrodan was a complex union of ?- and ?-glucans, which had (1?4)-linked ?-Glcp and (1?3)-linked ?-Glcp linkages to the carbohydrate chains via asparagine linked to protein site. Biologically, antrodan was confirmed to be totally non-detrimental to RAW 264.7 cell line even at dose as high as 400 ?g/mL. It showed potent suppressing effect on the lipopolysaccharide-induced inflammatory responses in RAW 264.7 cell line. Moreover, antrodan significantly reduced the nitrogen oxide production at doses as low as 18.75 ?g/mL. PMID:24451244

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

    PubMed Central

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

    2010-01-01

    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. PMID:23956624

  5. Anti-Inflammatory and Vasoprotective Activity of a Retroviral-Derived Peptide, Homologous to Human Endogenous Retroviruses: Endothelial Cell Effects

    PubMed Central

    Cianciolo, George J.; Pizzo, Salvatore V.

    2012-01-01

    Malignant and inflammatory tissues sometimes express endogenous retroviruses or their proteins. A highly-conserved sequence from retroviral transmembrane (TM) proteins, termed the “immunosuppressive domain (ID)”, is associated with inhibition of immune and inflammatory functions. An octadecapeptide (MN10021) from the ID of retroviral TM protein p15E inhibits in vitro release of pro-inflammatory cytokines and increases synthesis of anti-inflammatory IL-10. We sought to determine if MN10021 has significant in vivo effects. MN10021, prepared by solid-phase synthesis, was dimerized through a naturally-occurring, carboxy-terminal cysteine. In vivo anti-inflammatory activity was determined using a murine model of sodium periodate (NaIO4)-induced peritonitis. In vivo vasoprotective effects were determined using: (1) a carrageenan-induced model of disseminated intravascular coagulation (DIC) in mice; (2) a reverse passive Arthus model in guinea pigs; and (3) vasoregulatory effects in spontaneously hypertensive rats (SHR). In vitro studies included: (1) binding/uptake of MN10021 using human monocytes, cultured fibroblasts, and vascular endothelial cells (VEC); (2) gene expression by RT-PCR of MN10021-treated VEC; and (3) apoptosis of MN10021-treated VEC exposed to staurosporine or TNF-?. One-tenth nmol MN10021 inhibits 50 percent of the inflammatory response in the mouse peritonitis model. Furthermore, 73 nmol MN10021 completely protects mice in a lethal model of carrageenan-induced DIC and inhibits vascular leak in both the mouse DIC model and a guinea pig reverse passive Arthus reaction. MN10021 binds to and is taken up in a specific manner by both human monocytes and VEC but not by cultured human fibroblasts. Surprisingly, orally-administered MN10021 lowers blood pressure in SHR rats by 10–15% within 1 h suggesting a direct or indirect effect on the vascular endothelium. MN10021 and derived octapeptides induce iNOS (inducible nitric oxide synthase) mRNA in VEC and nitrate in VEC cell culture supernatants and protect VEC from induced apoptosis or necrosis. However, pretreatment of VEC with nitro-L-arginine methyl ester (L-NAME), while inhibiting the release of nitrate, does not block the anti-apoptotic effect of MN10021 and derived octapeptides suggesting that their potent vasoprotective and anti-inflammatory activity is not nitric oxide dependent. PMID:23285152

  6. Prediction of Anti-inflammatory Plants and Discovery of Their Biomarkers by Machine Learning Algorithms and Metabolomic Studies.

    PubMed

    Chagas-Paula, Daniela Aparecida; Oliveira, Tiago Branquinho; Zhang, Tong; Edrada-Ebel, RuAngelie; Da Costa, Fernando Batista

    2015-04-01

    Nonsteroidal anti-inflammatory drugs are the most used anti-inflammatory medicines in the world. Side effects still occur, however, and some inflammatory pathologies lack efficient treatment. Cyclooxygenase and lipoxygenase pathways are of utmost importance in inflammatory processes; therefore, novel inhibitors are currently needed for both of them. Dual inhibitors of cyclooxygenase-1 and 5-lipoxygenase are anti-inflammatory drugs with high efficacy and low side effects. In this work, 57 leaf extracts (EtOH-H2O 7?:?3, v/v) from Asteraceae species with in vitro dual inhibition of cyclooxygenase-1 and 5-lipoxygenase were analyzed by high-performance liquid chromatography-high-resolution-ORBITRAP-mass spectrometry analysis and subjected to in silico studies using machine learning algorithms. The data from all samples were processed by employing differential expression analysis software coupled to the Dictionary of Natural Products for dereplication studies. The 6052 chromatographic peaks (ESI positive and negative modes) of the extracts were selected by a genetic algorithm according to their respective anti-inflammatory properties; after this procedure, 1241 of them remained. A study using a decision tree classifier was carried out, and 11 compounds were determined to be biomarkers due to their anti-inflammatory potential. Finally, a model to predict new biologically active extracts from Asteraceae species using liquid chromatography-mass spectrometry information with no prior knowledge of their biological data was built using a multilayer perceptron (artificial neural networks) with the back-propagation algorithm using the biomarker data. As a result, a new and robust artificial neural network model for predicting the anti-inflammatory activity of natural compounds was obtained, resulting in a high percentage of correct predictions (81?%), high precision (100?%) for dual inhibition, and low error values (mean absolute error?=?0.3), as also shown in the validation test. Thus, the biomarkers of the Asteraceae extracts were statistically correlated with their anti-inflammatory activities and can therefore be useful to predict new anti-inflammatory extracts and their anti-inflammatory compounds using only liquid chromatography-mass spectrometry data. PMID:25615275

  7. Antidiabetic agents: Potential anti-inflammatory activity beyond glucose control.

    PubMed

    Scheen, A J; Esser, N; Paquot, N

    2015-06-01

    A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to chronic inflammation. These observations pave the way to the development of new pharmacological strategies that aim to reduce silent inflammation. However, besides specific anti-inflammatory agents, glucose-lowering medications may also exert anti-inflammatory effects that could contribute to improved outcomes in diabetic patients. Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPAR?) agonists. Both pharmacological classes (considered insulin-sparing agents or insulin sensitizers) appear to have greater anti-inflammatory activity than insulin-secreting agents such as sulphonylureas or glinides. In particular, TZDs have shown the widest range of evidence of lowered tissue (visceral fat and liver) and serum inflammation. In contrast, despite reducing postprandial hyperglycaemia, the effect of ?-glucosidase inhibitors on inflammatory markers appears rather modest, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and glucagon-like peptide-1 (GLP-1) receptor agonists appear more promising in this respect. These incretin-based therapies exert pleiotropic effects, including reports of anti-inflammatory activity. No human data are available so far regarding sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Although they may have indirect effects due to reduced glucotoxicity, their specific mode of action in the kidneys does not suggest systemic anti-inflammatory activity. Also, in spite of the complex relationship between insulin and atherosclerosis, exogenous insulin may also exert anti-inflammatory effects. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and potential anti-inflammatory effects related to intrinsic actions of the pharmacological class. Finally, it would also be of major clinical interest to define what role the anti-inflammatory effects of these glucose-lowering agents may play in the prevention of macrovascular and microvascular diabetic complications. PMID:25794703

  8. Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms.

    PubMed

    Golechha, Mahaveer; Sarangal, Vikas; Ojha, Shreesh; Bhatia, Jagriti; Arya, Dharmveer S

    2014-01-01

    Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO). Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p.) administration of HAEEO at all the tested doses (300, 500, and 700?mg/kg) significantly (P < 0.001) inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700?mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P < 0.001) increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions. PMID:25215258

  9. ATP-Binding Pocket-Targeted Suppression of Src and Syk by Luteolin Contributes to Its Anti-Inflammatory Action

    PubMed Central

    Lee, Jeong-Oog; Jeong, Deok; Kim, Mi-Yeon; Cho, Jae Youl

    2015-01-01

    Luteolin is a flavonoid identified as a major anti-inflammatory component of Artemisia asiatica. Numerous reports have demonstrated the ability of luteolin to suppress inflammation in a variety of inflammatory conditions. However, its exact anti-inflammatory mechanism has not been fully elucidated. In the present study, the anti-inflammatory mode of action in activated macrophages of luteolin from Artemisia asiatica was examined by employing immunoblotting analysis, a luciferase reporter gene assay, enzyme assays, and an overexpression strategy. Luteolin dose-dependently inhibited the secretion of nitric oxide (NO) and prostaglandin E2 (PGE2) and diminished the levels of mRNA transcripts of inducible NO synthase (iNOS), tumor necrosis factor- (TNF-) ?, and cyclooxygenase-2 (COX-2) in lipopolysaccharide- (LPS-) and pam3CSK-treated macrophage-like RAW264.7 cells without displaying cytotoxicity. Luteolin displayed potent NO-inhibitory activity and also suppressed the nuclear translocation of NF-?B (p65 and p50) via blockade of Src and Syk, but not other mitogen-activated kinases. Overexpression of wild type Src and point mutants thereof, and molecular modelling studies, suggest that the ATP-binding pocket may be the luteolin-binding site in Src. These results strongly suggest that luteolin may exert its anti-inflammatory action by suppressing the NF-?B signaling cascade via blockade of ATP binding in Src and Syk. PMID:26236111

  10. The Effect of Polyphenols Isolated from Cynanchi wilfordii Radix with Anti-inflammatory, Antioxidant, and Anti-bacterial Activity.

    PubMed

    Jeong, Sunyoung; Lee, Sunwoo; Choi, Woo Jin; Sohn, Uy Dong; Kim, Wonyong

    2015-03-01

    Recently, Cynanchi wilfordii Radix has gained wide use in Asian countries as a functional food effective for relieving fatigue, osteoporosis, and constipation, particularly in menopausal disorders. However, its anti-inflammatory and anti-microbial activities have not been explored in detail to date. The anti-inflammatory, antioxidant, and anti-bacterial properties of the Cynanchi wilfordii Radix extracts obtained with water, methanol, ethanol, and acetone were compared. All 4 polyphenol-containing extracts exhibited anti-inflammatory and antioxidant effects. The ethanol extract was found to elicit the most potent reduction of nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine (IL-1?, IL-6, IL-10, and TNF-?) levels, as well as inhibit the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner. The evaluation of antioxidant activity also revealed the ethanol extract to have the highest free radical scavenging activity, measured as 85.3±0.4%, which is equivalent to 99.9% of the activity of ? -tocopherol. In the assessment of anti-bacterial activity, only ethanol extract was found to inhibit the growth of the Bacillus species Bacillus cereus and Bacillus anthracis. These results show that polyphenols of Cynanchi wilfordii Radix have anti-inflammatory, antioxidant, and anti-bacterial properties that can be exploited and further improved for use as a supplementary functional food, in cosmetics, and for pharmaceutical purposes. PMID:25729277

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

    PubMed

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

    2013-03-01

    Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action. PMID:23364884

  12. Tetra- and Pentacyclic Triterpene Acids from the Ancient Anti-inflammatory Remedy Frankincense as Inhibitors of Microsomal Prostaglandin E2 Synthase-1

    PubMed Central

    2014-01-01

    The microsomal prostaglandin E2 synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E2 from cyclooxygenase (COX)-derived PGH2. We previously found that mPGES-1 is inhibited by boswellic acids (IC50 = 3–30 ?M), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1 with increased potencies. In particular, 3?-acetoxy-8,24-dienetirucallic acid (6) and 3?-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC50 = 0.4 ?M, each. Structure–activity relationship studies and docking simulations revealed concrete structure-related interactions with mPGES-1 and its cosubstrate glutathione. COX-1 and -2 were hardly affected by the triterpene acids (IC50 > 10 ?M). Given the crucial role of mPGES-1 in inflammation and the abundance of highly active triterpene acids in frankincence extracts, our findings provide further evidence of the anti-inflammatory potential of frankincense preparations and reveal novel, potent bioactivities of tirucallic acids, roburic acids, and lupeolic acids. PMID:24844534

  13. Highly potent fibrinolytic serine protease from Streptomyces.

    PubMed

    Uesugi, Yoshiko; Usuki, Hirokazu; Iwabuchi, Masaki; Hatanaka, Tadashi

    2011-01-01

    We introduce a highly potent fibrinolytic serine protease from Streptomyces omiyaensis (SOT), which belongs to the trypsin family. The fibrinolytic activity of SOT was examined using in vitro assays and was compared with those of known fibrinolytic enzymes such as plasmin, tissue-type plasminogen activator (t-PA), urokinase, and nattokinase. Compared to other enzymes, SOT showed remarkably higher hydrolytic activity toward mimic peptides of fibrin and plasminogen. The fibrinolytic activity of SOT is about 18-fold higher than that of plasmin, and is comparable to that of t-PA by fibrin plate assays. Furthermore, SOT had some plasminogen activator-like activity. Results show that SOT and nattokinase have very different fibrinolytic and fibrinogenolytic modes, engendering significant synergetic effects of SOT and nattokinase on fibrinolysis. These results suggest that SOT presents important possibilities for application in the therapy of thrombosis. PMID:22112764

  14. Biological evaluation of synthetic chalcone and flavone derivatives as anti-inflammatory agents

    PubMed Central

    Mateeva, Nelly; Gangapuram, Madhavi; Mazzio, Elizabeth; Eyunni, Suresh; Soliman, Karam F. A.

    2015-01-01

    Flavonoids and chalcones are natural plant derived compounds with inherent therapeutic value for a range of human pathologies. In this study, a series of 24 substituted chalcones and flavones were synthesized and subsequently screened for anti-inflammatory effects on lipopolysaccharide (1 µg/ml)-activated BV-2 microglial cells by assessing initial production/release of nitric oxide (NO). The data obtained eliminate the majority of compounds as weak or non-effective, whereas 2?-hydroxy-3,4,5,3?,4?-pentamethoxychalcone (1) and 2?-hydroxy-3,4,5-trimethoxychalcone (2) were potent, having an IC50 of 1.10 and 2.26 µM, respectively; with greater potency than L-N6-(1-iminoethyl)lysine selective iNOS inhibitor (IC50 = 3.1 µM) but less than steroidal dexamethasone (IC50 < 200 nM). The most potent compound (chalcone 1) attenuated NO parallel to reducing iNOS protein expression, events also corresponding to reduction of IL-1?, IL-10 and IL-6 pro-inflammatory cytokines. These findings suggest that the presence of electron donating groups OH and OCH3 on both A and B rings of synthetic compounds correlate to stronger anti-inflammatory potency. PMID:25866456

  15. Antioxidant activity and anti-inflammatory activity of ethanol extract and fractions of Doenjang in LPS-stimulated RAW 264.7 macrophages

    PubMed Central

    Son, Dahee; Chung, Young-Shin; Kwon, Young Hye

    2015-01-01

    BACKGROUND/OBJECTIVES Fermentation can increase functional compounds in fermented soybean products, thereby improving antioxidant and/or anti-inflammatory activities. We investigated the changes in the contents of phenolics and isoflavones, antioxidant activity and anti-inflammatory activity of Doenjang during fermentation and aging. MATERIALS/METHODS Doenjang was made by inoculating Aspergillus oryzae and Bacillus licheniformis in soybeans, fermenting and aging for 1, 3, 6, 8, and 12 months (D1, D3, D6, D8, and D12). Doenjang was extracted using ethanol, and sequentially fractioned by hexane, dichloromethane (DM), ethylacetate (EA), n-butanol, and water. The contents of total phenolics, flavonoids and isoflavones, 2,2-diphenyl-1 picryl hydrazyl (DPPH) radical scavenging activity, and ferric reducing antioxidant power (FRAP) were measured. Anti-inflammatory effects in terms of nitric oxide (NO), prostaglandin (PG) E2 and pro-inflammatory cytokine production and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions were also measured using LPS-treated RAW 264.7 macrophages. RESULTS Total phenolic and flavonoid contents showed a gradual increase during fermentation and 6 months of aging and were sustained thereafter. DPPH radical scavenging activity and FRAP were increased by fermentation. FRAP was further increased by aging, but DPPH radical scavenging activity was not. Total isoflavone and glycoside contents decreased during fermentation and the aging process, while aglycone content and its proportion increased up to 3 or 6 months of aging and then showed a slow decrease. DM and EA fractions of Doenjang showed much higher total phenolic and flavonoid contents, and DPPH radical scavenging activity than the others. At 100 µg/mL, DM and EA fractions of D12 showed strongly suppressed NO production to 55.6% and 52.5% of control, respectively, and PGE2 production to 25.0% and 28.3% of control with inhibition of iNOS or COX-2 protein expression in macrophages. CONCLUSIONS Twelve month-aged Doenjang has potent antioxidant and anti-inflammatory activities with high levels of phenolics and isoflavone aglycones, and can be used as a beneficial food for human health. PMID:26634044

  16. Treatment of traumatic brain injury with anti-inflammatory drugs.

    PubMed

    Bergold, Peter J

    2016-01-01

    Traumatic brain injury rapidly induces inflammation. This inflammation is produced both by endogenous brain cells and circulating inflammatory cells that enter from the brain. Together they drive the inflammatory response through a wide variety of bioactive lipids, cytokines and chemokines. A large number of drugs with anti-inflammatory action have been tested in both preclinical studies and in clinical trials. These drugs either have known anti-inflammatory action or inhibit the inflammatory response through unknown mechanisms. The results of these preclinical studies and clinical trials are reviewed. Recommendations are suggested on how to improve preclinical testing of drugs to make them more relevant to evaluate for clinical trials. PMID:26112314

  17. Anti-inflammatory activities of crocetin derivatives from processed Gardenia jasminoides.

    PubMed

    Hong, Yun-Jung; Yang, Ki-Sook

    2013-08-01

    This study was designed to investigate changes of anti-oxidant and anti-nitric oxide (NO) production activities of Gardenia jasminoides (Gj) by roast processing, and anti-inflammatory activities of crocetin derivatives isolated from Gj. In order to evaluate anti-oxidant and anti-inflammatory activities, DPPH radical scavenging activities and inhibitory activities against lipopolysaccharide (LPS)-induced NO production were determined. Then we isolated crocin (1), gentiobiosyl glucosyl crocetin (3), and mono-gentiobiosyl crocetin (4) from the fruit of Gj, and crocetin (2) from the processed fruit of Gj (PGj) by column chromatography. Their structures were based on spectroscopic methods including IR, MS, and NMR (1D and 2D). Then we assayed contents of crocetin derivatives by HPLC analysis. These crocetin derivatives were evaluated the inhibitory activities on NO production in LPS-stimulated macrophage RAW 264.7 cells and expressions of protein and m-RNA of iNOS and COX-2 by western blot analysis and RT-PCR experiment. The DPPH radical scavenging activities were increased and NO productions in LPS-stimulated RAW 264.7 cells were decreased dose-dependently by processing. Crocin contents were decreased and crocetin contents were increased by processing in HPLC analysis. Compounds 1, 2, 3 and 4 reduced NO production in a dose-dependent manner with IC50 values of 58.9 ?M (1), 29.9 ?M (2), 31.1 ?M (3), and 37.6 ?M (4) respectively. Crocetin (2) showed the most potent anti-inflammatory activity (IC?? = 29.9 ?M), and compound 3 and 4 were firstly measured for inhibitory activities on NO production. Their correlation between structure and activity was not clear but the activity of aglycone type showed the most potent activity. They also suppressed the protein and m-RNA expressions of iNOS and COX-2 in LPS-activated macrophage. These results suggest that anti-oxidant and anti-NO production activities of Gj were increased by processing, and increased anti-inflammatory activities of Gj by processing were due to the increase of crocetin, the aglycone that has greater activity than crocin. PMID:23636885

  18. Synthesis, Characterization and Screening for Analgesic and Anti-inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives.

    PubMed

    Dewangan, Dhansay; Nakhate, Kartik T; Tripathi, D K; Kashyap, Pranita; Dhongde, Hemant

    2015-01-01

    The aim of the present investigation was to synthesize, characterize and evaluate analgesic and anti- inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives. The reaction of starting material 4-chloro-m-cresol with ethyl chloroacetate in dry acetone affords ethyl (4-chloro-3-methylphenoxy) acetate, which after reacting with the hydrazine hydrate in ethanol yields 2(4-chloro-3-methylphenoxy) acetohydrazide. When 2(4-chloro-3-methylphenoxy) acetohydrazide was treated with different aromatic aldehydes, aromatic acids and carbon disulfide in alcoholic solution, different 3-acetyl-5-[(4-chloro-3-methylphenoxy) methyl]-2-aryl-2, 3-dihydro-1, 3, 4-oxadiazole and 2-[(4-chloro-3-methylphenoxy) methyl]-5-aryl-1, 3, 4-oxadiazole derivatives were obtained. Purity of the derivatives was confirmed by thin layer chromatography and melting point. Structure of these derivatives was set up by determining infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy. Further, the synthesized derivatives were evaluated for their analgesic and anti-inflammatory activities in rodents. In animal studies, the derivatives 3-acetyl-5-[(4-chloro-3- methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole and 4-{5-[(4-chloro-3- methylphenoxy)methyl]-1, 3, 4-oxadiazol-2-yl}pyridine show more potent analgesic activity and the derivatives 2-{3-acetyl-5-[(4-chloro-3-methylphenoxy)methyl]-2,3-dihydro-1, 3, 4-oxadiazol-2-yl}phenol and 3-acetyl-5- [(4-chloro-3-methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole exhibit more potent anti-inflammatory effect as compared to other derivatives. The results of the current study indicate that cyclization of acetohydrazide produces novel oxadiazole derivatives with potent analgesic and anti-inflammatory activities. PMID:26290079

  19. Ethynylphenyl carbonates and carbamates as dual-action acetylcholinesterase inhibitors and anti-inflammatory agents.

    PubMed

    Saxena, Jaya; Meloni, David; Huang, Mou-Tuan; Heck, Diane E; Laskin, Jeffrey D; Heindel, Ned D; Young, Sherri C

    2015-12-01

    Novel ethynylphenyl carbonates and carbamates containing carbon- and silicon-based choline mimics were synthesized from their respective phenol and aniline precursors and screened for anticholinesterase and anti-inflammatory activities. All molecules were micromolar inhibitors of acetylcholinesterase (AChE), with IC50s of 28-86?M; the carbamates were two-fold more potent than the carbonates. Two of the most potent AChE inhibitors suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation by 40%. Furthermore, these molecules have physicochemical properties in the range of other CNS drugs. These molecules have the potential to treat inflammation; they could also dually target Alzheimer's disease through restoration of cholinergic balance and inflammation suppression. PMID:26510670

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

    PubMed Central

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

    2011-01-01

    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. PMID:22028854

  1. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

    PubMed

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

    2011-01-01

    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. PMID:22028854

  2. Fatty acid-binding protein 5 limits the anti-inflammatory response in murine macrophages.

    PubMed

    Moore, Sherri M; Holt, Vivian V; Malpass, Lillie R; Hines, Ian N; Wheeler, Michael D

    2015-10-01

    The beginning stages of liver damage induced by various etiologies (i.e. high fat diet, alcohol consumption, toxin exposure) are characterized by abnormal accumulation of lipid in liver. Alterations in intracellular lipid transport, storage, and metabolism accompanied by cellular insult within the liver play an important role in the pathogenesis of liver disease, often involving a sustained inflammatory response. The intracellular lipid transporter, fatty acid binding protein 5 (FABP5), is highly expressed in macrophages and may play an important role in the hepatic inflammatory response after endotoxin exposure in mice. This study tested the hypothesis that FABP5 regulates macrophage response to LPS in male C57bl/6 (wild type) and FABP5 knockout mice, both in vitro and in vivo. Treatment with LPS revealed that loss of FABP5 enhances the number of hepatic F4/80(+) macrophages in the liver despite limited liver injury. Conversely, FABP5 knock out mice display higher mRNA levels of anti-inflammatory cytokines IL-10, arginase, YM-1, and Fizz-1 in liver compared to wild type mice. Bone marrow derived macrophages stimulated with inflammatory (LPS and IFN-?) or anti-inflammatory (IL-4) mediators also showed significantly higher expression of anti-inflammatory/regulatory factors. These findings reveal a regulatory role of FABP5 in the acute inflammatory response to LPS-induced liver injury, which is consistent with the principle finding that FABP5 is a regulator of macrophage phenotype. Specifically, these findings demonstrate that loss of FABP5 promotes a more anti-inflammatory response. PMID:26105806

  3. The Use of Nonsteroidal Anti-Inflammatory Drugs in Sports.

    ERIC Educational Resources Information Center

    Calabrese, Leonard H.; Rooney, Theodore W.

    1986-01-01

    Recent advances in the understanding of the mechanism of action and clinical pharmacology of the new nonsteroidal anti-inflammatory drugs (NSAIDs) can help practitioners decide which to use and how to administer them. Indications for and effects of NSAIDs are described. (MT)

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

    PubMed

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

    2015-01-01

    Potentilla species have been used in traditional medicine in the treatment of different ailment, disease or malady. Potentilla reptans (P. reptans) has been scarcely studied. The aim of this study was to test antioxidant and anti-inflammatory activity of P. reptans aerial part and rhizome. DPPH assay was used to measure antioxidant activity of aqueous plant extracts. Anti-inflammatory effect was evaluated by experimental animal model of phenol-in-acetone induced mice ear edema. DPPH radical-scavenging activity of both tested extracts was concentration dependent with IC50 values 12.11 ?g/mL (aerial part) and 2.57 ?g/mL (rhizome). Maximum anti-inflammatory effect (61.37%) was observed after administration of 10 mg/ear of the rhizome extract and it was 89.24% of effect induced by dexamethasone as a standard. In conclusion, P. reptans rhizome aqueous extract possesses anti-inflammatory effect and higher antioxidant activity than aerial part. PMID:25850209

  5. Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

    PubMed Central

    Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

    2014-01-01

    Objective To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil. Methods In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-? mRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR. Results Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-?-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC50 12-15 µg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-? mRNA expression in the cells at concentrations of 50 µg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses. Conclusions T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions. PMID:25182441

  6. Evolving Therapeutic Strategies to Improve Nonsteroidal Anti-inflammatory Drug Safety.

    PubMed

    McCarberg, Bill H; Cryer, Byron

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) possess potent anti-inflammatory and analgesic properties through inhibition of cyclooxygenase enzymes (COX-1 and COX-2), which are responsible for synthesis of proinflammatory mediators. NSAIDs are frequently used for treatment of acute and chronic pain conditions. However, their use is associated with serious dose-dependent gastrointestinal (GI), cardiovascular, renal, and hepatic adverse effects, which pose a serious clinical concern for both patients and physicians. During the past 2 decades, approaches to improving the tolerability of NSAIDs were mainly directed toward discovery of COX-2 selective NSAIDs (coxibs), which were expected to minimize the risk of GI injury. Unfortunately, the results from multiple clinical studies have shown that treatment with coxibs may increase the risk for cardiovascular complications. This review summarizes current strategies used to reduce the toxicity of NSAIDs and outlines novel therapeutic approaches still in preclinical development. To minimize the risk of GI ulcerations and bleeding, combination therapies with gastroprotective agents are currently recommended. The new therapeutic agents anticipated to have similar effects include nitric oxide- and hydrogen sulfide-releasing NSAIDs. Novel manufacturing technologies enhance dissolution and absorption of NSAID products, allowing for their administration at low doses, which could lead to improved drug tolerability without diminishing the analgesic and anti-inflammatory efficacy of NSAIDs. This principle is in line with the current recommendation by the US Food and Drug Administration that NSAIDs should be used at the lowest effective dosage. Finally, NSAID formulations targeted directly to the site of inflammation are expected to reduce systemic drug exposure and thus decrease the risk of systemic adverse effects. PMID:25251373

  7. NONSPECIFIC ANTI-INFLAMMATORY AGENTS—Some Notes on Their Practical Application, Especially in Rheumatic Disorders

    PubMed Central

    Boland, Edward W.

    1964-01-01

    A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented. Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases. Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight. Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages. Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia. A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive therapeutic trial; with dosages that can be tolerated the drug is fairly effective in the symptomatic control of ankylosing (rheumatoid) spondylitis but it is of questionable value in peripheral rheumatoid arthritis. PMID:14131394

  8. Discovery of Novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole Derivatives as Potential Anti-Inflammatory Agents.

    PubMed

    Li, Qing; Hu, Qinghua; Wang, Xinning; Zong, Yang; Zhao, Leilei; Xing, Junhao; Zhou, Jinpei; Zhang, Huibin

    2015-10-01

    A novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 5 with good anti-inflammatory activity was identified from our in-house library. Based on hit compound 5, two series of 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 6a-g and 7a-h were designed and synthesized as novel anti-inflammatory agents. Most of synthesized compounds exhibited good inhibitory activity on NO and TNF-? production in LPS-stimulated RAW 264.7 macrophages, in which the compound 6e showed most potent inhibitory activity on NO (IC50  = 0.86 ?m) and TNF-? (IC50  = 1.87 ?m) production. Further evaluation revealed that compound 6e displayed more potent in vivo anti-inflammatory activity than ibuprofen did on xylene-induced ear oedema in mice. Additionally, Western blot analysis revealed that compound 6e could restore phosphorylation level of I?B? and protein expression of p65 NF-?B in LPS-stimulated RAW 264.7 macrophages. PMID:25588891

  9. Antioxidant, Analgesic, Anti-Inflammatory, and Hepatoprotective Effects of the Ethanol Extract of Mahonia oiwakensis Stem

    PubMed Central

    Chao, Jung; Liao, Jiunn-Wang; Peng, Wen-Huang; Lee, Meng-Shiou; Pao, Li-Heng; Cheng, Hao-Yuan

    2013-01-01

    The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOSEtOH). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOSEtOH was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOSEtOH exhibited antioxidative activity using the DPPH assay (IC50, 0.743 mg/mL). The DPPH radical scavenging activity of MOSEtOH was five times higher that that of vitamin C. MOSEtOH was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOSEtOH (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl4-treated group. Histological evaluation showed that MOSEtOH reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOSEtOH were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOSEtOH has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOSEtOH for relieving pain and inflammation in folk medicine. PMID:23364614

  10. Nanoparticles with dual responses to oxidative stress and reduced ph for drug release and anti-inflammatory applications.

    PubMed

    Pu, Hsiao-Lan; Chiang, Wei-Lun; Maiti, Barnali; Liao, Zi-Xian; Ho, Yi-Cheng; Shim, Min Suk; Chuang, Er-Yuan; Xia, Younan; Sung, Hsing-Wen

    2014-02-25

    Oxidative stress and reduced pH are involved in many inflammatory diseases. This study describes a nanoparticle-based system that is responsive to both oxidative stress and reduced pH in an inflammatory environment to effectively release its encapsulated curcumin, an immune-modulatory agent with potent anti-inflammatory and antioxidant capabilities. Because of the presence of Förster resonance energy transfer between curcumin and the carrier, this system also allowed us to monitor the intracellular release behavior. The curcumin released upon triggering could efficiently reduce the excess oxidants produced by the lipopolysaccharide (LPS)-stimulated macrophages. The feasibility of using the curcumin-loaded nanoparticles for anti-inflammatory applications was further validated in a mouse model with ankle inflammation induced by LPS. The results of these studies demonstrate that the proposed nanoparticle system is promising for treating oxidative stress-related diseases. PMID:24386907

  11. Anti-Diabetic and Anti-Inflammatory Effects of Green and Red Kohlrabi Cultivars (Brassica oleracea var. gongylodes)

    PubMed Central

    Jung, Hyun Ah; Karki, Subash; Ehom, Na-Yeon; Yoon, Mi-Hee; Kim, Eon Ji; Choi, Jae Sue

    2014-01-01

    The aim of the present study was to evaluate the anti-diabetic, anti-inflammatory, antioxidant potential, and total phenolic content (TPC) of green and red kohlrabi cultivars. Anti-diabetic and anti-inflammatory activities were evaluated via protein tyrosine phosphatase (PTP1B) and rat lens aldose reductase inhibitory assays and cell-based lipopolysaccharide (LPS)-induced nitric oxide (NO) inhibitory assays in RAW 264.7 murine macrophages. In addition, scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2?-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical, and peroxynitrite (ONOO?) were used to evaluate antioxidant potential and TPC was selected to assess phytochemical characteristics. Between the two kohlrabi cultivars, red kohlrabi (RK) had two times more TPC than green kohlrabi (GK) and showed significant antioxidant effects in DPPH, ABTS, and ONOO? scavenging assays. Likewise, methanol (MeOH) extracts of RK and GK inhibited LPS-induced NO production in a dose dependent manner that was further clarified by suppression of iNOS and COX-2 protein production. The MeOH extracts of RK and GK exhibited potent inhibitory activities against PTP1B with the corresponding IC50 values of 207±3.48 and 287±3.22 ?g/mL, respectively. Interestingly, the RK MeOH extract exhibited significantly stronger anti-inflammatory, anti-diabetic, and antioxidant effects than that of GK MeOH extract. As a result, our study establishes that RK extract with a higher TPC might be useful as a potent anti-diabetic, antioxidant, and anti-inflammatory agent. PMID:25580392

  12. Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties.

    PubMed

    Kim, A-Reum; Shin, Tai-Sun; Lee, Min-Sup; Park, Ji-Young; Park, Kyoung-Eun; Yoon, Na-Young; Kim, Jong-Soon; Choi, Jae-Sue; Jang, Byeong-Churl; Byun, Dae-Seok; Park, Nam-Kyu; Kim, Hyeung-Rak

    2009-05-13

    Bioactivity-guided fractionation of Ecklonia stolonifera was used to determine the chemical identity of bioactive constituents, with potent antioxidant activities. The structures of the phlorotannins were determined on the basis of spectroscopic analysis, including NMR and mass spectrometry analysis. The antioxidant activities of the isolated compounds were evaluated by free radical scavenging activities in both in vitro and cellular systems. The anti-inflammatory effects of the isolated compounds were evaluated by determining their inhibitory effects on the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophage cells. The results indicated that phlorofucofuroeckol A, dieckol, and dioxinodehydroeckol showed potential radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl. Among them, phlorofucofuroeckol A and dieckol significantly suppressed the intracellular reactive oxygen species level assayed by 2',7'-dichlorofluorescein diacetate assay in LPS-induced RAW 264.7 cells. Phlorofucofuroeckol A significantly inhibited the LPS-induced production of NO and PGE(2) through the down-regulation of inducible nitric oxide synthase and cyclooxygenase 2 protein expressions. In conclusion, these results suggest that phlorofucofuroeckol A has a potential for functional foods with antioxidant and anti-inflammatory activities. PMID:19338274

  13. Convergence of Nitric Oxide and Lipid Signaling: Anti-Inflammatory Nitro-Fatty Acids

    PubMed Central

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

    2009-01-01

    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 sythesis that is strongly influenced by the local chemical environment. The relationship between the two pathways extends beyond co-regulation of ·NO and eicosanoid formation to converge via the nitration of unsaturated fatty acids to yield nitro derivatives (NO2-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 NO2-FA are diverse, with these species serving as a potential chemical reserve of ·NO, reacting with cellular nucleophiles to post-translationally modify protein structure, function and localization. In this regard these species act as potent endogenous ligands for peroxisome proliferator activated receptor ?. 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 pre-constricted rat aortic segments. These observations have propelled further in vitro and in vivo studies of mechanisms of NO2-FA signaling and metabolism, highlighting the therapeutic potential of this class of molecules as anti-inflammatory drug candidates. PMID:19200454

  14. Anti-inflammatory activity of Yanshu spraying agent in animal models

    PubMed Central

    ZHANG, JIANQIAO; WANG, HONGSHENG; WANG, TIAN; CHONG, YATING; YU, PENGFEI; LU, CHENGWEN; XUE, YUNLI; FU, FENGHUA; ZHANG, LEIMING

    2013-01-01

    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. PMID:23251244

  15. Antioxidant, Anti-inflammatory, and Chemoprotective Properties of Acacia catechu Heartwood Extracts.

    PubMed

    Stohs, Sidney J; Bagchi, Debasis

    2015-06-01

    Aqueous extracts of Acacia catechu heartwood are rich source of catechin and epicatechin (gallic acid derivatives), with smaller amounts of flavonoids. Extracts have also been prepared with ethyl acetate, ethanol, and methanol, and the properties of these extracts have been studied and are reviewed. Potent antioxidant activity has been well established in both in vitro and in vivo studies. This antioxidant activity is believed to be responsible for the anti-inflammatory, tissue protectant, antineoplastic, and analgesic activities that have been demonstrated and clearly established in animal and cell culture systems. Furthermore, antihyperglycemic, antidiarrheal, antinociceptive, and antipyretic activities have been demonstrated in animal studies. No adverse effects have been observed in animal or human studies or in cell culture systems. In spite of the fact that Acacia products have been used for many years and the general safety of catechins and epicatechins is well documented, few human studies have ever been conducted on the efficacy or safety of A.?catechu heartwood extracts. Several studies have shown that a two-ingredient combination product containing A.?catechu extract exhibited no adverse effects when administered daily for up to 12?weeks while exhibiting significant anti-inflammatory activity in subjects with osteoarthritis of the knee. There is a need for additional human clinical studies with regard to efficacy and safety. PMID:25802170

  16. Anti-inflammatory effect of Momordica charantia in sepsis mice.

    PubMed

    Chao, Che-Yi; Sung, Ping-Jyun; Wang, Wei-Hsien; Kuo, Yueh-Hsiung

    2014-01-01

    Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPAR? and PPAR?. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-? tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-?B, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis. PMID:25153878

  17. Anti-inflammatory and cytotoxic activities of Bursera copallifera

    PubMed Central

    Columba-Palomares, M. F. María C.; Villareal, Dra. María L.; Acevedo Quiroz, M. C. Macdiel E.; Marquina Bahena, M. C. Silvia; Álvarez Berber, Dra. Laura P.; Rodríguez-López, Dra. Verónica

    2015-01-01

    Background: The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain Objective: The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. Materials and Methods: We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. Results: The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 ?g/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 ?g/mL, IC50 = 5.7 ?g/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 ?g/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 ?g/mL), whereas DMeL exhibited an IC50 value of 19.9 ?g/mL. Conclusion: In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera. PMID:26664022

  18. Genome Sequence of Lactobacillus delbrueckii subsp. lactis CNRZ327, a Dairy Bacterium with Anti-Inflammatory Properties

    PubMed Central

    El Kafsi, Hela; Binesse, Johan; Loux, Valentin; Buratti, Julien; Boudebbouze, Samira; Dervyn, Rozenn; Hammani, Amal; Maguin, Emmanuelle

    2014-01-01

    Lactobacillus delbrueckii subsp. lactis CNRZ327 is a dairy bacterium with anti-inflammatory properties both in vitro and in vivo. Here, we report the genome sequence of this bacterium, which appears to contain no less than 215 insertion sequence (IS) elements, an exceptionally high number regarding the small genome size of the strain. PMID:25035318

  19. Genome Sequence of Lactobacillus delbrueckii subsp. lactis CNRZ327, a Dairy Bacterium with Anti-Inflammatory Properties.

    PubMed

    El Kafsi, Hela; Binesse, Johan; Loux, Valentin; Buratti, Julien; Boudebbouze, Samira; Dervyn, Rozenn; Hammani, Amal; Maguin, Emmanuelle; van de Guchte, Maarten

    2014-01-01

    Lactobacillus delbrueckii subsp. lactis CNRZ327 is a dairy bacterium with anti-inflammatory properties both in vitro and in vivo. Here, we report the genome sequence of this bacterium, which appears to contain no less than 215 insertion sequence (IS) elements, an exceptionally high number regarding the small genome size of the strain. PMID:25035318

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. Constituents from Vigna vexillata and Their Anti-Inflammatory Activity

    PubMed Central

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

    2012-01-01

    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. PMID:22949828

  2. Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases

    PubMed Central

    Ishiguro, Hitoshi; Kawahara, Takashi

    2014-01-01

    Prostatic diseases are characterized by increased activity of cytokines, growth factors, and cyclooxygenases- (COX-) 1 and 2. Activation of COX-1 and COX-2 results in increased levels of prostaglandins and the induction of angiogenic, antiapoptotic and inflammatory processes. Inhibition of COX enzymes by members of the widely used nonsteroidal anti-inflammatory drug (NSAID) class of drugs decreases prostaglandin production, and exerts a variety of anti-inflammatory, antipyretic, and antinociceptive effects. While numerous in vitro, in vivo, and clinical studies have shown that NSAIDs inhibit the risk and progression of prostatic diseases, the relationship between NSAIDs and such diseases remains controversial. Here we review the literature in this area, critically analyzing the benefits and caveats associated with the use of NSAIDs in the treatment of prostatic diseases. PMID:24900965

  3. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

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

    2013-01-01

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

  4. Non-steroid anti-inflammatory drugs, prostaglandins, and cancer

    PubMed Central

    2013-01-01

    Fatty acids are involved in multiple pathways and play a pivotal role in health. Eicosanoids, derived from arachidonic acid, have received extensive attention in the field of cancer research. Following release from the phospholipid membrane, arachidonic acid can be metabolized into different classes of eicosanoids through cyclooxygenases, lipoxygenases, or p450 epoxygenase pathways. Non-steroid anti-inflammatory drugs (NSAIDs) are widely consumed as analgesics to relieve minor aches and pains, as antipyretics to reduce fever, and as anti-inflammatory medications. Most NSAIDs are nonselective inhibitors of cyclooxygenases, the rate limiting enzymes in the formation of prostaglandins. Long term use of some NSAIDs has been linked with reduced incidence and mortality in many cancers. In this review, we appraise the biological activities of prostanoids and their cognate receptors in the context of cancer biology. The existing literature supports that these lipid mediators are involved to a great extent in the occurrence and progression of cancer. PMID:23388178

  5. Anti-inflammatory activity of Heliotropium strigosum in animal models.

    PubMed

    Khan, Haroon; Khan, Murad Ali; Gul, Farah; Hussain, Sajjid; Ashraf, Nadeem

    2015-12-01

    The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models. PMID:23823617

  6. Antioxidant and anti-inflammatory activities of silver nanoparticles biosynthesized from aqueous leaves extracts of four Terminalia species

    NASA Astrophysics Data System (ADS)

    El-Rafie, Hanaa Mohamed; Abdel-Aziz Hamed, Manal

    2014-09-01

    The environmentally friendly synthesis of nanoparticles process is a revolutionary step in the field of nanotechnology. In recent years plant mediated biological synthesis of nanoparticles has been gaining importance due to its simplicity and eco-friendliness. In this study, a simple and an efficient eco-friendly approach for the biosynthesis of stable, monodisperse silver nanoparticles using aqueous extracts of four Terminalia species, namely, Terminalia catappa, Terminalia mellueri, Terminalia bentazoe and Terminalia bellerica were described. The silver nanoparticles were characterized in terms of synthesis, capping functionalities (polysaccharides, phenolics and flavonoidal compounds) and microscopic evaluation by UV-visible spectroscopy, Fourier transform infrared spectroscopy and transmission electron microscopy. The results showed a simple and feasible approach for obtaining stable aqueous monodispersive silver nanoparticles. Furthermore, biological activity of the biosynthesized silver nanoparticles was examined. Concerning this, dose-dependent antioxidant activity of silver nanoparticles imparted by the plant phenolic and flavonoidal components was evaluated using in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and found to be comparable to standard ascorbic acid. The same holds true for the anti-inflammatory activity where Terminalia catappa and Terminalia mellueri have a high-test inhibition percentage better than that of ascorbic acid in the carrageenan induced hind paw edema. The results also revealed that the aqueous extract of Terminallia catapa and its silver nanoparticles recorded the most potent in vivo antioxidant effect.

  7. Analgesic and Anti-Inflammatory Properties of Arylnitroalkenes.

    PubMed

    Celano, Laura; Cupertino Da Silva, Yolanda K; Cataldo, Nicolás; Gabay, Martín; Merlino, Alicia; Alexandre-Moreira, Magna S; Lima, Lidia Moreira; Cerecetto, Hugo; González, Mercedes; Thomson, Leonor

    2015-01-01

    In a recent work, we described the design and synthesis of arylnitroalkenes, able to scavenge macrophagederived oxidants, in particular peroxynitrite and peroxynitrite derived radicals. Four compounds emerged as potential leads, 1,1-dimethylamino-4-(2-nitro-1Z-ethenyl)benzene (1), 1,1-dimethylamino-4-(2-nitro-1Z-propenyl)benzene (2), 5- (2-nitro-1Z-ethenyl)benzo[d][1,3]dioxol (3), and 5-(2-nitro-1Z-ethenyl)benzo[d][1,3]dioxol (4). In the present work, the possibility of the preclinical validation of these molecules as anti-inflammatory and analgesic was explored in appropriate in vivo mouse models. Compounds 1, 2 and 4, administered orally as a single dose (30 µmol kg-(1)) to the mice showed anti-inflammatory and analgesic properties similar to classic nonsteroidal anti-inflammatory agents. The pharmacological effects were consistent with the inhibitory effect observed on prostaglandin endoperoxide H synthase (PGHS). In fact, both PGHS-1 and PGHS-2 were inhibited by the compounds, with compound 2 being more specific as PGHS-2 inhibitor with a specificity index superior to 70%. Conversely to classical nonsteroidal anti-inflammatory drugs, compound 2 inhibited peroxidase half reaction of the enzyme (IC50 2.3 µM) while the cyclooxygenase activity of hrPGHS-2 remained unchanged. In vitro experiments were reinforced by docking and molecular dynamics simulations showing arylnitroalkene moiety located in the region of the peroxidase active site, competing with the peroxide intermediate. The absence of toxicity and mutagenicity of the compounds was also demonstrated. PMID:26490661

  8. Anti-inflammatory and anthelmintic activities of Solanum khasianum Clarke.

    PubMed

    Jarald, E Edwin; Edwin, S; Saini, V; Deb, L; Gupta, V B; Wate, S P; Busari, K P

    2008-02-15

    In order to scientifically appraise some of the folkloric uses of Solanum khasianum Clarke (Solanaceae), the present study was undertaken to examine the anti-inflammatory and anthelmintic properties of the berries of ethanol extract. Anti-inflammatory activity was tested in carrageenan induced rat hind paw edema method at three dose level of 200, 300, and 400 mg kg(-1) respectively, Diclofenac sodium (100 mg kg(-1)) was used as the reference standard. The anti-inflammatory activity of the extract was compared with standard and control. The anthelmintic activity of the extract was tested on tape worm, liver fluke, thread worm, and hook worm using two different concentrations, 100 and 200 mg mL(-1) respectively. Time taken for the inhibition of motility was noted and compared with the standard drug, Piperazine citrate 15 mg mL. The plant extract significantly (p < 0.01) reduced the inflammation of the rats when compared to the control group. Also, the ethanol extract of the plant paralyzed the worms followed by death, which was comparable with that of the standard. This study supports the folk claim. PMID:18266159

  9. Calcium fructoborate--potential anti-inflammatory agent.

    PubMed

    Scorei, Romulus Ion; Rotaru, Petre

    2011-12-01

    Calcium fructoborate is a boron-based nutritional supplement. Its chemical structure is similar to one of the natural forms 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 scavenger and anti-inflammatory agent. It may influence macrophage production of inflammatory mediators, can be beneficial for the suppression of cytokine production, and inhibits progression of endotoxin-associated diseases, as well as the boric acid and other boron sources. The mechanisms by which calcium fructoborate exerts its beneficial anti-inflammatory effects are not entirely clear, but some of its molecular biological in vitro activities are understood: inhibition of the superoxide within the cell; inhibition of the interleukin-1?, interleukin-6, and nitric oxide release in the culture media; and increase of the tumor necrosis factor-? production. Also, calcium fructoborate has no effects on lipopolysaccharide-induced cyclooxygenase-2 protein express. The studies on animals and humans with a dose range of 1-7 mg calcium fructoborate (0.025-0.175 mg elemental boron)/kg body weight/day exhibited a good anti-inflammatory activity, and it also seemed to have negligible adverse effect on humans. PMID:21274653

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

    PubMed Central

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

    2013-01-01

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

  11. Anti-inflammatory effects of Allium schoenoprasum L. leaves.

    PubMed

    Parvu, A E; Parvu, M; Vlase, L; Miclea, P; Mot, A C; Silaghi-Dumitrescu, R

    2014-04-01

    Allium schoenoprasum has antimicrobial and antifungal properties and is used to relieve pain from sunburn and sore throat. The aim of the present study was to evaluate the anti-inflammatory effects of the extracts from A. schoenoprasum leaves. A 1:1 (w:v) extract was prepared by a modified Squibb repercolation method. The total phenolic content of 68.5±2 g gallic acid aquivalent (GAE)/g plant was determined using the Folin-Ciocalteu method. The in vitro antioxidant activity was determined using the 1,1-diphenyl-2-picrylhydrazyl bleaching method (6.72±0.44 g/mg DPPH) and the trolox equivalent antioxidant capacity (132.8±23 g trolox eq./g plant) assay. Analysis of the extracts using the hemoglobin ascorbate peroxidase activity inhibition assay or the electron spin resonance did not yield signals above the detection limit. The anti-inflammatory effects of three extract concentrations (25%, 50%, 100%) were evaluated in vivo on a model turpentine oil-induced inflammation in rats. These three extracts were also evaluated in vitro for the ability to inhibit phagocytosis, the accumulation of total nitrites and nitrates in the serum, the total oxidative status, the total antioxidant response and the oxidative stress index. Pure extracts (100% concentration) had the best inhibitory activity on phagocytosis and oxidative stress. In conclusion, these results support the hypothesis that extracts from A. schoenoprasum leaves exert anti-inflammatory activities by inhibiting phagocytosis through the reduction of nitro-oxidative stress. PMID:24781739

  12. Anti-inflammatory activity of traditional Chinese medicinal herbs

    PubMed Central

    Pan, Min-Hsiung; Chiou, Yi-Shiou; Tsai, Mei-Ling; Ho, Chi-Tang

    2011-01-01

    Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for various human diseases. Thus, suppressing chronic inflammation has the potential to delay, prevent, and control various chronic diseases, including cerebrovascular, cardiovascular, joint, skin, pulmonary, blood, lymph, liver, pancreatic, and intestinal diseases. Various natural products from traditional Chinese medicine (TCM) have been shown to safely suppress proinflammatory pathways and control inflammation-associated disease. In vivo and/or in vitro studies have demonstrated that anti-inflammatory effects of TCM occur by inhibition of the expression of master transcription factors (for example, nuclear factor-?B (NF-?B)), pro-inflammatory cytokines (for example, tumor necrosis factor-? (TNF-?), chemokines (for example, chemokine (C-C motif) ligand (CCL)-24), intercellular adhesion molecule expression and pro-inflammatory mediators (for example, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)). However, a handful of review articles have focused on the anti-inflammatory activities of TCM and explore their possible mechanisms of action. In this review, we summarize recent research attempting to identify the anti-inflammatory constituents of TCM and their molecular targets that may create new opportunities for innovation in modern pharmacology. PMID:24716101

  13. Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

    PubMed

    Kim, Seong-Min; Lim, So-Mang; Yoo, Jeong-Ah; Woo, Moon-Jea; Cho, Kyung-Hyun

    2015-11-01

    Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers. PMID:26333284

  14. Lipidated cyclic ?-AApeptides display both antimicrobial and anti-inflammatory activity.

    PubMed

    Li, Yaqiong; Smith, Christina; Wu, Haifan; Padhee, Shruti; Manoj, Namitha; Cardiello, Joseph; Qiao, Qiao; Cao, Chuanhai; Yin, Hang; Cai, Jianfeng

    2014-01-17

    Antimicrobial peptides (AMPs) are host-defense agents capable of both bacterial membrane disruption and immunomodulation. However, the development of natural AMPs as potential therapeutics is hampered by their moderate activity and susceptibility to protease degradation. Herein we report lipidated cyclic ?-AApeptides that have potent antibacterial activity against clinically relevant Gram-positive and Gram-negative bacteria, many of which are resistant to conventional antibiotics. We show that lipidated cyclic ?-AApeptides mimic the bactericidal mechanism of AMPs by disrupting bacterial membranes. Interestingly, they also harness the immune response and inhibit lipopolysaccharide (LPS) activated Toll-like receptor 4 (TLR4) signaling, suggesting that lipidated cyclic ?-AApeptides have dual roles as novel antimicrobial and anti-inflammatory agents. PMID:24144063

  15. Anti-inflammatory pharmacotherapy during pregnancy.

    PubMed

    Østensen, Monika E; Skomsvoll, Johan F

    2004-03-01

    NSAIDs or cyclooxygenase inhibitors (COX inhibitors), including aspirin, are widely used to treat pain, fever and the articular symptoms of chronic rheumatic diseases. Manifestations of connective tissue or autoimmune diseases are commonly treated with glucocorticosteroids. The effect and side effects of NSAIDs depend on the isoforms of cyclooxygenases that they preferentially or selectively inhibit. The use of COX inhibitors has recently been associated with infertility and miscarriage. The classical nonselective COX inhibitors, including aspirin, do not increase the risk of congenital malformations in humans but administered in the latter part of gestation, they can affect pregnancy and the fetus. The ability of nonselective and selective COX inhibitors to prolong gestation has been used by obstetricians to inhibit premature delivery. The vascular effects of prostaglandin inhibitors can cause constriction of the fetal ductus arteriosus and reduce renal blood flow. These complications have been described for most nonselective COX inhibitors but are increasingly reported also for the selective COX-2 inhibitors. Aspirin, which causes irreversible inhibition of cyclooxygenases, differs from other NSAIDs with regard to indication, effects and side effects. Prematurity, which is increased in pregnancies of women with connective tissue diseases, is an additional risk factor for adverse effects of antenatal exposure to NSAIDs. Therefore, treatment with COX inhibitors should be discontinued at week 32 of gestation. The ability of NSAIDs to compromise reproductive function by inhibition of ovulation and as causative agents for miscarriage is still under debate. Glucocorticosteroids given in early pregnancy are a risk factor for the development of oral clefts. Therefore, the daily dose should be kept to High doses of glucocorticosteroids in the second and third trimester are reserved for flares of autoimmune diseases. Intrauterine fetal growth restriction and premature delivery are possible side effects of high doses. PMID:15013926

  16. Improved antioxidant and anti-inflammatory potential in mice consuming sour cherry juice (Prunus Cerasus cv. Maraska).

    PubMed

    Sari?, Ana; Sobocanec, Sandra; Balog, Tihomir; Kusi?, Borka; Sverko, Visnja; Dragovi?-Uzelac, Verica; Levaj, Branka; Cosi?, Zrinka; Macak Safranko, Zeljka; Marotti, Tatjana

    2009-12-01

    The present investigation tested the in vivo antioxidant efficacy (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase; Gpx), lipid peroxidation (LPO) and anti-inflammatory properties (cyclooxygenase-2; COX-2) of sour cherry juices obtained from an autochthonous cultivar (Prunus cerasus cv. Maraska) that is grown in coastal parts of Croatia. Antioxidant potential was tested in mouse tissue (blood, liver, and brain), LPO (liver, brain) and anti-inflammatory properties in glycogen elicited macrophages. Additionally, the concentration of cyanidin-3-glucoside, cyanidin-3-rutinoside, pelargonidin-3-glucoside, pelargonidin-3-rutinoside and total anthocyanins present in Prunus cerasus cv. Maraska cherry juice was determined. Mice were randomly divided into a control group (fed with commercial food pellets) and 2 experimental groups (fed with commercial food pellets with 10% or 50% of cherry juice added). Among the anthocyanins, the cyanidin-3-glucoside was present in the highest concentration. These results show antioxidant action of cherry juice through increased SOD (liver, blood) and Gpx (liver) activity and decreased LPO concentration. The study highlights cherry juice as a potent COX-2 inhibitor and antioxidant in the liver and blood of mice, but not in the brain. Thus, according to our study, Prunus cerasus cv. Maraska cherry juice might potentially be used as an antioxidant and anti-inflammatory product with beneficial health-promoting properties. PMID:19763832

  17. Analgesic and Anti-Inflammatory Activities of the Methanolic Stem Bark Extract of Nyctanthes arbor-tristis Linn.

    PubMed Central

    Kakoti, Bibhuti Bhusan; Pradhan, Paresh; Borah, Sudarshana; Mahato, Kabita; Kumar, Mritunjay

    2013-01-01

    Stem bark of Nyctanthes arbor-tristis Linn. was extracted in methanol to evaluate their analgesic and anti-inflammatory activities. The analgesic activity was determined on Wistar albino rats by hot plate method, tail flick assay, and tail immersion method using Morphine sulphate as standard drug at a dose of 5?mg/kg of body weight and the results were expressed as mean increase in latency after drug administration?±?SEM. The anti-inflammatory activity was assessed by Carrageenan-induced rat paw oedema using diclofenac sodium as standard drug at a dose of 100?mg/kg of body weight and expressed in terms of mean increase in paw volume?±?SEM. Stem bark extract was given at a dose of 250?mg/kg and 500?mg/kg of body weight. Both standard drugs and extract were administered orally to the animals. Control received distilled water orally. Results showed that Nyctanthes arbor-tristis Linn. had potent analgesic and anti-inflammatory activities. PMID:23984409

  18. Synthesis, anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum.

    PubMed

    Romero, Juan Carlos; Martínez-Vázquez, Adriana; Herrera, Maribel Pineda; Martinez-Mayorga, Karina; Parra-Delgado, Hortensia; Pérez-Flores, Francisco J; Martínez-Vázquez, Mariano

    2014-12-15

    The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the anti-inflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED50=1.5×10(-4)mmol/ear) and argentatin A (ED50=2.8×10(-4)mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED50=4.5×10(-4)mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPA-induced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24-oic acid, obtained from argentatin A (ED50=1.4×10(-4)mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15?M doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity. PMID:25456078

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

    PubMed

    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

    2014-02-15

    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

  20. Differences in Anti-Inflammatory Actions of Intravenous Immunoglobulin between Mice and Men: More than Meets the Eye

    PubMed Central

    Tjon, Angela S. W.; van Gent, Rogier; Geijtenbeek, Teunis B.; Kwekkeboom, Jaap

    2015-01-01

    Intravenous immunoglobulin (IVIg) is a therapeutic preparation of polyspecific human IgGs purified from plasma pooled from thousands of individuals. When administered at a high dose, IVIg inhibits inflammation and has proven efficacy in the treatment of various autoimmune and systemic inflammatory diseases. Importantly, IVIg therapy can ameliorate both auto-antibody-mediated and T-cell mediated immune pathologies. In the last few decades, extensive research in murine disease models has resulted in the elucidation of two novel anti-inflammatory mechanisms-of-action of IVIg: induction of Fc?RIIB expression by sialylated Fc, and stimulation of regulatory T cells. Whereas controversial findings in mice studies have recently inspired intense scientific debate regarding the validity of the sialylated Fc-Fc?RIIB model, the most fundamental question is whether these anti-inflammatory mechanisms of IVIg are operational in humans treated with IVIg. In this review, we examine the evidence for the involvement of these anti-inflammatory mechanisms in the therapeutic effects of IVIg in humans. We demonstrate that although several elements of both immune-modulatory pathways of IVIg are activated in humans, incorrect extrapolations from mice to men have been made on the molecular and cellular components involved in these cascades that warrant for critical re-evaluation of these anti-inflammatory mechanisms of IVIg in humans. PMID:25972869

  1. Anti-inflammatory glycoterpenoids from Scrophularia auriculata.

    PubMed

    Giner, R M; Villalba, M L; Recio, M C; Máñez, S; Cerdá-Nicolás, M; Ríos, J

    2000-02-18

    The activity of the four glycoterpenoids: two saponins, verbascosaponin A and verbascosaponin, and two iridoids, scropolioside A and scrovalentinoside, isolated from Scrophularia auriculata ssp. pseudoauriculata, were studied in different models of acute and chronic inflammation. Both saponins significantly inhibited the mouse paw edema induced by carrageenan and ear edema induced by single and multiple doses of 12-O-tetradecanoylphorbol 13-acetate (TPA). Verbascosaponin A showed a potency twice as high as that of indomethacin in the acute TPA model. Verbascosaponin A and scropolioside A were active after a long latency period against ethyl phenylpropiolate edema, as are glucocorticoids. When the putative corticoid-like mechanism of the two compounds was studied, verbascosaponin A activity was notably reduced by the mRNA synthesis inhibitor, actinomycin D, while the effect of scropolioside A was partially interfered with by the anti-glucocorticoid drugs used. Both iridoids were active on the delayed type hypersensitivity reaction. They significantly reduced the inflammatory lesion and suppressed the cellular infiltration. PMID:10688990

  2. Anti-inflammatory effect of dual nociceptin and opioid receptor agonist, BU08070, in experimental colitis in mice.

    PubMed

    Zieli?ska, Marta; Haddou, Tanila Ben; Cami-Kobeci, Gerta; Sa?aga, Maciej; Jarmu?, Agata; Padysz, Milena; Kordek, Radzis?aw; Spetea, Mariana; Husbands, Stephen M; Fichna, Jakub

    2015-10-15

    Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and µ-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU08070, induces anti-inflammatory response in experimental colitis. The anti-inflammatory effect of BU08070 (1mg/kg i.p.) was characterized in the mouse model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, based on the assessment of the macroscopic and microscopic total damage scores and determination of myeloperoxidase (MPO) activity and TNF-? level in the colon. The effect of BU08070 on cell viability and NF-?B was characterized in THP-1 Blue cell line. The antinociceptive activity of BU08070 was examined in mustard oil-induced mouse model of abdominal pain. A potent anti-inflammatory effect of BU08070 (1mg/kg i.p.) was observed as indicated by decrease in macroscopic damage score (1.88±0.39 vs. 5.19±0.43 units in TNBS alone treated mice), MPO activity (2.29±0.37 vs. 9.64±2.55 units) and TNF-? level in the colon (35.85±2.45 vs. 49.79±3.81pg/ml). The anti-inflammatory effect of BU08070 was reversed by selective NOP and MOP receptor antagonists. BU08070 produced concentration-dependent inhibition of TNF-? and LPS-induced NF-?B activation. BU08070 exerted antinociceptive action in mice with experimental colitis. In conclusion, BU08070 significantly reduced the severity of colitis in TNBS-treated mice compared with controls. These results suggest that BU08070 is a potential therapeutic agent for inflammatory bowel diseases therapy. PMID:26404500

  3. Anti-inflammatory effects of OBA-09, a salicylic acid/pyruvate ester, in the postischemic brain.

    PubMed

    Lee, Hye-Kyung; Kim, Seung-Woo; Jin, Yinchuan; Kim, Il-Doo; Park, Ju-Young; Yoon, Sung-Hwa; Lee, Ja-Kyeong

    2013-08-28

    Cerebral ischemia leads to brain injury via a complex series of pathophysiological events, and therefore, multi-drug treatments or multi-targeting drug treatments provide attractive options with respect to limiting brain damage. Previously, we reported that a novel multi-functional compound oxopropanoyloxy benzoic acid (OBA-09, a simple ester of pyruvate and salicylic acid) affords robust neuroprotective effects in the postischemic rat brain. OBA-09 exhibited anti-oxidative effects that appeared to be executed by OBA-09 and by the salicylic acid afforded by hydrolysis. Here, we report the anti-inflammatory effects of OBA-09. Microglial activation observed at 2 days post-middle cerebral artery occlusion (MCAO, 90 min) and at 1 day after a LPS injection (0.5 mg/kg, intravenously) in the brains of Sprague-Dawley rats were markedly suppressed by the administration of OBA-09 (10 mg/kg). Inductions of proinflammatory markers (TNF-?, IL-1?, iNOS, and COX-2) were also suppressed by OBA-09 in both the LPS and MCAO models. Moreover, the anti-inflammatory effect of OBA-09 was accompanied by the suppression of infarct formation in the postischemic brain, but appeared to be independent of neuroprotection in LPS-treated rats. The inductions of proinflammatory markers were also inhibited by OBA-09 in LPS-treated BV2 cells (a microglia cell line) and in LPS-treated-primary neutrophils, possibly due to the suppression of NF-?B activity. Interestingly, the anti-inflammatory effect of OBA-09 was greater than that of equivalent co-treatment with pyruvate and salicylic acid. Together these results indicate that OBA-09 is a potent multi-modal neuroprotectant in the postischemic brain, and that its anti-inflammatory effect contributes to its neuroprotective function. PMID:23850644

  4. Anti-inflammatory and immunomodulating properties of grape melanin. Inhibitory effects on paw edema and adjuvant induced disease.

    PubMed

    Avramidis, N; Kourounakis, A; Hadjipetrou, L; Senchuk, V

    1998-07-01

    Natural or synthetic melanin (CAS 8049-97-6) is a high molecular weight heteropolymer, product of the enzyme tyrosinase, found to possess radical scavenging and antioxidant functions. It was of interest, therefore, to study in detail the possible anti-inflammatory and/or immunosuppressive properties of a melanin isolated from grapes. The inhibitory effect of melanin on carrageenin-induced edema, as well as on edemas produced by other phlogistics, was remarkable suggesting that melanin interferes with the prostaglandin as well as the leukotriene and/or complement system mediated inflammation. Grape melanin showed potent inhibitory effect on adjuvant induced disease (AID) in rat, suppressing significantly the primary inflammation and almost totally the secondary lesions of arthritis. Melanin under the present experimental conditions not only strongly inhibited the in vitro lipid peroxidation of rat liver microsomal membranes, but furthermore protected the in vivo hepatic peroxidation occurring in AID rats, demonstrating its antioxidant and cytoprotective properties. The serum proinflammatory cytokines IL-1, IL-6 and TNF-a and the serum globulin fraction were elevated in AID rats, parameters which were more or less normalised by melanin treatment in contrast to the reduced serum levels of IL-2 which were not affected. Similarly to other lipoxygenase inhibitors and hydroxyl radical scavenger NSAIDs, melanin treatment did not affect IL-1 neither increased the splenic mitogenic responses, unlike the classical cyclooxygenase inhibitory NSAIDs. The subpopulation Th1 (T4+ or T8+) of lymphocytes is mainly responsible for cellular immune responses and thus their possible inhibition by melanin could lead to suppression of the development of AID, a model for cell-mediated immunity. The effect of melanin on T-cells is exhibited by the reduced spleen mitogenic responses to a T-cell mitogen and the reduced serum levels of IL-2 of treated rats. In conclusion, grape melanin is an interesting anti-inflammatory and immunomodulating natural product which appears to have multiple cellular targets within the reticuloendothelial and immune system. PMID:9706378

  5. Biogenic Synthesis, Purification, and Chemical Characterization of Anti-inflammatory Resolvins Derived from Docosapentaenoic Acid (DPAn-6)

    PubMed Central

    Dangi, Bindi; Obeng, Marcus; Nauroth, Julie M.; Teymourlouei, Mah; Needham, Micah; Raman, Krishna; Arterburn, Linda M.

    2009-01-01

    Enzymatically oxygenated derivatives of the ?-3 fatty acids cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and cis-5,8,11,14,17-eicosapentaenoic acid, known as resolvins, have potent inflammation resolution activity (Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., and Gronert, K. (2000) J. Exp. Med. 192, 1197–1204; Hong, S., Gronert, K., Devchand, P. R., Moussignac, R., and Serhan, C. N. (2003) J. Biol. Chem. 278, 14677–14687). Our objective was to determine whether similar derivatives are enzymatically synthesized from other C-22 fatty acids and whether these molecules possess inflammation resolution properties. The reaction of DHA, DPAn-3, and DPAn-6 with 5-, 12-, and 15-lipoxygenases produced oxylipins, which were identified and characterized by liquid chromatography coupled with tandem mass-spectrometry. DPAn-6 and DPAn-3 proved to be good substrates for 15-lipoxygenase. 15-Lipoxygenase proved to be the most efficient enzyme of the three tested for conversion of long chain polyunsaturated fatty acids to corresponding oxylipins. Since DPAn-6 is a major component of Martek DHA-S™ oil, we focused our attention on reaction products obtained from the DPAn-6 and 15-lipoxygenase reaction. (17S)-hydroxy-DPAn-6 and (10,17S)-dihydroxy-DPAn-6 were the main products of this reaction. These compounds were purified by preparatory high performance liquid chromatography techniques and further characterized by NMR, UV spectrophotometry, and tandem mass spectrometry. We tested both compounds in two animal models of acute inflammation and demonstrated that both compounds are potent anti-inflammatory agents that are active on local intravenous as well as oral administration. These oxygenated DPAn-6 compounds can thus be categorized as a new class of DPAn-6-derived resolvins. PMID:19324874

  6. Anti-inflammatory, anti-bacterial, and cytotoxic activity of fibrous clays.

    PubMed

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio-; Ramírez-Apan, María Teresa; Gómez-Vidales, Virginia; Palacios, Eduardo; Montoya, Ascención; Ronquillo de Jesús, Elba

    2015-05-01

    Produced worldwide at 1.2m tons per year, fibrous clays are used in the production of pet litter, animal feed stuff to roof parcels, construction and rheological additives, and other applications needing to replace long-fiber length asbestos. To the authors' knowledge, however, information on the beneficial effects of fibrous clays on health remains scarce. This paper reports on the anti-inflammatory, anti-bacterial, and cytotoxic activity by sepiolite (Vallecas, Spain) and palygorskite (Torrejon El Rubio, Spain). The anti-inflammatory activity was determined using the 12-O-tetradecanoylphorbol-13-acetate (TPA) and myeloperoxidase (MPO) methods. Histological cuts were obtained for quantifying leukocytes found in the epidermis. Palygorkite and sepiolite caused edema inhibition and migration of neutrophils ca. 68.64 and 45.54%, and 80 and 65%, respectively. Fibrous clays yielded high rates of infiltration, explained by cleavage of polysomes and exposure of silanol groups. Also, fibrous clays showed high inhibition of myeloperoxidase contents shortly after exposure, but decreased sharply afterwards. In contrast, tubular clays caused an increasing inhibition of myeloperoxidase with time. Thus, clay structure restricted the kinetics and mechanism of myeloperoxidase inhibition. Fibrous clays were screened in vitro against human cancer cell lines. Cytotoxicity was determined using the protein-binding dye sulforhodamine B (SRB). Exposing cancer human cells to sepiolite or palygorskite showed growth inhibition varying with cell line. This study shows that fibrous clays served as an effective anti-inflammatory, limited by chemical transfer and cellular-level signals responding exclusively to an early exposure to clay, and cell viability decreasing significantly only after exposure to high concentrations of sepiolite. PMID:25819359

  7. Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs).

    PubMed

    Wynne, H A; Campbell, M

    1993-02-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of the symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), sprains and strains, sports injuries and menstrual disorders, and have a small role in the management of patent ductus arteriosus in the neonate. In patients with RA, symptom relief through use of NSAIDs is firmly established, although it remains unclear whether they influence the course and outcome of the disease. For the average patient with RA taking NSAIDs, the attributable risk of hospitalisation with gastrointestinal problems related to NSAIDs is 1.3 to 1.6% annually and risk of death is 0.15%. Associations of therapy with risk are greatest with age, corticosteroid use and previous NSAID-related gastrointestinal adverse effects, and less marked with disability and high NSAID dose. These are important data in attempting to balance risk of therapy with clinical efficacy in an individual patient, and assessing the cost-effectiveness of prophylaxis. Although half of all NSAID consumption is for control of pain associated with degenerative conditions, their superiority over simple analgesics in osteoarthritis is poorly documented. This finding supports the use of the simple analgesic paracetamol (acetaminophen) as the preferred therapy of osteoarthritis, especially when its lower cost and low incidence of adverse effects are taken into consideration. Consistent differences in clinical effectiveness of individual NSAIDs have not been demonstrated, although unpredictable interpatient variation in response to individual agents is of considerable clinical importance, and a more expensive NSAID may prove cost effective for some patients. Cost effectiveness can be improved by a self-adjusted dosage regime which also leads to lower overall drug consumption. The adverse gastrointestinal effects of these drugs account for about 30% of the overall cost of arthritis treatment, and although studies to date have been too limited to assess the relative risk of gastrointestinal toxicity of the different NSAIDs reliably, ibuprofen appears to be one of the least hazardous, and azapropazone one of the most hazardous. Although the effectiveness of prophylaxis with H 2-antagonists and with prostaglandin E 1 analogues (prostaglandin-E 1 analogues) has been established, estimates of cost-benefit ratios are widely divergent. To establish the most cost-effective therapy with NSAIDs, more data are required to establish multivariable risk profiles for identification of patients at particular risk, the optimal drug, and its optimal dosage and duration of treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:10146960

  8. Evaluation of Anti-Inflammatory Activity of Aqueous Extract of Leaves of Solanum Melongena Linn. in Experimental Animals

    PubMed Central

    Maniyar, Yasmeen A

    2015-01-01

    Introduction: Aqueous extract of leaves of Solanum melongena Linn was investigated for its anti-inflammatory activity. Materials and Methods: Acute oral toxicity study according to OECD425 guidelines was done to find out the LD50 of test drug. Carrageenan induced paw oedema method in Wistar Albino rats were used in this study. Aspirin in the dose of 300mg/kg was used as the standard drug and three doses of aqueous extract of leaves of Solanum melongena L. (100mg/kg, 200mg/kg, 400mg/kg b.w.) was used as the test drug. The results were measured at 1st h, 3rd h, and 5th h after the carrageenan injection. Results: In acute oral toxicity study none of the animals died at the dose of 2000mg/kg. Aqueous extract of Solanum melongena Linn leaf in the dose of 200mg/kg showed significant anti-inflammatory activity (p <0.05) at 3rd hr and highly significant anti-inflammatory activity (p<0.001) at 5th hr; in the dose of 400 mg/kg, test drug showed p<0.01 at 3rd and p<0.001 at 5th hr and in the dose of 100mg/kg it showed significant (p<0.05) anti-inflammatory activity at 5th hr. In doses of 200mg/kg and 400 mg/kg of aqueous extract of S. melongena L showed the percentage of inhibition of 42.62% which is less than the standard drug aspirin which showed 64.5% inhibition. Conclusion: Aqueous extract of leaves of Solanum melongena Linn has anti-inflammatory activity. PMID:25738003

  9. Magnetoliposomes Loaded with Poly-Unsaturated Fatty Acids as Novel Theranostic Anti-Inflammatory Formulations

    PubMed Central

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (?-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ?-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1H NMR Spectroscopy of the liposomal preparations containing ?-3 PUFA-EE revealed well resolved 1H resonances from highly mobile ?-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ?-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ?-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ?-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ?-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ?-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery. PMID:25767616

  10. Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic anti-inflammatory formulations.

    PubMed

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (?-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ?-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning (1)H NMR Spectroscopy of the liposomal preparations containing ?-3 PUFA-EE revealed well resolved (1)H resonances from highly mobile ?-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ?-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ?-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ?-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ?-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ?-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery. PMID:25767616

  11. Pterostilbene exerts an anti-inflammatory effect via regulating endoplasmic reticulum stress in endothelial cells.

    PubMed

    Liu, Jun; Fan, Chongxi; Yu, Liming; Yang, Yang; Jiang, Shuai; Ma, Zhiqiang; Hu, Wei; Li, Tian; Yang, Zhi; Tian, Tian; Duan, Weixun; Yu, Shiqiang

    2016-01-01

    Pterostilbene (PT), an analog of resveratrol, exerts a potent anti-inflammatory effect. However, the protective effects of PT against inflammation in endothelial cells have not been elucidated. Previous studies have confirmed that endoplasmic reticulum stress (ERS) plays an important role in regulating the pathological process of endothelial cell inflammation. In this study, we explored the effect of PT on the tumor necrosis factor-? (TNF-?)-induced inflammatory response in human umbilical vein endothelial cells (HUVECs) and elaborated the role of ERS in this process. TNF-? treatment significantly upregulated the levels of inflammation-related molecules in cell culture media, increased the adhesion of monocytes to HUVECs, and enhanced the expression of the MMP9 and ICAM proteins in HUVECs. Additionally, TNF-? potently increased ERS-related protein levels, such as GRP78 and p-eIF2?. However, PT treatment reversed the increased production of inflammatory cytokines and the adhesion of monocytes to HUVECs, as well as reduced the TNF-?-induced effects exerted by ERS-related molecules. Furthermore, thapsigargin (THA), an ERS inducer, attenuated the protective effect of PT against TNF-?-induced inflammation and ERS in HUVECs. Additionally, the downregulation of ERS signaling using siRNA targeting eIF2? and IRE1 not only inhibited ERS-related molecules but also simulated the therapeutic effects of PT on TNF-?-induced inflammation. In summary, PT treatment potently attenuates inflammation in vascular endothelial cells, which at least partly depends on the reduction of ERS. PMID:26551859

  12. Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

    DOE PAGESBeta

    Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; Chain, Florian; Lenoir, Marion; Raguideau, Sébastien; Hudault, Sylvie; Bridonneau, Chantal; Northen, Trent; Bowen, Benjamin; et al

    2015-04-21

    Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable andmore »stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (?-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.« less

  13. Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat.

    PubMed

    Akihisa, Toshihiro; Kojima, Nobuo; Kikuchi, Takashi; Yasukawa, Ken; Tokuda, Harukuni; T Masters, Eliot; Manosroi, Aranya; Manosroi, Jiradej

    2010-01-01

    Four triterpene acetates, alpha-amyrin acetate (1a), beta-amyrin acetate (2a), lupeol acetate (3a), and butyrospermol acetate (4a), and four triterpene cinnamates, alpha-amyrin cinnamate (1c), beta-amyrin cinnamate (2c), lupeol cinnamate (3c), and butyrospermol cinnamate (4c), were isolated from the kernel fat (n-hexane extract) of the shea tree (Vitellaria paradoxa; Sapotaceae). Upon evaluation of these eight triterpene esters for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds tested exhibited marked anti-inflammatory activity, with ID50 values in the range of 0.15-0.75 micromol/ear, and among which compound 3c showed the highest activity with ID(50) of 0.15 micromol/ear. Compound 3c (10 mg/kg) further exhibited anti-inflammatory activity on rat hind paw edema induced by carrageenan, with the percentage of inflammation at 1, 3, and 5 h of 35.4, 41.5, and 45.5%, respectively. The eight triterpene esters were then evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the compounds showed moderate inhibitory effects. Furthermore, compound 3c exhibited inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz [a] anthracene (DMBA) as an initiator and TPA as a promoter. The biological activities of triterpene acetate and cinnamate esters, together with the exceptionally high levels of these triterpenes in shea fat, indicate that shea nuts and shea fat (shea butter) constitute a significant source of anti-inflammatory and anti-tumor promoting compounds. PMID:20484832

  14. Intracellular signaling pathways modulated by phenolic compounds: application for new anti-inflammatory drugs discovery.

    PubMed

    Costa, G; Francisco, V; Lopes, M C; Cruz, M T; Batista, M T

    2012-01-01

    Extensive research within the last two decades revealed that most chronic illnesses, including cancer, neurological, autoimmune and cardiovascular diseases are mediated through chronic inflammation. Thus, suppressing chronic inflammation has the potential to delay, prevent, and treat those diseases. However, side effects and high costs of current anti-inflammatory drugs force the development of new drugs. Natural products represent an important source of new bioactive compounds. Among them, phenolic compounds, which are widely distributed in plants, have been described as having many therapeutic effects. Several reviews have addressed the anti-inflammatory activity of phenols, attributing their properties not only to the antioxidant capacity, but also to inflammatory mediators' modulation, namely cytokines and pro-inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase-2. Signal transduction pathways precede changes in inflammatory mediators' expression. However, only a restricted number of studies have addressed the effect of phenols on a specific signal transduction pathway. The present review attempts to summarize and highlight a broad range of inflammation-associated signaling pathways modulated by phenols namely: nuclear factor (NF)-?B, activator protein (AP)-1, peroxisome proliferator-activated receptor (PPAR) and nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors; mitogen-activated protein kinases (MAPKs); protein tyrosine kinases (PTKs); tyrosine phosphatidylinositol 3-kinase (PI3K)/Akt and ubiquitin-proteasome system. As a consequence of phenols effect on signaling pathways, described above, their action on inflammatory mediators' production is mentioned. Finally, it is established that the structure-activity relationships of phenolic compounds are a valuable information source on the development of new anti-inflammatory drugs from natural products. PMID:22519398

  15. Identification of Metabolic Signatures Linked to Anti-Inflammatory Effects of Faecalibacterium prausnitzii

    PubMed Central

    Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; Chain, Florian; Lenoir, Marion; Raguideau, Sébastien; Hudault, Sylvie; Bridonneau, Chantal; Northen, Trent; Bowen, Benjamin; Bermúdez-Humarán, Luis G.; Sokol, Harry; Thomas, Muriel

    2015-01-01

    ABSTRACT Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (?-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood. PMID:25900655

  16. Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

    PubMed Central

    Lee, In-Ah; Kamba, Alan; Low, Daren; Mizoguchi, Emiko

    2014-01-01

    Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1 (CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD), bronchial asthma and several other inflammatory disorders. Based on the data from high-throughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-inflammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivative-mediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine, -based anti-inflammatory therapeutics in the field of IBD and IBD-associated carcinogenesis. PMID:24574789

  17. Biochemical effects, hypolipidemic and anti-inflammatory activities of Artemisia vulgaris extract in hypercholesterolemic rats.

    PubMed

    El-Tantawy, Walid Hamdy

    2015-07-01

    The purpose of the present study was to investigate hypolipidemic and anti-inflammatory effects of Artemisia vulgaris extract in hypercholesterolemic rats. Hypercholesterolemia was induced by feeding of rats with high fat diet containing 3% cholesterol in olein oil, for 8 weeks. Feeding of rats with high fat diet for 8 weeks, leading to a significant increase in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, malondialdehyde and nitric oxide, tumor necrosis factor-? levels and a significant decrease in serum high density lipoprotein cholesterol level, liver hydroxymethylglutaryl-CoA reductase activity and paraoxonase-1 activities as compared to the normal control group. Treatment of high fat diet rats with Artemisia vulgaris extract for 4 weeks at a dose of 100 mg/kg per day, resulted in normalized serum lipid profile, a significant increase in paraoxonase-1 activity and decrease in serum malondialdehyde, nitric oxide and tumor necrosis factor-? level as compared to high fat diet-treated animals. Also the extract caused a significant decrease in hydroxymethylglutaryl-CoA reductase activity as compared with both high fat diet-treated animals and control ones. In conclusion, Artemisia vulgaris extract has hypolipidemic, anti-inflammatory, antioxidant properties; it may serve as a source for the prevention of atherosclerosis and cardiovascular diseases. PMID:26236098

  18. Biochemical effects, hypolipidemic and anti-inflammatory activities of Artemisia vulgaris extract in hypercholesterolemic rats

    PubMed Central

    El-Tantawy, Walid Hamdy

    2015-01-01

    The purpose of the present study was to investigate hypolipidemic and anti-inflammatory effects of Artemisia vulgaris extract in hypercholesterolemic rats. Hypercholesterolemia was induced by feeding of rats with high fat diet containing 3% cholesterol in olein oil, for 8 weeks. Feeding of rats with high fat diet for 8 weeks, leading to a significant increase in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, malondialdehyde and nitric oxide, tumor necrosis factor-? levels and a significant decrease in serum high density lipoprotein cholesterol level, liver hydroxymethylglutaryl-CoA reductase activity and paraoxonase-1 activities as compared to the normal control group. Treatment of high fat diet rats with Artemisia vulgaris extract for 4 weeks at a dose of 100 mg/kg per day, resulted in normalized serum lipid profile, a significant increase in paraoxonase-1 activity and decrease in serum malondialdehyde, nitric oxide and tumor necrosis factor-? level as compared to high fat diet-treated animals. Also the extract caused a significant decrease in hydroxymethylglutaryl-CoA reductase activity as compared with both high fat diet-treated animals and control ones. In conclusion, Artemisia vulgaris extract has hypolipidemic, anti-inflammatory, antioxidant properties; it may serve as a source for the prevention of atherosclerosis and cardiovascular diseases. PMID:26236098

  19. Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; dell'Omo, Roberto

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications. PMID:24227908

  20. Imbricaric acid and perlatolic acid: multi-targeting anti-inflammatory depsides from Cetrelia monachorum.

    PubMed

    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

    2013-01-01

    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

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

    PubMed Central

    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.

    2013-01-01

    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

  2. Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative colitis

    PubMed Central

    Montrose, David C.; Horelik, Nicole A.; Madigan, James P.; Stoner, Gary D.; Wang, Li-Shu; Bruno, Richard S.; Park, Hea Jin; Giardina, Charles; Rosenberg, Daniel W.

    2011-01-01

    Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa that can dramatically increase the risk of colon cancers. In the present study, we evaluated the effects of a dietary intervention of freeze-dried black raspberries (BRB), a natural food product with antioxidant and anti-inflammatory bioactivities, on disease severity in an experimental mouse model of UC using 3% dextran sodium sulfate (DSS). C57BL/6J mice were fed either a control diet or a diet containing BRB (5 or 10%) for 7–14 days and then the extent of colonic injury was assessed. Dietary BRB markedly reduced DSS-induced acute injury to the colonic epithelium. This protection included better maintenance of body mass and reductions in colonic shortening and ulceration. BRB treatment, however, did not affect the levels of either plasma nitric oxide or colon malondialdehyde, biomarkers of oxidative stress that are otherwise increased by DSS-induced colonic injury. BRB treatment for up to 7 days suppressed tissue levels of several key pro-inflammatory cytokines, including tumor necrosis factor ? and interleukin 1?. Further examination of the inflammatory response by western blot analysis revealed that 7 day BRB treatment reduced the levels of phospho-I?B? within the colonic tissue. Colonic cyclooxygenase 2 levels were also dramatically suppressed by BRB treatment, with a concomitant decrease in the plasma prostaglandin E2 (276 versus 34 ng/ml). These findings demonstrate a potent anti-inflammatory effect of BRB during DSS-induced colonic injury, supporting its possible therapeutic or preventive role in the pathogenesis of UC and related neoplastic events. PMID:21098643

  3. Hugan Qingzhi Exerts Anti-Inflammatory Effects in a Rat Model of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Tang, WaiJiao; Zeng, Lu; Yin, JinJin; Yao, YuFa; Feng, LiJuan; Yao, XiaoRui; Sun, XiaoMin; Zhou, BenJie

    2015-01-01

    Ethnopharmacological Relevance. The Hugan Qingzhi tablet (HQT) is a traditional Chinese medicine used for treating NAFLD (nonalcoholic fatty liver disease). The present study evaluated the anti-inflammatory effects of HQT in rats with NAFLD. Materials and Methods. HQT was administered daily to the NAFLD experimental groups. Biochemical markers, histopathological data, and oxidative stress/antioxidant biomarkers were determined. Proinflammatory cytokines interleukin-1? (IL-1?), tumor necrosis factor ? (TNF-?), and interleukin-6 (IL-6) were detected by enzyme-linked immunoassay. Expressions of silent information regulator 1 (SIRT1) and acetylated-nuclear-factor kappaB-p65 (Ac-NF-?B-p65) were performed by western blotting. Results. At high and moderate doses, HQT was highly effective in decreasing serum alanine aminotransferase (P < 0.01), aspartate aminotransferase (P < 0.01), hepatic total cholesterol (P < 0.01), triglycerides (P < 0.01), and free fatty acid levels (P < 0.01). Moreover, high and moderate doses of HQT reduced hepatic levels of the proinflammatory cytokines TNF-? (P < 0.01), IL-1? (P < 0.01), and IL-6 (P < 0.01), enhanced SIRT1 expression, and depressed Ac-NF-?B-p65 expression at protein level. Conclusions. In our NAFLD rat model, HQT exerted substantial anti-inflammatory and antioxidant activities, possibly involving the regulation of SIRT1 and Ac-NF-?B-p65 expression. PMID:26146507

  4. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials

    PubMed Central

    Ilinskaya, A N; Dobrovolskaia, M A

    2014-01-01

    Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24724793

  5. Anticancer and anti-inflammatory activities of some dietary cucurbits.

    PubMed

    Sharma, Dhara; Rawat, Indu; Goel, H C

    2015-04-01

    In this study, we investigated few dietary cucurbits for anticancer activity by monitoring cytotoxic (MTT and LDH assays), apoptotic (caspase-3 and annexin-V assays), and also their anti-inflammatory effects by IL-8 cytokine assay. Aqua-alcoholic (50:50) whole extracts of cucurbits [Lagenaria siceraria (Ls), Luffa cylindrica (Lc) and Cucurbita pepo (Cp)] were evaluated in colon cancer cells (HT-29 and HCT-15) and were compared with isolated biomolecule, cucurbitacin-B (Cbit-B). MTT and LDH assays revealed that the cucurbit extracts and Cbit-B, in a concentration dependent manner, decreased the viability of HT-29 and HCT-15 cells substantially. The viability of lymphocytes was, however, only marginally decreased, yielding a potential advantage over the tumor cells. Caspase-3 assay revealed maximum apoptosis with Ls while annexin V assay demonstrated maximum efficacy of Lc in this context. These cucurbits have also shown decreased secretion of IL-8, thereby revealing their anti-inflammatory capability. The results have demonstrated the therapeutic potential of dietary cucurbits in inhibiting cancer and inflammatory cytokine. PMID:26011982

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

    PubMed Central

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

    2013-01-01

    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. PMID:23578285

  7. ?-Mangostin: anti-inflammatory activity and metabolism by human cells.

    PubMed

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

    2013-04-24

    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. PMID:23578285

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

    PubMed

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

    2015-01-01

    Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti-inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti-inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan-induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose-dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis 3-ethylbenzothiazoline 6-sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50 : 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity. PMID:25256913

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

    PubMed Central

    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.

    2007-01-01

    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. PMID:17383881

  10. [Fetal toxicity of non-steroidal anti-inflammatory agents].

    PubMed

    Bavoux, F

    1992-11-28

    All non-steroidal anti-inflammatory drugs (NSAIDs) are prostaglandin inhibitors, which explains their foetal toxicity. So far, no epidemiological study of their cardiopulmonary and renal effects has been carried out, but case-reports have been published. The cardiopulmonary effects of NSAIDs include closure of the ductus arteriosus, pulmonary hypertension cardiopathy and tricuspid valve insufficiency. They were responsible for 31 neonatal accidents, 8 of which were fatal (for 22 pregnant women, 7 bearing twins, 1 bearing triplets). The renal effects of NSAIDs consisted of acute renal failure with oedema, oliguria, hyponatraemia and marked hyperkalaemia. They affected 23 neonates, 8 of whom died (for 17 pregnant women, 4 bearing twins, 1 bearing triplets). A few epidemiological studies have reported foetal haemorrhages when aspirin was used by the mother as anti-inflammatory agent. In comparative trials of indomethacin as short treatment of premature labour and polyhydramnios the drug proved to be effective. In obstetrical tocolysis NSAIDs can be given in the absence of alternative therapy with beta-adrenergic agents, and their risk can be minimized by ultrasonographic examination and monitoring of foetal cardiac function and diuresis. In the field of rheumatology, corticosteroids would be a good alternative to NSAIDs for rheumatic diseases, but using NSAIDs for low back pain, sciatica, haemorrhoids, toothaches, sinusitis, etc., would not be justified in pregnant women. Self medication must be discouraged. PMID:1293602

  11. Antioxidant activity of anti-inflammatory plant extracts.

    PubMed

    Schinella, G R; Tournier, H A; Prieto, J M; Mordujovich de Buschiazzo, P; Ríos, J L

    2002-01-18

    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 peroxidation in model membranes and also showed scavenging property on the superoxide radical. All extracts were assayed at a concentration of 100 microg/ml. Most of the extracts were weak scavengers of the hydroxyl radical and C. chinensis and P. cocos exhibited the highest scavenging activity. Although S. baicalensis inhibited the lipid peroxidation in rat liver microsomes and red blood cells, the extract showed inhibitory actions on aminopyrine N-demethylase and xanthine oxidase activities as well as an pro-oxidant effect observed in the Fe3+-EDTA-H2O2 system. The results of the present work suggest that the anti-inflammatory activities of the same extracts could be explained, at least in part, by their antioxidant properties. PMID:11860151

  12. Anti - inflammatory and analgesic properties of the leaves of tamarindus indicus.

    PubMed

    Thomas, A; Gangadharan, R; Amma, S V

    1998-10-01

    The ethanolic extract of the leaves of Tamarindus indicus was investigated for its anti inflammatory and analgesic actions. The anti inflammatory activity was studied using carrageenin induced hind paw edema in rats and analgesic activity using chemical writhing test and tail clip method in mice and tail flick method yin rats. Test drug exhibited significant dose dependent anti inflammatory and analgesic and analgesic actions and found to be not superior to that of acetyl acid. PMID:22556878

  13. The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.

    PubMed

    Fleming, Bryan D; Chandrasekaran, Prabha; Dillon, Laura A L; Dalby, Elizabeth; Suresh, Rahul; Sarkar, Arup; El-Sayed, Najib M; Mosser, David M

    2015-09-01

    Macrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and phenotypic alterations were correlated with changes in gene expression. We identified 3 transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands in the presence of 3 different "reprogramming" signals: high-density ICs, PGE2, or Ado. All 3 of these cell populations produced high levels of transcripts for IL-10 and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1?, IL-6, and IL-12. All 3 macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore, we consider each to have anti-inflammatory activity. This ability to regulate innate-immune responses occurred equally well in macrophages from STAT6-deficient mice. The lack of STAT6 did not affect the ability of macrophages to change cytokine production reciprocally or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These anti-inflammatory macrophages are transcriptionally and functionally related to each other and are quite distinct from macrophages treated with IL-4. PMID:26048978

  14. Anti-inflammatory effects of anthocyanins-rich extract from bilberry (Vaccinium myrtillus L.) on croton oil-induced ear edema and Propionibacterium acnes plus LPS-induced liver damage in mice.

    PubMed

    Luo, Hui; Lv, Xiao-Dan; Wang, Guo-En; Li, Yi-Fang; Kurihara, Hiroshi; He, Rong-Rong

    2014-08-01

    Bilberry (Vaccinium myrtillus L.) has been known to play a protective role in human health due to its high anthocyanin content. This study investigated the anti-inflammatory effects of bilberry extract (BE, containing 42.04% anthocyanin) on Propionibacterium acnes (P. acnes) plus lipopolysaccharide (LPS) induced liver injury and croton oil-induced ear edema in mice. Results showed that BE could effectively inhibit croton oil-induced ear edema and liver inflammation provoked by P. acnes plus LPS, as reflected by the reduced plasma alanine aminotransferase and aspartate aminotransferase activities. These findings were confirmed by hepatic pathological examination. Moreover, BE administration markedly suppressed the increase of liver mRNA levels of iNOS, TNF-?, IL-1? and IL-6, and the protein levels of iNOS, TNF-? and NF-?B. In addition, liver malondialdehyde and NO contents were significantly reduced by BE treatment. These results indicated that BE has potent protective effects on acute and immunological inflammation, which might contribute to the study of the anti-inflammatory effects of natural products and healthy food. PMID:24548119

  15. 1,5-Diphenylpent-3-en-1-ynes and methyl naphthalene carboxylates from Lawsonia inermis and their anti-inflammatory activity.

    PubMed

    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

    2013-04-01

    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

  16. Aspirin analogues as dual cyclooxygenase-2/5-lipoxygenase inhibitors: synthesis, nitric oxide release, molecular modeling, and biological evaluation as anti-inflammatory agents.

    PubMed

    Kaur, Jatinder; Bhardwaj, Atul; Huang, Zhangjian; Knaus, Edward E

    2012-01-01

    Analogues of aspirin were synthesized through an efficient one-step reaction in which the carboxyl group was replaced by an ethyl ester, and/or the acetoxy group was replaced by an N-substituted sulfonamide (SO(2)NHOR(2):R(2) =H, Me, CH(2)Ph) pharmacophore. These analogues were designed for evaluation as dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors. In vitro COX-1/COX-2 isozyme inhibition studies identified compounds 11 (CO(2) H, SO(2)NHOH), 12 (CO(2)H, SO(2)NHOCH(2)Ph), and 16 (CO(2)Et, SO(2)NHOH) as highly potent and selective COX-2 inhibitors (IC(50) range: 0.07-0.7 ?M), which exhibited appreciable in vivo anti-inflammatory activity (ED(50) range: 23.1-31.4 mg kg(-1)). Moreover, compounds 11 (IC(50) =0.2 ?M) and 16 (IC(50) =0.3 ?M), with a sulfohydroxamic acid (SO(2)NHOH) moiety showed potent 5-LOX inhibitory activity. Furthermore, the SO(2)NHOH moiety present in compounds 11 and 16 was found to be a good nitric oxide (NO) donor upon incubation in phosphate buffer at pH 7.4. Molecular docking studies in the active binding site of COX-2 and 5-LOX provided complementary theoretical support for the experimental biological structure-activity data acquired. PMID:22095955

  17. A cluster randomised stepped wedge trial to evaluate the effectiveness of a multifaceted information technology-based intervention in reducing high-risk prescribing of non-steroidal anti-inflammatory drugs and antiplatelets in primary medical care: The DQIP study protocol

    PubMed Central

    2012-01-01

    Background High-risk prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents accounts for a significant proportion of hospital admissions due to preventable adverse drug events. The recently completed PINCER trial has demonstrated that a one-off pharmacist-led information technology (IT)-based intervention can significantly reduce high-risk prescribing in primary care, but there is evidence that effects decrease over time and employing additional pharmacists to facilitate change may not be sustainable. Methods/design We will conduct a cluster randomised controlled with a stepped wedge design in 40 volunteer general practices in two Scottish health boards. Eligible practices are those that are using the INPS Vision clinical IT system, and have agreed to have relevant medication-related data to be automatically extracted from their electronic medical records. All practices (clusters) that agree to take part will receive the data-driven quality improvement in primary care (DQIP) intervention, but will be randomised to one of 10 start dates. The DQIP intervention has three components: a web-based informatics tool that provides weekly updated feedback of targeted prescribing at practice level, prompts the review of individual patients affected, and summarises each patient's relevant risk factors and prescribing; an outreach visit providing education on targeted prescribing and training in the use of the informatics tool; and a fixed payment of 350 GBP (560 USD; 403 EUR) up front and a small payment of 15 GBP (24 USD; 17 EUR) for each patient reviewed in the 12 months of the intervention. We hypothesise that the DQIP intervention will reduce a composite of nine previously validated measures of high-risk prescribing. Due to the nature of the intervention, it is not possible to blind practices, the core research team, or the data analyst. However, outcome assessment is entirely objective and automated. There will additionally be a process and economic evaluation alongside the main trial. Discussion The DQIP intervention is an example of a potentially sustainable safety improvement intervention that builds on the existing National Health Service IT-infrastructure to facilitate systematic management of high-risk prescribing by existing practice staff. Although the focus in this trial is on Non-steroidal anti-inflammatory drugs and antiplatelets, we anticipate that the tested intervention would be generalisable to other types of prescribing if shown to be effective. Trial registration ClinicalTrials.gov, dossier number: NCT01425502 PMID:22444945

  18. Anti-inflammatory activity of hamamelis distillate applied topically to the skin. Influence of vehicle and dose.

    PubMed

    Korting, H C; Schäfer-Korting, M; Hart, H; Laux, P; Schmid, M

    1993-01-01

    The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle. UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P < or = 0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry. The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity. PMID:8513841

  19. Substrate-anchored and degradation-sensitive anti-inflammatory coatings for implant materials

    NASA Astrophysics Data System (ADS)

    Wu, Duo; Chen, Xingyu; Chen, Tianchan; Ding, Chunmei; Wu, Wei; Li, Jianshu

    2015-06-01

    Implant materials need to be highly biocompatible to avoid inflammation in clinical practice. Although biodegradable polymeric implants can eliminate the need for a second surgical intervention to remove the implant materials, they may produce acidic degradation products in vivo and cause non-bacterial inflammation. Here we show the strategy of “substrate-anchored and degradation-sensitive coatings” for biodegradable implants. Using poly(lactic acid)/hydroxyapatite as an implant material model, we constructed a layer-by-layer coating using pH-sensitive star polymers and dendrimers loaded with an anti-inflammatory drug, which was immobilised through a hydroxyapatite-anchored layer. The multifunctional coating can effectively suppress the local inflammation caused by the degradation of implant materials for at least 8 weeks in vivo. Moreover, the substrate-anchored coating is able to modulate the degradation of the substrate in a more homogeneous manner. The “substrate-anchored and degradation-sensitive coating” strategy therefore exhibits potential for the design of various self-anti-inflammatory biodegradable implant materials.

  20. Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases

    PubMed Central

    Aggarwal, Bharat B.; Prasad, Sahdeo; Reuter, Simone; Kannappan, Ramaswamy; Yadev, Vivek R.; Park, Byoungduck; Kim, Ji Hye; Gupta, Subash C.; Phromnoi, Kanokkarn; Sundaram, Chitra; Prasad, Seema; Chaturvedi, Madan M.; Sung, Bokyung

    2011-01-01

    Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-?B) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-?B and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to “reverse pharmacology” or “bed to benchside” approach. We found that Ayurveda, a science of long life, almost 6000 years old, can serve as a “goldmine” for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit. PMID:21561421

  1. Substrate-anchored and degradation-sensitive anti-inflammatory coatings for implant materials

    PubMed Central

    Wu, Duo; Chen, Xingyu; Chen, Tianchan; Ding, Chunmei; Wu, Wei; Li, Jianshu

    2015-01-01

    Implant materials need to be highly biocompatible to avoid inflammation in clinical practice. Although biodegradable polymeric implants can eliminate the need for a second surgical intervention to remove the implant materials, they may produce acidic degradation products in vivo and cause non-bacterial inflammation. Here we show the strategy of “substrate-anchored and degradation-sensitive coatings” for biodegradable implants. Using poly(lactic acid)/hydroxyapatite as an implant material model, we constructed a layer-by-layer coating using pH-sensitive star polymers and dendrimers loaded with an anti-inflammatory drug, which was immobilised through a hydroxyapatite-anchored layer. The multifunctional coating can effectively suppress the local inflammation caused by the degradation of implant materials for at least 8 weeks in vivo. Moreover, the substrate-anchored coating is able to modulate the degradation of the substrate in a more homogeneous manner. The “substrate-anchored and degradation-sensitive coating” strategy therefore exhibits potential for the design of various self-anti-inflammatory biodegradable implant materials. PMID:26077243

  2. Recent Breakthroughs in the Antioxidant and Anti-Inflammatory Effects of Morella and Myrica Species

    PubMed Central

    Silva, Bruno J. C.; Seca, Ana M. L.; Barreto, Maria do Carmo; Pinto, Diana C. G. A.

    2015-01-01

    Oxidative stress is one of the risk factors for the development of several chronic diseases, such as diabetes, cancer, cardiovascular and neurodegenerative diseases. Antioxidants are therefore highly sought and can be seen as a type of preventive medicine against several diseases. Myrica and Morella genus (Myricaceae) are taxonomically very close and their species are trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine, for instance in Chinese or Japanese folk medicine they are used to treat diarrhea, digestive problems, headache, burns and skin diseases. Nearly 36 compounds were isolated from different morphological parts of Myrica and/or Morella species and their antioxidant and anti-inflammatory activities evaluated. Thirteen of these compounds exhibit greater effects than the positive controls used. Adenodimerin A was the most active compound reported (in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay EC50= 7.9 ± 0.3 µM). These results are just one aspect of the antioxidant and anti-inflammatory evaluations reported regarding Myrica and Morella species, so a comprehensive overview on the current status, highlighting the antioxidant health promoting effect of these species, their key antioxidant compounds as well as the compounds with protective effects against oxidative stress related diseases such as inflammation, is relevant.

  3. Recent Breakthroughs in the Antioxidant and Anti-Inflammatory Effects of Morella and Myrica Species.

    PubMed

    Silva, Bruno J C; Seca, Ana M L; Barreto, Maria do Carmo; Pinto, Diana C G A

    2015-01-01

    Oxidative stress is one of the risk factors for the development of several chronic diseases, such as diabetes, cancer, cardiovascular and neurodegenerative diseases. Antioxidants are therefore highly sought and can be seen as a type of preventive medicine against several diseases. Myrica and Morella genus (Myricaceae) are taxonomically very close and their species are trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine, for instance in Chinese or Japanese folk medicine they are used to treat diarrhea, digestive problems, headache, burns and skin diseases. Nearly 36 compounds were isolated from different morphological parts of Myrica and/or Morella species and their antioxidant and anti-inflammatory activities evaluated. Thirteen of these compounds exhibit greater effects than the positive controls used. Adenodimerin A was the most active compound reported (in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay EC50= 7.9 ± 0.3 µM). These results are just one aspect of the antioxidant and anti-inflammatory evaluations reported regarding Myrica and Morella species, so a comprehensive overview on the current status, highlighting the antioxidant health promoting effect of these species, their key antioxidant compounds as well as the compounds with protective effects against oxidative stress related diseases such as inflammation, is relevant. PMID:26308834

  4. Recent Breakthroughs in the Antioxidant and Anti-Inflammatory Effects of Morella and Myrica Species.

    PubMed

    Silva, Bruno J C; Seca, Ana M L; Barreto, Maria do Carmo; Pinto, Diana C G A

    2015-01-01

    Oxidative stress is one of the risk factors for the development of several chronic diseases, such as diabetes, cancer, cardiovascular and neurodegenerative diseases. Antioxidants are therefore highly sought and can be seen as a type of preventive medicine against several diseases. Myrica and Morella genus (Myricaceae) are taxonomically very close and their species are trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine, for instance in Chinese or Japanese folk medicine they are used to treat diarrhea, digestive problems, headache, burns and skin diseases. Nearly 36 compounds were isolated from different morphological parts of Myrica and/or Morella species and their antioxidant and anti-inflammatory activities evaluated. Thirteen of these compounds exhibit greater effects than the positive controls used. Adenodimerin A was the most active compound reported (in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay EC50= 7.9 ± 0.3 µM). These results are just one aspect of the antioxidant and anti-inflammatory evaluations reported regarding Myrica and Morella species, so a comprehensive overview on the current status, highlighting the antioxidant health promoting effect of these species, their key antioxidant compounds as well as the compounds with protective effects against oxidative stress related diseases such as inflammation, is relevant. PMID:26225964

  5. Recent Breakthroughs in the Antioxidant and Anti-Inflammatory Effects of Morella and Myrica Species.

    PubMed

    Silva, Bruno J C; Seca, Ana M L; Barreto, Maria do Carmo; Pinto, Diana C G A

    2015-01-01

    Oxidative stress is one of the risk factors for the development of several chronic diseases, such as diabetes, cancer, cardiovascular and neurodegenerative diseases. Antioxidants are therefore highly sought and can be seen as a type of preventive medicine against several diseases. Myrica and Morella genus (Myricaceae) are taxonomically very close and their species are trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine, for instance in Chinese or Japanese folk medicine they are used to treat diarrhea, digestive problems, headache, burns and skin diseases. Nearly 36 compounds were isolated from different morphological parts of Myrica and/or Morella species and their antioxidant and anti-inflammatory activities evaluated. Thirteen of these compounds exhibit greater effects than the positive controls used. Adenodimerin A was the most active compound reported (in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay EC50= 7.9 ± 0.3 µM). These results are just one aspect of the antioxidant and anti-inflammatory evaluations reported regarding Myrica and Morella species, so a comprehensive overview on the current status, highlighting the antioxidant health promoting effect of these species, their key antioxidant compounds as well as the compounds with protective effects against oxidative stress related diseases such as inflammation, is relevant. PMID:26287159

  6. Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives.

    PubMed

    Kontogiorgis, Christos; Nicolotti, Orazio; Mangiatordi, Giuseppe Felice; Tognolini, Massimiliano; Karalaki, Foteini; Giorgio, Carmine; Patsilinakos, Alexandros; Carotti, Angelo; Hadjipavlou-Litina, Dimitra; Barocelli, Elisabetta

    2015-12-01

    The interest towards coumarin-based structures stems from their polypharmacological profile. Herein, we present a series of Mannich bases and 7-azomethine-linked coumarin derivatives exhibiting antiplatelet and antithrombotic activities, in addition to the already known anti-inflammatory and antioxidant activities. Among others, compounds 15 and 16 were found to be the most potent and selective inhibitors of platelet aggregation whereas compound 3 also proved to be the most potent in the clot retraction assay. Structure-activity relationship studies were conducted to elucidate the molecular determinants responsible for the herein observed activities. The chance of inhibiting cyclooxygenase-1 was also investigated for evaluating the platelet aggregation induced by arachidonic acid. Taken together, these results suggest that the investigation of other targets connected to the antiplatelet activity, such as phosphodiesterase-3 (PDE3), could be a viable strategy to shed light on the polypharmacological profile of coumarin-based compounds. Docking simulations towards PDE3 were also carried out. PMID:25807297

  7. Anti-inflammatory and antifibrotic effects of methyl palmitate

    SciTech Connect

    El-Demerdash, Ebtehal

    2011-08-01

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

  8. Human genome screen to identify the genetic basis of the anti-inflammatory effects of Boswellia in microvascular endothelial cells.

    PubMed

    Roy, Sashwati; Khanna, Savita; Shah, Hiral; Rink, Cameron; Phillips, Christina; Preuss, Harry; Subbaraju, Gottumukkala V; Trimurtulu, Golakoti; Krishnaraju, Alluri V; Bagchi, Manashi; Bagchi, Debasis; Sen, Chandan K

    2005-04-01

    Inflammatory disorders represent a substantial health problem. Medicinal plants belonging to the Burseraceae family, including Boswellia, are especially known for their anti-inflammatory properties. The gum resin of Boswellia serrata contains boswellic acids, which inhibit leukotriene biosynthesis. A series of chronic inflammatory diseases are perpetuated by leukotrienes. Although Boswellia extract has proven to be anti-inflammatory in clinical trials, the underlying mechanisms remain to be characterized. TNF alpha represents one of the most widely recognized mediators of inflammation. One mechanism by which TNFalpha causes inflammation is by potently inducing the expression of adhesion molecules such as VCAM-1. We sought to test the genetic basis of the antiinflammatory effects of BE (standardized Boswellia extract, 5-Loxin) in a system of TNF alpha-induced gene expression in human microvascular endothelial cells. We conducted the first whole genome screen for TNF alpha- inducible genes in human microvascular cells (HMEC). Acutely, TNF alpha induced 522 genes and downregulated 141 genes in nine out of nine pairwise comparisons. Of the 522 genes induced by TNF alpha in HMEC, 113 genes were clearly sensitive to BE treatment. Such genes directly related to inflammation, cell adhesion, and proteolysis. The robust BE-sensitive candidate genes were then subjected to further processing for the identification of BE-sensitive signaling pathways. The use of resources such as GenMAPP, KEGG, and gene ontology led to the recognition of the primary BE-sensitive TNF alpha-inducible pathways. BE prevented the TNF alpha-induced expression of matrix metalloproteinases. BE also prevented the inducible expression of mediators of apoptosis. Most strikingly, however, TNF alpha-inducible expression of VCAM-1 and ICAM-1 were observed to be sensitive to BE. Realtime PCR studies showed that while TNF alpha potently induced VCAM-1 gene expression, BE completely prevented it. This result confirmed our microarray findings and built a compelling case for the anti-inflammatory property of BE. In an in vivo model of carrageenan-induced rat paw inflammation, we observed a significant antiinflammatory property of BE consistent with our in vitro findings. These findings warrant further research aimed at identifying the signaling mechanisms by which BE exerts its anti-inflammatory effects. PMID:15812241

  9. Glitazones inhibit human monoamine oxidase but their anti-inflammatory actions are not mediated by VAP-1/semicarbazide-sensitive amine oxidase inhibition.

    PubMed

    Carpéné, Christian; Bizou, Mathilde; Tréguer, Karine; Hasnaoui, Mounia; Grès, Sandra

    2015-09-01

    Glitazones are peroxisome proliferator-activated receptor gamma (PPAR?) agonists widely used as antidiabetic drugs also known as thiazolidinediones. Most of them exert other effects such as anti-inflammatory actions via mechanisms supposed to be independent from PPAR? activation (e.g., decreased plasma monocyte chemoattractant protein-1 (MCP-1) levels). Recently, pioglitazone has been shown to inhibit the B form of monoamine oxidase (MAO) in mouse, while rosiglitazone and troglitazone were described as non-covalent inhibitors of both human MAO A and MAO B. Since molecules interacting with MAO might also inhibit semicarbazide-sensitive amine oxidase (SSAO), known as vascular adhesion protein-1 (VAP-1), and since VAP-1/SSAO inhibitors exhibit anti-inflammatory activity, our aim was to elucidate whether VAP-1/SSAO inhibition could be a mechanism involved in the anti-inflammatory behaviour of glitazones. To this aim, MAO and SSAO activities were measured in human subcutaneous adipose tissue biopsies obtained from overweight women undergoing plastic surgery. The production of hydrogen peroxide, an end-product of amine oxidase activity, was determined in tissue homogenates using a fluorometric method. The oxidation of 1 mM tyramine was inhibited by pargyline and almost resistant to semicarbazide, therefore predominantly MAO-dependent. Rosiglitazone was more potent than pioglitazone in inhibiting tyramine oxidation. By contrast, benzylamine oxidation was only abolished by semicarbazide: hence SSAO-mediated. Pioglitazone hampered SSAO activity only when tested at 1 mM while rosiglitazone was inefficient. However, rosiglitazone exhibited anti-inflammatory activity in human adipocytes by limiting MCP-1 expression. Our observations rule out any involvement of VAP-1/SSAO inhibition and subsequent limitation of leukocyte extravasation in the anti-inflammatory action of glitazones. PMID:25572340

  10. Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy

    PubMed Central

    Lim, Yun Jeong

    2012-01-01

    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. PMID:22866254

  11. Anti-inflammatory cyclopeptides from exocarps of sugar-apples.

    PubMed

    Wu, Ping; Wu, Min; Xu, Liangxiong; Xie, Haihui; Wei, Xiaoyi

    2014-01-01

    Two new cyclic peptides, fanlizhicyclopeptide A, cyclo(Pro(1)-Pro(2)-Tyr(3)-Leu(4)-Pro(5)-Gly(6)-Val(7)) (1), and fanlizhicyclopeptide B, cyclo(Pro(1)-Ile(2)-Tyr(3)-Ala(4)-Gly(5)) (2), were isolated along with six known kaurane diterpenoids and a known clovane sesquiterpene from the exocarps of sugar-apples, the fruit of Annona squamosa. Their structures were elucidated by ESI MS/MS experiments, 1D and 2D NMR data and chemical degradation. In the anti-inflammatory assay, both 1 and 2 showed in vitro inhibitory effects on the production of pro-inflammatory cytokines, TNF-? and IL-6, in LPS-stimulated RAW 264.7 macrophages. PMID:24444902

  12. Phytochemical Compositions and Antioxidant and Anti-Inflammatory Activities of Crude Extracts from Ficus pandurata H. (Moraceae)

    PubMed Central

    Lv, Huiqing; Zhang, Xiaoping; Chen, XueZhi; Xie, Zhijun; Wen, Chengping; Jiang, Kezhi

    2013-01-01

    Background. Ficus pandurata H. (Moraceae) is widely used in traditional Chinese medicine as a healthy food condiment or a medicine for treatment of various diseases including inflammation. Objective. The purpose of the present study is to investigate the phytochemical compositions and antioxidant and anti-inflammatory activities of crude water (FPW) and ethanolic extracts (FPE) from Ficus pandurata H. Methods. Phytochemical compositions were identified by a high-performance liquid chromatography-electrospray ionization-mass spectrometry method (HPLC-ESI-MS). The antioxidant activities were evaluated by diphenylpicrylhydrazyl (DPPH) and hydroxyl radical assays, and the anti-inflammatory activities were evaluated by paw edema and levels of inflammatory mediator TNF-? and PGE2 in monosodium urate (MSU) crystal-induced rats. Results. Six compounds were identified by HPLC-MS method, and abundance of phenolics was found in FPE. The FPE showed concentration-dependent-significant scavenging of DPPH and hydroxyl radicals with IC50 values 118.4 and 192.9??g/mL, respectively. The FPE treatment significantly inhibited the paw edema and the production of TNF-? and PGE2 in MSU crystal-induced rats. Conclusion. The FPE exerted stronger antioxidant and anti-inflammatory activities which may be attributed to its high phenolic content. PMID:24191163

  13. Antimicrobial and Anti-Inflammatory Activities of Endophytic Fungi Talaromyces wortmannii Extracts against Acne-Inducing Bacteria

    PubMed Central

    Schwendinger, Katja; Kreiseder, Birgit; Wiederstein, Martina; Pretsch, Dagmar; Genov, Miroslav; Hollaus, Ralph; Zinssmeister, Daniela; Debbab, Abdesamad; Hundsberger, Harald; Eger, Andreas; Proksch, Peter; Wiesner, Christoph

    2014-01-01

    Acne vulgaris is the most common skin disease, causing significant psychosocial problems such as anxiety and depression similar to a chronic illness for those afflicted. Currently, obtainable agents for acne treatment have limited use. Thus, development of novel agents to treat this disease is a high medical need. The anaerobic bacterium Propionibacterium acnes has been implicated in the inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such as the interleukin-8 (IL-8) via the NF-?B and MAPK pathways. Talaromyces wortmannii is an endophytic fungus, which is known to produce high bioactive natural compounds. We hypothesize that compound C but also the crude extract from T. wortmannii may possess both antibacterial activity especially against P. acnes and also anti-inflammatory properties by inhibiting TNF-?-induced ICAM-1 expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT) with P. acnes significantly increased NF-?B and activator protein-1 (AP-1) activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated activation of NF-?B and AP-1 by inhibiting I?B degradation and the phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent manner. Based on these results, compound C has effective antimicrobial activity against P. acnes and anti-inflammatory activity, and we suggest that this substance or the crude extract are alternative treatments for antibiotic/anti-inflammatory therapy for acne vulgaris. PMID:24887557

  14. Antimicrobial and anti-inflammatory activities of endophytic fungi Talaromyces wortmannii extracts against acne-inducing bacteria.

    PubMed

    Pretsch, Alexander; Nagl, Michael; Schwendinger, Katja; Kreiseder, Birgit; Wiederstein, Martina; Pretsch, Dagmar; Genov, Miroslav; Hollaus, Ralph; Zinssmeister, Daniela; Debbab, Abdesamad; Hundsberger, Harald; Eger, Andreas; Proksch, Peter; Wiesner, Christoph

    2014-01-01

    Acne vulgaris is the most common skin disease, causing significant psychosocial problems such as anxiety and depression similar to a chronic illness for those afflicted. Currently, obtainable agents for acne treatment have limited use. Thus, development of novel agents to treat this disease is a high medical need. The anaerobic bacterium Propionibacterium acnes has been implicated in the inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such as the interleukin-8 (IL-8) via the NF-?B and MAPK pathways. Talaromyces wortmannii is an endophytic fungus, which is known to produce high bioactive natural compounds. We hypothesize that compound C but also the crude extract from T. wortmannii may possess both antibacterial activity especially against P. acnes and also anti-inflammatory properties by inhibiting TNF-?-induced ICAM-1 expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT) with P. acnes significantly increased NF-?B and activator protein-1 (AP-1) activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated activation of NF-?B and AP-1 by inhibiting I?B degradation and the phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent manner. Based on these results, compound C has effective antimicrobial activity against P. acnes and anti-inflammatory activity, and we suggest that this substance or the crude extract are alternative treatments for antibiotic/anti-inflammatory therapy for acne vulgaris. PMID:24887557

  15. 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...

  16. 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...

  17. Issues surrounding the anti-inflammatory actions of the citrus polymethoxylated flavones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The polymethoxylated flavones in citrus have been evaluated for their in vivo anti-inflammatory actions in several animal assays. Strong anti-inflammatory effects were observed following administration of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) dissolved in vegetable oil by intraperitoneal (i.p.) ...

  18. Comparison of Piroxicam Pharmacokinetics and Anti-Inflammatory Effect in Rats after Intra-Articular and Intramuscular Administration

    PubMed Central

    Park, Chan Woong; Ma, Kyung Wan; Jang, Sun Woo; Son, Miwon; Kang, Myung Joo

    2014-01-01

    This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin E2 in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis. PMID:25009708

  19. Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages

    SciTech Connect

    He, Xiao-dong; Tobo, Masayuki; Mogi, Chihiro; Nakakura, Takashi; Komachi, Mayumi; Murata, Naoya; Takano, Mutsumi; Tomura, Hideaki; Sato, Koichi; Okajima, Fumikazu

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Glucocorticoid (GC) induced the expression of proton-sensing TDAG8 in macrophages. Black-Right-Pointing-Pointer GC enhanced acidic pH-induced cAMP accumulation and inhibition of TNF-{alpha} production. Black-Right-Pointing-Pointer The enhancement of the GC-induced actions was lost by TDAG8 deficiency. Black-Right-Pointing-Pointer GC-induced anti-inflammatory actions are partly mediated by TDAG8 expression. -- Abstract: Dexamethasone (DEX), a potent glucocorticoid, increased the expression of T-cell death associated gene 8 (TDAG8), a proton-sensing G protein-coupled receptor, which is associated with the enhancement of acidic pH-induced cAMP accumulation, in peritoneal macrophages. We explored the role of increased TDAG8 expression in the anti-inflammatory actions of DEX. The treatment of macrophages with either DEX or acidic pH induced the cell death of macrophages; however, the cell death was not affected by TDAG8 deficiency. While DEX inhibited lipopolysaccharide-induced production of tumor necrosis factor-{alpha}, an inflammatory cytokine, which was independent of TDAG8, at neutral pH, the glucocorticoid enhanced the acidic pH-induced inhibition of tumor necrosis factor-{alpha} production in a manner dependent on TDAG8. In conclusion, the DEX-induced increase in TDAG8 expression is in part involved in the glucocorticoid-induced anti-inflammatory actions through the inhibition of inflammatory cytokine production under the acidic pH environment. On the other hand, the role of TDAG8 in the DEX-induced cell death is questionable.

  20. The flavonoid content and antiproliferative, hypoglycaemic, anti-inflammatory and free radical scavenging activities of Annona dioica St. Hill

    PubMed Central

    2013-01-01

    Background Annona dioica St. Hill (Annonacaeae) is a Brazilian plant used in folk medicine for the treatment of several types of rheumatisms and diarrhoea. The focus of this work was to evaluate the in vitro antiproliferative and antioxidant activity and the in vivo hypoglycaemic and anti-inflammatory activity of A. dioica and identify the principal constituents of this plant. Methods The crude methanol extract (EAD) and hexane (HF), chloroform (CF), ethyl acetate (EAF) and hydromethanol fractions (HMF) were evaluated for free radical scavenging activity using the DPPH assay. The EAD and EAF were assayed for hypoglycaemic activity in rats. The EAD was tested in an antiproliferation assay and for anti-inflammatory effects in paw oedema, in addition to myeloperoxidase activity induced by carrageenan (Cg) in mice. The EAF was assayed using chromatographic methods. Results The fractionation of the EAF through chromatographic methods identified derivatives of the flavonoids quercetin and kaempferol. Among all the tested fractions, the ethyl acetate and hydromethanol fractions were the most potent, exhibiting an IC50 of 8.53 and 10.57 ?g/mL, respectively, which is comparable to that of the commercial antioxidant butylated hydroxytoluene (BHT). The oral administration of the EAD (100 mg/kg) and EAF (15 mg/kg) inhibited the increase of glucose levels, resulting in a hypoglycaemic effect. The EAD (30 to 300 mg/kg) exhibited an anti-oedematogenic effect in Cg-induced paw oedema in a time- and dose-dependent manner. The results showed a reduction of MPO activity by A. dioica 6 h after the induction of paw oedema at all doses tested with maximal inhibition at 300 mg/kg. Conclusions Our results reveal for the first time that compounds contained in the A. dioica leaves exert anti-inflammatory, hypoglycaemic, antiproliferative, and antioxidant effects. The antioxidant activity may be associated with the presence of flavonoids. PMID:23311341

  1. A nicotinic receptor-mediated anti-inflammatory effect of the flavonoid rhamnetin in BV2 microglia

    PubMed Central

    Lutz, Joseph A.; Kulshrestha, Manish; Rogers, Dennis T.; Littleton, John M.

    2014-01-01

    The alpha7 nicotinic acetylcholine receptor (nAChR) is a potential target in neuroinflammation. Screening a plant extract library identified Solidago nemoralis as containing methyl-quercetin derivatives that are relatively selective ligands for the alpha7 nAChR. Flavonoids are not known for this activity, so we screened a small library of pure flavonoids to confirm our findings. Some flavonoids, e.g. rhamnetin, displaced a selective alpha7 nAChR radioligand from rat brain membranes whereas similar structures e.g. sakuranetin, did not. To evaluate the contribution of this putative nAChR activity to the known anti-inflammatory properties of these flavonoids, we compared their effects on lipopolysaccharide induced release of inflammatory mediators from BV2 microglia. Both rhamnetin and sakuranetin reduced mediator release, but differed in potency (rhamnetin>sakuranetin) and the Hill slope of their concentration response curves. For rhamnetin the Hill coefficient was >3.0 whereas for sakuranetin the coefficient was 1.0, suggesting that effects of rhamnetin are mediated through more than one mechanism, whereas sakuranetin has a single mechanism. nACHR antagonists decreased the Hill coefficient for rhamnetin toward unity, which suggests that a nAChR-mediated mechanism contributes cooperatively to its overall anti-inflammatory effect. In contrast nAChR antagonists had no effect on the potency or Hill coefficient for sakuranetin, but a concentration of nicotine (1?M) that had no effect alone, significantly increased the Hill coefficient of this flavonoid. In conclusion, the anti-inflammatory effects of rhamnetin benefit cooperatively from a nAChR-mediated mechanism. This action, together with potent free radical scavenging activity, suggests that flavonoids with alpha7 nAChR activity have therapeutic potential in neuroinflammatory conditions. PMID:24972350

  2. A nicotinic receptor-mediated anti-inflammatory effect of the flavonoid rhamnetin in BV2 microglia.

    PubMed

    Lutz, Joseph A; Kulshrestha, Manish; Rogers, Dennis T; Littleton, John M

    2014-10-01

    The alpha7 nicotinic acetylcholine receptor (nAChR) is a potential target in neuroinflammation. Screening a plant extract library identified Solidago nemoralis as containing methyl-quercetin derivatives that are relatively selective ligands for the alpha7 nAChR. Flavonoids are not known for this activity, so we screened a small library of pure flavonoids to confirm our findings. Some flavonoids, e.g. rhamnetin, displaced a selective alpha7 nAChR radioligand from rat brain membranes whereas similar structures e.g. sakuranetin, did not. To evaluate the contribution of this putative nAChR activity to the known anti-inflammatory properties of these flavonoids, we compared their effects on lipopolysaccharide induced release of inflammatory mediators from BV2 microglia. Both rhamnetin and sakuranetin reduced mediator release, but differed in potency (rhamnetin>sakuranetin) and the Hill slope of their concentration-response curves. For rhamnetin the Hill coefficient was >3.0 whereas for sakuranetin the coefficient was 1.0, suggesting that effects of rhamnetin are mediated through more than one mechanism, whereas sakuranetin has a single mechanism. nAChR antagonists decreased the Hill coefficient for rhamnetin toward unity, which suggests that a nAChR-mediated mechanism contributes cooperatively to its overall anti-inflammatory effect. In contrast nAChR antagonists had no effect on the potency or Hill coefficient for sakuranetin, but a concentration of nicotine (1?M) that had no effect alone, significantly increased the Hill coefficient of this flavonoid. In conclusion, the anti-inflammatory effects of rhamnetin benefit cooperatively from a nAChR-mediated mechanism. This action, together with potent free radical scavenging activity, suggests that flavonoids with alpha7 nAChR activity have therapeutic potential in neuroinflammatory conditions. PMID:24972350

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

    PubMed Central

    2012-01-01

    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. PMID:23031211

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

    PubMed Central

    2012-01-01

    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. PMID:23038995

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

    PubMed

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

    2012-01-01

    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

  6. Esculin exhibited anti-inflammatory activities in vivo and regulated TNF-? and IL-6 production in LPS-stimulated mouse peritoneal macrophages in vitro through MAPK pathway.

    PubMed

    Niu, Xiaofeng; Wang, Yu; Li, Weifeng; Zhang, Hailin; Wang, Xiumei; Mu, Qingli; He, Zehong; Yao, Huan

    2015-12-01

    Esculin, a coumarinic derivative found in Aesculus hippocastanum L. (Horse-chestnut), has been reported to have potent anti-inflammatory properties. The present study is designed to investigate the protective effects of esculin on various inflammation models in vivo and in vitro and to clarify the possible mechanism. Induced-animal models of inflammation and lipopolysaccharide (LPS)-challenged mouse peritoneal macrophages were used to examine the anti-inflammatory activity of esculin. In present study, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, and carrageenan-induced mouse pleurisy were attenuated by esculin. In vitro, the pro-inflammatory cytokine levels of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in supernatant were reduced by esculin. Meanwhile, we found that esculin significantly inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathway in peritoneal macrophages. These results suggest that esculin has potent anti-inflammatory activities in vivo and in vitro, which may involve the inhibition of the MAPK pathway. Esculin may be a promising preventive agent for inflammatory diseases in human. PMID:26391063

  7. Antioxidant, Antibacterial, Cytotoxic, and Anti-Inflammatory Potential of the Leaves of Solanum lycocarpum A. St. Hil. (Solanaceae)

    PubMed Central

    da Costa, Guilherme Augusto Ferreira; Morais, Melissa Grazielle; Saldanha, Aline Aparecida; Assis Silva, Izabela Caputo; Aleixo, Álan Alex; Ferreira, Jaqueline Maria Siqueira; Soares, Adriana Cristina; Duarte-Almeida, Joaquim Maurício; Lima, Luciana Alves Rodrigues dos Santos

    2015-01-01

    Ethanol extract and fractions obtained from leaves of Solanum lycocarpum were examined in order to determine their phenolic composition, antioxidant, antibacterial, anti-inflammatory, and cytotoxic potential. High performance liquid chromatography coupled with DAD analysis indicated that the flavonoids apigenin and kaempferol were the main phenolic compounds present in dichloromethane and ethyl acetate fractions, respectively. The antioxidant activity was significantly more pronounced for dichloromethane, ethyl acetate, and hydroethanol fractions than that of the commercial antioxidant 2,6-di-tert-butyl-4-methylphenol. The hexane and dichloromethane fractions were more active against the tested bacteria. The hydroethanol fraction exhibited significant anti-inflammatory activity at the dose of 75 and 150?mg/kg in the later phase of inflammation. However, the antiedematogenic effect of the higher dose of the ethyl acetate fraction (150?mg/kg) was more pronounced. The ethyl acetate fraction also presented a less cytotoxic effect than the ethanol extract and other fractions. These activities found in S. lycocarpum leaves can be attributed, at least in part, to the presence of phenolic constituents such as flavonoids. This work provided the knowledge of phenolic composition in the extract and fractions and the antioxidant, antibacterial, anti-inflammatory, and cytotoxic activities of leaves of S. lycocarpum. PMID:26064159

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

    PubMed Central

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

    2011-01-01

    Many synthetic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Since the last few decades, herbal drugs have regained their popularity in treatment against several human ailments. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA. The basic aim of this review is to give updated knowledge regarding plants which will be valuable for the scientists working in the field of anti-inflammatory natural chemistry. PMID:22279370

  9. Anti-Inflammatory and Anticancer Activities of Taiwanese Purple-Fleshed Sweet Potatoes (Ipomoea batatas L. Lam) Extracts.

    PubMed

    Sugata, Marcelia; Lin, Chien-Yih; Shih, Yang-Chia

    2015-01-01

    Purple-fleshed sweet potato (PFSP) (Ipomoea batatas L. Lam) has been known to possess high amount of anthocyanins which contribute to its antioxidant activity. However, a few reports are available concerning its anti-inflammatory and anticancer properties. In this study, PFSP "Tainung 73," which is locally grown in Taiwan, was steamed and extracted using acidified ethanol pH 3.5 under 80°C. Two kinds of crude anthocyanins extracts were obtained, namely, SP (Steamed, Peeled) and SNP (Steamed, No Peeled). Then, anti-inflammatory and anticancer activities of these extracts were investigated. Cell viability assay (MTT) showed that SP and SNP extracts were not toxic to RAW 264.7 cells. They even exhibited anti-inflammatory activities by suppressing the production of NO and proinflammatory cytokines, such as NF-??, TNF-?, and IL-6, in LPS-induced macrophage cells. Anticancer activities of these extracts were displayed through their ability to inhibit the growth of cancer cell lines, such as MCF-7 (breast cancer), SNU-1 (gastric cancer), and WiDr (colon adenocarcinoma), in concentration- and time-dependent manner. Further studies also revealed that SP extracts could induce apoptosis in MCF-7 and SNU-1 cancer cells through extrinsic and intrinsic pathway. In the future, PSFP extracts may have potential to be applied in nutraceutical, pharmaceutical, and food industries. PMID:26509161

  10. Anti-Inflammatory and Anticancer Activities of Taiwanese Purple-Fleshed Sweet Potatoes (Ipomoea batatas L. Lam) Extracts

    PubMed Central

    Sugata, Marcelia; Lin, Chien-Yih; Shih, Yang-Chia

    2015-01-01

    Purple-fleshed sweet potato (PFSP) (Ipomoea batatas L. Lam) has been known to possess high amount of anthocyanins which contribute to its antioxidant activity. However, a few reports are available concerning its anti-inflammatory and anticancer properties. In this study, PFSP “Tainung 73,” which is locally grown in Taiwan, was steamed and extracted using acidified ethanol pH 3.5 under 80°C. Two kinds of crude anthocyanins extracts were obtained, namely, SP (Steamed, Peeled) and SNP (Steamed, No Peeled). Then, anti-inflammatory and anticancer activities of these extracts were investigated. Cell viability assay (MTT) showed that SP and SNP extracts were not toxic to RAW 264.7 cells. They even exhibited anti-inflammatory activities by suppressing the production of NO and proinflammatory cytokines, such as NF-??, TNF-?, and IL-6, in LPS-induced macrophage cells. Anticancer activities of these extracts were displayed through their ability to inhibit the growth of cancer cell lines, such as MCF-7 (breast cancer), SNU-1 (gastric cancer), and WiDr (colon adenocarcinoma), in concentration- and time-dependent manner. Further studies also revealed that SP extracts could induce apoptosis in MCF-7 and SNU-1 cancer cells through extrinsic and intrinsic pathway. In the future, PSFP extracts may have potential to be applied in nutraceutical, pharmaceutical, and food industries. PMID:26509161

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

    PubMed Central

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

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

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

    PubMed

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

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

  13. Anti-Inflammatory Effects of a Polyphenols-Rich Extract from Tea (Camellia sinensis) Flowers in Acute and Chronic Mice Models

    PubMed Central

    Chen, Bang-Tian; Li, Wei-Xi; He, Rong-Rong; Li, Yi-Fang; Tsoi, Bun; Zhai, Yu-Jia; Kurihara, Hiroshi

    2012-01-01

    While beneficial health properties of tea leaves have been extensively studied, less attention is paid to the flowers of tea. In this study, the anti-inflammatory effects of hot water extract of tea (Camellia sinensis) flowers were investigated. Pharmacological studies found that administration of tea flowers extract (TFE) could effectively inhibit croton oil-induced ear edema and carrageenin-induced paw edema. Furthermore, administration of TFE also protected against Propionibacterium acnes (P. ances) plus lipopolysaccharide-(LPS-) induced liver inflammation by reversing the histologic damage and plasma alanine aminotransferase (ALT) increase. Moreover, the levels of nitric oxide (NO), tumor necrosis factor-(TNF)-? and interleukin-(IL-) 1? mRNA in mouse liver were markedly suppressed after treatment with TFE in mice with immunological liver inflammation. These results indicated that tea flowers had potent anti-inflammatory effects on acute and immunological inflammation in vivo, and may be used as a functional natural food. PMID:22900128

  14. A facile synthesis, anti-inflammatory and analgesic activity of isoxazolyl-2,3-dihydrospiro[benzo[f]isoindole-1,3'-indoline]-2',4,9-triones.

    PubMed

    Rajanarendar, E; Ramakrishna, S; Govardhan Reddy, K; Nagaraju, D; Reddy, Y N

    2013-07-01

    A new series of isoxazolyl-2,3-dihydrospiro[benzo[f]isoindole-1,3'-indoline]-2',4,9-triones (14) were synthesized by reaction of 4-amino-3-methyl-5-styrylisoxazole 10 with chloroacetic acid followed by a three component reaction with substituted isatins 12 and 1,4-naphthoquinone 13 using Ceric ammonium nitrate (CAN) catalyst under aerial oxidation condition. Structures of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and mass spectral data. The title compounds 14a-j were evaluated for their anti-inflammatory and analgesic activity. Compounds 14d, 14e and 14f exhibited potent anti-inflammatory and analgesic activity as that of standard drugs. PMID:23673015

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

    PubMed

    Marginean, Alexandru; Sharma-Walia, Neelam

    2015-08-01

    Lipoxin A4 (LXA4) is an endogenously produced host molecule with anti-inflammatory resolution effects. Previous studies demonstrated it to be involved in anti-vascular endothelial growth factor (VEGF)-mediated angiogenesis and in a possible anticancer role via interaction with its receptor, lipoxin A 4 receptor (ALXR). Here, we examined the effects of LXA4 and its epimer 15-epi-LXA4 in inhibiting proinflammatory and angiogenic functions in a human Kaposi's sarcoma tumor-derived cell line (KS-IMM). KS-IMM cells expressed increased levels of inflammatory cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LO) pathway enzymes when compared with human microvascular dermal endothelial cells (HMVEC-d). KS-IMM cells secreted high levels of prostaglandin E2 (PGE2) and chemotactic leukotriene B4 (LTB4). Treatment with LXA4 or 15-epi-LXA4 effectively reduced the levels of COX-2, 5-LO proteins, and secretion of PGE2 and LTB4 in KS-IMM cells. LXA4 or 15-epi-LXA4 treatment also decreased secretion of proinflammatory interleukin 6 (IL-6) and IL-8 cytokines but induced the secretion of anti-inflammatory IL-10. LXA4 treatment reduced the phosphorylation of VEGF receptor (VEGFR) and ephrin family receptor tyrosine kinases. LXA4 treatment effectively induced dephosphorylation of multiple cellular kinases such as Focal Adhesion Kinase, Protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and Extracellular signal-regulated kinases (ERK)1/2, and reduced angiogenic factor VEGF-C secretion in KS cells. LX treatment drastically induced the Src-homology 2 domain-containing phosphatase tyrosine (Y542) phosphatase and reduced VEGFR-2 phosphorylation at sites Y1059, Y1175, and Y1212. Treatment of KS-IMM cells with LXA4 resulted in selective localization of VEGFR-2 in nonlipid raft (non-LR) and ALXR to LR fractions. These results demonstrated that LXA4 or 15-epi-LXA4 induce anti-inflammatory and antiangiogenic effects in KS cells and suggest that treatment with LXs is an attractive novel strategy against KS. PMID:25814167

  16. Characterization of Phenolic Compounds and Antioxidant and Anti-inflammatory Activities from Mamuyo (Styrax ramirezii Greenm.) Fruit.

    PubMed

    Timmers, Michael A; Guerrero-Medina, Jorge L; Esposito, Debora; Grace, Mary H; Paredes-López, Octavio; García-Saucedo, Pedro A; Lila, Mary Ann

    2015-12-01

    Extracts of Styrax ramirezii Greenm., a fruit traditionally valued for health and wellness in Mexico, were analyzed phytochemically and evaluated for antioxidant and anti-inflammatory activity. Six norneolignans were identified by HPLC-TOF-MS, and the two major compounds were isolated for further evaluation. The effects of the isolated norneolignans, egonol and homoegonol, on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, reactive oxygen species (ROS) production, and biomarkers of inflammation were evaluated. Of the tested compounds, egonol potently inhibited the production of NO and also significantly reduced the release of ROS. Consistent with these observations, the mRNA expression levels of inducible nitric oxide synthase (iNOS) (0.668 ± 0.108), cyclooxygenase-2 (COX-2) (0.553 ± 0.007), interleukin-1? (IL-1?) (0.093 ± 0.005), and interleukin-6 (IL-6) (0.298 ± 0.076) were reduced by egonol. The activity for both egonol and homoegonol increased in a concentration-dependent manner. These results suggest the potential of S. ramirezii Greenm. fruit to contribute to a healthy diet, rich in antioxidant and anti-inflammatory compounds. PMID:26575200

  17. Anti-Inflammatory, Antioxidant, Anti-Angiogenic and Skin Whitening Activities of Phryma leptostachya var. asiatica Hara Extract

    PubMed Central

    Jung, Hyun-Joo; Cho, Young-Wook; Lim, Hye-Won; Choi, Hojin; Ji, Dam-Jung; Lim, Chang-Jin

    2013-01-01

    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. PMID:24009862

  18. Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs.

    PubMed

    Jain, Sarthak; Tran, Susan; El Gendy, Mohamed A M; Kashfi, Khosrow; Jurasz, Paul; Velázquez-Martínez, Carlos A

    2012-01-26

    The objective of this work was to evaluate the biological properties of a new series of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) possessing a tyrosol linker between the NSAID and the NO-releasing moiety (PROLI/NO); however, initial screening of ester intermediates without the PROLI/NO group showed the required (desirable) efficacy/safety ratio, which questioned the need for NO in the design. In this regard, NSAID ester intermediates were potent and selective COX-2 inhibitors in vitro, showed equipotent anti-inflammatory activity compared to the corresponding parent NSAID, but showed a markedly reduced gastric toxicity when administered orally. These results provide complementary evidence to challenge the currently accepted notion that hybrid NO-NSAIDs exert their cytoprotective effects by releasing NO. Results obtained in this work constitute a good body of evidence to initiate a debate about the future replacement of NSAID prodrugs for unprotected NSAIDs (possessing a free carboxylic acid group) currently in clinical use. PMID:22148253

  19. In vivo anti-inflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus.

    PubMed

    Jung, Hyun-Ju; Park, Hee-Juhn; Kim, Ryung-Gue; Shin, Kyoung-Min; Ha, Joohun; Choi, Jong-Won; Kim, Hyoung Ja; Lee, Yong Sup; Lee, Kyung-Tae

    2003-07-01

    In the present study, liriodendrin isolated by activity-guided fractionation from the ethyl acetate (EtOAc) extracts of the stem bark of Acanthopanax senticosus, was evaluated for anti-inflammatory and antinociceptive activities. Liriodendrin (5, 10 mg/kg/day, p. o.) significantly inhibited the increase of vascular permeability induced by acetic acid in mice and reduced an acute paw edema induced by carrageenan in rats. When the analgesic activity was measured by the acetic acid-induced writhing test and hot plate test, liriodendrin showed a dose-dependent inhibition in animal models. In addition, syringaresinol, the hydrolysate of liriodendrin, more potently inhibited the LPS-induced production of NO, PGE 2 and TNF-alpha production of macrophages than liriodendrin. Consistent with these observations, the expression level of iNOS and COX-2 enzyme was decreased by syringaresinol in a concentration-dependent manner. These results suggest that the anti-inflammatory and antinociceptive effects of liriodendrin after oral administration were attributable to the in vivo transformation to syringaresinol, which may function as the active constituent. PMID:12898415

  20. Anti-Inflammatory Effect of Streptochlorin via TRIF-Dependent Signaling Pathways in Cellular and Mouse Models

    PubMed Central

    Shim, Do-Wan; Shin, Hee Jae; Han, Ji-Won; Shin, Woo-Young; Sun, Xiao; Shim, Eun-Jeong; Kim, Tack-Joong; Kang, Tae-Bong; Lee, Kwang-Ho

    2015-01-01

    Streptochlorin, a small compound derived from marine actinomycete, has been shown to have anti-angiogenic, anti-tumor, and anti-allergic activities. However, the anti-inflammatory effects and underlying mechanisms have not yet been reported. In the present study, we investigated the effect of streptochlorin on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Streptochlorin attenuated the production of proinflammatory mediators such as nitric oxide, cyclooxygenase-2, pro-interleukin (IL)-1?, and IL-6 in LPS-stimulated RAW264.7 cells through inhibition of the Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-? (TRIF)-dependent signaling pathway. Furthermore, streptochlorin suppressed the infiltration of immune cells such as neutrophils into the lung and proinflammatory cytokine production such as IL-6 and TNF-? in broncho-alveolar lavage fluid (BALF) in the LPS-induced acute lung injury (ALI) mouse model. Streptochlorin has potent anti-inflammatory effects through regulating TRIF-dependent signaling pathways, suggesting that streptochlorin may provide a valuable therapeutic strategy in treating various inflammatory diseases. PMID:25822875

  1. Antidepressant-like effects of curcumin in chronic mild stress of rats: involvement of its anti-inflammatory action.

    PubMed

    Jiang, Hong; Wang, Zhen; Wang, Yihe; Xie, Kai; Zhang, Qingrui; Luan, Qinsong; Chen, Wenqiang; Liu, Dexiang

    2013-12-01

    Mounting evidence suggests that inflammation may contribute to the pathophysiology of depression. Curcumin, a polyphenol extracted from the plant Curcuma longa, exhibits a number of pharmacological properties, including potent anti-inflammatory action. Hence, the current study aimed to explore the immunomodulatory effects of curcumin in an animal model of chronic mild stress (CMS). Rats were subjected to CMS protocol for a period of 21 days to induce depressive-like behavior. The body weight, sucrose preference and locomotor activity were evaluated. Both RT-PCR and ELISA were used to determine the expression of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in the prefrontal cortex and hippocampus. Modulation of nuclear factor-?B (NF-?B) activation was assessed by western blotting. Chronic treatment with curcumin significantly reversed the CMS-induced behavioral abnormalities (reduced sucrose preference and decreased locomotor activity) in stressed rats. Additionally, curcumin effectively inhibited cytokine gene expression at both the mRNA and the protein level and reduced the activation of NF-?B. The study revealed that curcumin exerted antidepressant-like effects in CMS rats, partially due to its anti-inflammatory aptitude. PMID:23876788

  2. Antioxidant and Anti-inflammatory Activities of Broccoli Florets in LPS-stimulated RAW 264.7 Cells

    PubMed Central

    Hwang, Joon-Ho; Lim, Sang-Bin

    2014-01-01

    Broccoli (Brassica oleracea var. italia) florets were extracted with 80% methanol and the extract was sequentially fractionated with n-hexane, ethyl acetate, n-butanol, and distilled water. The extract and the fractions were evaluated for total phenolic content, sulforaphane content, antioxidant activity, and anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The total phenolic content and sulforaphane content of the ethyl acetate fraction (EF) were 35.5 mg gallic acid equivalents/g and 620.2 ?g/g, respectively. These values were higher than those of the 80% methanol extract and organic solvent fractions. The oxygen radical absorbance capacity of the EF [1,588.7 ?M Trolox equivalents (TE)/mg] was 11-fold higher than that of the distilled water fraction (143.7 ?M TE/mg). The EF inhibited nitric oxide release from LPS-stimulated RAW 264.7 cells in a dose-dependent manner and inhibited I?B-? degradation and nuclear factor-?B activation in LPS-stimulated RAW 264.7 cells. In conclusion, the EF of broccoli florets exerted potent antioxidant and anti-inflammatory effects. PMID:25054107

  3. Activation of Endogenous Anti-Inflammatory Mediator Cyclic AMP Attenuates Acute Pyelonephritis in Mice Induced by Uropathogenic Escherichia coli

    PubMed Central

    Wei, Yang; Li, Ke; Wang, Na; Cai, Gui-Dong; Zhang, Ting; Lin, Yan; Gui, Bao-Song; Liu, En-Qi; Li, Zong-Fang; Zhou, Wuding

    2015-01-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. PMID:25478807

  4. Antioxidant, anti-inflammatory and antiproliferative activities of Kalanchoe gracilis (L.) DC stem.

    PubMed

    Lai, Zhen-Rung; Ho, Yu-Ling; Huang, Shun-Chieh; Huang, Tai-Hung; Lai, Shang-Chih; Tsai, Jen-Chieh; Wang, Ching-Ying; Huang, Guan-Jhong; Chang, Yuan-Shiun

    2011-01-01

    Oxidative stress and inflammation are related to several chronic diseases including cancer and atherosclerosis. Kalanchoe gracilis (L.) DC 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 methanolic extract and fractions of the stem of K. gracilis. TEAC, total phenolic compound content, total flavonoid content, DPPH radical scavenging activity, reducing power, inhibition of NO production in LPS-induced RAW264.7 cells, and inhibition of cancer cell proliferation were analyzed. Among all fractions, the chloroform fraction showed the highest TEAC and DPPH radical scavenging activities. The chloroform fraction also had the highest content of polyphenols and flavonoids. Chloroform fractions also decreased LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. The antiproliferative activities of the methanolic extract and fractions were studied in vitro using HepG2 cells, and the results were consistent with their antioxidant capacities. Chloroform fractions had the highest antiproliferative activity with an IC(50) of 136.85 ± 2.32 ?g/ml. Eupafolin also had good pharmacological activity in the antioxidant, anti-inflammation and antiproliferative. Eupafolin might be an important bioactive compound in the stem of K. gracilis. The above experimental data indicated that the stem of K. gracilis is a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds. PMID:22083996

  5. Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist

    PubMed Central

    2014-01-01

    Background Interleukin 1 (IL-1) is implicated in neuroinflammation, an essential component of neurodegeneration. We evaluated the potential anti-inflammatory effect of a novel peptide antagonist of IL-1 signaling, Ilantide. Methods We investigated the binding of Ilantide to IL-1 receptor type I (IL-1RI) using surface plasmon resonance, the inhibition of Il-1?-induced activation of nuclear factor ?B (NF-?B) in HEK-Blue cells that contained an IL-1?-sensitive reporter, the secretion of TNF-? in macrophages, protection against IL-1-induced apoptosis in neonatal pancreatic islets, and the penetration of Ilantide through the blood–brain barrier using competitive enzyme-linked immunosorbent assay (ELISA). We studied the effects of the peptide on social behavior and memory in rat models of lipopolysaccharide (LPS)- and amyloid-induced neuroinflammation, respectively, and its effect in a rat model of experimental autoimmune enchephalomyelitis. Results Ilantide bound IL-1RI, inhibited the IL-1?-induced activation of NF-?B, and inhibited the secretion of TNF-? in vitro. Ilantide protected pancreatic islets from apoptosis in vitro and reduced inflammation in an animal model of arthritis. The peptide penetrated the blood–brain barrier. It reduced the deficits in social activity and memory in LPS- and amyloid-treated animals and delayed the development of experimental autoimmune enchephalomyelitis. Conclusions These findings indicate that Ilantide is a novel and potent IL-1RI antagonist that is able to reduce inflammatory damage in the central nervous system and pancreatic islets. PMID:24490798

  6. Tristetraprolin is required for full anti-inflammatory response of murine macrophages to IL-10 1

    PubMed Central

    Schaljo, Barbara; Kratochvill, Franz; Gratz, Nina; Sadzak, Iwona; Sauer, Ines; Hammer, Michael; Vogl, Claus; Strobl, Birgit; Müller, Mathias; Blackshear, Perry J.; Poli, Valeria; Lang, Roland; Murray, Peter J.; Kovarik, Pavel

    2009-01-01

    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. PMID:19542371

  7. Phenolic profile, antioxidant capacity and anti-inflammatory activity of Anethum graveolens L. essential oil.

    PubMed

    Kazemi, M

    2015-01-01

    This study reports the chemical composition, antioxidant and anti-inflammatory properties of Anethum graveolens essential oil and its main compounds. The essential oil was obtained from the aerial parts of the plant by hydrodistillation and analysed by using GC/MS. ?-Phellandrene (19.12%), limonene (26.34%), dill ether (15.23%), sabinene (11.34%), ?-pinene (2%), n-tetracosane (1.54%), neophytadiene (1.43%), n-docosane (1.04), n-tricosane (1%), n-nonadecane (1%), n-eicosane (0.78%), n-heneicosane (0.67%), ?-myrcene (0.23%) and ?-tujene (0.21%) were found to be the major constituents of the oil. A. graveolens oil exhibit a higher activity in each antioxidant system with a special attention for ?-carotene bleaching test (IC50: 15.3 ?g/mL) and reducing power (EC50: 11.24 ?g/mL). The TLC-bioautography screening and fractionation resulted in the separation of the main antioxidant compounds, which were identified as limonene (45%) and sabinene (32%). The essential oil and its main compounds exhibited a potent NO-scavenging effect and inhibited the expression of inducible NO synthase. PMID:25154406

  8. Characterizing the metabolic fingerprint and anti-inflammatory activity of Hypericum gentianoides.

    PubMed

    Hillwig, Matthew L; Hammer, Kimberly D P; Birt, Diane F; Wurtele, Eve Syrkin

    2008-06-25

    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 E 2 synthesis in mammalian macrophages. PMID:18512936

  9. A comparison of an effect of different anti-inflammatory drugs on human platelets.

    PubMed

    O'Brien, J R; Finch, W; Clark, E

    1970-09-01

    Different doses of aspirin, indomethacin, paracetamol, benorylate, and sodium salicylate were taken by four volunteers. The minimal dose that altered a platelet function test and the persistence of this alteration at different dose levels were studied. Minute doses of indomethacin (0.035 mg/kg) were effective but the effect of even a large single dose did not persist. A tenth of the therapeutic dose of aspirin (1 mg/kg) was effective, and higher doses altered the platelets' function for several days. Benorylate in a high therapeutic dose gave aspirin-like results. Paracetamol and sodium salicylate were relatively inactive. The persistence of the aspirin effect may be related to the acetyl group. These findings are surveyed in relation to a general theory of the action of anti-inflammatory drugs. PMID:5476879

  10. Anti-inflammatory activity of horseradish (Armoracia rusticana) root extracts in LPS-stimulated macrophages.

    PubMed

    Marzocco, Stefania; Calabrone, Luana; Adesso, Simona; Larocca, Marilena; Franceschelli, Silvia; Autore, Giuseppina; Martelli, Giuseppe; Rossano, Rocco

    2015-12-01

    Horseradish (Armoracia rusticana) is a perennial crop belonging to the Brassicaceae family. Horseradish root is used as a condiment due to its extremely pungent flavour, deriving from the high content of glucosinolates and their breakdown products such as isothiocyanates and other sulfur compounds. Horseradish also has a long history in ethnomedicine. In this study the anti-inflammatory potential of three accessions of Armoracia rusticana on lipopolysaccharide from E. coli treated J774A.1 murine macrophages was evaluated. Our results demonstrate that Armoracia rusticana reduced nitric oxide, tumor necrosis factor-? and interleukin-6 release and nitric oxide synthase and cyclooxygenase-2 expression in macrophages, acting on nuclear transcription factor NF-?B p65 activation. Moreover Armoracia rusticana reduced reactive oxygen species release and increased heme-oxygenase-1 expression, thus contributing to the cytoprotective cellular effect during inflammation. PMID:26411988

  11. Anti-inflammatory procyanidins and triterpenes in 109 apple varieties.

    PubMed

    Andre, Christelle M; Greenwood, Jeffrey M; Walker, Edward G; Rassam, Maysoon; Sullivan, Michael; Evers, Danièle; Perry, Nigel B; Laing, William A

    2012-10-24

    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

  12. Anti-Inflammatory Dimethylfumarate: A Potential New Therapy for Asthma?

    PubMed Central

    Roth, Michael

    2013-01-01

    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

  13. Anti-Inflammatory Components from the Root of Solanum erianthum

    PubMed Central

    Chen, Yu-Chang; Lee, Hong-Zin; Chen, Hsin-Chun; Wen, Chi-Luan; Kuo, Yueh-Hsiung; Wang, Guei-Jane

    2013-01-01

    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. PMID:23771024

  14. Pain control: non-steroidal anti-inflammatory agents.

    PubMed

    Jacqz-Aigrain, Evelyne; Anderson, Brian J

    2006-08-01

    The non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (paracetamol) are the most common analgesic drugs used in neonates and infants despite limited pharmacodynamic data. Both drugs act through inhibition of cyclooxygenase enzymes. Neonatal acetaminophen clearance is reduced in premature neonates (0.7 L h(-1) x 70 kg(-1)) and increases to 5 L h(-1) x 70 kg(-1) at term (40% adult rates); adult rates are reached within the first year of life; NSAID clearance follows similar trends. Volume of distribution is increased in the neonatal period. Dosing of both drug groups is tempered by concerns about toxicity. Acetaminophen hepatotoxicity is less common in neonates than in older children and adults, possibly due to reduced oxidative enzyme activity (e.g. CYP 2E1). Data concerning NSAID adverse effects in the neonatal period are few. Renal function is reduced 20% after NSAID use for patent ductus arteriosus closure in premature neonates and there is no increased frequency of intraventricular haemorrhage. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo in neonates. Future studies should define concentration-response relationships for these drugs that are age and pathology specific. PMID:16679073

  15. Triterpenoid saponins and anti-inflammatory activity of Codonopsis lanceolata.

    PubMed

    Li, Jian-Ping; Liang, Zhi-Min; Yuan, Zhong

    2007-06-01

    The ethanolic root extract of Codonopsis lanceolata were evaluated for anti-inflammatory activity using the carrageenan induced rat hind paw edema model and displayed a significant activity of 51.82% inhibition at 200 mg/kg at 3 h (p < 0.05). Further isolation of the extract yielded two new triterpenoid saponins, named codonolaside I (1) and codonolaside II (2). The spectroscopic and chemical data revealed their structures to be 3-O-[beta-D-xylopyranosyl (1->3)-(6'-O-methyl)-beta-D-glucuronopyranosyl]-30, 16a-dihydroxyolean-12-ene-28-oic acid 28-O-[P-D-xylopyranosyl (1-->4)-alpha-L-rhamnpyranosyl (1-->2)-alpha-L-arabinopyranosyl] ester (1), and 3beta, 16alpha-dihydroxyolean-12-ene-28-oic acid 28-O-[beta-D-xylopyranosyl (1-->3)-beta-D-xylopyranosyl (1-->4)-alpha-L-rhamnpyranosyl (1-->2)-alpha-L-arabinopyranosyl] ester (2). PMID:17663196

  16. Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

    PubMed

    Hodkinson, Duncan J; Khawaja, Nadine; O?Daly, Owen; Thacker, Michael A; Zelaya, Fernando O; Wooldridge, Caroline L; Renton, Tara F; Williams, Steven C R; Howard, Matthew A

    2015-07-01

    Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction, and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow under pain-free conditions (presurgery). However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management. PMID:25851460

  17. Non-steroidal Anti-inflammatory Drugs in Raptors

    USGS Publications Warehouse

    Oaks, J. Lindsay; Meteyer, Carol U.

    2012-01-01

    The use of analgesia has become standard, and appropriate, practice in avian medicine. As in mammals, pain control in avian patients is usually accomplished with opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) used singly or in combination for a multimodal approach. Despite their usefulness, widespread use, and relative safety in clinical use, few controlled studies in birds have been conducted on efficacy, safety, and dosing. The guidelines for the use of NSAIDs in raptors and other birds have mainly been empirical. More recently, NSAIDs in free-living raptors have emerged as a major conservation issue with the discovery that diclofenac sodium was responsible for the population crash of three species of Gyps vultures in southern Asia. In this context, residues of veterinary NSAIDs in domestic animals are now considered environmental contaminants that can be significantly toxic to vultures and possibly other avian scavengers. Ironically, the disaster with Asian vultures has led to a considerable body of research on NSAIDs in raptors to the benefit of clinicians who now have scientific information available to help assess dosing, safety, toxicity, and pharmacokinetics of NSAIDs in their raptor patients.

  18. Cannabinoid-like anti-inflammatory compounds from flax fiber.

    PubMed

    Styrczewska, Monika; Kulma, Anna; Ratajczak, Katarzyna; Amarowicz, Ryszard; Szopa, Jan

    2012-09-01

    Flax is a valuable source of fibers, linseed and oil. The compounds of the latter two products have already been widely examined and have been proven to possess many health-beneficial properties. In the course of analysis of fibers extract from previously generated transgenic plants overproducing phenylpropanoids a new terpenoid compound was discovered.The UV spectra and the retention time in UPLC analysis of this new compound reveal similarity to a cannabinoid-like compound, probably cannabidiol (CBD). This was confirmed by finding two ions at m/z 174.1 and 231.2 in mass spectra analysis. Further confirmation of the nature of the compound was based on a biological activity assay. It was found that the compound affects the expression of genes involved in inflammatory processes in mouse and human fibroblasts and likely the CBD from Cannabis sativa activates the specific peripheral cannabinoid receptor 2 (CB2) gene expression. Besides fibers, the compound was also found in all other flax tissues. It should be pointed out that the industrial process of fabric production does not affect CBD activity.The presented data suggest for the first time that flax products can be a source of biologically active cannabinoid-like compounds that are able to influence the cell immunological response. These findings might open up many new applications for medical flax products, especially for the fabric as a material for wound dressing with anti-inflammatory properties. PMID:22706678

  19. Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis

    PubMed Central

    Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

    2015-01-01

    Objectives: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Materials and Methods: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Results: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. Conclusions: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions. PMID:25767759

  20. Anti-inflammatory Hydrolyzable Tannins from Myricaria bracteata.

    PubMed

    Liu, Jia-Bao; Ding, Ya-Si; Zhang, Ying; Chen, Jia-Bao; Cui, Bao-Song; Bai, Jin-Ye; Lin, Ming-Bao; Hou, Qi; Zhang, Pei-Cheng; Li, Shuai

    2015-05-22

    Twelve hydrolyzable tannins were obtained from the twigs of Myricaria bracteata, including two new hellinoyl-type dimers, bracteatinins D1 (1) and D2 (2); a new hellinoyl-type trimer, bracteatinin T1 (3); two known monomers, nilotinin M4 (4) and 1,3-di-O-galloyl-4,6-O-(aS)-hexahydroxydiphenoyl-?-d-glucose (5); six known dimers, tamarixinin A (6), nilotinin D8 (7), hirtellins A (10), B (9), and E (8), and isohirtellin C (11); and a known trimer, hirtellin T3 (12). The structures of the tannins were elucidated by spectroscopic data analysis and comparisons to known tannins. All compounds were evaluated as free radical scavengers using 1,1-diphenyl-2-picrylhydrazyl and hydroxy radicals and compared to the activity of BHT and Trolox. Compound 6 showed a significant anti-inflammatory effect on croton oil-induced ear edema in mice (200 mg/kg, inhibition rate 69.8%) and on collagen-induced arthritis in DBA/1 mice (20 mg/kg, inhibition rate 46.0% at day 57). PMID:25918997

  1. Anti-inflammatory effects of glaucocalyxin B in microglia cells.

    PubMed

    Gan, Ping; Zhang, Li; Chen, Yanke; Zhang, Yu; Zhang, Fali; Zhou, Xiang; Zhang, Xiaohu; Gao, Bo; Zhen, Xuechu; Zhang, Jian; Zheng, Long Tai

    2015-05-01

    Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB), one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO), tumor necrosis factor (TNF)-?, interleukin (IL)-1?, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-?B (NF-?B), p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO)-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases. PMID:26003084

  2. A review on anti-inflammatory activity of phenylpropanoids found in essential oils.

    PubMed

    de Cássia da Silveira E Sá, Rita; Andrade, Luciana Nalone; Dos Reis Barreto de Oliveira, Rafael; de Sousa, Damião Pergentino

    2014-01-01

    The search for alternative drugs capable of disrupting the inflammatory process has become an important issue in scientific research, especially with reference to the use of natural substances and the reduction of undesirable side effects. Essential oils represent an important source of such substances, since their active constituents often exhibit an array of pharmacological properties, including anti-inflammatory activity. This review presents an overview of the anti-inflammatory action exerted by phenylpropanoids from essential oils and discusses possible mechanisms of action involved in the anti-inflammatory response, assessed through specific experimental models. PMID:24473208

  3. Lignans from the rhizomes of Coptis japonica differentially act as anti-inflammatory principles.

    PubMed

    Cho, J Y; Kim, A R; Park, M H

    2001-06-01

    Coptis japonica Makino (Ranunculaceae) is known to possess several biological activities such as anti-inflammatory effects. In this study, five lignans, isolariciresinol (1), lariciresinol glycoside (2), pinoresinol (3), pinoresinol glycoside (4) and syringaresinol glycoside (5), isolated from the rhizomes of C. japonica were tested to evaluate their in vitro anti-inflammatory effects. Pinoresinol and isolariciresinol showed higher inhibitory effects on TNF-alpha production, whereas syringaresinol glycoside strongly suppressed lymphocyte proliferation. The results indicate that the lignans may differentially modulate inflammatory cell responses, suggesting that these compounds may participate in anti-inflammatory processes by C. japonica. PMID:11458445

  4. Synthesis and Evaluation of Benzophenone-N-ethyl Morpholine Ethers as Anti-inflammatory Agents

    PubMed Central

    Khanum, Shaukath A.; Begum, Bushra A.; Girish, V.; Khanum, Noor Fatima

    2010-01-01

    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. PMID:23675177

  5. Anti-inflammatory action of sulfoaryl 3,3-disubstituted triazenes in rat experimental edema models.

    PubMed

    Kazemekaite, M; Talaikyte, Z; Udrenaite, E; Labanauskas, L; Staniulyte, Z; Palaima, A

    2003-10-01

    The acute toxicity and anti-inflammatory activity of eleven potassium salts of sulfobenzene and sulfonaphthalene 3,3-disubstituted triazenes have been examined in rats with carrageenin- and bentonite-induced edema using a 50 mg/kg p.o. dose. All compounds were found to exhibit anti-inflammatory activity significantly exceeding that of acetylsalicylic acid and ibuprofen, and were less toxic than these reference drugs. The most pronounced anti-inflammatory activity was shown by the potassium salt of 4-(piperazin-1-ylazo)benzenesulfonic acid. PMID:14609286

  6. Anti-Inflammatory Diet for Atherosclerosis and Coronary Artery Disease: Antioxidant Foods

    PubMed Central

    Saita, Emi; Kondo, Kazuo; Momiyama, Yukihiko

    2014-01-01

    Oxidative stress plays a role in atherosclerotic diseases such as coronary artery disease (CAD), and much attention has been paid to antioxidant foods. The relationships between the consumption of vegetables and fruits and atherosclerotic diseases have been reported in many epidemiological studies showing a reduced risk of such diseases. In addition to the antioxidant vitamins C and E, green and yellow vegetables contain abundant quantities of carotenoids and polyphenols. The consumption of carotenoids and vitamins C and E has been shown to be inversely associated with CAD. However, supplementation with beta-carotene and vitamins C and E shows no beneficial effect, but rather mortality is increased with beta-carotene and vitamin E supplements. Therefore, it is recommended to consume vegetables and fruits, but vitamin supplementation is not recommended. Many epidemiological studies also report that higher consumption of fish, rich in n-3 polyunsaturated fatty acids (PUFAs), is associated with a lower risk of CAD and stroke. Antiatherosclerotic effects of n-3 PUFAs include reduced platelet aggregation, triglyceride-lowering effect, anti-inflammatory effect, and plaque stabilization, but the anti-inflammatory effect is principally responsible for preventing atherosclerosis. It is recommended to consume fish at least twice a week in patients without CAD and to consider n-3 PUFA supplements in patients with documented CAD. Regarding soy products, soy protein consumption reduces low-density-lipoprotein cholesterol and triglyceride levels. Isoflavone, a polyphenol contained in soybeans, has antiatherosclerotic property because it has a structure similar to that of estrogen and bonds with estrogen receptors. High consumption of isoflavone has been reported to be associated with a reduced risk of CAD and stroke only in women, but the preventative effect of soy products in the general population has not yet been clarified. Thus, many epidemiological studies report the promising effects of antioxidant foods, but there are many unclear points remaining with regard to the contribution of the nutritional elements found in antioxidant foods to the prevention of atherosclerotic diseases. PMID:26279633

  7. Mechanisms of peroxisome proliferator activated receptor ? regulation by non-steroidal anti-inflammatory drugs

    PubMed Central

    Puhl, Ana C.; Milton, Flora A.; Cvoro, Aleksandra; Sieglaff, Douglas H.; Campos, Jéssica C.L.; Bernardes, Amanda; Filgueira, Carly S.; Lindemann, Jan Lammel; Deng, Tuo; Neves, Francisco A.R.; Polikarpov, Igor; Webb, Paul

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) display anti-inflammatory, antipyretic and analgesic properties by inhibiting cyclooxygenases and blocking prostaglandin production. Previous studies, however, suggested that some NSAIDs also modulate peroxisome proliferator activated receptors (PPARs), raising the possibility that such off target effects contribute to the spectrum of clinically relevant NSAID actions. In this study, we set out to understand how peroxisome proliferator activated receptor-? (PPAR?/PPARG) interacts with NSAIDs using X-ray crystallography and to relate ligand binding modes to effects on receptor activity. We find that several NSAIDs (sulindac sulfide, diclofenac, indomethacin and ibuprofen) bind PPAR? and modulate PPAR? activity at pharmacologically relevant concentrations. Diclofenac acts as a partial agonist and binds to the PPAR? ligand binding pocket (LBP) in typical partial agonist mode, near the ?-sheets and helix 3. By contrast, two copies of indomethacin and sulindac sulfide bind the LBP and, in aggregate, these ligands engage in LBP contacts that resemble agonists. Accordingly, both compounds, and ibuprofen, act as strong partial agonists. Assessment of NSAID activities in PPAR?-dependent 3T3-L1 cells reveals that NSAIDs display adipogenic activities and exclusively regulate PPAR?-dependent target genes in a manner that is consistent with their observed binding modes. Further, PPAR? knockdown eliminates indomethacin activities at selected endogenous genes, confirming receptor-dependence of observed effects. We propose that it is important to consider how individual NSAIDs interact with PPAR? to understand their activities, and that it will be interesting to determine whether high dose NSAID therapies result in PPAR activation. PMID:26445566

  8. A study of the energy absorption and exposure buildup factors of some anti-inflammatory drugs.

    PubMed

    Ekinci, Neslihan; Kavaz, Esra; Özdemir, Yüksel

    2014-08-01

    Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015-15 MeV energy region up to a penetration depth of 40 mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent atomic number (Z(eq)) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06 MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials. PMID:24859334

  9. The Anti-Inflammatory Effects of Flavanol-Rich Lychee Fruit Extract in Rat Hepatocytes

    PubMed Central

    Yamanishi, Ryota; Yoshigai, Emi; Okuyama, Tetsuya; Mori, Masatoshi; Murase, Hiromitsu; Machida, Toru; Okumura, Tadayoshi; Nishizawa, Mikio

    2014-01-01

    Flavanol (flavan-3-ol)-rich lychee fruit extract (FRLFE) is a mixture of oligomerized polyphenols primarily derived from lychee fruit and is rich in flavanol monomers, dimers, and trimers. Supplementation with this functional food has been shown to suppress inflammation and tissue damage caused by high-intensity exercise training. However, it is unclear whether FRLFE has in vitro anti-inflammatory effects, such as suppressing the production of the proinflammatory cytokine tumor necrosis factor ? (TNF-?) and the proinflammatory mediator nitric oxide (NO), which is synthesized by inducible nitric oxide synthase (iNOS). Here, we analyzed the effects of FRLFE and its constituents on the expression of inflammatory genes in interleukin 1? (IL-1?)-treated rat hepatocytes. FRLFE decreased the mRNA and protein expression of the iNOS gene, leading to the suppression of IL-1?-induced NO production. FRLFE also decreased the levels of the iNOS antisense transcript, which stabilizes iNOS mRNA. By contrast, unprocessed lychee fruit extract, which is rich in flavanol polymers, and flavanol monomers had little effect on NO production. When a construct harboring the iNOS promoter fused to the firefly luciferase gene was used, FRLFE decreased the luciferase activity in the presence of IL-1?, suggesting that FRLFE suppresses the promoter activity of the iNOS gene at the transcriptional level. Electrophoretic mobility shift assays indicated that FRLFE reduced the nuclear transport of a key regulator, nuclear factor ?B (NF-?B). Furthermore, FRLFE inhibited the phosphorylation of NF-?B inhibitor ? (I?B-?). FRLFE also reduced the mRNA levels of NF-?B target genes encoding cytokines and chemokines, such as TNF-?. Therefore, FRLFE inhibited NF-?B activation and nuclear translocation to suppress the expression of these inflammatory genes. Our results suggest that flavanols may be responsible for the anti-inflammatory and hepatoprotective effects of FRLFE and may be used to treat inflammatory diseases. PMID:24705335

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

    PubMed Central

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

    2015-01-01

    A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs) were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines tumor necrosis factor-? and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 MAPK and suppressed I?B? degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-?B) and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure–activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases. PMID:25834403

  11. Analgesic and Anti-Inflammatory Properties of Extracts from the Bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae) in Mice and Rats

    PubMed Central

    Mbiantcha, M.; Kamanyi, A.; Teponno, R. B.; Tapondjou, A. L.; Watcho, P.; Nguelefack, T. B.

    2011-01-01

    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. PMID:20953397

  12. Analgesic and Anti-Inflammatory Properties of Extracts from the Bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae) in Mice and Rats.

    PubMed

    Mbiantcha, M; Kamanyi, A; Teponno, R B; Tapondjou, A L; Watcho, P; Nguelefack, T B

    2011-01-01

    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. PMID:20953397

  13. Molecular Mechanisms Underlying the In Vitro Anti-Inflammatory Effects of a Flavonoid-Rich Ethanol Extract from Chinese Propolis (Poplar Type)

    PubMed Central

    Wang, Kai; Ping, Shun; Huang, Shuai; Hu, Lin; Xuan, Hongzhuan; Zhang, Cuiping; Hu, Fuliang

    2013-01-01

    China produces the greatest amount of propolis but there is still lack of basic studies on its pharmacological mechanisms. Our previous study found that ethanol extract from Chinese propolis (EECP) exerted excellent anti-inflammatory effects in vivo but mechanisms of action were elusive. To further clarify the possible mechanisms underlying the anti-inflammatory effects of Chinese propolis (poplar type), we utilized EECP to analyze its chemical composition and evaluated its potential anti-inflammatory effects in vitro. High-performance liquid chromatography (HPLC) profile indicated that EECP contained abundant flavonoids, including rutin, myricetin, quercetin, kaempferol, apigenin, pinocembrin, chrysin, and galangin. Next we found that EECP could significantly inhibit the production of NO, IL-1?, and IL-6 in lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and suppress mRNA expression of iNOS, IL-1?, and IL-6 in a time- and dose-dependent manner. Furthermore, we found that EECP could suppress the phosphorylation of I?B? and AP-1 but did not affect I?B?'s degradation. In addition, using a reporter assay, we found that EECP could block the activation of NF-?B in TNF-?-stimulated HEK 293T cells. Our findings give new insights for understanding the mechanisms involved in the anti-inflammatory effects by Chinese propolis and provide additional references for using propolis in alternative and complementary therapies. PMID:23401705

  14. Nickel(II) Complex of Polyhydroxybenzaldehyde N4-Thiosemicarbazone Exhibits Anti-Inflammatory Activity by Inhibiting NF-?B Transactivation

    PubMed Central

    Loh, Sheng Wei; Looi, Chung Yeng; Hassandarvish, Pouya; Phan, Alicia Yi Ling; Wong, Won Fen; Wang, Hao; Paterson, Ian C.; Ea, Chee Kwee; Mustafa, Mohd Rais; Maah, Mohd Jamil

    2014-01-01

    Background The biological properties of thiosemicarbazone have been widely reported. The incorporation of some transition metals such as Fe, Ni and Cu to thiosemicarbazone complexes is known to enhance its biological effects. In this study, we incorporated nickel(II) ions into thiosemicarbazone with N4-substitution groups H3L (H; H3L1, CH3; H3L2, C6H5; H3L3 and C2H5; H3L4) and examined its potential anti-inflammatory activity. Methodology/Principal Findings Four ligands (1–4) and their respective nickel-containing complexes (5–8) were synthesized and characterized. The compounds synthesized were tested for their effects on NF-?B nuclear translocation, pro-inflammatory cytokines secretion and NF-?B transactivation activity. The active compound was further evaluated on its ability to suppress carrageenan-induced acute inflammation in vivo. A potential binding target of the active compound was also predicted by molecular docking analysis. Conclusions/Significance Among all synthesized compounds tested, we found that complex [Ni(H2L1)(PPh3)]Cl (5) (complex 5), potently inhibited I?B? degradation and NF-?B p65 nuclear translocation in LPS-stimulated RAW264.7 cells as well as TNF?-stimulated HeLa S3 cells. In addition, complex 5 significantly down-regulated LPS- or TNF?-induced transcription of NF-?B target genes, including genes that encode the pro-inflammatory cytokines TNF?, IFN? and IL6. Luciferase reporter assays confirmed that complex 5 inhibited the transactivation activity of NF-?B. Furthermore, the anti-inflammatory effect of complex 5 was also supported by its suppressive effect on carrageenan-induced paw edema formation in wild type C57BL/6 mice. Interestingly, molecular docking study showed that complex 5 potentially interact with the active site of IKK?. Taken together, we suggest complex 5 as a novel NF-?B inhibitor with potent anti-inflammatory effects. PMID:24977407

  15. Determination of Teloschistes flavicans (sw) norm anti-inflammatory activity

    PubMed Central

    Pereira, Eugênia C.; da Silva, Nicácio H.; Santos, Renata Almeida; Sudário, Ana Patrícia Paiva; Rodrigues e Silva, Antonio Alfredo; de Sousa Maia, Maria Bernadete

    2010-01-01

    Background: Lichens produce a variety of substances that possesses pharmacological actions. However, rare products are submitted to rigorous scientific tests or have the risk potential or side effects evaluated. The lack of medical and sanitary control, absence of accurate botanical identification or purity certification, founded in diverse natural products, may represent great danger to population health. This work aimed to evaluate toxic effects and anti-inflammatory action in vivo of Teloschistes flavicans (Sw.) Norm. (TFN) unrefined extracts, as well as determinate its main constituents. Methods: The carrageenan induced paw edema and cotton pellet implant induced granuloma methods were utilized, besides a classic acute toxicity test. TFN acetone extract inhibited carrageenan paw edema on 60, 120, and 180 min (inhibition percentiles of 45.03%, 60.59% and 41.72%). Results: TFN ethereal (inhibition percentiles of 23.95% and 29.01%) and chloroform (inhibition percentiles of 28.8% and 22.04%) extracts inhibited edema on 120 and 180 min. None of the extract inhibited the granuloma development. None of the extract caused death or other acute toxicity signs. Vicanicine (60.26% in ethereal extract and 51.17% in acetone extract), parietine (9.60% in ethereal extract and 15.38% on second), falacinol (0.78% in ether and 14.95% in acetone) and very low concentration of falacinal (0.15% in ethereal extract and 3.32% in acetone extract) were detected in the medicine. Conclusions: The tested extracts have antiedematogenic activity, but are not effective on subchronic inflammation. The extracts do not present toxic effects in administered doses. PMID:21808568

  16. Licofelone--a novel analgesic and anti-inflammatory agent.

    PubMed

    Kulkarni, S K; Singh, Vijay Pal

    2007-01-01

    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

  17. Phenolic composition, anitproliferative and anti-inflammatory properties of conventional and organic cinnamon and peppermint

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conventional and organic cinnamon and peppermint were investigated for their phenolic profile, antiproliferative, anti-inflammatory, and antioxidant properties. Accelerated solvent extraction (ASE) with 75% acetone was a better method than Soxhlet and overnight extraction for phenolic content and a...

  18. Experimental evaluation of analgesic and anti-inflammatory potential of Oyster mushroom Pleurotus florida

    PubMed Central

    Ganeshpurkar, Aditya; Rai, Gopal

    2013-01-01

    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. PMID:23543896

  19. Anticancer, Anti-Inflammatory, and Analgesic Activities of Synthesized 2-(Substituted phenoxy) Acetamide Derivatives

    PubMed Central

    Pal, Dilipkumar; Hegde, Rahul Rama; Hashim, Syed Riaz

    2014-01-01

    The aphorism was to develop new chemical entities as potential anticancer, anti-inflammatory, and analgesic agents. The Leuckart synthetic pathway was utilized in development of novel series of 2-(substituted phenoxy)-N-(1-phenylethyl)acetamide derivatives. The compounds containing 1-phenylethylamine as basic moiety attached to substituted phenols were assessed for their anticancer activity against MCF-7 (breast cancer), SK-N-SH (neuroblastoma), anti-inflammatory activity, and analgesic activity. These investigations revealed that synthesized products 3a–j with halogens on the aromatic ring favors as the anticancer and anti-inflammatory activity. Among all, compound 3c N-(1-(4-chlorophenyl)ethyl)-2-(4-nitrophenoxy)acetamide exhibited anticancer, anti-inflammatory, and analgesic activities. In conclusion, 3c may have potential to be developed into a therapeutic agent. PMID:25197642

  20. Chemical Constituents from the Fruiting Bodies of Hexagonia apiaria and Their Anti-inflammatory Activity.

    PubMed

    Thang, Tran Dinh; Kuo, Ping-Chung; Ngoc, Nguyen Thi Bich; Hwang, Tsong-Long; Yang, Mei-Lin; Ta, Shih-Huang; Lee, E-Jian; Kuo, Dai-Huang; Hung, Nguyen Huy; Tuan, Nguyen Ngoc; Wu, Tian-Shung

    2015-11-25

    A chemical investigation of the fruiting bodies of Hexagonia apiaria resulted in the identification of nine compounds including five new triterpenoids, hexagonins A-E (1-5), along with four known compounds. The purified constituents were examined for their anti-inflammatory activity. Among the tested compounds, hexatenuin A displayed the most significant inhibition of superoxide anion generation and elastase release. These triterpenoids may have potentials as anti-inflammatory agents. PMID:26575215

  1. The antioxidant properties of salicylate derivatives: A possible new mechanism of anti-inflammatory activity.

    PubMed

    Borges, Rosivaldo S; Castle, Steven L

    2015-11-01

    The synthesis and antioxidant evaluation by DPPH scavenging of a series of salicylic acid derivatives is described. Gentisic acid and its ester, amide, and amino analogs possess more radical scavenging capacity than salicylic acid and other salicylate derivatives. This property can possibly provide an additional pathway for anti-inflammatory activity through either single electron or hydrogen atom transfer, leading to a new strategy for the design of anti-inflammatory agents. PMID:26183083

  2. A Comparative Study of Sodium Houttuyfonate and 2-Undecanone for Their in Vitro and in Vivo Anti-Inflammatory Activities and Stabilities

    PubMed Central

    Chen, Jing; Wang, Wenqing; Shi, Chunyang; Fang, Jianguo

    2014-01-01

    Houttuynia cordata Thunb. (H. cordata) is an anti-inflammatory herbal drug that is clinically used in Asia. The essential oil obtained from H. cordata is known to contain 2-undecanone (2-methyl nonyl ketone). In addition, sodium houttuyfonate is a compound that can be derived from H. cordata and has important clinical uses as an anti-inflammatory agent. Sodium houttuyfonate can be converted to decanoyl acetaldehyde (houttuynin) and then to 2-undecanone. Therefore, the experiments described here explore the comparative anti-inflammatory activities of these compounds. Sodium houttuyfonate showed more potent anti-inflammatory activities than that of 2-undecanone at the same dosage, both in vitro and in vivo, although both compounds significantly inhibited the production of tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) and the expression of toll-like receptor 4 (TLR4), but increased the secretion of interleukin-10 (IL-10) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In addition, both compounds showed dose-dependent inhibitory effects on xylene-induced mouse ear edema. In a previous study, we found sodium houttuyfonate to be transformed to 2-undecanone during steam distillation (SD). Optimum therapeutic effects are related to the stability and pharmacological activity of the drugs. Consequently, we studied the stability of sodium houttuyfonate under a simulated gastrointestinal environment with the main influencing factors being solvent, temperature and pH effects. For the first time, sodium houttuyfonate and 2-undecanone were detected simultaneously in the mouse serum and the gastrointestinal tissue after oral administration. Sodium houttuyfonate is detected within a short period of time in the systemic circulation and tissues without conversion to 2-undecanone. PMID:25514406

  3. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

    PubMed Central

    2010-01-01

    Background Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results. Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic activity of the complement/coagulation cascade has been shown in patients suffering from a chronic form of ciguatera poisoning and is of particular interest in this model. Anti-inflammatory processes were at work not only in the brain but were also seen in whole blood and liver of these animals, creating a systemic anti-inflammatory environment to protect against the initial cellular damage caused by the toxin. PMID:20796285

  4. Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs.

    PubMed

    Theoduloz, Cristina; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Cádiz, Solange; Bustamante, Fernanda; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2015-01-01

    The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes. PMID:26096431

  5. Amorfrutins Are Natural PPAR? Agonists with Potent Anti-inflammatory Properties.

    PubMed

    Fuhr, Luise; Rousseau, Morten; Plauth, Annabell; Schroeder, Frank C; Sauer, Sascha

    2015-05-22

    Amorfrutins are isoprenoid-substituted benzoic acid derivatives, which were found in Amorpha fruticosa L. (bastard indigo) and in Glycyrrhiza foetida Desf. (licorice). Recently, amorfrutins were shown to be selective activators of the nuclear receptor PPAR?. Here, we investigated the effects and PPAR?-based mechanisms of reducing inflammation in colon cells by treatment with amorfrutins. In TNF-?-stimulated colon cells amorfrutin A (1) reduced significantly the expression and secretion of several inflammation mediators, in part due to interaction with PPAR?. These results support the hypothesis that amorfrutins may have the potential to treat inflammation disorders such as chronic inflammatory bowel diseases. PMID:25938459

  6. Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

    PubMed

    Moreira, Daniel Medeiros; da Silva, Roberto Leo; Vieira, Jefferson Luís; Fattah, Tammuz; Lueneberg, Maria Emilia; Gottschall, Carlos Antonio Mascia

    2015-02-01

    Coronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1?, IL-6 and tumor necrosis factor (TNF)-?, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the "foam cells." Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD. PMID:25369900

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

    PubMed Central

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

    2008-01-01

    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 mg of complete Freund's adjuvant. Rats were treated orally for 21 days with pioglitazone 3, 10 or 30 mg/kg/day, rosiglitazone 3 or 10 mg/kg/day, or with vehicle only. The time course of AIA was evaluated by biotelemetry to monitor body temperature and locomotor activity, by clinical score and plethysmographic measurement of hindpaw oedema. At necropsy, RT-PCR analysis was performed on synovium, liver and subcutaneous fat. Changes in cartilage were evaluated by histological examination of ankle joints, radiolabelled sulphate incorporation (proteoglycan synthesis), glycosaminoglycan content (proteoglycan turnover) and aggrecan expression in patellar cartilage. Whole-body bone mineral content was measured by dual-energy X-ray absorptiometry. Results The highest doses of rosiglitazone (10 mg/kg/day) or pioglitazone (30 mg/kg/day) were required to reduce fever peaks associated with acute or chronic inflammation, respectively, and to decrease arthritis severity. At these doses, thiazolidinediones reduced synovitis and synovial expression of TNF-?, IL-1? and basic fibroblast growth factor without affecting neovascularization or the expression of vascular endothelial growth factor. Thiazolidinediones failed to prevent cartilage lesions and arthritis-induced inhibition of proteoglycan synthesis, aggrecan mRNA level or glycosaminoglycan content in patellar cartilage, but reduced bone erosions and inflammatory bone loss. A trend towards lower urinary levels of deoxipyridinolin was also noted in arthritic rats treated with thiazolidinediones. Rosiglitazone 10 mg/kg/day or pioglitazone 30 mg/kg/day increased the expression of PPAR-? and adiponectin in adipose tissue, confirming that they were activating PPAR-? in inflammatory conditions, although an increase in fat mass percentage was observed for the most anti-arthritic dose. Conclusion These data emphasize that higher dosages of thiazolidinediones are required for the treatment of arthritis than for restoring insulin sensitivity but that thiazolidinediones prevent inflammatory bone loss despite exposing animals to increased fatness possibly resulting from excessive activation of PPAR-?. PMID:18199331

  8. Toll-like Receptors as a Target of Food-derived Anti-inflammatory Compounds*

    PubMed Central

    Shibata, Takahiro; Nakashima, Fumie; Honda, Kazuya; Lu, Yu-Jhang; Kondo, Tatsuhiko; Ushida, Yusuke; Aizawa, Koichi; Suganuma, Hiroyuki; Oe, Sho; Tanaka, Hiroshi; Takahashi, Takashi; Uchida, Koji

    2014-01-01

    Toll-like receptors (TLRs) play a key role in linking pathogen recognition with the induction of innate immunity. They have been implicated in the pathogenesis of chronic inflammatory diseases, representing potential targets for prevention/treatment. Vegetable-rich diets are associated with the reduced risk of several inflammatory disorders. In the present study, based on an extensive screening of vegetable extracts for TLR-inhibiting activity in HEK293 cells co-expressing TLR with the NF-?B reporter gene, we found cabbage and onion extracts to be the richest sources of a TLR signaling inhibitor. To identify the active substances, we performed activity-guiding separation of the principal inhibitors and identified 3-methylsulfinylpropyl isothiocyanate (iberin) from the cabbage and quercetin and quercetin 4?-O-?-glucoside from the onion, among which iberin showed the most potent inhibitory effect. It was revealed that iberin specifically acted on the dimerization step of TLRs in the TLR signaling pathway. To gain insight into the inhibitory mechanism of TLR dimerization, we developed a novel probe combining an isothiocyanate-reactive group and an alkyne functionality for click chemistry and detected the probe bound to the TLRs in living cells, suggesting that iberin disrupts dimerization of the TLRs via covalent binding. Furthermore, we designed a variety of iberin analogues and found that the inhibition potency was influenced by the oxidation state of the sulfur. Modeling studies of the iberin analogues showed that the oxidation state of sulfur might influence the global shape of the isothiocyanates. These findings establish the TLR dimerization step as a target of food-derived anti-inflammatory compounds. PMID:25294874

  9. Anti-allergic and anti-inflammatory properties of Zizyphus mauritiana root bark.

    PubMed

    Talmale, Suhas; Bhujade, Arti; Patil, Mandakini

    2015-09-01

    An allergy may sometimes be very dangerous and one of the main factors responsible for allergy is the complement system which can lead to a life-threatening reaction called anaphylaxis. Cycloxygenase-1 (COX-1), Cycloxygenase-2 (COX-2) and 5-Lipoxygenase (5-LOX) trigger allergic and inflammatory reactions. A number of anti-allergic synthetic drugs are available but are costly and show many side effects. Hence, the ancient traditional system of medication mentioned in Ayurveda finds an edge over various synthetic drugs. Zizyphus mauritiana is referred to as the store house of phytochemicals in Ayurveda. The stem and root barks of Zizyphus mauritiana were dried and powdered under controlled conditions. Extractions of the dried powders were performed separately in different solvents in increasing order of their polarity and were tested for their ability to inhibit the complement system. The aqueous extract of the root bark was found to be more effective in inhibiting the complement system. Fractionation of the aqueous extract resulted in the isolation of the Most Active Fraction (MAF) which inhibited the complement system, COX-1, COX-2, and 5-LOX with IC50 values of 0.006 ?g ml(-1), 0.065 ?g ml(-1), 0.008 ?g ml(-1), and 0.083 ?g ml(-1), respectively. The MAF was proven to be successful in down-regulating pro-inflammatory mediators like TNF-?, COX-2, and iNOS when tested on a RAW 264.7 cell line. In vivo, the MAF was found to be preventive against anaphylactic shock and the Arthus reaction, when orally administered daily to Wistar rats. Phytochemical analysis of the MAF has indicated that it is rich in tannins. Results indicate that the MAF, a fraction isolated from the aqueous extract of the root bark of Zizyphus mauritiana, has potent anti-allergic and anti-inflammatory properties. PMID:26189881

  10. Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

    SciTech Connect

    Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; Chain, Florian; Lenoir, Marion; Raguideau, Sébastien; Hudault, Sylvie; Bridonneau, Chantal; Northen, Trent; Bowen, Benjamin; Bermúdez-Humarán, Luis G.; Sokol, Harry; Thomas, Muriel; Langella, Philippe

    2015-04-21

    Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (?-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.

  11. Anti-inflammatory and antinociceptive properties of BP 2-94, a histamine H(3)-receptor agonist prodrug.

    PubMed

    Rouleau, A; Stark, H; Schunack, W; Schwartz, J C

    2000-10-01

    BP 2-94 is an azomethine prodrug of (R)-alpha-methylhistamine [(R)-alpha-MeHA], a potent and selective histamine H(3)-receptor agonist. When administered orally to mice BP 2-94 was distributed to various peripheral tissues where it released the active drug. BP 2-94 displayed anti-inflammatory and antinociceptive properties in mice. It dose-dependently inhibited carrageenan-induced paw edema with an ED(50) value of 0.17 +/- 0.05 micromol/kg (p.o.) and a maximal effect of 47%. It also reduced Freund's complete adjuvant-induced paw edema in preventive as well as in curative fashion. Repeated oral administrations of BP 2-94 reduced the pre-established Freund's complete adjuvant-induced edema with an ED(50) value of 5 +/- 2 micromol/kg (p.o.) and a maximal effect of 47%. The antiedema effects of BP 2-94 and indomethacin were additive. BP 2-94 was also efficient in reducing cyclophosphamide-induced cystitis in mice: it decreased leukocyte infiltration by 62% and plasma protein extravasation by 73% in urinary bladder. In addition, BP 2-94 displayed antinociceptive activity in the capsaicin-induced licking test via H(3)-receptor stimulation. Its antinociceptive effect was dose dependent, occurring with an ED(50) value of 0.4 +/- 0.1 micromol/kg (p.o.) and a maximal reduction of licking duration by 69%. No tolerance to the antinociceptive effect was observed after repeated administration of BP 2-94 for 3 days. These observations with BP 2-94 suggest that H(3)-receptor agonists might represent a novel class of anti-inflammatory and antinociceptive agents. PMID:10991982

  12. Rosuvastatin enhances anti-inflammatory and inhibits pro-inflammatory functions in cultured microglial cells.

    PubMed

    Kata, D; Földesi, I; Feher, L Z; Hackler, L; Puskas, L G; Gulya, K

    2016-02-01

    Microglial activation results in profound morphological, functional and gene expression changes that affect the pro- and anti-inflammatory mechanisms of these cells. Although statins have beneficial effects on inflammation, they have not been thoroughly investigated for their ability to affect microglial functions. Therefore the effects of rosuvastatin, one of the most commonly prescribed drugs in cardiovascular therapy, either alone or in combination with bacterial lipopolysaccharide (LPS), were profiled in pure microglial cultures derived from the forebrains of 18-day-old rat embryos. To reveal the effects of rosuvastatin on a number of pro- and anti-inflammatory mechanisms, we performed morphometric, functional and gene expression studies relating to cell adhesion and proliferation, phagocytosis, pro- and anti-inflammatory cytokine (IL-1?, tumor necrosis factor ? (TNF-?) and IL-10, respectively) production, and the expression of various inflammation-related genes, including those related to the above morphological parameters and cellular functions. We found that microglia could be an important therapeutic target of rosuvastatin. In unchallenged (control) microglia, rosuvastatin inhibited proliferation and cell adhesion, but promoted microspike formation and elevated the expression of certain anti-inflammatory genes (Cxcl1, Ccl5, Mbl2), while phagocytosis or pro- and anti-inflammatory cytokine production were unaffected. Moreover, rosuvastatin markedly inhibited microglial activation in LPS-challenged cells by affecting both their morphology and functions as it inhibited LPS-elicited phagocytosis and inhibited pro-inflammatory cytokine (IL-1?, TNF-?) production, concomitantly increasing the level of IL-10, an anti-inflammatory cytokine. Finally, rosuvastatin beneficially and differentially affected the expression of a number of inflammation-related genes in LPS-challenged cells by inhibiting numerous pro-inflammatory and stimulating several anti-inflammatory genes. Since the microglia could elicit pro-inflammatory responses leading to neurodegeneration, it is important to attenuate such mechanisms and promote anti-inflammatory properties, and develop prophylactic therapies. By beneficially regulating both pro- and anti-inflammatory microglial functions, rosuvastatin may be considered as a prophylactic agent in the prevention of inflammation-related neurological disorders. PMID:26633263

  13. Anti-Inflammatory Action of an Antimicrobial Model Peptide That Suppresses the TRIF-Dependent Signaling Pathway via Inhibition of Toll-Like Receptor 4 Endocytosis in Lipopolysaccharide-Stimulated Macrophages

    PubMed Central

    Shim, Do-Wan; Heo, Kang-Hyuck; Kim, Young-Kyu; Sim, Eun-Jeong; Kang, Tae-Bong; Choi, Jae-Wan; Sim, Dae-Won; Cheong, Sun-Hee; Lee, Seung-Hong; Bang, Jeong-Kyu; Won, Hyung-Sik; Lee, Kwang-Ho

    2015-01-01

    Antimicrobial peptides (AMPs), also called host defense peptides, particularly those with amphipathic helical structures, are emerging as target molecules for therapeutic development due to their immunomodulatory properties. Although the antimicrobial activity of AMPs is known to be exerted primarily by permeation of the bacterial membrane, the mechanism underlying its anti-inflammatory activity remains to be elucidated. We report potent anti-inflammatory activity of WALK11.3, an antimicrobial model peptide with an amphipathic helical conformation, in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. This peptide inhibited the expression of inflammatory mediators, including nitric oxide, COX-2, IL-1?, IL-6, INF-?, and TNF-?. Although WALK11.3 did not exert a major effect on all downstream signaling in the MyD88-dependent pathway, toll-like receptor 4 (TLR4)- mediated pro-inflammatory signals were markedly attenuated in the TRIF-dependent pathway due to inhibition of the phosphorylation of STAT1 by attenuation of IRF3 phosphorylation. WALK11.3 specifically inhibited the endocytosis of TLR4, which is essential for triggering TRIF-mediated signaling in macrophage cells. Hence, we suggest that specific interference with TLR4 endocytosis could be one of the major modes of the anti-inflammatory action of AMPs. Our designed WALK11 peptides, which possess both antimicrobial and anti-inflammatory activities, may be promising molecules for the development of therapies for infectious inflammation. PMID:26017270

  14. Uncoupling of Pro- and Anti-Inflammatory Properties of Staphylococcus aureus

    PubMed Central

    Peres, Adam G.; Stegen, Camille; Li, Junbin; Xu, An Qi; Levast, Benoit; Surette, Michael G.; Cousineau, Benoit; Desrosiers, Martin

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that is carried by a quarter of the healthy human population and that can cause severe infections. This pathobiosis has been linked to a balance between Toll-like receptor 2 (TLR2)-dependent pro- and anti-inflammatory responses. The relationship between these two types of responses is unknown. Analysis of 16 nasal isolates of S. aureus showed heterogeneity in their capacity to induce pro- and anti-inflammatory responses, suggesting that these two responses are independent of each other. Uncoupling of these responses was corroborated by selective signaling through phosphoinositol 3-kinase (PI3K)-Akt-mTOR and extracellular signal-regulated kinase (ERK) for the anti-inflammatory response and through p38 for the proinflammatory response. Uncoupling was also observed at the level of phagocytosis and phagosomal processing of S. aureus, which were required solely for the proinflammatory response. Importantly, the anti-inflammatory properties of an S. aureus isolate correlated with its ability to modulate T cell immunity. Our results suggest the presence of anti-inflammatory TLR2 ligands in the staphylococcal cell wall, whose identification may provide templates for novel immunomodulatory drugs. PMID:25644014

  15. Anti-inflammatory sesquiterpene lactones from Lychnophora trichocarpha Spreng. (Brazilian Arnica).

    PubMed

    Ferrari, Fernanda C; Ferreira, Leidiane C; Souza, Maíra R; Grabe-Guimarães, Andrea; Paula, Carmen A; Rezende, Simone A; Saúde-Guimarães, Dênia A

    2013-03-01

    The aerial parts of Lychnophora trichocarpha Spreng. (Asteraceae) are used macerated in water or ethanol to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. In this study, anti-inflammatory activity of ethanol extract from aerial parts of L. trichocarpha and its ethyl acetate fraction was investigated. Sesquiterpene lactones, lychnopholide (Lyc) and eremantholide C (EreC), isolated of ethyl acetate fraction, were also assayed for in vitro and in vivo anti-inflammatory activity. Topical treatment with ointments containing ethanol extract, its ethyl acetate fraction and sesquiterpene lactones significantly reduced carrageenan-induced mice paw oedema. In vitro assays demonstrated that Lyc inhibited interferon -?/lipopolysaccharide -stimulated nitric oxide (NO) production in J774A.1 macrophages and increased production of IL-10 anti-inflammatory cytokine. The reduction of tumor necrosis factor-? (TNF-?) production by EreC was accompanied by an increased production of IL-10 in a concentration-dependent manner in J774A.1 macrophages. The anti-inflammatory effect of Lyc seems to involve the inhibition of production of NO and increased production of IL-10. The mechanism of the effect of EreC on the reduction of carrageenan-induced paw oedema may be attributed to inhibition of production of TNF-? and stimulation of IL-10 production. The results corroborate the use of ethanol extract from Lychnophora trichocarpha in folk medicine for anti-inflammatory action and indicate that the topical route is suitable for use. PMID:22619042

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

    PubMed

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

    2013-01-01

    Several species of the family Bromeliaceae are characterized by the production of proteases in unusual amounts, especially in fruits. Bromelain, an extract rich in cysteine endopeptidases obtained from Ananas comosus L., and a few other proteases have been used as anti-inflammatory agents for some years, but bromelain is still mainly being used as alternative and/or complementary therapy to the treatment with glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. In this study, the anti-inflammatory action of a partially purified extract from Pseudananas macrodontes (Morr.) Harms fruits (PPE(Pm)) is presented, whose main components are cysteine endopeptidases. The effect of PPE(Pm) was assessed in carrageenan-induced and serotonin-induced rat paw edema, as well as in the cotton pellet granuloma model. Doses with equal proteolytic activity of PPE(Pm) and bromelain produced significantly similar anti-inflammatory responses in the acute inflammatory models assayed, supporting the hypothesis that proteolytic activity could be responsible for the anti-inflammatory action. On the contrary, comparable anti-inflammatory effects of PPE(Pm) and bromelain in the chronic inflammatory assay required a much lower proteolytic activity content of PPE(Pm), which could be due to a differential affinity for the protein target involved in this process. PMID:24601082

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

    PubMed Central

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

    2015-01-01

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

  18. Chloroformic and Methanolic Extracts of Olea europaea L. Leaves Present Anti-Inflammatory and Analgesic Activities

    PubMed Central

    Chebbi Mahjoub, R; Khemiss, M.; Dhidah, M.; Dellaï, A.; Bouraoui, A.; Khemiss, F.

    2011-01-01

    Olea europaea L. is used in traditional medicine in the Mediterranean areas. Its natural products are used in the treatment of different disorders, like fighting fever and some infectious diseases such as malaria, the treatment of arrhythmia, and relief of intestinal spasms. The aim of the current study is to investigate the possible anti-inflammatory and anatinociceptive effects of methanol and chloroformic extracts prepared from leaves of Olea europaea L. The anti-inflammatory and antinociceptive effects of the different extracts of Olea europaea leaves were assessed after intraperitoneal administration into rats and mice, using the carrageenan-induced paw edema model in rats to test the anti-inflammatory effect and the acetic acid-induced writhing in mice to test the analgesic effect. The chloroformic and methanolic leaves extracts, studied at the doses of 50, 100, and 200?mg/kg (Body Weight: BW), exhibited significant dose-dependent anti-inflammatory and analgesic activities. Based on the results obtained, it can be concluded that Olea europaea leaves extracts have anti-inflammatory and antinociceptive effects. PMID:22084717

  19. Uncoupling of pro- and anti-inflammatory properties of Staphylococcus aureus.

    PubMed

    Peres, Adam G; Stegen, Camille; Li, Junbin; Xu, An Qi; Levast, Benoit; Surette, Michael G; Cousineau, Benoit; Desrosiers, Martin; Madrenas, Joaquín

    2015-04-01

    Staphylococcus aureus is a Gram-positive bacterium that is carried by a quarter of the healthy human population and that can cause severe infections. This pathobiosis has been linked to a balance between Toll-like receptor 2 (TLR2)-dependent pro- and anti-inflammatory responses. The relationship between these two types of responses is unknown. Analysis of 16 nasal isolates of S. aureus showed heterogeneity in their capacity to induce pro- and anti-inflammatory responses, suggesting that these two responses are independent of each other. Uncoupling of these responses was corroborated by selective signaling through phosphoinositol 3-kinase (PI3K)-Akt-mTOR and extracellular signal-regulated kinase (ERK) for the anti-inflammatory response and through p38 for the proinflammatory response. Uncoupling was also observed at the level of phagocytosis and phagosomal processing of S. aureus, which were required solely for the proinflammatory response. Importantly, the anti-inflammatory properties of an S. aureus isolate correlated with its ability to modulate T cell immunity. Our results suggest the presence of anti-inflammatory TLR2 ligands in the staphylococcal cell wall, whose identification may provide templates for novel immunomodulatory drugs. PMID:25644014

  20. The anti-inflammatory and analgesic properties of prosopis chilenses in rats

    PubMed Central

    Abodola, MA; Lutfi, MF; Bakhiet, AO; Mohamed, AH

    2015-01-01

    Background Prosopis chilensis is used locally in Sudan for inflammatory conditions of joints; however, literature lacks scientific evidence for anti-inflammatory effect of this plant. Aims To evaluate anti-inflammatory and analgesic effects of prosopis chilenses. Material and Methods Edema inhibition percent (EI %) and hot plate method were used to evaluate anti-inflammatory and analgesic effects of Prosopis chilenses in Wistar albino rats. Anti-inflammatory and analgesic effects of Prosopis chilenses were compared to indomethacin and acetylsalicylic acid respectively. Results Ethanolic extract of prosopis chilensis at a dose of 200 and 100mg/kg body weight achieved peak EI% (EI% = 96.1%) and (EI% = 94.4%) three and four hours after oral dosing respectively. The maximum EI% for indomethacin was 97.0% and was recorded after 4 hours following oral administration of the drug at a dose of 5 mg/kg body weight. Prosopis chilensis extracts at doses of 100 and 200 mg/kg body weight significantly increased the rats’ response time to hot plate compared to acetylsalicylic acid at a dose rate of 100mg/kg body weight (P<0.05). Conclusion The current results suggest potential anti-inflammatory and analgesic effects of prosopis chilenses. Relevance of these effects to prosopis chilenses phy-to-constituents was discussed. PMID:26609291

  1. Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus

    PubMed Central

    Geng, Ya-Na; Kong, Wei-Jia

    2014-01-01

    Oxidative stress and inflammation are proved to be critical for the pathogenesis of diabetes mellitus. Berberine (BBR) is a natural compound isolated from plants such as Coptis chinensis and Hydrastis canadensis and with multiple pharmacological activities. Recent studies showed that BBR had antioxidant and anti-inflammatory activities, which contributed in part to its efficacy against diabetes mellitus. In this review, we summarized the antioxidant and anti-inflammatory activities of BBR as well as their molecular basis. The antioxidant and anti-inflammatory activities of BBR were noted with changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines after BBR administration in diabetic animals. BBR inhibited oxidative stress and inflammation in a variety of tissues including liver, adipose tissue, kidney and pancreas. Mechanisms of the antioxidant and anti-inflammatory activities of BBR were complex, which involved multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear factor-?B (NF-?B) pathway. Detailed mechanisms and pathways for the antioxidant and anti-inflammatory activities of BBR still need further investigation. Clarification of these issues could help to understand the pharmacology of BBR in the treatment of diabetes mellitus and promote the development of antidiabetic natural products. PMID:24669227

  2. Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis

    PubMed Central

    LI, JUN; ZHAO, FUTAO

    2015-01-01

    The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis. PMID:26170903

  3. Computational Structure-Based De Novo Design of Hypothetical Inhibitors against the Anti- Inflammatory Target COX-2

    PubMed Central

    Bafna, Khushboo; Katiyar, Shashank Prakash; Goyal, Sukriti; Grover, Abhinav; Sundar, Durai

    2015-01-01

    Cyclooxygenase-2 (COX-2) produces prostaglandins in inflamed tissues and hence has been considered as an important target for the development of anti-inflammatory drugs since long. Administration of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and other COX-2 selective inhibitors (COXIBS) for the treat of inflammation has been found to be associated with side effects, which mainly includes gastro-intestinal (GI) toxicity. The present study involves developing a virtual library of novel molecules with high druglikeliness using structure-based de novo drug designing and 2D fingerprinting approach. A library of 2657 drug like molecules was generated. 2D fingerprinting based screening of the designed library gave a unique set of compounds. Molecular docking approach was then used to identify two compounds highly specific for COX-2 isoform. Molecular dynamics simulations of protein-ligand complexes revealed that the candidate ligands were dynamically stable within the cyclooxygenase binding site of COX-2. The ligands were further analyzed for their druglikeliness, ADMET properties and synthetic accessibility using knowledge based set of rules. The results revealed that the molecules are predicted to selectively bind to COX-2 enzyme thereby potentially overcoming the limitations posed by the drugs in clinical use. PMID:26241744

  4. Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs.

    PubMed

    Zuo, Jing; Du, Lina; Li, Miao; Liu, Boming; Zhu, Weinan; Jin, Yiguang

    2014-05-15

    Iontophoresis is an important approach to improve transdermal drug delivery. However, The transdermal enhancement mechanism of iontophoresis was not well known. The relationship between the physicochemical properties of drugs and the transdermal enhancement effect of iontophoresis was revealed in this study. Non-steroidal anti-inflammatory drugs (NSAIDs) were used as the models, including aspirin, ibuprofen and indomethacin. Their oil-water partition coefficients were measured. The carbomer-based hydrogels of them were prepared. Iontophoresis significantly enhanced in vitro transdermal delivery across the rat skins. Strong lipophilicity could lead to high permeation of drugs. However, the dissociation extent (indicated as pKa) of drugs was the key factor to determine the transdermal enhancement effect of iontophoresis. The more dissociation the drugs were, the higher the transdermal enhancement effect of iontophoresis. The drug-loaded hydrogels combined with iontophoresis improved the treatment of rat raw's inflammatory syndrome. Iontophoresis significantly improved the drugs penetrating into the hypodermis, dermis and epidermis, more deeply than the application of drugs alone according to the experimental result of 5-carboxylfluorescein hydrogels. Iontophoresis led to the unordered arrangement of skin intercellular lipids, the significantly increased flowability and loose stratum corneum structure. Iontophoresis is a promising approach to improve transdermal drug delivery with safety and high efficiency. PMID:24607207

  5. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

    PubMed Central

    Coutinho, Agnes E.; Chapman, Karen E.

    2011-01-01

    Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here. PMID:20398732

  6. Screening of anti-inflammatory and antipyretic activity of Vitex leucoxylon Linn

    PubMed Central

    Shukla, Padmini; Shukla, P.; Mishra, S.B.; Gopalakrishna, B.

    2010-01-01

    Objective: This study was designed to evaluate the anti-inflammatory and antipyretic activity of ethyl acetate extract of Vitex leucoxylon Linn. in various animal experimental models. Materials and Methods: Ethyl acetate extract of V. leucoxylon Linn. evaluated for anti-inflammatory activity in carrageenan, mediator-induced rat paw edema, and cotton pellet-induced granuloma model. The antipyretic activity was evaluated by yeast-induced pyrexia model. Results: Single administration of the ethyl acetate extract of V. leucoxylon Linn. at dose of 500 mg/kg p.o. showed significant (P < 0.001) inhibition of rat paw edema. The ethyl acetate extract showed significant antipyretic activity in brewer yeast-induced pyrexia in rats throughout the observation period of 4 h. Conclusion: This study shows that ethyl acetate extract of V. leucoxylon Linn. has significant anti-inflammatory and antipyretic activity. PMID:21189917

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

    PubMed Central

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

    2015-01-01

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

  8. Analgesic and Anti-inflammatory action of Opuntia elatior Mill fruits

    PubMed Central

    Chauhan, Sanjay P.; Sheth, Navin R.; Suhagia, Bhanubhai N.

    2015-01-01

    Background: Opuntia elatio Mill is a xerophytic plant with potentially active nutrients. It is traditionally appreciated for its pharmacological properties; however, the scientific information on this plant is insufficient. Objective: The present study evaluates the antinociceptive and anti-inflammatory action of prickly pear. Materials and Methods: Writhing and tail-immersion tests were carried out to evaluate analgesic action, while the carrageenan-induced paw edema and neutrophil adhesion tests were conducted in Albino wistar rats to assess anti-inflammatory action. Results: ED50 values of the fruit juice in writhing, tail immersion, and paw edema test were 0.919, 2.77, and 9.282 ml/kg, respectively. The fruits of Opuntia produced analgesic and anti-inflammatory action in a dose-dependent manner. Conclusion: The results establish the folklore use of prickly pear may be due to the presence of betacyanin and/or other phenolic compounds. PMID:26166996

  9. Phytochemical analysis, antioxidant and anti-inflammatory activity of calyces from Physalis peruviana.

    PubMed

    Toro, Reina M; Aragón, Diana M; Ospina, Luis F; Ramos, Freddy A; Castellanos, Leonardo

    2014-11-01

    Physalis peruviana calyces are used extensively in folk medicine. The crude ethanolic extract and some fractions of calyces were evaluated in order to explore antioxidant and anti-inflammatory activities. The anti-inflammatory activity was evaluated by the TPA-induced ear edema model. The antioxidant in vitro activity was measured by means of the superoxide and nitric oxide scavenging activity of the extracts and fractions. The butanolic fraction was found to be promising due to its anti-inflammatory and antioxidant activities. Therefore, a bio-assay guided approach was employed to isolate and identify rutin (1) and nicotoflorin (2) from their NMR spectroscopic and MS data. The identification of rutin in calyces of P. peruviana supports the possible use of this waste material for phytotherapeutic, nutraceutical and cosmetic preparations. PMID:25532284

  10. Synthesis and anti-inflammatory properties of 2-methyl-5-(3-phenylpropionyl)-1-benzoxolane.

    PubMed

    Dauksas, V; Gaidelis, P; Petrauskas, O; Udrenaite, E

    1995-05-01

    2-Methyl-5-(3-phenylpropionyl)-1-benzoxolane (CAS 159264-96-7) was synthesized and studied for anti-inflammatory properties. This new aryl ketone was more active than the previously reported 5-acyl substituted 1-benzoxolanes except 5-cinnamoyl-2-methyl-1-benzoxolane (the unsaturated analogue) which exhibited similar anti-inflammatory activity and similar toxicity but was more gastrotoxic. Anti-inflammatory and analgesic effects of 2-methyl-5-(3-phenylpropionyl)-1-benzoxolane were less pronounced than those of indometacin but greater than those of acetylsalicylic acid (ASA). The new ketone was less toxic and less gastrotoxic than both the reference drugs mentioned above. Therapeutic indices of the new compound were significantly greater than those of ASA and indometacin. PMID:7612057

  11. ?-Amino acid and amino-alcohol conjugation of a nonsteroidal anti-inflammatory drug (NSAID) imparts hydrogelation displaying remarkable biostability, biocompatibility, and anti-inflammatory properties.

    PubMed

    Majumder, Joydeb; Das, Mahua Rani; Deb, Jolly; Jana, Siddhartha Sankar; Dastidar, Parthasarathi

    2013-08-13

    A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with ?-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable (1)H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure-property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E2 (PGE2) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns). PMID:23859562

  12. A role for melatonin in maintaining the pro- and anti-inflammatory balance by influencing leukocyte migration and apoptosis in carp.

    PubMed

    Kepka, Magdalena; Szwejser, Ewa; Pijanowski, Lukasz; Verburg-van Kemenade, B M Lidy; Chadzinska, Magdalena

    2015-11-01

    Melatonin is responsible for the synchronization of many physiological processes, including the immune response. Here we focus on the expression of melatonin MT1 receptors in/on leukocytes, and on the effects of melatonin administration on the inflammatory processes of carp. For the first time, we showed that fish leukocytes express MT1 receptors, implicating direct responsiveness to melatonin stimulation. Moreover, both in vitro and in vivo, melatonin modulated the immune response. The most potent effects of melatonin concerned the regulation of leukocyte migration. Melatonin reduced chemotaxis of leukocytes towards CXC chemokines in vitro. In vivo, during zymosan induced peritonitis, i.p. administration of melatonin reduced the number of neutrophils. This correlated with a melatonin-induced decrease of gene expression of the CXCa chemokine. Moreover, melatonin induced a decrease of the respiratory burst in inflammatory leukocytes. Although these data do suggest a potent anti-inflammatory function for this hormone, melatonin-induced inhibition of leukocyte apoptosis clearly indicates towards a dual function. These results show that also in carp, melatonin performs a pleiotropic and extra-pineal function that is important in maintaining the delicate pro- and anti-inflammatory balance during infection. They furthermore demonstrate that neuroendocrine-immune interaction via melatonin is evolutionary conserved. PMID:26188098

  13. Food Byproducts as a New and Cheap Source of Bioactive Compounds: Lignans with Antioxidant and Anti-inflammatory Properties from Crataegus pinnatifida Seeds.

    PubMed

    Huang, Xiao-Xiao; Bai, Ming; Zhou, Le; Lou, Li-Li; Liu, Qing-Bo; Zhang, Yan; Li, Ling-Zhi; Song, Shao-Jiang

    2015-08-19

    During the process of manufacturing hawthorn (Crataegus pinnatifida) juice and jam, a significant quantity of byproducts (leaves, seeds) is generated. The antioxidant and anti-inflammatory bioassay-guided fractionation of the extract of hawthorn seeds has led to the isolation of eight new lignans, hawthornnins A-H (1-8), and seven known analogues (9-15). Their structures were elucidated by spectroscopic techniques, including 1D and 2D NMR and CD spectra. The radical-scavenging effects of all isolated compounds were investigated. 1-6 and 8 showed moderate activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), whereas 1-6 and 14 displayed good 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical-scavenging activities that were even more potent than that of trolox. In addition, all isolates were evaluated for their anti-inflammatory activities by detecting the nitric oxide (NO) and tumor necrosis factor ? (TNF-?) production by the LPS-induced murine macrophage cell line RAW264.7, and compounds 1-7, 13, and 14 exhibited potent inhibition of NO and TNF-? production. The structure-activity relationships of isolated lignans were also examined, and the results obtained show that C. pinnatifida seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors. PMID:26237121

  14. Analgesic, Anti- inflammatory, Anti- lipoxygenase Activity and Characterization of Three Bioactive Compounds in the Most Active Fraction of Leptadenia reticulata (Retz.)Wight & Arn. – A Valuable Medicinal Plant

    PubMed Central

    Mohanty, Sudipta Kumar; Swamy, Mallappa Kumara; Middha, Sushil Kumar; Prakash, Lokesh; Subbanarashiman, Balasubramanya; Maniyam, Anuradha

    2015-01-01

    Leptadenia reticulata was reported to be used for several medicinal purposes. The present study was undertaken to evaluate anti-inflammatory, analgesic and lipid peroxidation inhibition activities of L. reticulata. The anti-inflammatory assay was performed by ?-carrageenan and formalin induced paw edema test. Pro inflammatory mediators (IL2, IL6, TNF-?) in serum of treated and control organism were analyzed by quantitative ELISA. Lipid peroxidation inhibition was measured by thiobarbituric acid reactive substances (TBARS) assay. Analysis of the most active fraction revealed the presence of one phenolic compound (p-coumaric acid), two flavonoids (rutin and quercetin) which also determined quantitatively. The ethyl acetate fraction at 600 mg/Kg significantly inhibited ?-carrageenan and formalin induced paw edema by 60.59% and 59.24% respectively. Notable reduction in percentage of writhing (76.25%), induced by acetic acid signifies the potent analgesic activity. Lower level of pro-inflammatory cytokines (IL-2, IL-6, TNF-?) in serum at the 4th hour of ?-Carrageenan injection indicated the inhibition of cyclooxigenase-2 (Cox-2), Nitric oxide (NO) and release of prostaglandin to prevent inflammation. The study also demonstrated the decrease in malonaldehyde (MDA) concentration which revealed the lipid peroxidation inhibition potential of the plant. Our finding provides evidence for potent biological activities in tested model which is supported by its characterized bioactive compounds and ethnomedicinal relevance. PMID:26330883

  15. Phenolic acids of the two major blueberry species in the US Market and their antioxidant and anti-inflammatory activities.

    PubMed

    Kang, Jie; Thakali, Keshari M; Jensen, Gitte S; Wu, Xianli

    2015-03-01

    Highbush (cultivated) and lowbush (wild) are the two major blueberry species in the US market. Eight phenolic acids were detected and quantified from these two species by HPLC-MS. Chlorogenic acid was found to be the predominant phenolic acid in both species, with 0.44 mg/g fresh weight in lowbush blueberries and 0.13 mg/g fresh weight in highbush blueberries. Total phenolic content in lowbush blueberries is over three times higher than that of highbush blueberries. The phenolic acid mixtures representing those in the two species were prepared by using authentic standards to assess their contribution to total antioxidant and anti-inflammatory activities of the whole berries. Neither lowbush nor highbush blueberry phenolic acid mixture contributed significantly to the total antioxidant capacity of their relevant whole berries measured by oxygen radical absorbance capacity (ORAC). Both phenolic acid mixtures were able to enter the cell and showed in cell antioxidant activities from the cell based antioxidant protection of erythrocytes (CAP-e) assay. Lowbush blueberry phenolic acid mixture was found to show anti-inflammatory activities by inhibiting the nuclear factor-?B (NF-?B) activation and the production of inflammatory cytokines (TNF-? and IL-6) at the high dose. PMID:25535004

  16. Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions.

    PubMed

    Chen, Ouyang; Ye, Zhouheng; Cao, Zhiyong; Manaenko, Anatol; Ning, Ke; Zhai, Xiao; Zhang, Rongjia; Zhang, Ting; Chen, Xiao; Liu, Wenwu; Sun, Xuejun

    2016-01-01

    Myocardial infarction (MI) remains the most frequent cardiovascular disease with high mortality. Recently, methane has been shown protective effects on small intestinal ischemia-reperfusion injury. We hypothesized that methane-rich saline (MS) could protect the myocardium again MI via its anti-oxidative, anti-apoptotic and anti-inflammatory effects. In experiment 1, tetrazolium chloride staining and detection of myocardial enzymes and oxidative and inflammatory parameters were performed at 12h after MI to determine the optimal dose at which intraperitoneal MS exerted the best protective effects on MI. In experiment 2, rats were treated with 10ml/kg MS. Myocyte apoptosis was detected 72h after MI, and cardiac function and myocardial remodeling were evaluated 4 weeks after MI. Results showed different dose of MS reduced infarct area, decreased myocardial enzymes, inhibited inflammation and oxidative stress following MI. The optimal dose of MS was 10mg/kg. Moreover, treatment with 10mg/kg MS for 3 days significantly reduced myocyte apoptosis, improved cardiac function and inhibited myocardial remodeling (reduced anterior wall thickness, attenuated myocyte hypertrophy, and decreased myocardial collagen). MS protects the myocardium of MI rats via its anti-oxidative, anti-inflammatory, anti-apoptotic and anti-remodeling activities. Thus, MS provides a novel and promising strategy for the treatment of ischemic heart diseases. PMID:26585905

  17. Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKC? Signaling Pathway

    PubMed Central

    Yu, Wan-Guo; He, Hao; Yao, Jing-Yun; Zhu, Yi-Xiang; Lu, Yan-Hua

    2015-01-01

    Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key “late” proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2?,4?-dihydroxy-6?-methoxy-3?,5?-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-?, IL-1?, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC?). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-?, IL-1?, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC? signaling pathway. PMID:26535080

  18. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine.

    PubMed

    Marlicz, Wojciech; Loniewski, Igor; Grimes, David S; Quigley, Eamonn M

    2014-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are among the most frequently prescribed groups of drugs worldwide. The use of NSAIDs is associated with a high number of significant adverse effects. Recently, the safety of PPIs has also been challenged. Capsule endoscopy studies reveal that even low-dose NSAIDs are responsible for gut mucosal injury and numerous clinical adverse effects, for example, bleeding and anemia, that might be difficult to diagnose. The frequent use of PPIs can exacerbate NSAID-induced small intestinal injury by altering intestinal microbiota. Thus, the use of PPI is considered to be an independent risk factor associated with NSAID-associated enteropathy. In this review, we discuss this important clinical problem and review relevant aspects of epidemiology, pathophysiology, and management. We also present the hypothesis that even minor and subclinical injury to the intestinal mucosa can result in significant, though delayed, metabolic consequences, which may seriously affect the health of an individual. PubMed was searched using the following key words (each key word alone and in combination): gut microbiota, microbiome, non-steroidal anti inflammatory drugs, proton pump inhibitors, enteropathy, probiotic, antibiotic, mucosal injury, enteroscopy, and capsule endoscopy. Google engine search was also carried out to identify additional relevant articles. Both original and review articles published in English were reviewed. PMID:25440891

  19. Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKC? Signaling Pathway.

    PubMed

    Yu, Wan-Guo; He, Hao; Yao, Jing-Yun; Zhu, Yi-Xiang; Lu, Yan-Hua

    2015-11-01

    Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-?, IL-1?, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC?). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-?, IL-1?, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC? signaling pathway. PMID:26535080

  20. Flavonoid-modified surfaces: multifunctional bioactive biomaterials with osteopromotive, anti-inflammatory, and anti-fibrotic potential.

    PubMed

    Córdoba, Alba; Satué, María; Gómez-Florit, Manuel; Hierro-Oliva, Margarita; Petzold, Christiane; Lyngstadaas, Staale P; González-Martín, María Luisa; Monjo, Marta; Ramis, Joana M

    2015-03-11

    Flavonoids are small polyphenolic molecules of natural origin with antioxidant, anti-inflammatory, and antibacterial properties. Here, a bioactive surface based on the covalent immobilization of flavonoids taxifolin and quercitrin on titanium substrates is presented, using (3-aminopropyl)triethoxysilane (APTES) as coupling agent. FTIR and XPS measurements confirm the grafting of the flavonoids to the surfaces. Using 2-aminoethyl diphenylborinate (DPBA, a flavonoid-specific dye), the modified surfaces are imaged by fluorescence microscopy. The bioactivity of the flavonoid-modified surfaces is evaluated in vitro with human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and human gingival fibroblasts (HGFs) and compared to that of simple flavonoid coatings prepared by drop casting. Flavonoid-modified surfaces show anti-inflammatory and anti-fibrotic potential on HGF. In addition, Ti surfaces covalently functionalized with flavonoids promote the differentiation of hUC-MSCs to osteoblasts--enhancing the expression of osteogenic markers, increasing alkaline phosphatase activity and calcium deposition; while drop-casted surfaces do not. These findings could have a high impact in the development of advanced implantable medical devices like bone implants. Given the broad range of bioactivities of flavonoid compounds, these surfaces are ready to be explored for other biomedical applications, e.g., as stent surface or tumor-targeted functionalized nanoparticles for cardiovascular or cancer therapies. PMID:25335455

  1. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research.

    PubMed

    Jurenka, Julie S

    2009-06-01

    Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin. PMID:19594223

  2. Interactions between non-steroidal anti-inflammatory drugs and lipid membranes

    NASA Astrophysics Data System (ADS)

    Boggara, Mohan; Krishnamoorti, Ramanan

    2008-03-01

    Chronic usage of Non-steroidal anti-inflammatory drugs(NSAIDs) leads to gastrointestinal toxicity and clinical evidences point the cause to direct interactions between NSAIDs and phospholipid membranes. Also, NSAIDs pre-associated with phospholipid vesicles are shown to be safer and therapeutically more effective than unmodified ones. Our initial experiments and simulations on the partitioning of Aspirin and Ibuprofen clearly indicate role played by the drug structure in drug-membrane interactions. Those results motivated systematic molecular dynamics simulations of membranes with NSAIDs of different size, structure and pKa values. Our results suggest high partition coefficients for these NSAIDs in the membrane compared to water and thinning effect on the bilayer. Our small angle neutron scattering and reflectivity studies on DMPC-Ibuprofen systems indicate that the drug affects both ˜5 nm thick bilayer and overall ˜100 nm diameter vesicle, indicating that NSAIDs affect vesicles on various length scales. We will discuss the structural perturbations to membranes due to NSAIDs at clinically relevant molar ratios and their implications on the use of vesicles as delivery vehicles for NSAIDs.

  3. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

    PubMed Central

    Lee, Kim-Chung; Tam, Emily W. T.; Lo, Ka-Ching; Tsang, Alan K. L.; Lau, Candy C. Y.; To, Kelvin K. W.; Chan, Jasper F. W.; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K. P.; Woo, Patrick C. Y.

    2015-01-01

    Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species. PMID:26090713

  4. Interaction of the nonsteroidal anti-inflammatory drug indomethacin with micelles and its release.

    PubMed

    Maity, Banibrata; Chatterjee, Aninda; Ahmed, Sayeed Ashique; Seth, Debabrata

    2015-03-01

    In this study, we have reported the binding interaction and photophysics of a nonsteroidal anti-inflammatory drug (NSAID) indomethacin (IMC) in the presence of different micelles. We have used several spectroscopic techniques such as UV-vis absorption, steady state fluorescence and time-resolved fluorescence emission spectroscopy. The spectral properties of IMC were modulated in the presence of micelles compared to that in neat water. The weak emitting drug molecule (IMC) becomes highly fluorescent after binding with the micelles. The fluorescence quantum yield and fluorescence lifetime increase in the presence of micelles compared to those in neat water. The isothermal titration calorimetry (ITC) method was used to study the binding interaction of IMC with different micelles. The thermodynamic parameters and the nature of binding between IMC and different micelles have been estimated. Moreover, addition of KCl salt in the respective micelles releases IMC molecule from the micelles to the aqueous medium. This study will help elicidate the binding behavior of IMC in the presence of different micelles for possible use as potential drug delivery systems. PMID:25668149

  5. Anti-Inflammatory Effects of the Chinese Herbal Formula Sini Tang in Myocardial Infarction Rats

    PubMed Central

    Liu, Jiangang; Peter, Karoline; Shi, Dazhuo; Zhang, Lei; Dong, Guoju; Zhang, Dawu; Breiteneder, Heimo; Bauer, Rudolf; Ma, Yan

    2014-01-01

    The aim of this study was to evaluate the anti-inflammatory profiling of the Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a decoction consisting of four herbs: Aconitum carmichaelii, Cinnamomum cassia, Zingiber officinale, and Glycyrrhiza uralensis, was characterized as a remedy to treat syndromes corresponding to heart failure and MI in China. Potential biomarkers, which reflect the extent of myocardial necrosis and correlate with cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as tumor necrosis factor-?, interleukin-6, and interleukin-1? (TNF-?, IL-6, and IL-1?) were determined in plasma, serum, and in myocardial tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased significantly the levels of hs-CRP, TNF-?, IL-6, and IL-1? in MI rats. SNT decreased the expression of ANP levels in plasma and increased the vascular active marker nitric oxide, which limits vascular inflammation. In addition, SNT could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our data suggest that the Chinese herbal formula SNT has the potential to improve cardiac function after MI. SNT may be a candidate for treating MI and its associated inflammatory responses. PMID:24723959

  6. Structural Studies of an Anti-Inflammatory Lectin from Canavalia boliviana Seeds in Complex with Dimannosides

    PubMed Central

    Moura, Tales Rocha; Delatorre, Plínio; Rocha, Bruno Anderson Matias; do Nascimento, Kyria Santiago; Figueiredo, Jozi Godoy; Bezerra, Ingrid Gonçalves; Teixeira, Cicero Silvano; Simões, Rafael Conceição; Nagano, Celso Shiniti; de Alencar, Nylane Maria Nunes; Gruber, Karl; Cavada, Benildo Sousa

    2014-01-01

    Plant lectins, especially those purified from species of the Leguminosae family, represent the best-studied group of carbohydrate-binding proteins. Lectins purified from seeds of the Diocleinae subtribe exhibit a high degree of sequence identity notwithstanding that they show very distinct biological activities. Two main factors have been related to this feature: variance in key residues influencing the carbohydrate-binding site geometry and differences in the pH-dependent oligomeric state profile. In this work, we have isolated a lectin from Canavalia boliviana (Cbol) and solved its x-ray crystal structure in the unbound form and in complex with the carbohydrates Man(?1-3)Man(?1-O)Me, Man(?1-4)Man(?1-O)Me and 5-bromo-4-chloro-3-indolyl-?-D-mannose. We evaluated its oligomerization profile at different pH values using Small Angle X-ray Scattering and compared it to that of Concanavalin A. Based on predicted pKa-shifts of amino acids in the subunit interfaces we devised a model for the dimer-tetramer equilibrium phenomena of these proteins. Additionally, we demonstrated Cbol anti-inflammatory properties and further characterized them using in vivo and in vitro models. PMID:24865454

  7. Cerebral ischemia in the aged. Limited anti-inflammatory efficacy of the indomethacin treatment.

    PubMed

    Sandu, Raluca Elena; Uzoni, Adriana; Coman, Cristin; Popa-Wagner, Aurel

    2015-01-01

    Ischemic stroke is a disease of aging and causes high mortality or long-term disability. Diminished neurological recovery after stroke in aged subjects is possibly associated with exaggerated non-specific inflammatory reaction. The focus of the present study was on neurobiological and behavioral differences between young and old rats modulated by indomethacin daily treatment starting at four hours after acute cerebral ischemia in animal model. Our results indicate age-independent positive consequences of non-specific inhibition of inflammation by indomethacin including increased NeuN-positive surviving neurons, reduced infarct volume and enhanced neuroprotective response of innate immune system evidenced by increased Iba1 and Anx3 immunoreactivities and moderately activated microglia in the peri-infarcted area. Quite relevantly, the efficacy of therapy with indomethacin was reduced. In the aged rats, specifically indomethacin is ineffective in inhibiting phagocytic activity, which is probably due failure of the aged brain to up-regulate the expression of several cytokines including TNF? and Cxcl4. At protein level, we observed no change of lysosomal ED1 immunoreactivity under treatment. Our study demonstrates the beneficial anti-inflammatory treatment with indomethacin. However, aging blunted the positive effect. PMID:26662147

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

    PubMed Central

    Asplund, Maria; Boehler, Christian; Stieglitz, Thomas

    2014-01-01

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

  9. Phosphorylation site analysis of the anti-inflammatory and mRNA destabilizing protein tristetraprolin

    PubMed Central

    Deterding, Leesa J; Blackshear, Perry J

    2009-01-01

    Tristetraprolin (TTP) is a member of the CCCH zinc finger proteins and is an anti-inflammatory protein. Mice deficient in TTP develop a profound inflammatory syndrome with erosive arthritis, autoimmunity and myeloid hyperplasia. TTP binds to mRNA AU-rich elements with high affinity for UUAUUUAUU nucleotides and causes destabilization of those mRNA molecules. TTP is phosphorylated extensively in vivo and is a substrate for multiple protein kinases in vitro. A number of approaches have been used to identify its phosphorylation sites. This article highlights the recent progress and different approaches utilized for the identification of phosphorylation sites in mammalian TTP. Important but limited results are obtained using traditional methods including in vivo labeling, site-directed mutagenesis, phosphopeptide mapping and protein sequencing. Mass spectrometry including MALDI/MS, MALDI/MS/MS, LC/MS/MS, IMAC/MALDI/MS/MS and multidimensional protein identification technology (MudPIT) has led the way in identifying TTP phosphorylation sites. The combination of these approaches has identified multiple phosphorylation sites in mammalian TTP, some of which are predicted by motif scanning to be phosphorylated by several protein kinases. This information should provide the molecular basis for future investigation of TTP’s regulatory functions in controlling pro-inflammatory cytokines. PMID:18067411

  10. Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

    PubMed Central

    Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M.; Giannoudis, Peter V.

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

  11. The zone diet: an anti-inflammatory, low glycemic-load diet.

    PubMed

    Sears, Barry; Bell, Stacey

    2004-01-01

    The Zone Diet was developed on the concept that the hormonal responses of macronutrients could be orchestrated to maintain key hormones within therapeutic zones to control inflammatory responses. In particular, the two hormonal systems that are directly affected by dietary macronutrients are (1) the insulin/glucagon axis and (2) eicosanoids. Each of these hormonal systems can have a significant impact on the inflammatory process. This hormonal approach to optimizing an anti-inflammatory diet has significant ramifications in treatment of those chronic diseases (obesity, type 2 diabetes, and cardiovascular disease) that are known to produce inflammatory responses. On the other hand, an inappropriate balance of macronutrients (especially high glycemic- load carbohydrates) can lead to increased inflammation. A primary example of this is the promotion of the United States Department of Agriculture's Food Guide Pyramid. Since its adoption, the prevalence of obesity and type 2 diabetes has risen substantially. Both conditions also demonstrate a significant increase in inflammatory markers. The purpose of this article is to review the historical factors that led to the development of the Zone Diet, to understand how the Zone Diet can alter inflammatory responses, and to review the published literature on its ability to affect hormonal and metabolic responses. PMID:18370674

  12. Synthesis and biological evaluation of a novel baicalein glycoside as an anti-inflammatory agent.

    PubMed

    Kim, Kyun Ha; Park, Young-Don; Park, Heejin; Moon, Keum-Ok; Ha, Ki-Tae; Baek, Nam-In; Park, Cheon-Seok; Joo, Myungsoo; Cha, Jaeho

    2014-12-01

    Baicalein-6-?-glucoside (BG), a glycosylated derivative of baicalein, was synthesized by using sucrose and the amylosucrase of Deinococcus geothermalis and tested for its solubility, chemical stability, and anti-inflammatory activity. BG was 26.3 times more soluble than baicalein and highly stable in buffered solutions and Dulbecco?s modified Eagle medium containing 10% fetal bovine serum. BG treatment decreased the production of nitric oxide in RAW 264.7 cells treated with lipopolysaccharide (LPS). Luciferase reporter assays, western blots, reverse transcription-polymerase chain reaction, and flow cytometric analyses indicated that BG activated nuclear factor erythroid 2-related factor 2 (Nrf2), an antioxidant transcription factor that confers protection from various inflammatory diseases, induced Nrf2-dependent gene expression, and suppressed the production of reactive oxygen species elicited by LPS more effectively than baicalein. Cellular uptake of BG assessed by confocal microscopy and HPLC analysis of the cell-free extracts of RAW 264.7 cells demonstrated that BG was gradually converted to baicalein inside the cells. These results explain that glycosylation increased the bioavailability of baicalein by helping to protect this vital molecule from chemical or enzymatic oxidation. Therefore, BG, a glycosylated derivative of baicalein, can be an alternative to baicalein as a therapeutic drug. PMID:25446915

  13. Anti-inflammatory tirucallane triterpenoids from Anopyxis klaineana Pierre (Engl.), (Rhizophoraceae).

    PubMed

    Mireku, Evelyn Afua; Kusari, Souvik; Eckelmann, Dennis; Mensah, Abraham Yeboah; Talontsi, Ferdinand M; Spiteller, Michael

    2015-10-01

    Phytochemical investigation of the stem bark extract of Anopyxis klaineana was carried out by various chromatographic techniques resulting in the isolation and characterization of three new tirucallane triterpenoids, namely 3,23-dioxotirucalla-7,24-dien-21-oic acid (1), 3,4-secotirucalla-23-oxo-4(28)7,24-trien-3,21-dioic acid (2) and 3,4-secotirucalla-4-hydroxy-23-oxo-7,24-diene-3,21-dioic acid-21-methyl ester (3), along with nine known compounds (4-12). The structural elucidation of the compounds was performed by means of high-resolution mass spectrometry (HRMS(n)), nuclear magnetic resonance (NMR), and by comparison to literature data. Although none of the isolated compounds showed antibacterial efficacy against selected environmental and clinically important pathogenic Gram-positive and -negative bacteria, they demonstrated moderate DPPH free radical scavenging properties. Furthermore, compounds 1 and 7 exhibited remarkable anti-inflammatory potential in a prostaglandin E2 (PGE2) competitive enzyme immunoassay with IC50 values of 3.63?M and 10.23?M, respectively. PMID:26291645

  14. Anti-allergic, anti-pruritic, and anti-inflammatory activities of Centella asiatica extracts.

    PubMed

    George, Mathew; Joseph, Lincy; Ramaswamy

    2009-01-01

    This study investigated antipruritic and anti-inflammatory effect of Centella asiatica extract in rats and anti-allergic in vitro using sheep (Capra hircus) serum method and compound 48/80 induced mast cell degranulation method, compared with standard drug ketotifen fumarate. In rats, extract of Centella asiatica administered orally was examined for anti-pruritic study and chlorpheniramine maleate was used as standard drug while carageenan paw induced inflammatory method was used for the antiinfammatory study. The results show that the extracts of Centella asiatica exhibited antiallergic, anti-pruritic and anti-inflammatory activities. PMID:20606777

  15. Biological evaluation of angular disubstituted naphthoimidazoles as anti-inflammatory agents.

    PubMed

    Cuadrado-Berrocal, Irene; Guedes, Gema; Estevez-Braun, Ana; Hortelano, Sonsoles; de Las Heras, Beatriz

    2015-10-01

    A series of naphthoimidazoles derivatives (3a-3f) were tested for potential anti-inflammatory activity on lipopolysaccharide (LPS)-treated macrophages. Naphthoimidazole 3e exhibited significant inhibitory effects on nitric oxide (NO) production (IC50 <10?M) and decreased the expression of nitric oxide synthase-2 (NOS-2) and cycloxygenase-2 (COX-2) enzymes. It also inhibited the activation of transcription factor NF-?B. Naphthoimidazole 3e might represent a starting point for the synthesis of new anti-inflammatory naphthoimidazoles derivatives. PMID:26264502

  16. Development of anti-inflammatory drugs - the research and development process.

    PubMed

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. PMID:23981595

  17. Synthesis of Some 4,5-Dihydrothieno[3,2-e][1,2,4]Triazolo[4,3-a] Pyrimi-dine-2-Carboxamides as Anti-Inflammatory and Analgesic Agents

    PubMed Central

    Shaaban, Omaima G.; Rizk, Ola H.; Bayad, Aida E.; El-Ashmawy, Ibrahim M.

    2013-01-01

    A new series 4,5-dihydrothieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidine-2-carboxamide was synthesized. Twenty one newly synthesized compounds were investigated for their anti-inflammatory and analgesic activity using acute and subacute formalin-induced paw edema models and diclofenac Na as a reference. The acute toxicity (ALD50) and ulcerogenic effects of the active compounds were also determined. The thienotriazolopyrimidines 10a, 10c and 11c were found to exhibit remarkable anti-inflammatory activity at both models in addition to good analgesic activity with a delayed onset of action. Moreover, the active compounds showed high GI safety level and are well tolerated by experimental animals with high safety margin (ALD50 > 0.4 g/kg). Docking study using Molecular Operating Environment (MOE) version 2008.10 into COX-2 has been made for derivatives of highest anti-inflammatory activity. PMID:24379893

  18. Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic approach to disease progression and recurrence

    PubMed Central

    2014-01-01

    The chronic, progressive clinical characteristics of many adult solid tumor malignancies suggest that a more effective therapeutic approach to cancer management may require long-term intervention using nontoxic systemic agents that block critical components of abnormal tumor physiology. Two highly promising systemic targets common to the development, progression and recurrence of many common cancers are dysregulated inflammatory and oxidation/reduction (redox) pathways. Compelling clinical data support the use of anti-inflammatory and antioxidant agents as a therapeutic modality for long-term use in patients diagnosed with several common cancers, including colon cancer and breast cancer. The therapeutic paradigm presented in this paper is the product of a synthesis of what is currently understood about the biological effects of inflammation and oxidative stress that contribute to tumorigenesis, disease progression and recurrence as well as results obtained from research on the use of prophylactics with anti-inflammatory or antioxidant properties in cancer prevention and treatment. PMID:24587831

  19. Synthesis, characterization, anti-inflammatory and anti-proliferative activity against MCF-7 cells of O-alkyl and O-acyl flavonoid derivatives.

    PubMed

    Hoang, T Kim-Dung; Huynh, T Kim-Chi; Nguyen, Thanh-Danh

    2015-12-01

    A series of O-alkyl and O-acyl flavonoid derivatives was synthesized in high efficiency. Alkylation and acylation of 5-hydroxyflavonoids showed that the low reactivity hydroxyl group, 5-OH, well reacted with strong reagents whereas with weaker reagents, the different products were obtained dependently on structural characteristic of ring C of respective flavonoid. In order to evaluate anti-inflammatory activity, all compounds were tested for in vitro inhibition of bovine serum albumin denaturation and in vivo inhibition of carrageenan-induced mouse paw edema. Among them, the compounds 3, 3b, 4b and 4c demonstrated more effective anti-inflammatory activity than standard drugs (diclofenac sodium and ketoprofen) in both tests. Meanwhile, the flavonoids 2, 2c, 3a and 4b displayed anti-proliferative activity against MCF-7 cell lines. Triacetyl derivative of hesperetin 4b inducing degradation of DNA in MCF-7 cells was observed. PMID:26432615

  20. Unbiased Screening of Marine Sponge Extracts for Anti-Inflammatory Agents Combined with Chemical Genomics Identifies Girolline as an Inhibitor of Protein Synthesis

    PubMed Central

    Fung, Shan-Yu; Sofiyev, Vladimir; Schneiderman, Julia; Hirschfeld, Aaron F.; Victor, Rachel E.; Woods, Kate; Piotrowski, Jeff S.; Deshpande, Raamesh; Li, Sheena C.; de Voogd, Nicole J.; Myers, Chad L.; Boone, Charlie; Andersen, Raymond J.; Turvey, Stuart E.

    2013-01-01

    Toll-like receptors (TLRs) play a critical role in innate immunity, but activation of TLR signaling pathways is also associated with many harmful inflammatory diseases. Identification of novel anti-inflammatory molecules targeting TLR signaling pathways is central to the development of new treatment approaches for acute and chronic inflammation. We performed high throughput screening from crude marine sponge extracts on TLR5 signaling and identified girolline. We demonstrated that girolline inhibits signaling through both MyD88-dependent and –independent TLRs (i.e. TLR2, 3, 4, 5 and 7), and reduces cytokine (IL-6 and IL-8) production in human peripheral blood mononuclear cells and macrophages. Using a chemical genomics approach, we identified Elongation factor 2 as the molecular target of girolline, which inhibits protein synthesis at the elongation step. Together these data identify the sponge natural product girolline as a potential anti-inflammatory agent acting through inhibition of protein synthesis. PMID:24117378

  1. Dermal Cell Damage Induced by Topical Application of Non-Steroidal Anti-Inflammatory Drugs is Suppressed by Trehalose Co-Lyophilization in Ex Vivo Analysis

    PubMed Central

    KAYASUGA-KARIYA, Yuko; IWANAGA, Shintaroh; FUJISAWA, Ayano; LIN, Lee-Shuan; SUZUKI, Shigeki; CHUNG, Ung-il; SASAKI, Nobuo; SHIMOHATA, Nobuyuki; MOCHIZUKI, Manabu

    2013-01-01

    ABSTRACT Topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) is generally considered safer than oral administration, although the former can occasionally induce cutaneous irritation. We hypothesized that the cutaneous irritation by topical NSAIDs might be suppressed by trehalose, which has protective effects on biological membranes. Using the three-dimensional cultured human skin model, Living Skin Equivalent-high, we found that cutaneous damage due to NSAIDs was reduced by concomitant use of trehalose and that this effect of trehalose was reinforced by co-lyophilization of NSAIDs with trehalose. The anti-inflammatory effect of co-lyophilized NSAIDs with trehalose was comparable to that seen with NSAIDs alone in a rat model. Our results suggest that co-lyophilization of NSAIDs with trehalose might be a novel procedure that can help prevent NSAIDs-induced skin irritation. PMID:23884023

  2. Inhalable dry-emulsion formulation of cyclosporine A with improved anti-inflammatory effects in experimental asthma/COPD-model rats.

    PubMed

    Onoue, Satomi; Sato, Hideyuki; Ogawa, Kumiko; Kojo, Yoshiki; Aoki, Yosuke; Kawabata, Yohei; Wada, Koichi; Mizumoto, Takahiro; Yamada, Shizuo

    2012-01-01

    The main purpose of the present study was to develop a novel respirable powder (RP) formulation of cyclosporine A (CsA) using a spray-dried O/W-emulsion (DE) system. DE formulation of CsA (DE/CsA) was prepared by spray-drying a mixture of erythritol and liquid O/W emulsion containing CsA, polyvinylpyrrolidone, and glyceryl monooleate as emulsifying agent. The DE/CsA powders were mixed with lactose carriers to obtain an RP formulation of DE/CsA (DE/CsA-RP), and its physicochemical, pharmacological, and pharmacokinetic properties were evaluated. Spray-dried DE/CsA exhibited significant improvement in dissolution behavior with ca. 4500-fold increase of dissolution rate, and then, nanoemulsified particles were reconstituted with a mean diameter of 317 nm. Laser diffraction analysis on the DE/CsA-RP suggested high dispersion of DE/CsA on the surface of the lactose carrier. Anti-inflammatory properties of the inhaled DE/CsA-RP were characterized in antigen-sensitized asthma/COPD-model rats, in which the DE/CsA-RP was more potent than the RP formulation of physical mixture containing CsA and erythritol in inhibiting inflammatory responses, possibly due to the improved dissolution behavior. Pharmacokinetic studies demonstrated that systemic exposure of CsA after intratracheal administration of the DE/CsA-RP at a pharmacologically effective dose (100 ?g-CsA/rat) was 50-fold less than that of the oral CsA dosage form at a toxic dose (10 mg/kg). From these findings, use of inhalable DE formulation of CsA might be a promising approach for the treatment of airway inflammatory diseases with improved pharmacodynamics and lower systemic exposure. PMID:22008148

  3. New Anti-Inflammatory Aromatic Components from Antrodia camphorata

    PubMed Central

    Chen, Yu-Chang; Chiu, His-Lin; Chao, Che-Yi; Lin, Wen-Hsin; Chao, Louis Kuoping; Huang, Guan-Jhong; Kuo, Yueh-Hsiung

    2013-01-01

    Three new benzenoids, 3-isopropenyl-2-methoxy-6-methyl-4,5-methylenedioxyphenol (1), 2-hydroxy-4,4?-dimethoxy-3,3?-dimethyl-5,6,5?,6?-bimethylenedioxybiphenyl (2), 4,4?-dihydroxy-3,3?-dimethoxy-2,2?-dimethyl-5,6,5?,6?-bimethylenedioxybiphenyl (3), together with two known benzenoids, 2,3,6-trimethoxy-5-methylphenol (4) and 2,3-methylenedioxy-4-methoxy-5-methylphenol (5), were isolated from Antrodia camphorata. Our results support that compounds 1–5 potently inhibited LPS (lipopolysaccharide)-induced nitric oxide (NO) production in a dose-dependent manner. The IC50 values of compounds 1, 3 and 5 were 1.8 ± 0.2, 18.8 ± 0.6 and 0.8 ± 0.3 ?g/mL, respectively. PMID:23443162

  4. Evaluation of the Anti-inflammatory Properties of Juice from Grape Varieties Grown in PI: Dr. Edralin Lucas, Nutritional Sciences

    E-print Network

    Evaluation of the Anti-inflammatory Properties of Juice from Grape Varieties Grown in Oklahoma PI of this project is to examine the anti-inflammatory properties of juice from grape varieties grown in Oklahoma. Our central hypothesis is that the juice from the grape variety with the highest total phenolic

  5. Anti-inflammatory and wound healing activities of Aloe littoralis in rats

    PubMed Central

    Hajhashemi, V.; Ghannadi, A.; Heidari, A.H.

    2012-01-01

    Aloe littoralis Baker (Asphodelaceae family) is a well known plant in southern parts of Iran. Because of its use in Iranian folk medicine as a wound-healing agent, the present study was carried out to investigate anti-inflammatory and wound healing activities of this plant in Wistar rats. A. littoralis raw mucilaginous gel (ALRMG) and also two gel formulations prepared from the raw mucilaginous gel were used in this study. Gel formulations (12.5% and 100% v/w Aloe mucilage in a carbomer base) were applied topically (500 mg once daily) for 24 days in the thermal wound model. Also Aloe gel formulation (100%) and ALRMG (500 mg daily) were evaluated in incisional wound model. Carrageenan-induced paw edema was used to assess the anti-inflammatory effect of intraperitoneal injection of ALRMG. In burn wound, ALRMG and Aloe formulated gel (100%) showed significant (P<0.05) healing effect. Topical application of ALMRG and Aloe formulated gel (100%) promoted healing rate of incisional wound. In carrageenan test, ALRMG (2.5 and 5 ml/Kg) revealed significant (P<0.05) anti-inflammatory activity. Results showed that A. littoralis is a potential wound-healing and anti-inflammatory agent in rats. Further studies are needed to find out the mechanism of these biological effects and also the active constituents responsible for the effects. PMID:23181083

  6. Structural investigation of chitosan-based microspheres with some anti-inflammatory drugs

    NASA Astrophysics Data System (ADS)

    Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Dragan, Felicia; Bende, A.; Borodi, Gh.; Bratu, I.

    2011-06-01

    The use of chitosan as an excipient in oral formulations, as a drug delivery vehicle for ulcerogenic anti-inflammatory drugs and as base in polyelectrolyte complex systems, to prepare solid release systems as sponges was investigated. The preparation by double emulsification of chitosan hydrogels carrying diclofenac, acetyl-salycilic acid and hydrocortisone acetate as anti-inflammatory drugs is reported. The concentration of anti-inflammatory drug in the chitosan hydrogel generating the sponges was 0.08 mmol. Chitosan-drug loaded sponges with anti-inflammatory drugs were prepared by freeze-drying at -60 °C and 0.009 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared and ultraviolet-visible spectroscopy, spectrofluorimetry, differential scanning calorimetry and X-ray diffractometry. The results indicated that the drug molecules are forming temporary chelates in chitosan hydrogels and sponges. Electron paramagnetic resonance demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan-drug supramolecular cross-linked assemblies.

  7. [Screening of anti-inflammatory and analgesic activities in marines macroalgae from Mediterranean Sea].

    PubMed

    Chatter Riahi, R; Tarhouni, S; Kharrat, R

    2011-01-01

    Methanolic extracts of 13 seaweeds collected from the Mediterranean sea (Tunisian, Moroccan and Greek coasts) from different classes (Chlorophycae, Pheopbycae and Rhodophycae) are testedfor their analgesic and antiinflammatory effects. These activities were estimated in vivo, respectively by writhing test and carrageenan test. Nine species among 13 tested seaweeds showed an important analgesic activity. On the other hand only 5 seaweeds showed a significant anti-inflammatory activity (< 0.001 compared to control group). The percentage of inhibition reached 80% for the red algae Laurencia glandulifera but was only 50% for aspirin. The screening showed different pharmacological profiles. The red algae (Laurencia glandulfera and Hypnea musciformis) and brown algae (Cystoseira barbata and Sargassum vulgare) had endowed with the double analgesic and anti-inflammatory activity. The red algae Geliduim sesquipedale have only anti-inflammatory activity and the other one endowed only with an analgesic activity (Enteromorpha compressa, Chaetomorpha linum, Cystoseira ericoidies, Sacchoriza bulbosa et Corralina officinalis). The simultaneous or individual presence of the analgesic and\\or anti-inflammatory activities of the various extracts can find its application in the therapeutic domain. PMID:23461139

  8. Anti-Inflammatory Activity of N-(3-Florophenyl) ethylcaffeamide in Mice

    PubMed Central

    Liao, Jung-Chun; Tsai, Jen-Chieh; Peng, Wen-Huang; Chiu, Yung-Jia; Sung, Ping-Jyun; Tsuzoki, Minoru; Kuo, Yueh-Hsiung

    2013-01-01

    In this study, we evaluated the anti-inflammatory activity of one synthetic product, N-(3-Florophenyl)ethylcaffeamide (abbrev. FECA), by using animal model of ?-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of FECA was determined by measuring 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 results showed that FECA reduced the paw edema at three, four and five hours after ?-carrageenan administration. The levels of COX-2, NO, TNF-?, and MDA in the ?-carrageenan-induced edema paws were reduced and the activities of SOD, GPx, and GRd in liver tissues were raised by FECA. These results suggested that FECA possessed anti-inflammatory activities and the anti-inflammatory mechanisms might be related to the decrease of the levels of COX-2, NO, and TNF-? in inflamed tissues and the increase in the MDA level by increasing the activities of SOD, GPx, and GRd. PMID:23887648

  9. Anti-inflammatory activity of N-(3-florophenyl)ethylcaffeamide in mice.

    PubMed

    Liao, Jung-Chun; Tsai, Jen-Chieh; Peng, Wen-Huang; Chiu, Yung-Jia; Sung, Ping-Jyun; Tsuzoki, Minoru; Kuo, Yueh-Hsiung

    2013-01-01

    In this study, we evaluated the anti-inflammatory activity of one synthetic product, N-(3-Florophenyl)ethylcaffeamide (abbrev. FECA), by using animal model of ?-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of FECA was determined by measuring 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 results showed that FECA reduced the paw edema at three, four and five hours after ?-carrageenan administration. The levels of COX-2, NO, TNF-?, and MDA in the ?-carrageenan-induced edema paws were reduced and the activities of SOD, GPx, and GRd in liver tissues were raised by FECA. These results suggested that FECA possessed anti-inflammatory activities and the anti-inflammatory mechanisms might be related to the decrease of the levels of COX-2, NO, and TNF-? in inflamed tissues and the increase in the MDA level by increasing the activities of SOD, GPx, and GRd. PMID:23887648

  10. Inhibition of amyloidogenesis by non-steroidal anti-inflammatory drugs and their hybrid nitrates

    PubMed Central

    Schiefer, Isaac T.; Abdul-Hay, Samer; Wang, Huali; Vanni, Michael; Qin, Zhihui; Thatcher, Gregory R. J.

    2011-01-01

    Poor blood-brain barrier penetration of non-steroidal anti-inflammatory drugs (NSAIDs) has been blamed for the failure of the selective amyloid lowering agent (SALA) R-flurbiprofen in phase 3 clinical trials for Alzheimer’s disease (AD). NO-donor NSAIDs (NO-NSAIDs) provide an alternative, gastric-sparing approach to NSAID SALAs, which may improve bioavailability. NSAID analogs were studied for anti-inflammatory activity and for SALA activity in N2a neuronal cells transfected with human amyloid precursor protein (APP). Flurbiprofen (1) analogs were obtained with enhanced anti-inflammatory and anti-amyloidogenic properties compared to 1, however, esterification led to elevated A?1–42 levels. Hybrid nitrate prodrugs possessed superior anti-inflammatory activity and reduced toxicity relative to the parent NSAIDs, including clinical candidate, CHF5074. Although hybrid nitrates elevated A?1–42 at higher concentration, SALA activity was observed at low concentrations (? 1 µM): both A?1–42 and the ratio of A?1–42/A?1–40 were lowered. This biphasic SALA activity was attributed to the intact nitrate drug. For several compounds the selective modulation of amyloidogenesis was tested using an immunoprecipitation MALDI-TOF approach. These data support the development of NO-NSAIDs as an alternative approach towards a clinically useful SALA. PMID:21405086

  11. Can the anti-inflammatory activities of ?2-agonists be harnessed in the clinical setting?

    PubMed Central

    Theron, Annette J; Steel, Helen C; Tintinger, Gregory R; Feldman, Charles; Anderson, Ronald

    2013-01-01

    Beta2-adrenoreceptor agonists (?2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled ?2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of ?2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of ?2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of ?2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3?,5?-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells. PMID:24285920

  12. Anti-Inflammatory and Antiarthritic Activity of Anthraquinone Derivatives in Rodents

    PubMed Central

    Kshirsagar, Ajay D.; Panchal, Prashant V.; Harle, Uday N.; Nanda, Rabindra K.; Shaikh, Haidarali M.

    2014-01-01

    Aloe emodin is isolated compound of aloe vera which is used traditionally as an anti-inflammatory agent. In vitro pharmacokinetic data suggest that glucuronosyl or sulfated forms of aloe emodin may provide some limitations in its absorption capacity. Aloe emodin was reported to have in vitro anti-inflammatory activity due to inhibition of inducible nitric oxide (iNO) and prostaglandin E2, via its action on murine macrophages. However, present work evidenced that molecular docking of aloe emodin modulates the anti-inflammatory activity, as well as expression of COX-2 (cyclooxygenase-2) in rodent. The AEC (4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2 carboxylic acid) was synthesized using aloe emodin as starting material. The study was planned for evaluation of possible anti-inflammatory and antiarthritic activity in carrageenan rat induced paw oedema and complete Freund's adjuvant induced arthritis in rats. The AE (aloe emodin) and AEC significantly (P < 0.001) reduced carrageenan induced paw edema at 50 and 75?mg/kg. Complete Freund's adjuvant induced arthritis model showed significant (P < 0.001) decrease in injected and noninjected paw volume, arthritic score. AE and AEC showed significant effect on various biochemical, antioxidant, and hematological parameters. Diclofenac sodium 10?mg/kg showed significant (P < 0.001) inhibition in inflammation and arthritis. PMID:25610704

  13. In vivo anti-inflammatory, analgesic and antipyretic activities of a medicinal plant, Caesalpinia bonducella F.

    PubMed

    Shukla, Shruti; Mehta, Archana

    2015-07-01

    This research examined antipyretic, anti-inflammatory, and analgesic activities of ethanolic extract of C. bonducella whole seeds in experimental albino rats. Three doses, 100, 200 and 400 mg/kg of the whole seed ethanolic extract prepared as a suspension in 2 ml of 2% gum acacia were used. Acute inflammatory and antipyretic activities were evaluated in experimental animals by carrageenan induced paw edema and brewer's yeast-induced pyrexia models, respectively. A significant (p<0.05) reduction in paw volumes, and pyrexia was noted in experimental animals when compared with control animals. The ethanol see extract (400 mg/kg) displayed in vivo anti-inflammatory, antipyretic and analgesic in terms of reduction in paw edema, % writhes inhibition and rectal temperature by (0.24±0.03), (31.38%) and (36.2±0.1), respectively. Overall the whole ethanolic seed extract at all tested concentrations produced significant (p<0.05) anti-inflammatory, antipyretic and analgesic activities. The results obtained in this study clearly indicated the ethno-medicinal potential of C. bonducella in curing pain and inflammation related disorders, supporting its efficacy as a natural analgesic, antipyretic and anti-inflammatory agent. PMID:26431663

  14. Anti-inflammatory effects of linezolid on carrageenan-induced paw edema in rats.

    PubMed

    Matsumoto, Kazuaki; Obara, Shigeaki; Kuroda, Yuko; Kizu, Junko

    2015-12-01

    The immunomodulatory activity of linezolid has recently been reported using in vitro experimental models. However, the anti-inflammatory activity of linezolid has not yet been demonstrated using in vivo experimental models. Therefore, the aim of the present study was to demonstrate the anti-inflammatory activity of linezolid and other anti-MRSA agents using the carrageenan-induced rat paw edema model. The pretreatment with 50 mg/kg linezolid significantly suppressed edema rates, compared with control (5% glucose), with edema rates at 0.5 and 3 h after the administration of carrageenan being 17.3 ± 3.5 and 30.8 ± 3.0%, respectively. On the other hand, edema rates were not suppressed by the pretreatments with 50 mg/kg vancomycin, teicoplanin, arbekacin, and daptomycin. Furthermore, we demonstrated that linezolid exhibited anti-inflammatory activity in a concentration-dependent manner. These effects were observed at linezolid concentrations that are achievable in human serum with conventional dosing. In conclusion, the results of the present study suggest that the anti-inflammatory activities of linezolid, in addition to its antimicrobial effects, have a protective effect against destructive inflammatory responses in areas of inflammation. PMID:26362409

  15. Novel coumarin–benzimidazole derivatives as antioxidants and safer anti-inflammatory agents

    PubMed Central

    Arora, Radha Krishan; Kaur, Navneet; Bansal, Yogita; Bansal, Gulshan

    2014-01-01

    Inspired from occurrence of anti-inflammatory activity of 3-substituted coumarins and antiulcer activity of various 2-substituted benzimidazoles, novel compounds have been designed by coupling coumarin derivatives at 3-position directly or through amide linkage with benzimidazole nucleus at 2-position. The resultant compounds are expected to exhibit both anti-inflammatory and antioxidant activities along with less gastric toxicity profile. Two series of coumarin–benzimidazole derivatives (4a–e and 5a–e) were synthesized and evaluated for anti-inflammatory activity and antioxidant activity. Compounds 4c, 4d and 5a displayed good anti-inflammatory (45.45%, 46.75% and 42.85% inhibition, respectively, versus 54.54% inhibition by indomethacin) and antioxidant (IC50 of 19.7, 13.9 and 1.2 µmol/L, respectively, versus 23.4 µmol/L for butylatedhydroxytoluene) activities. Evaluation of ulcer index and in vivo biochemical estimations for oxidative stress revealed that compounds 4d and 5a remain safe on gastric mucosa and did not induce oxidative stress in tissues. Calculation of various molecular properties suggests the compounds to be sufficiently bioavailable. PMID:26579406

  16. Analgesic, Anti-Inflammatory and Anticancer Activities of Extra Virgin Olive Oil

    PubMed Central

    Senovilla, Laura; Jemaà, Mohamed; Ben-Attia, Mossadok

    2013-01-01

    Background. In folk medicine, extra virgin olive oil (EVOO) is used as a remedy for a variety of diseases. This study investigates the in vivo antinociceptive, anti-inflammatory, and anti-cancer effects of EVOO on mice and rats. Materials and Methods. In this experimental study, using the acetic acid-induced writhing and formalin tests in mice, the analgesic effect of EVOO was evaluated. Acetylsalicylic acid and morphine were used as standard drugs, respectively. The anti-inflammatory activity was investigated by means of the carrageenan-induced paw edema model in rats using acetylsalicylic acid and dexamethasone as standard drugs. Last, the xenograft model in athymic mice was used to evaluate the anticancer effect in vivo. Results. EVOO significantly decreased acetic acid-induced abdominal writhes and reduces acute and inflammatory pain in the two phases of the formalin test. It has also a better effect than Dexamethasone in the anti-inflammatory test. Finally, the intraperitoneal administration of EVOO affects the growth of HCT 116 tumours xenografted in athymic mice. Conclusion. EVOO has a significant analgesic, anti-inflammatory, and anticancer properties. However, further detailed studies are required to determine the active component responsible for these effects and mechanism pathway. PMID:24455277

  17. Amauroderma rugosum (Blume & T. Nees) Torrend: Nutritional Composition and Antioxidant and Potential Anti-Inflammatory Properties

    PubMed Central

    Chan, Pui-Mun; Kanagasabapathy, Gowri; Tan, Yee-Shin; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Amauroderma rugosum is a wild mushroom that is worn as a necklace by the indigenous communities in Malaysia to prevent fits and incessant crying by babies. The aim of this study was to investigate the nutritive composition and antioxidant potential and anti-inflammatory effects of A. rugosum extracts on LPS-stimulated RAW264.7 cells. Nutritional analysis of freeze-dried mycelia of A. rugosum (KUM 61131) from submerged culture indicated a predominant presence of carbohydrates, proteins, dietary fibre, phosphorus, potassium, and sodium. The ethanol crude extract (EE), its hexane (HF), ethyl acetate (EAF), and aqueous (AF) fractions of mycelia of A. rugosum grown in submerged culture were evaluated for antioxidant potential and anti-inflammatory effects. EAF exhibited the highest total phenolic content and the strongest antioxidant activity based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2?-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. HF showed dose-dependent inhibition of NO production in LPS-stimulated RAW264.7 cells and NO radical scavenging activity. Gas chromatographic analysis of HF revealed the presence of ethyl linoleate and ergosterol, compounds with known anti-inflammatory properties. In conclusion, the nutritive compositions and significant antioxidant potential and anti-inflammatory effects of mycelia extracts of A. rugosum have the potential to serve as a therapeutic agent or adjuvant in the management of inflammatory disorders. PMID:24371454

  18. Anti-inflammatory effect of fucoidan extracted from Ecklonia cava in zebrafish model.

    PubMed

    Lee, Seung-Hong; Ko, Chang-Ik; Jee, Youngheun; Jeong, Yoonhwa; Kim, Misook; Kim, Jin-Soo; Jeon, You-Jin

    2013-01-30

    Fucoidan extracted from Ecklonia cava had strong anti-inflammatory activities. However, the direct effects of fucoidan of E. cava on anti-inflammatory activities in vivo model remained to be determined. Therefore, the present study was designed to assess in vivo anti-inflammatory effect of fucoidan extracted from E. cava (ECF) using tail-cutting-induced and lipopolysaccharide (LPS)-stimulated zebrafish model. Treating zebrafish model with tail-cutting and LPS-treatment significantly increased the ROS and NO level. However, ECF inhibited this tail-cutting-induced and LPS-stimulated ROS and NO generation. These results show that ECF alleviated inflammation by inhibiting the ROS and NO generation induced by tail-cutting and LPS-treatment. In addition, ECF has a protective effect against the toxicity induced by LPS exposure in zebrafish embryos. This outcome could explain the potential anti-inflammatory activity of ECF, which might have a beneficial effect during the treatment of inflammatory diseases. PMID:23218269

  19. Can the anti-inflammatory activities of ?2-agonists be harnessed in the clinical setting?

    PubMed

    Theron, Annette J; Steel, Helen C; Tintinger, Gregory R; Feldman, Charles; Anderson, Ronald

    2013-01-01

    Beta2-adrenoreceptor agonists (?2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled ?2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of ?2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of ?2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of ?2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3',5'-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells. PMID:24285920

  20. In vivo anti-inflammatory and antiarthritic activities of aqueous extracts from Thymelaea hirsuta

    PubMed Central

    Azza, Zora; Oudghiri, Mounia

    2015-01-01

    Background: The aerial parts of Thymelaea hirsuta (TH) are used as a decoction in the treatment of different pathologies in folk medicine in Morocco. Objective: The aqueous extracts were evaluated for its anti-inflammatory activity and in inhibition of adjuvant induction arthritis in male Wistar rats. Materials and Methods: The anti-inflammatory activity was carried out using carrageenan-induced rat paw edema model, and the antiarthritic activity was carried out using complete Freund's adjuvant-induced arthritis model. Results: The plant extract (500 mg/kg body weight) exhibited significant activity in acute inflammation produced 60% of inhibition after 4 h as compared with that of the standard anti-inflammatory drug, the diclofenac (100 mg/kg) which showed 40% of inhibition. In arthritis model, the extract produced 85% inhibition after 18 days when compared with the diclofenac (10 mg/kg; 72%). Conclusion: These results indicate that the aqueous extract of TH had an anti-inflammatory activity and inhibited the induction of adjuvant arthritis in male Wistar rats. PMID:25829798

  1. AntiInflammatory Properties of Wheat Germ Oil (WGO) Formulations Developed at Oklahoma State University

    E-print Network

    AntiInflammatory Properties of Wheat Germ Oil (WGO) Formulations Developed at Oklahoma State health benefits is wheat and its by products. Oklahoma is one of the largest wheat growing states in the country. In this project, we will study the antiinflammatory effects of wheat germ oil (WGO) which has

  2. AMP-activated protein kinase is activated by non-steroidal anti-inflammatory drugs.

    PubMed

    King, Tanya S; Russe, Otto Quintus; Möser, Christine V; Ferreirós, Nerea; Kynast, Katharina L; Knothe, Claudia; Olbrich, Katrin; Geisslinger, Gerd; Niederberger, Ellen

    2015-09-01

    AMP-activated kinase (AMPK) is a cellular energy sensor, which is activated in stages of increased adenosine triphosphate (ATP) consumption. Its activation has been associated with a number of beneficial effects such as decrease of inflammatory processes and inhibition of disease progression of diabetes and obesity. A recent study suggested that salicylate, the active metabolite of the non-steroidal anti-inflammatory drug (NSAID) acetyl-salicylic acid (aspirin), is able to activate AMPK pharmacologically. This observation raised the question whether or not other NSAIDs might also act as AMPK activators and whether this action might contribute to their cyclooxygenase (COX)-independent anti-inflammatory properties. In this study, we investigated mouse and human neuronal cells and liver tissue of mice after treatment with various NSAIDs. Our results showed that the non-selective acidic NSAIDs ibuprofen and diclofenac induced AMPK activation similar to aspirin while the COX-2 selective drug etoricoxib and the non-opioid analgesic paracetamol, both drugs have no acidic structure, failed to activate AMPK. In conclusion, our results revealed that AMPK can be activated by specific non-steroidal anti-inflammatory drugs such as salicylic acid, ibuprofen or diclofenac possibly depending on the acidic structure of the drugs. AMPK might therefore contribute to their antinociceptive and anti-inflammatory properties. PMID:26049010

  3. Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble

    E-print Network

    Hammock, Bruce D.

    Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs-inflammatory drugs (NSAIDs) and previously undescribed soluble epoxide hydrolase inhibitors (sEHIs) in lipo that these drug combinations (NSAIDs and sEHIs) produce a valuable beneficial analgesic and anti-inflamma- tory

  4. An investigation of antioxidant and anti-inflammatory activities from blood components of Crocodile (Crocodylus siamensis).

    PubMed

    Phosri, Santi; Mahakunakorn, Pramote; Lueangsakulthai, Jiraporn; Jangpromma, Nisachon; Swatsitang, Prasan; Daduang, Sakda; Dhiravisit, Apisak; Thammasirirak, Sompong

    2014-10-01

    Antioxidant and anti-inflammatory activities were found from Crocodylus siamensis (C. siamensis) blood. The 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, nitric oxide scavenging, hydroxyl radical scavenging and linoleic peroxidation assays were used to investigate the antioxidant activities of the crocodile blood. Results show that crocodile blood components had antioxidant activity, especially hemoglobin (40.58 % nitric oxide radical inhibition), crude leukocyte extract (78 % linoleic peroxidation inhibition) and plasma (57.27 % hydroxyl radical inhibition). Additionally, the anti-inflammatory activity of the crocodile blood was studied using murine macrophage (RAW 264.7) as a model. The results show that hemoglobin, crude leukocyte extract and plasma were not toxic to RAW 264.7 cells. Also they showed anti-inflammatory activity by reduced nitric oxide (NO) and interleukin 6 (IL-6) productions from lipopolysaccharide (LPS)-stimulated cells. The NO inhibition percentages of hemoglobin, crude leukocyte extract and plasma were 31.9, 48.24 and 44.27 %, respectively. However, only crude leukocyte extract could inhibit IL-6 production. So, the results of this research directly indicate that hemoglobin, crude leukocyte extract and plasma of C. siamensis blood provide both antioxidant and anti-inflammatory activities, which could be used as a supplementary agent in pharmaceutical products. PMID:25216803

  5. Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

    PubMed Central

    SORIANO-HERNANDEZ, ALEJANDRO D.; MADRIGAL-PÉREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; MARTINEZ-FIERRO, MARGARITA L.; VALDEZ-VELAZQUEZ, LAURA L.; ESPINOZA-GÓMEZ, FRANCISCO; VAZQUEZ-VUELVAS, OSCAR F.; OLMEDO-BUENROSTRO, BERTHA A.; GUZMAN-ESQUIVEL, JOSE; RODRIGUEZ-SANCHEZ, IRAM P.; LARA-ESQUEDA, AGUSTIN; MONTES-GALINDO, DANIEL A.; DELGADO-ENCISO, IVAN

    2015-01-01

    Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10–40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50–90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug. PMID:26622892

  6. Neutrophilia and an Anti-Inflammatory Drug as Markers of Inflammation in Delayed Muscle Soreness.

    ERIC Educational Resources Information Center

    Smith, Lucille L.; And Others

    This study reexamined the concept that delayed muscle soreness (DMS) is a form of inflammatory pain. This was accomplished by having 32 male volunteers perform exercise known to induce DMS and then assess the total and differential white blood cell changes. In addition, an anti-inflammatory drug, idomethacin, was administered to determine whether…

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

    PubMed

    Fajardo, Alexandra M; Piazza, Gary A

    2015-07-15

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  8. Evaluation of the anti-inflammatory, analgesic and anti-ulcerogenic potentials of Achillea fragrantissima (Forssk.)

    E-print Network

    Paré, Paul W.

    -inflammatory Analgesic Anti-ulcerogenic Egyptian folk medicine Achillea fragrantissima is a perennial herb grown in Egypt, Lubbock, TX 79409, USA. f Chemistry of Medicinal Plants Department, and Center of Excellence for Advanced and traditionally employed medicinally for its anti- inflammatory and analgesic properties among Sinai inhabitants

  9. Analgesic and Anti-Inflammatory Activities of Leaf Extract of Mallotus repandus (Willd.) Muell. Arg.

    PubMed Central

    Hasan, Md. Mahadi; Uddin, Nizam; Hasan, Md. Rakib; Islam, A. F. M. Mahmudul; Hossain, Md. Monir; Rahman, Akib Bin; Hossain, Md. Sazzad; Chowdhury, Ishtiaque Ahmed; Rana, Md. Sohel

    2014-01-01

    In folk medicine Mallotus repandus (Willd.) Muell. Arg. is used to treat muscle pain, itching, fever, rheumatic arthritis, snake bite, hepatitis, and liver cirrhosis. This study aimed to evaluate the antinociceptive as well as the anti-inflammatory activities of the methanol extract of leaf. The leaves were extracted with methanol following hot extraction and tested for the presence of phytochemical constituents. Analgesic and anti-inflammatory activities were evaluated using acetic acid induced writhing test, xylene induced ear edema, cotton pellet induced granuloma, and tail immersion methods at doses of 500, 1000, and 2000?mg/kg body weight. The presence of flavonoids, saponins, and tannins was identified in the extract. The extract exhibited considerable antinociceptive and anti-inflammatory activities against four classical models of pain. In acetic acid induced writhing, xylene induced ear edema, and cotton pellet granuloma models, the extract revealed dose dependent activity. Additionally, it increased latency time in tail immersion model. It can be concluded that M. repandus possesses significant antinociceptive potential. These findings suggest that this plant can be used as a potential source of new antinociceptive and anti-inflammatory candidates. The activity of methanol extract is most likely mediated through central and peripheral inhibitory mechanisms. This study justified the traditional use of leaf part of this plant. PMID:25629031

  10. Auraptene Acts as an Anti-Inflammatory Agent in the Mouse Brain.

    PubMed

    Okuyama, Satoshi; Morita, Mayu; Kaji, Miki; Amakura, Yoshiaki; Yoshimura, Morio; Shimamoto, Koji; Ookido, Yu; Nakajima, Mitsunari; Furukawa, Yoshiko

    2015-01-01

    The anti-inflammatory activity of auraptene (AUR), a citrus coumarin, in peripheral tissues is well-known, and we previously demonstrated that AUR exerts anti-inflammatory effects in the ischemic brain; the treatment of mice with AUR for eight days immediately after ischemic surgery suppressed demise and neuronal cell death in the hippocampus, possibly through its anti-inflammatory effects in the brain. We suggested that these effects were at least partly mediated by the suppression of inflammatory mediators derived from astrocytes. The present study showed that (1) AUR, as a pretreatment for five days before and another three days after ischemic surgery, suppressed microglial activation, cyclooxygenase (COX)-2 expression in astrocytes, and COX-2 mRNA expression in the hippocampus; (2) AUR suppressed the lipopolysaccharide-induced expression of COX-2 mRNA and the mRNA of pro-inflammatory cytokines in cultured astrocytes; (3) AUR was still detectable in the brain 60 min after its intraperitoneal administration. These results support our previous suggestion that AUR directly exerts anti-inflammatory effects on the brain. PMID:26569206

  11. Expression and contributions of the Kir2.1 inward-rectifier K+ channel to proliferation, migration and chemotaxis of microglia in unstimulated and anti-inflammatory states

    PubMed Central

    Lam, Doris; Schlichter, Lyanne C.

    2015-01-01

    When microglia respond to CNS damage, they can range from pro-inflammatory (classical, M1) to anti-inflammatory, alternative (M2) and acquired deactivation states. It is important to determine how microglial functions are affected by these activation states, and to identify molecules that regulate their behavior. Microglial proliferation and migration are crucial during development and following damage in the adult, and both functions are Ca2+-dependent. In many cell types, the membrane potential and driving force for Ca2+ influx are regulated by inward-rectifier K+ channels, including Kir2.1, which is prevalent in microglia. However, it is not known whether Kir2.1 expression and contributions are altered in anti-inflammatory states. We tested the hypothesis that Kir2.1 contributes to Ca2+ entry, proliferation and migration of rat microglia. Kir2.1 (KCNJ2) transcript expression, current amplitude, and proliferation were comparable in unstimulated microglia and following alternative activation (IL-4 stimulated) and acquired deactivation (IL-10 stimulated). To examine functional roles of Kir2.1 in microglia, we first determined that ML133 was more effective than the commonly used blocker, Ba2+; i.e., ML133 was potent (IC50 = 3.5 ?M) and voltage independent. Both blockers slightly increased proliferation in unstimulated or IL-4 (but not IL-10)-stimulated microglia. Stimulation with IL-4 or IL-10 increased migration and ATP-induced chemotaxis, and blocking Kir2.1 greatly reduced both but ML133 was more effective. In all three activation states, blocking Kir2.1 with ML133 dramatically reduced Ca2+ influx through Ca2+-release-activated Ca2+ (CRAC) channels. Thus, Kir2.1 channel activity is necessary for microglial Ca2+ signaling and migration under resting and anti-inflammatory states but the channel weakly inhibits proliferation. PMID:26029054

  12. Kaposi's Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis.

    PubMed

    Fontana, Judith M; Mygatt, Justin G; Conant, Katelyn L; Parsons, Chris H; Kaleeba, Johnan A R

    2014-01-01

    KSHV is the etiologic agent for Kaposi's sarcoma (KS), a neoplasm that manifests most aggressively as multifocal lesions on parts of human skin with a propensity for inflammatory reactivity. However, mechanisms that control evolution of KS from a benign hyperplasia to the histologically complex cutaneous lesion remain unknown. In this study, we found that KSHV induces proteomic and morphological changes in melanocytes and melanoma-derived cell lines, accompanied by deregulation of the endogenous anti-inflammatory responses anchored by the MC1-R/ ? -MSH signaling axis. We also identified two skin-derived cell lines that displayed differences in ability to support long-term KSHV infection and mapped this dichotomy to differences in (a) NF- ? B activation status, (b) processing and expression of KSHV latency-associated nuclear antigen isoforms putatively associated with the viral lytic cycle, and (c) susceptibility to virus-induced changes in expression of key anti-inflammatory response genes that antagonize NF- ? B, including MC1-R, POMC, TRP-1, and xCT. Viral subversion of molecules that control the balance between latency and lytic replication represents a novel correlate of KSHV pathogenesis and tropism in skin and underscores the potential benefit of harnessing the endogenous anti-inflammatory processes as a therapeutic option for attenuating cutaneous KS and other proinflammatory outcomes of KSHV infection in high-risk individuals. PMID:24701351

  13. Kaposi's Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis

    PubMed Central

    Fontana, Judith M.; Mygatt, Justin G.; Conant, Katelyn L.; Parsons, Chris H.; Kaleeba, Johnan A. R.

    2014-01-01

    KSHV is the etiologic agent for Kaposi's sarcoma (KS), a neoplasm that manifests most aggressively as multifocal lesions on parts of human skin with a propensity for inflammatory reactivity. However, mechanisms that control evolution of KS from a benign hyperplasia to the histologically complex cutaneous lesion remain unknown. In this study, we found that KSHV induces proteomic and morphological changes in melanocytes and melanoma-derived cell lines, accompanied by deregulation of the endogenous anti-inflammatory responses anchored by the MC1-R/?-MSH signaling axis. We also identified two skin-derived cell lines that displayed differences in ability to support long-term KSHV infection and mapped this dichotomy to differences in (a) NF-?B activation status, (b) processing and expression of KSHV latency-associated nuclear antigen isoforms putatively associated with the viral lytic cycle, and (c) susceptibility to virus-induced changes in expression of key anti-inflammatory response genes that antagonize NF-?B, including MC1-R, POMC, TRP-1, and xCT. Viral subversion of molecules that control the balance between latency and lytic replication represents a novel correlate of KSHV pathogenesis and tropism in skin and underscores the potential benefit of harnessing the endogenous anti-inflammatory processes as a therapeutic option for attenuating cutaneous KS and other proinflammatory outcomes of KSHV infection in high-risk individuals. PMID:24701351

  14. Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti-inflammatory cytokines and anabolic growth factors.

    PubMed

    O'Shaughnessey, Krista; Matuska, Andrea; Hoeppner, Jacy; Farr, Jack; Klaassen, Mark; Kaeding, Christopher; Lattermann, Christian; King, William; Woodell-May, Jennifer

    2014-10-01

    The objective of this clinical study was to test if blood from osteoarthritis (OA) patients (n?=?105) could be processed by a device system to form an autologous protein solution (APS) with preferentially increased concentrations of anti-inflammatory cytokines compared to inflammatory cytokines. To address this objective, APS was prepared from patients exhibiting radiographic evidence of knee OA. Patient metrics were collected including: demographic information, medical history, medication records, and Knee Injury and Osteoarthritis Outcome Score (KOOS) surveys. Cytokine and growth factor concentrations in whole blood and APS were measured using enzyme-linked immunosorbent assays. Statistical analyses were used to identify relationships between OA patient metrics and cytokines. The results of this study indicated that anti-inflammatory cytokines were preferentially increased compared to inflammatory cytokines in APS from 98% of OA patients. APS contained high concentrations of anti-inflammatory proteins including 39,000?±?20,000?pg/ml IL-1ra, 21,000?±?5,000?pg/ml sIL-1RII, 2,100?±?570?pg/ml sTNF-RI, and 4,200?±?1,500?pg/ml sTNF-RII. Analysis of the 82 patient metrics indicated that no single patient metric was strongly correlated (R(2) ?>?0.7) with the key cytokine concentrations in APS. Therefore, APS can be prepared from a broad range of OA patients. PMID:24981198

  15. Antioxidant and Anti-Inflammatory Effects of Selected Natural Compounds Contained in a Dietary Supplement on Two Human Immortalized Keratinocyte Lines

    PubMed Central

    Serini, Simona; Mondella, Nadia; Celleno, Leonardo; Lanza, Paola; Calviello, Gabriella

    2014-01-01

    Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, ?-tocopherol, and selenium) contained in a dietary supplement used for the prevention of skin disorders were investigated in vitro. Each component was administered, alone or in combination, to human keratinocytes, and the inhibition of Reactive Oxygen Species production and lipid peroxidation as well as the ability to reduce inflammatory cytokine secretion and to modulate Nuclear Factor-?B pathway was evaluated. The combination exhibited high antioxidant activity and in specific conditions the combination's efficiency was higher than that of the most powerful components administered individually. Moreover, the combination showed remarkable anti-inflammatory properties. It reduced more efficiently than each component the secretion of Monocyte Chemoattractant Protein-1, a crucial cytokine for the development of chronic inflammation in skin, and inhibited Nuclear Factor-?B molecular pathway. Overall, our findings suggest that the combined formulation may have the potential to powerfully inhibit oxidative stress and inflammation at skin level. PMID:25197638

  16. Validation of a RP-HPLC-DAD Method for Chamomile (Matricaria recutita) Preparations and Assessment of the Marker, Apigenin-7-glucoside, Safety and Anti-Inflammatory Effect

    PubMed Central

    Miguel, Felipe Galeti; Cavalheiro, Amanda Henriques; Spinola, Nathália Favaretto; Ribeiro, Diego Luis; Barcelos, Gustavo Rafael Mazzaron; Antunes, Lusânia Maria Greggi; Hori, Juliana Issa; Marquele-Oliveira, Franciane; Rocha, Bruno Alves; Berretta, Andresa Aparecida

    2015-01-01

    Chamomile is a medicinal plant, which presents several biological effects, especially the anti-inflammatory effect. One of the compounds related to this effect is apigenin, a flavonoid that is mostly found in its glycosylated form, apigenin-7-glucoside (APG), in natural sources. However, the affectivity and safety of this glycoside have not been well explored for topical application. In this context, the aim of this work was to develop and validate a reversed-phase high-performance liquid chromatography (RP-HPLC-DAD) method to quantify APG in chamomile preparations. Additionally, the safety and the anti-inflammatory potential of this flavonoid were verified. The RP-HPLC-DAD method was developed and validated with linearity at 24.0–36.0??g/mL range (r = 0.9994). Intra- and interday precision (RSD) were 0.27–2.66% and accuracy was 98.27–101.21%. The validated method was applied in the analysis of chamomile flower heads, glycolic extract, and Kamillen cream, supporting the method application in the quality control of chamomile preparations. Furthermore, the APG safety was assessed by MTT cytotoxicity assay and mutagenic protocols and the anti-inflammatory activity was confirmed by a diminished TNF-? production showed by mice macrophages treated with APG following LPS treatment. PMID:26421053

  17. The effect of adsorbant and anti-inflammatory drugs on secretion in ligated segments of pig intestine infected with Escherichia coli.

    PubMed

    Gyles, C L; Zigler, M

    1978-07-01

    Four adsorbant drug preparations, Kaopectate, colloidal Attapulgite, noncolloidal Attapulgite and Pepto-bismol were investigated for their effects on fluid accumulation in ligated segments of pig intestine inoculated with enteropathogenic Escherichia coli. Two anti-inflammatory drugs. aspirin and methylprednisolone, and two antibiotics, lincomycin and polymyxin B, were also tested. All the drugs except the two anti-inflammatory products were given by injection into the lumen of the intestine. Aspirin was given orally and methylprednisolone was given intramuscularly. The antibiotics were tested at levels at which they had no significant antibacterial effect in in vitro tests. The adsorbant drugs colloidal Attapulgite and Pepto-bismol were shown to be effective in reducing fluid accumulation in ligated segments of pig intestine infected with enteropathogenic E. coli. In the case of Peptobismol this effect was associated with an antibacterial effect as well as an antitoxic effect, probably due to its adsorbant properties. It is possible that an aspirin-like effect in the gut due to the active ingredient bismuth subsalicylate may have contributed to the effectiveness of Pepto-bismol. Colloidal Attapulgite was demonstrated to have an antitoxic effect but did not have an antibacterial effect. In high doses, the anti-inflammatory drugs acetylsalicylic acid and methylprednisolone were marginally effective in reduction of fluid accumulation in the same test system. Lincomycin was shown to reduce intestinal fluid secretion, whereas polymyxin B had no effect. PMID:356940

  18. Antioxidant and Anti-Inflammatory Phenolic Glycosides from Clematis tashiroi.

    PubMed

    Zhang, Li-Jie; Huang, Hung-Tse; Huang, Shih-Yen; Lin, Zhi-Hu; Shen, Chien-Chang; Tsai, Wei-Jern; Kuo, Yao-Haur

    2015-07-24

    From the 95% EtOH extract of dried aerial parts of Clematis tashiroi, eight new and four known phenolic (caffeic acid, coumaric acid, ferrulic acid) glycosides were isolated and characterized. The structures of the new isolates (clematisides A-H) were elucidated by spectroscopic data interpretation as trans-4-O-(6-O-trans-caffeoyl-?-D- glucopyranosyl)-9-O-?-D-glucopyranosyl caffeic acid (1), trans-4-O-(6-O-trans-feruloyl-?-D-glucopyranosyll)-9-O-?-D-glucopyranosyl caffeic acid (2), trans-4-O-(6-O-trans-p-coumaroyl-?-D-glucopyranosyl)-9-O-?-D-glucopyranosyl caffeic acid (3), trans-4-O-(6-O-trans-caffeoyl-?-D-glucopyranosyl)-9-O-?-D-glucopyranosyl p-coumaric acid (4), trans-3-O-(6-O-trans-caffeoyl-?-D-glucopyranosyl)-9-O-?-D-glucopyranosyl caffeic acid (5), trans-3-O-(6-O-trans-p-coumaroyl-?-D-glucopyranosyl)-9-O-?-D-glucopyranosyl caffeic acid (6), 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-(6-O-trans-caffeoyl)-?-D-glucopyranoside (7), and 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-{6-O-[4-O-(6-O-trans-caffeoyl)-?-D-glucopyranosyl]-trans-caffeoyl}-?-D-glucopyranoside (8), respectively. In a DPPH radical-scavenging test, compounds 1, 7, and 8 showed more potent antioxidant activity than that of the positive control, vitamin E. In addition, compound 7 also showed inhibitory activity in an antinitric oxide release assay. PMID:26143931

  19. Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice

    PubMed Central

    Ma, Tao; Liaset, Bjørn; Hao, Qin; Petersen, Rasmus Koefoed; Fjære, Even; Ngo, Ha Thi; Lillefosse, Haldis Haukås; Ringholm, Stine; Sonne, Si Brask; Treebak, Jonas Thue; Pilegaard, Henriette; Frøyland, Livar; Kristiansen, Karsten; Madsen, Lise

    2011-01-01

    Background Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance. Methodology/Principal Findings We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein?sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state. Conclusions/Significance The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice. PMID:21738749

  20. An emphasis on molecular mechanisms of anti-inflammatory effects and glucocorticoid resistance.

    PubMed

    Ingawale, Deepa K; Mandlik, Satish K; Patel, Snehal S

    2015-03-01

    Glucocorticoids (GC) are universally accepted agents for the treatment of anti-inflammatory and immunosuppressive disorders. They are used in the treatment of rheumatic diseases and various inflammatory diseases such as allergy, asthma and sepsis. They bind with GC receptor (GR) and form GC-GR complex with the receptor and exert their actions. On activation the GC-GR complex up-regulates the expression of nucleus anti-inflammatory proteins called as transactivation and down-regulates the expression of cytoplasmic pro-inflammatory proteins called as transrepression. It has been observed that transactivation mechanisms are notorious for side effects and transrepressive mechanisms are identified for beneficial anti-inflammatory effects of GC therapy. GC hampers the function of numerous inflammatory mediators such as cytokines, chemokines, adhesion molecules, arachidonic acid metabolites, release of platelet-activating factor (PAF), inflammatory peptides and enzyme modulation involved in the process of inflammation. The GC resistance is a serious therapeutic problem and limits the therapeutic response of GC in chronic inflammatory patients. It has been observed that the GC resistance can be attributed to cellular microenvironment changes, as a consequence of chronic inflammation. Various other factors responsible for resistance have been identified, including alterations in both GR-dependent and GR-independent signaling pathways of cytokine action, hypoxia, oxidative stress, allergen exposure and serum-derived factors. The present review enumerates various aspects of inflammation such as use of GC for treatment of inflammation and its mechanism of action. Molecular mechanisms of anti-inflammatory action of GC and GC resistance, alternative anti-inflammatory treatments and new strategy for reversing the GC resistance have also been discussed. PMID:25503867

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

    PubMed

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

    2014-03-01

    The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 ?g/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors. PMID:24318481

  2. Indirect role of beta2-adrenergic receptors in the mechanism of anti-inflammatory action of NSAIDS.

    PubMed

    Suleyman, H; Halici, Z; Cadirci, E; Hacimuftuoglu, A; Bilen, H

    2008-12-01

    In this study we investigated both intact and adrenalectomized rats to determine whether or not the anti-inflammatory effects of indomethacin, diclofenac sodium, ibuprofen, nimesulide, tenoxicam and aspirin (IDINTA) are related to adrenal gland hormones in carrageenan-induced inflammation model of rats. Also, we investigated the anti-inflammatory action mechanism of hormones (adrenalin, cortisol) which perform a role in the anti-inflammatory effect of IDINTAon the adrenergic receptors. he results show that IDINTA produces significant anti-inflammatory effects in intact rats (ID(50): 9.82, 10.81, 95.21, 75.23, 8.21 and 61.84 mg/kg), but insignificant effects in adrenalectomized rats (ID(50): 152.97, 188.17, 1275.0, 433.67, 188.16 and 1028.17 mg/kg). In addition, adrenalin and prednisolone caused anti-inflammatory effect rates of 78.3% and 95.7% respectively in adrenalectomized rats. The anti-inflammatory effects of adrenalin and prednisolone did not change when prazosin (alpha(1)-receptor blocker), yohimbine (alpha(2)a2-receptor blocker) and phenoxybenzamine (alpha(2)- and alpha(2)-receptor blocker) were given to rat groups; however, in adrenalectomized rats administered with propranolol (a non-selective blocker of beta(1) and beta(2)-receptors) the anti-inflammatory effect of adrenalin was lost, and that of prednisolone decreased to 36.2%. It was also found that metoprolol (a selective blocker of beta(1)-receptors) did not alter the anti-inflammatory effects of the drugs. As a result, it was shown that anti-inflammatory effects of IDINTA are related to adrenalin and cortisol (corticosterone in rats). It was also determined for the first time that adrenalin (totally) and prednisolone (partially) triggered anti-inflammatory effects via the beta(2)-receptors but not via the alpha(1), alpha(2) and beta(1)-receptors. PMID:19212002

  3. Nitroxide derivatives of non-steroidal anti-inflammatory drugs exert anti-inflammatory and superoxide dismutase scavenging properties in A459 cells

    PubMed Central

    Flores-Santana, Wilmarie; Moody, Terry; Chen, Weibin; Gorczynski, Michael J; Shoman, Mai E; Velázquez, Carlos; Thetford, Angela; Mitchell, James B; Cherukuri, Murali K; King, S Bruce; Wink, David A

    2012-01-01

    BACKGROUND AND PURPOSE Inflammation and reactive oxygen species are associated with the promotion of various cancers. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in cancer prevention treatments has been promising in numerous cancers. We report the evaluation of NSAIDs chemically modified by the addition of a redox-active nitroxide group. TEMPO-aspirin (TEMPO-ASA) and TEMPO-indomethacin (TEMPO-IND) were synthesized and evaluated in the lung cancer cell line A549. EXPERIMENTAL APPROACHES We evaluated physico-chemical properties of TEMPO-ASA and TEMPO-IND by electron paramagnetic resonance and cyclic voltammetry. Superoxide dismutase-like properties was assayed by measuring cytochrome c reduction and anti-inflammatory effects were assayed by measuring production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). MTT proliferation assay and clonogenic assay were evaluated in the A549 lung carcinoma cell line. Maximum tolerated doses (MTD) and acute ulcerogenic index were also evaluated in in vivo. KEY RESULTS MTD were: TEMPO (140 mg·kg?1), ASA (100 mg·kg?1), indomethacin (5 mg·kg?1), TEMPO-ASA (100 mg·kg?1) and TEMPO-IND (40 mg·kg?1). While TEMPO-ASA was as well tolerated as ASA, TEMPO-IND showed an eightfold improvement over indomethacin. TEMPO-IND showed markedly less gastric toxicity than the parent NSAID. Both TEMPO-ASA and TEMPO-IND inhibited production of PGE2 and LTB4 in A549 cells with maximum effects at 100 µg·mL?1 or 10 µg·mL?1 respectively. CONCLUSIONS AND IMPLICATIONS The nitroxide-NSAIDs retained superoxide scavenging capacity of the parent nitroxide and anti-inflammatory effects, inhibiting cyclooxygenase and 5-lipoxygenase enzymes. These redox-modified NSAIDs might be potential drug candidates, as they exhibit the pharmacological properties of the parent NSAID with antioxidant activity decreasing NSAID-associated toxicity. PMID:21658022

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

    PubMed

    Engelhardt, G; Homma, D; Schlegel, K; Utzmann, R; Schnitzler, C

    1995-10-01

    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. With respect to the total effect of a single oral dose, the anti-exudative effect of meloxicam on carrageenan-induced oedema in the rat exceeded that of all the NSAIDs included in the comparison. Additionally, meloxicam showed the greatest potency of all the compounds examined with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in exudate volume and also inhibition of leucocyte migration. Meloxicam showed a strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests, which are used to identify weak central analgesic effects. Unlike dipyrone and like indomethacin, meloxicam had no effect in a model of visceral distention pain. In common with other NSAIDs, meloxicam had no influence on the body temperature of normothermic rats in the anti-inflammatory dose range, but did reduce yeast-induced fever in the rat in a dose-dependent manner. Like piroxicam, meloxicam had a uricosuric effect on rats treated with oxonic acid. Low-dose meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the guinea-pig, but had no effect on acetylcholine-induced bronchospasm. Piroxicam had greater ulcerogenic effects in the rat stomach than meloxicam. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of piroxicam, indomethacin, diclofenac and naproxen. PMID:8564518

  5. Cell selectivity and anti-inflammatory activity of a Leu/Lys-rich alpha-helical model antimicrobial peptide and its diastereomeric peptides.

    PubMed

    Wang, Peng; Nan, Yong Hai; Yang, Sung-Tae; Kang, Shin Won; Kim, Yangmee; Park, Il-Seon; Hahm, Kyung-Soo; Shin, Song Yub

    2010-07-01

    To investigate the effect of the number and distribution of d-amino acids introduced into non-cell-selective alpha-helical antimicrobial peptides on the cell selectivity, protease stability and anti-inflammatory activity, we synthesized an 18-meric Leu/Lys-rich alpha-helical model peptide (K(9)L(8)W) and d-amino acid-containing diastereomeric peptides. Increasing in cell selectivity of the peptides was increased in parallel with increasing in the number of d-amino acids introduced. Despite having the same number of d-amino acids, D(9)-K(9)L(8)W-1 had better cell selectivity than D(9)-K(9)L(8)W-2, indicating that a dispersed distribution of d-amino acids in diastereomeric peptides is more effective for cell selectivity than their segregated distribution. D(3)-K(9)L(8)W-2, D(6)-K(9)L(8)W, D(9)-K(9)L(8)W-1 and D(9)-K(9)L(8)W-2 showed complete resistance to tryptic digestion. Furthermore, K(9)L(8)W and all of its diastereomeric peptides significantly inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) mRNA expression and tumor necrosis factor-alpha (TNF-alpha) release in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells at a lower concentration than bactericidal concentration. The order of anti-inflammatory activity for the peptides was K(9)L(8)W approximately D(3)-K(9)L(8)W-1 approximately D(3)-K(9)L(8)W-2 approximately D(6)-K(9)L(8)W approximately D(9)-K(9)L(8)W-2>D(4)-K(9)L(8)W>D(9)-K(9)L(8)W-1. Increasing in hydrophobicity or alpha-helicity of the peptides was more closely correlated with increasing in hemolytic activity and anti-inflammatory activity than antimicrobial and LPS-disaggregation activities. Collectively, we successfully developed several d-amino acid-containing antimicrobial peptides (D(4)-K(9)L(8)W, D(6)-K(9)L(8)W and D(9)-K(9)L(8)W-1) with good cell selectivity, protease stability and potent anti-inflammatory activity. These antimicrobial peptides could serve as templates for the development of peptide antibiotics for the treatment of sepsis, as well as microbial infection. PMID:20363271

  6. Chemical Composition and Anti-Inflammatory, Cytotoxic and Antioxidant Activities of Essential Oil from Leaves of Mentha piperita Grown in China

    PubMed Central

    Wang, Jing; Zhou, Lianming; Yang, Peiming

    2014-01-01

    The chemical composition, anti-inflammatory, cytotoxic and antioxidant activities of essential oil from leaves of Mentha piperita (MEO) grown in China were investigated. Using GC-MS analysis, the chemical composition of MEO was characterized, showing that it was mainly composed of menthol, menthone and menthy acetate. MEO exhibited potent anti-inflammatory activities in a croton oil-induced mouse ear edema model. It could also effectively inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The cytotoxic effect was assessed against four human cancer cells. MEO was found to be significantly active against human lung carcinoma SPC-A1, human leukemia K562 and human gastric cancer SGC-7901 cells, with an IC50 value of 10.89, 16.16 and 38.76 µg/ml, respectively. In addition, MEO had moderate antioxidant activity. The results of this study may provide an experimental basis for further systematic research, rational development and clinical utilization of peppermint resources. PMID:25493616

  7. Anti-Inflammatory Properties of the Medicinal Mushroom Cordyceps militaris Might Be Related to Its Linear (1?3)-?-D-Glucan

    PubMed Central

    Smiderle, Fhernanda R.; Baggio, Cristiane H.; Borato, Débora G.; Santana-Filho, Arquimedes P.; Sassaki, Guilherme L.; Iacomini, Marcello; Van Griensven, Leo J. L. D.

    2014-01-01

    The Ascomycete Cordyceps militaris, an entomopathogenic fungus, is one of the most important traditional Chinese medicines. Studies related to its pharmacological properties suggest that this mushroom can exert interesting biological activities. Aqueous (CW and HW) and alkaline (K5) extracts containing polysaccharides were prepared from this mushroom, and a ?-D-glucan was purified. This polymer was analysed by GC-MS and NMR spectrometry, showing a linear chain composed of ?-D-Glcp (1?3)-linked. The six main signals in the 13C-NMR spectrum were assigned by comparison to reported data. The aqueous (CW, HW) extracts stimulated the expression of IL-1?, TNF-?, and COX-2 by THP-1 macrophages, while the alkaline (K5) extract did not show any effect. However, when the extracts were added to the cells in the presence of LPS, K5 showed the highest inhibition of the pro-inflammatory genes expression. This inhibitory effect was also observed for the purified ?-(1?3)-D-glucan, that seems to be the most potent anti-inflammatory compound present in the polysaccharide extracts of C. militaris. In vivo, ?-(1?3)-D-glucan also inhibited significantly the inflammatory phase of formalin-induced nociceptive response, and, in addition, it reduced the migration of total leukocytes but not the neutrophils induced by LPS. In conclusion, this study clearly demonstrates the anti-inflammatory effect of ?-(1?3)-D-glucan. PMID:25330371

  8. Chemical Composition and Anti-Inflammatory, Cytotoxic and Antioxidant Activities of Essential Oil from Leaves of Mentha piperita Grown in China.

    PubMed

    Sun, Zhenliang; Wang, Huiyan; Wang, Jing; Zhou, Lianming; Yang, Peiming

    2014-01-01

    The chemical composition, anti-inflammatory, cytotoxic and antioxidant activities of essential oil from leaves of Mentha piperita (MEO) grown in China were investigated. Using GC-MS analysis, the chemical composition of MEO was characterized, showing that it was mainly composed of menthol, menthone and menthy acetate. MEO exhibited potent anti-inflammatory activities in a croton oil-induced mouse ear edema model. It could also effectively inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The cytotoxic effect was assessed against four human cancer cells. MEO was found to be significantly active against human lung carcinoma SPC-A1, human leukemia K562 and human gastric cancer SGC-7901 cells, with an IC50 value of 10.89, 16.16 and 38.76 µg/ml, respectively. In addition, MEO had moderate antioxidant activity. The results of this study may provide an experimental basis for further systematic research, rational development and clinical utilization of peppermint resources. PMID:25493616

  9. New insights into the use of currently available non-steroidal anti-inflammatory drugs

    PubMed Central

    Brune, Kay; Patrignani, Paola

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively) associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination), and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (~80% inhibition of COX-2) while minimizing COX-1 inhibition and associated side effects, such as gastrointestinal toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half-lives can additionally be dosed to provide near-constant analgesia while minimizing plasma concentrations to permit recovery of COX-mediated prostaglandin production in the vascular wall and other organs. Each patient’s clinical background, including gastrointestinal and cardiovascular risk factors, should be taken into account when selecting appropriate NSAIDs. New methods are emerging to assist clinicians in the selection of appropriate NSAIDs and their doses/schedules, such as biomarkers that may predict the response to NSAID treatment in individual patients. PMID:25759598

  10. Diabetes Alters Activation and Repression of Pro- and Anti-Inflammatory Signaling Pathways in the Vasculature

    PubMed Central

    Di Marco, Elyse; Gray, Stephen P.; Jandeleit-Dahm, Karin

    2013-01-01

    A central mechanism driving vascular disease in diabetes is immune cell-mediated inflammation. In diabetes, enhanced oxidation and glycation of macromolecules, such as lipoproteins, insults the endothelium, and activates both innate and adaptive arms of the immune system by generating new antigens for presentation to adaptive immune cells. Chronic inflammation of the endothelium in diabetes leads to continuous infiltration and accumulation of leukocytes at sites of endothelial cell injury. We will describe the central role of the macrophage as a source of signaling molecules and damaging by-products which activate infiltrating lymphocytes in the tissue and contribute to the pro-oxidant and pro-inflammatory microenvironment. An important aspect to be considered is the diabetes-associated defects in the immune system, such as fewer or dysfunctional athero-protective leukocyte subsets in the diabetic lesion compared to non-diabetic lesions. This review will discuss the key pro-inflammatory signaling pathways responsible for leukocyte recruitment and activation in the injured vessel, with particular focus on pro- and anti-inflammatory pathways aberrantly activated or repressed in diabetes. We aim to describe the interaction between advanced glycation end products and their principle receptor RAGE, angiotensin II, and the Ang II type 1 receptor, in addition to reactive oxygen species (ROS) production by NADPH-oxidase enzymes that are relevant to vascular and immune cell function in the context of diabetic vasculopathy. Furthermore, we will touch on recent advances in epigenetic medicine that have revealed high glucose-mediated changes in the transcription of genes with known pro-inflammatory downstream targets. Finally, novel anti-atherosclerosis strategies that target the vascular immune interface will be explored; such as vaccination against modified low-density lipoprotein and pharmacological inhibition of ROS-producing enzymes. PMID:23761786

  11. Antinociceptive and Anti-Inflammatory Activity from Algae of the Genus Caulerpa

    PubMed Central

    da Matta, Carolina Babosa Brito; de Souza, Éverton Tenório; de Queiroz, Aline Cavalcanti; de Lira, Daysianne Pereira; de Araújo, Morgana Vital; Cavalcante-Silva, Luiz Henrique Agra; de Miranda, George Emmanuel C.; de Araújo-Júnior, João Xavier; Barbosa-Filho, José Maria; de Oliveira Santos, Bárbara Viviana; Alexandre-Moreira, Magna Suzana

    2011-01-01

    Marine natural products have been the focus of discovery for new products of chemical and pharmacological interest. The aim of this study was to evaluate the antinociceptive activity of the methanolic (ME), acetate (AE), hexanic (HE) and chloroform (CE) extracts obtained from Caulerpa mexicana, and ME, CE and HE obtained from Caulerpa sertularioides. These marine algae are found all over the world, mainly in tropical regions. Models such as the writhing test, the hot plate test and formalin-induced nociception test were used to evaluate antinociceptive activity in laboratory mice. In the writhing test, all the extracts were administered orally at a concentration of 100 mg/kg, and induced high peripheral antinociceptive activity, with a reduction in the nociception induced by acetic acid above 65%. In the hot plate test, treatment with extracts from C. sertularioides (100 mg/kg, p.o.) did not significantly increase the latency of response, although the ME, AE and HE from C. mexicana showed activity in this model. This result suggests that these extracts exhibit antinociceptive activity. In the formalin test, it was observed that ME, AE and HE obtained from C. mexicana reduced the effects of formalin in both phases. On the other hand only CE from C. sertularioides induced significant inhibition of the nociceptive response in the first phase. To better assess the potential anti-inflammatory activity of the extracts, the carrageenan-induced peritonitis test was used to test Caulerpa spp. extracts on cell migration into the peritoneal cavity. In this assay, all extracts evaluated were able to significantly inhibit leukocyte migration into the peritoneal cavity in comparison with carrageenan. These data demonstrate that extracts from Caulerpa species elicit pronounced antinociceptive and anti-inflamatory activity against several nociception models. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in the Caulerpa species. PMID:21556161

  12. Uncovering novel 3-hydroxy-4-pyridinone metal ion complexes with potential anti-inflammatory properties.

    PubMed

    Chisté, Renan Campos; Ribeiro, Daniela; Freitas, Marisa; Leite, Andreia; Moniz, Tânia; Rangel, Maria; Fernandes, Eduarda

    2016-02-01

    Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) type, with one (Hmpp) or two methyl groups (Hdmpp), have been reported to possess biomedical, chemical and analytical applications. In this first screening study aiming to uncover new promising agents to mitigate the oxidative damage highly present in several metabolic disorders, such as diabetes mellitus, we assessed the potential of twelve 3,4-HPO metal ion complexes to modulate oxidative burst in human neutrophils. Metal ion 3,4-HPO complexes of Ni, Fe, V, Co, Cu and Zn were synthesized and tested up to 15?M. Among all the compounds, [Cu(mpp)2] and [Cu(dmpp)2] exhibited the highest scavenging capacity against superoxide radical (O2(-)) (IC50=0.36±0.07 and 0.30±0.06?M, respectively) and against hypochlorous acid (HOCl) (IC50=0.6±0.3 and 0.4±0.1?M, respectively). In the particular case of O2(-), [Fe(mpp)3] and [Fe(dmpp)3] (both at 15?M) presented 35% and 22% of inhibition, respectively, while all the other compounds were neither able to scavenge O2(-) nor stimulate its production. Regarding the scavenging capacity against hydrogen peroxide (H2O2), all the compounds showed low efficiency (from 6-39%). Finally, with exception of [VO(mpp)2] and [VO(dmpp)2], all compounds exhibited scavenging activity against HOCl (39-81%) and the most efficient compounds were Cu(II) and Zn(II) complexes. Thus, these preliminary results uncover promising new metal ion complexes, inhibitors of neutrophil's oxidative burst, with potential anti-inflammatory properties, which may be seen as an useful strategy for further studies in the treatment of a number of diseases where oxidative damage is a serious issue. PMID:26606288

  13. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects

    PubMed Central

    Heier, Christopher R; Damsker, Jesse M; Yu, Qing; Dillingham, Blythe C; Huynh, Tony; Van der Meulen, Jack H; Sali, Arpana; Miller, Brittany K; Phadke, Aditi; Scheffer, Luana; Quinn, James; Tatem, Kathleen; Jordan, Sarah; Dadgar, Sherry; Rodriguez, Olga C; Albanese, Chris; Calhoun, Michael; Gordish-Dressman, Heather; Jaiswal, Jyoti K; Connor, Edward M; McCall, John M; Hoffman, Eric P; Reeves, Erica K M; Nagaraju, Kanneboyina

    2013-01-01

    Absence of dystrophin makes skeletal muscle more susceptible to injury, resulting in breaches of the plasma membrane and chronic inflammation in Duchenne muscular dystrophy (DMD). Current management by glucocorticoids has unclear molecular benefits and harsh side effects. It is uncertain whether therapies that avoid hormonal stunting of growth and development, and/or immunosuppression, would be more or less beneficial. Here, we discover an oral drug with mechanisms that provide efficacy through anti-inflammatory signaling and membrane-stabilizing pathways, independent of hormonal or immunosuppressive effects. We find VBP15 protects and promotes efficient repair of skeletal muscle cells upon laser injury, in opposition to prednisolone. Potent inhibition of NF-?B is mediated through protein interactions of the glucocorticoid receptor, however VBP15 shows significantly reduced hormonal receptor transcriptional activity. The translation of these drug mechanisms into DMD model mice improves muscle strength, live-imaging and pathology through both preventive and post-onset intervention regimens. These data demonstrate successful improvement of dystrophy independent of hormonal, growth, or immunosuppressive effects, indicating VBP15 merits clinical investigation for DMD and would benefit other chronic inflammatory diseases. PMID:24014378

  14. Anti-Inflammatory Effects of Rebamipide Eyedrop Administration on Ocular Lesions in a Murine Model of Primary Sjögren's Syndrome

    PubMed Central

    Arakaki, Rieko; Eguchi, Hiroshi; Yamada, Akiko; Kudo, Yasusei; Iwasa, Akihiko; Enkhmaa, Tserennadmid; Hotta, Fumika; Mitamura-Aizawa, Sayaka; Mitamura, Yoshinori; Hayashi, Yoshio; Ishimaru, Naozumi

    2014-01-01

    Background Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown. Methods and Finding Reb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment. Conclusion Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces. PMID:24866156

  15. Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation.

    PubMed

    Flacher, Vincent; Neuberg, Patrick; Point, Floriane; Daubeuf, François; Muller, Quentin; Sigwalt, David; Fauny, Jean-Daniel; Remy, Jean-Serge; Frossard, Nelly; Wagner, Alain; Mueller, Christopher G; Schaeffer, Evelyne

    2015-12-18

    Inhibition of excessive Toll-like receptor 4 (TLR4) signaling is a therapeutic approach pursued for many inflammatory diseases. We report that Mannoside Glycolipid Conjugates (MGCs) selectively blocked TLR4-mediated activation of human monocytes and monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS). They potently suppressed pro-inflammatory cytokine secretion and maturation of DCs exposed to LPS, leading to impaired T cell stimulation. MGCs did not interfere with LPS and could act in a delayed manner, hours after LPS stimulation. Their inhibitory action required both the sugar heads and the lipid chain, although the nature of the sugar and the structure of the lipid tail could be modified. They blocked early signaling events at the cell membrane, enhanced internalization of CD14 receptors, and prevented colocalization of CD14 and TLR4, thereby abolishing NF-?B nuclear translocation. When the best lead conjugate was tested in a mouse model of LPS-induced acute lung inflammation, it displayed an anti-inflammatory action by suppressing the recruitment of neutrophils. Thus, MGCs could serve as promising leads for the development of selective TLR4 antagonistic agents for inflammatory diseases. PMID:26389521

  16. LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPAR? ligand synthesis

    PubMed Central

    Lefèvre, Lise; Authier, Hélène; Stein, Sokrates; Majorel, Clarisse; Couderc, Bettina; Dardenne, Christophe; Eddine, Mohamad Ala; Meunier, Etienne; Bernad, José; Valentin, Alexis; Pipy, Bernard; Schoonjans, Kristina; Coste, Agnès

    2015-01-01

    Liver receptor homologue-1 (LRH-1) is a nuclear receptor involved in the repression of inflammatory processes in the hepatointestinal tract. Here we report that LRH-1 is expressed in macrophages and induced by the Th2 cytokine IL-13 via a mechanism involving STAT6. We show that loss-of-function of LRH-1 in macrophages impedes IL-13-induced macrophage polarization due to impaired generation of 15-HETE PPAR? ligands. The incapacity to generate 15-HETE metabolites is at least partially caused by the compromised regulation of CYP1A1 and CYP1B1. Mice with LRH-1-deficient macrophages are, furthermore, highly susceptible to gastrointestinal and systemic Candida albicans infection. Altogether, these results identify LRH-1 as a critical component of the anti-inflammatory and fungicidal response of alternatively activated macrophages that acts upstream from the IL-13-induced 15-HETE/PPAR? axis. PMID:25873311

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

    PubMed

    Younger, Jarred; Parkitny, Luke; McLain, David

    2014-04-01

    Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders. PMID:24526250

  18. The action of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the isolated perfused rat liver.

    PubMed

    Lopez, C H; Bracht, A; Yamamoto, N S; Ishii-Iwamoto, E L; Sampaio, E; Kelmer-Bracht, A M

    1999-06-01

    The influence of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the liver was investigated. The experimental system was the isolated perfused rat liver. Perfusion was accomplished in an open, nonrecirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of oxygen and carbon dioxide (95:5) by means of a membrane oxygenator and heated to 37 degrees C. Sulfate transport (equilibrium exchange) was measured by employing the multiple-indicator dilution technique with simultaneous injection (impulse input) of [35S]sulfate. [3H]sucrose (indicator for the distribution of the sinusoidal transit times), and [3H]water (indicator for the total aqueous space). Analysis was accomplished by means of a space-distributed variable transit time model. Flufenamic acid and other anti-inflammatories inhibited sulfate transport in the liver. For a concentration of 100 microM, the following decreasing series of potency could be established: flufenamic acid (53.4 +/- 2.9%) > niflumic acid (41.1 +/- 1.4%) > mefenamic acid (35.6 +/- 3.3%) > piroxicam (16.6 +/- 1.9%) > naproxen (13.5 +/- 8.4)%) nimesulide (11.6 +/- 5.8%). Inhibition of sulfate transport by flufenamic acid was clearly concentration dependent; 250 microM flufenamic acid produced more than 95% inhibition. Flufenamic acid in the range between 50 and 250 microM did not affect the mean transit times of tritiated water (t water) and [3H]sucrose (t suc), the same applying to all other anti-inflammatory agents (100 microM) tested in this work. This means that these agents do not affect vascular and cellular spaces, even when present at high concentrations. The ratio of the intra- to extracellular sulfate concentrations ([C]i/[C]e), generally between 0.4 and 0.5 under control conditions, was affected only by 250 microM flufenamic acid and 100 microM niflumic acid. In the first case, this phenomenon is possibly due to the high degree of transport inhibition (more than 95%), which does not allow a uniform tracer distribution over the whole cellular space during a single passage through the liver. The degree of inhibition of sulfate transport by 100 microM flufenamic acid was a function of the concentration of nontracer sulfate. With sulfate in the range between 1.2 and 25 mM, the inhibition degree increased linearly with the concentration. In the presence of flufenamic acid, the saturation curve of equilibrium exchange showed a substrate inhibition-like phenomenon, which was absent in the control curve. As inhibitors of sulfate transport in hepatocytes, flufenamic and niflumic acids are less active than in erythrocytes by a factor of 10(2). This observation is most probably indicative of structural differences between the hepatic sulfate carrier and the anion carrier of erythrocytes. It is unlikely that the action of flufenamic acid and its analogs on sulfate transport is a consequence of energy metabolism inhibition. Nimesulide is as active as flufenamic or niflumic acid in inhibiting energy metabolism but considerably less efficient as an inhibitor of sulfate transport. Our results as well as literature data reveal that the interactions of the nonsteroidal anti-inflammatories with the liver membranes and intracellular structures are ample and complex. Even at high concentrations, however, these interactions are not so intense as to change the vascular and cellular spaces. PMID:10401997

  19. Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

    PubMed Central

    K?ikavová, Radka; Hošek, Jan; Van?o, Ján; Hutyra, Jakub; Dvo?ák, Zden?k; Trávní?ek, Zden?k

    2014-01-01

    A series of gold(I) complexes involving triphenylphosphine (PPh3) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HLn) of the general composition [Au(Ln)(PPh3)] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4–6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4–6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC50 ? 1–30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-? (TNF-?) and interleukin-1? (IL-1?), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study. PMID:25226034

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

    PubMed Central

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

    2013-01-01

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

  1. Variable transcription of pro- and anti-inflammatory cytokines in phocine lymphocytes following canine distemper virus infection.

    PubMed

    Seibel, H; Siebert, U; Rosenberger, T; Baumgärtner, W

    2014-10-15

    Canine distemper virus (CDV) is a highly contagious viral pathogen. Domesticated dogs are the main reservoir of CDV. Although phocine distemper virus was responsible for the recent epidemics in seals in the North and Baltic Seas, most devastating epidemics in seals were also caused by CDV. To further study the pathogenesis of CDV infection in seals, it was the aim of the present study to investigate the mechanisms of CDV induced immunosuppression in seals by analyzing the gene transcription of different pro- and anti-inflammatory cytokines in Concanavalin A (Con A) stimulated and non-stimulated phocine lymphocytes in vitro following infection with the CDV Onderstepoort (CDV-OND) strain. Phocine lymphocytes were isolated via density gradient centrifugation. The addition of 1 ?g/ml Con A and virus was either performed simultaneously or lymphocytes were stimulated for 48 h with Con A prior to virus infection. Gene transcription of interleukin (IL)-6, IL-12 and tumor necrosis factor alpha (TNF?) as pro-inflammatory cytokines and IL-4, IL-10 and transforming growth factor beta (TGF?) as anti-inflammatory cytokines were determined by using RT-qPCR. CDV-OND infection caused an initial increase of pro-inflammatory phocine cytokines mRNA 24h after infection, followed by a decrease in gene transcription after 48 h. A strong increase in the transcription of IL-4 and TGF? was detected after 48 h when virus and mitogen were added simultaneously. An increased IL-10 production occurred only when stimulation and infection were performed simultaneously. Furthermore, an inhibition of IL-12 on IL-4 was noticed in phocine lymphocytes which were stimulated for 48 h prior to infection. In summary, the duration of the stimulation or the lymphocytes seem to have an important influence on the cytokine transcription and indicates that the outcome of CDV infection is dependent on various factors that might sensitize lymphocytes or make them more susceptible or reactive to CDV infection. PMID:25190509

  2. Anti-inflammatory and analgesic potential of a novel steroidal derivative from Bryophyllum pinnatum.

    PubMed

    Afzal, Muhammad; Gupta, Gaurav; Kazmi, Imran; Rahman, Mahfoozur; Afzal, Obaid; Alam, Jahangir; Hakeem, Khalidur Rahman; Pravez, Mohammad; Gupta, Ritu; Anwar, Firoz

    2012-07-01

    A new steroidal derivative, urs Stigmast-4, 20 (21), 23-trien-3-one and other four compounds were isolated from the leaves of Bryophyllum pinnatum. The structure of this new steroid was elucidated and established by standard spectroscopic methods. Carrageenan induced paw edema model was used for anti-inflammatory and acetic acid induced model used for analgesic activity. This new steroidal compound was found to be active in reducing inflammation (% inhibition 87.29 and 84.45 respectively) when compared with diclofenac. Further, it showed 75.72% protection in analgesic activity in acetic acid induced writhing test in mice. In conclusion the % inhibition against carrageenan induced rat paw edema and % protection against acetic acid induced writhings showed by new compound revealed that the anti-inflammatory and analgesic activity of aqueous extract B. pinnatum are mainly due to the presence of this steroidal compound. PMID:22465504

  3. Mediators, Receptors, and Signalling Pathways in the Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture

    PubMed Central

    McDonald, John L.; Cripps, Allan W.; Smith, Peter K.

    2015-01-01

    Acupuncture has been used for millennia to treat allergic diseases including both intermittent rhinitis and persistent rhinitis. Besides the research on the efficacy and safety of acupuncture treatment for allergic rhinitis, research has also investigated how acupuncture might modulate immune function to exert anti-inflammatory effects. A proposed model has previously hypothesized that acupuncture might downregulate proinflammatory neuropeptides, proinflammatory cytokines, and neurotrophins, modulating transient receptor potential vallinoid (TRPV1), a G-protein coupled receptor which plays a central role in allergic rhinitis. Recent research has been largely supportive of this model. New advances in research include the discovery of a novel cholinergic anti-inflammatory pathway activated by acupuncture. A chemokine-mediated proliferation of opioid-containing macrophages in inflamed tissues, in response to acupuncture, has also been demonstrated for the first time. Further research on the complex cross talk between receptors during inflammation is also helping to elucidate the mediators and signalling pathways activated by acupuncture. PMID:26339274

  4. Discovery of new orally effective analgesic and anti-inflammatory hybrid furoxanyl N-acylhydrazone derivatives.

    PubMed

    Hernández, Paola; Cabrera, Mauricio; Lavaggi, María Laura; Celano, Laura; Tiscornia, Inés; Rodrigues da Costa, Thiago; Thomson, Leonor; Bollati-Fogolín, Mariela; Miranda, Ana Luisa P; Lima, Lidia M; Barreiro, Eliezer J; González, Mercedes; Cerecetto, Hugo

    2012-03-15

    We report the design, the synthesis and the biological evaluation of the analgesic and anti-inflammatory activities of furoxanyl N-acylhydrazones (furoxanyl-NAH) by applying molecular hybridization approach. Hybrid compounds with IL-8-release inhibition capabilities were identified. Among them, furoxanyl-NAH, 17, and benzofuroxanyl-derivative, 24, together with furoxanyl-NAH derivative, 31, without IL-8 inhibition displayed both orally analgesic and anti-inflammatory activities. These hybrid derivatives do not have additional LOX- or COX-inhibition activities. For instance, LOX-inhibition by furoxanyl-NAH derivative, 42, emerged as a structural lead to develop new inhibitors. The lack of mutagenicity of the active derivatives 17, 31, and 42, allow us to propose them as candidates for further clinical studies. These results confirmed the success in the exploitation of hybridization strategy for identification of novel N-acylhydrazones (NAH) with optimized activities. PMID:22356737

  5. New insights into insulin: The anti-inflammatory effect and its clinical relevance

    PubMed Central

    Sun, Qiang; Li, Jia; Gao, Feng

    2014-01-01

    Hyperglycemia, a commonly exhibited metabolic disorder in critically ill patients, activates the body’s inflammatory defense mechanism, causing the waterfall release of numerous inflammatory mediators and cytokines, and eventually leads to organ damage. As the only glucose-lowering hormone in the body, insulin not only alleviates the detrimental effects of hyperglycemia through its metabolic regulation, but also directly modulates inflammatory mediators and acts upon immune cells to enhance immunocompetence. In this sense, hyperglycemia is pro-inflammatory whereas insulin is anti-inflammatory. Therefore, during the past 50 years, insulin has not only been used in the treatment of diabetes, but has also been put into practical use in dealing with cardiovascular diseases and critical illnesses. This review summarizes the recent advances regarding the anti-inflammatory effects of insulin in both basic research and clinical trials, with the hope of aiding in the design of further experimental research and promoting effective insulin administration in clinical practice. PMID:24765237

  6. Free radical scavenging and anti-inflammatory properties of Lagerstroemia speciosa (L).

    PubMed

    Priya, T T; Sabu, M C; Jolly, C I

    2008-08-01

    The in vitro antioxidant activity of the successive extracts (ethyl acetate, ethanol, methanol and water) of the leaves of Lagerstroemia speciosa L. (Lythraceae) were studied by examining their superoxide, hydroxyl ion scavenging and by measuring lipid peroxidation. The ethyl acetate and ethanol extracts were found to possess greater antioxidant property than the methanol and water extracts. Anti-inflammatory activity of the ethyl acetate and ethanol extracts were examined using the carrageenan-induced acute inflammation and formalin-induced (chronic) paw edema models. In acute and chronic inflammation models, the ethyl acetate extract reduced the paw edema significantly in a dose-dependent manner. Whereas, ethanol extract did not show dose-dependent activity. This results suggests that the anti-inflammatory activity is possibly attributed to its free radical scavenging activity. It was found that ethyl acetate extract reduced the inflammation more significantly than the ethanol extract. PMID:18759076

  7. Antinociceptive and anti-inflammatory activity of the ethanolic extract of Cymbidium aloifolium (L.).

    PubMed

    Howlader, Md Amran; Alam, Mahmudul; Ahmed, Kh Tanvir; Khatun, Farjana; Apu, Apurba Sarker

    2011-10-01

    The ethanol leaf extract of Cymbidium aloifolium (L.) was evaluated for its analgesic and antiinflammatory activities. The extract, at the dose of 200 and 400 mg kg(-1) body weight, exerted the analgesic activity by observing the number of abdominal contractions and anti-inflammatory activity against Carrageenin induced paw edema in mice by measuring the paw volume. The ethanolic extract of Cymbidium aloifolium (L.) showed statistically significant (p < 0.05) reduction of percentage of writhing of 33.57 and 61.31% at 200 and 400 mg kg(-1) oral dose, respectively, when compared to negative control. The Ethanolic plant extract also showed significant (p < 0.05) dose dependent reduction of mean increase of formation of paw edema. The results of the experiment and its statistical analysis showed that the ethanolic plant extract had shown significant (p < 0.05) dose dependent analgesic and anti-inflammatory activities when compared to the control. PMID:22518936

  8. Non-steroidal anti-inflammatory drugs and benign oesophageal stricture.

    PubMed Central

    Heller, S R; Fellows, I W; Ogilvie, A L; Atkinson, M

    1982-01-01

    Drug histories were obtained from 76 patients at the time of initial Eder-Puestow dilatation for benign oesophageal stricture. Six patients had consumed drugs known to cause oesophageal ulceration (emepronium bromide and potassium preparations). Of the remaining 70 patients, 22 had regularly taken a non-steroidal anti-inflammatory drug before the onset of dysphagia compared with 10 patients in a control group matched for age and sex; this difference was significant (p less than 0.02). Non-steroidal anti-inflammatory drugs may have a causative role in the formation of oesophageal stricture in patients with gastro-oesophageal reflux, in whom they should be prescribed with caution. PMID:6807392

  9. Antioxidant, Antinociceptive, and Anti-Inflammatory Effects of Carotenoids Extracted from Dried Pepper (Capsicum annuum L.)

    PubMed Central

    Hernández-Ortega, Marcela; Ortiz-Moreno, Alicia; Hernández-Navarro, María Dolores; Chamorro-Cevallos, Germán; Dorantes-Alvarez, Lidia; Necoechea-Mondragón, Hugo

    2012-01-01

    Carotenoids extracted from dried peppers were evaluated for their antioxidant, analgesic, and anti-inflammatory activities. Peppers had a substantial carotenoid content: guajillo 3406 ± 4??g/g, pasilla 2933 ± 1??g/g, and ancho 1437 ± 6??g/g of sample in dry weight basis. A complex mixture of carotenoids was discovered in each pepper extract. The TLC analysis revealed the presence of chlorophylls in the pigment extract from pasilla and ancho peppers. Guajillo pepper carotenoid extracts exhibited good antioxidant activity and had the best scavenging capacity for the DPPH+ cation (24.2%). They also exhibited significant peripheral analgesic activity at 5, 20, and 80?mg/kg and induced central analgesia at 80?mg/kg. The results suggest that the carotenoids in dried guajillo peppers have significant analgesic and anti-inflammatory benefits and could be useful for pain and inflammation relief. PMID:23091348

  10. Antioxidant and Anti-Inflammatory Properties of Longan (Dimocarpus longan Lour.) Pericarp

    PubMed Central

    Huang, Guan-Jhong; Wang, Bor-Sen; Lin, Wei-Chao; Huang, Shyh-Shyun; Lee, Chao-Ying; Yen, Ming-Tsung; Huang, Ming-Hsing

    2012-01-01

    This study examined the antioxidant and anti-inflammatory activities of the water extract of longan pericarp (WLP). The results showed that WLP exhibited radical scavenging, reducing activity and liposome protection activity. In addition, WLP also inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages. Further, administration of WLP, in the range of 100–400?mg/kg, showed a concentration-dependent inhibition on paw edema development following carrageenan (Carr) treatment in mice. The anti-inflammatory effects of WLP may be related to NO and tumor necrosis factor (TNF-?) suppression and associated with the increase in the activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Overall, the results showed that WLP might serve as a natural antioxidant and inflammatory inhibitor. PMID:22966244

  11. Anti-inflammatory properties of a triterpenoidal glycoside from Momordica cochinchinensis in LPS-stimulated macrophages.

    PubMed

    Jung, Kiwon; Chin, Young-Won; Yoon, Kee dong; Chae, Hee-Sung; Kim, Chul Young; Yoo, Hunseung; Kim, Jinwoong

    2013-02-01

    Two triterpenoidal saponins were isolated from the seeds of Momordica cochinchinensis Sprenger (Cucurbitaceae). Identification of chemical structures has been performed by (1)H- and (13)C-NMR spectroscopy and gas chromatography (GC). One of the saponins is a new gypsogenin glycoside, named as gypsogenin 3-O-?-D-galactopyranosyl(1?2)-[?-L-rhamnopyranosyl(1?3)]-?-D-glucuronopyranoside (compound 1), which is reported for the first time from natural resources. The other saponin is a quillaic acid glycoside (compound 2), which showed anti-inflammatory activities in RAW 264.7 cells. The mechanistic understanding of anti-inflammatory activities demonstrates that compound 2 inhibits lipopolysaccharide-induced expression of nitric oxide and IL-6 via NF-?B pathway. PMID:22916793

  12. GILZ as a Mediator of the Anti-Inflammatory Effects of Glucocorticoids

    PubMed Central

    Ronchetti, Simona; Migliorati, Graziella; Riccardi, Carlo

    2015-01-01

    Glucocorticoid-induced leucine zipper (GILZ) is a dexamethasone-inducible gene that mediates glucocorticoid (GC) actions in a variety of cell types, including many cells of immune system. In particular, GILZ can control T cell activities, such as activation and differentiation, mainly through its ability to homo- and hetero-dimerize with partner proteins, such as NF-?B, Ras, and C/EBP. These protein–protein interactions control the regulation of pro-inflammatory target genes. A number of in vitro and in vivo studies using mouse models of inflammatory diseases demonstrate an anti-inflammatory role for GILZ. Here, authors summarize the studies that make GILZ eligible as an anti-inflammatory protein through which GCs can act. These findings permit the future development of pharmacological tools that mimic the therapeutic effects of GCs while avoiding the detrimental ones. PMID:26617572

  13. Benzimidazole derivatives: search for GI-friendly anti-inflammatory analgesic agents

    PubMed Central

    Gaba, Monika; Gaba, Punam; Uppal, Deepika; Dhingra, Neelima; Bahia, Malkeet Singh; Silakari, Om; Mohan, Chander

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been successfully used for the alleviation of pain and inflammation in the past and continue to be used daily by millions of patients worldwide. However, gastrointestinal (GI) toxicity associated with NSAIDs is an important medical and socioeconomic problem. Local generation of various reactive oxygen species plays a significant role in the formation of gastric ulceration associated with NSAIDs therapy. Co-medication of antioxidants along with NSAIDs has been found to be beneficial in the prevention of GI injury. This paper describes the synthesis and biological evaluation of N-1-(phenylsulfonyl)-2-methylamino-substituted-1H-benzimidazole derivatives as anti-inflammatory analgesic agents with lower GI toxicity. Studies in vitro and in vivo demonstrated that the antioxidant activity of the test compounds decreased GI toxicity. PMID:26579464

  14. Synthesis, anti-inflammatory, and antiproliferative activity evaluation of isoindole, pyrrolopyrazine, benzimidazoisoindole, and benzimidazopyrrolopyrazine derivatives.

    PubMed

    Kumar, Sandeep; Kumar, Nikhil; Roy, Partha; Sondhi, Sham M

    2013-11-01

    A number of isoindole (3x, 3y, 6xa-6ye), pyrrolopyrazine (3z, 6za-6ze), benzimidazoisoindole (4x, 4y, 7xa-7ye), and benzimidazopyrrolopyrazine (4z, 7za-7ze) derivatives has been synthesized in excellent yields. All these compounds were fully characterized and evaluated against five human cancer cell lines for their anti-inflammatory and antiproliferative activity. Compounds 6yc and 7zd exhibited good anti-inflammatory activity whereas compounds 6zc, 7zd (lung NCl H-522), 6ye, 7xd, 7yd, 7zc, 7zd (colon HCT-15), 6xc, 7zc (ovary PA-1), 6xc, 6yb, 6zc (liver HepG-2) exhibited good antiproliferative activity. PMID:23979512

  15. Antimetastatic and Anti-Inflammatory Potentials of Essential Oil from Edible Ocimum sanctum Leaves

    PubMed Central

    Thirugnanasampandan, Ramaraj; Jayakumar, Rajarajeswaran; Ramya, Gunasekar; Ramnath, Gogul

    2014-01-01

    Antimetastatic and anti-inflammatory activities of Ocimum sanctum essential oil (OSEO) have been assessed in this study. OSEO at the concentration of 250??g/mL and above showed a significant (*P < 0.05) decrease in the number of migrated cancer cells. In addition, OSEO at concentration of 250??g/mL and above suppressed MMP-9 activity in lipopolysaccharide (LPS) induced inflammatory cells. A dose-dependent downregulation of MMP-9 expression was observed with the treatment of OSEO compared to the control. Our findings indicate that OSEO has both antimetastatic and anti-inflammatory potentials, advocating further investigation for clinical applications in the treatment of inflammation associated cancer. PMID:25431779

  16. Briarenolides K and L, New Anti-Inflammatory Briarane Diterpenoids from an Octocoral Briareum sp. (Briareidae)

    PubMed Central

    Su, Yin-Di; Su, Tzu-Rong; Wen, Zhi-Hong; Hwang, Tsong-Long; Fang, Lee-Shing; Chen, Jih-Jung; Wu, Yang-Chang; Sheu, Jyh-Horng; Sung, Ping-Jyun

    2015-01-01

    Two new briarane-type diterpenoids, briarenolides K (1) and L (2), were isolated from an octocoral identified as Briareum sp. The structures of new briaranes 1 and 2 were elucidated by spectroscopic methods. In the in vitro anti-inflammatory effects test, briaranes 1 and 2 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. PMID:25689566

  17. Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review

    PubMed Central

    Mousavi, Sarah; Moradi, Mandana; Khorshidahmad, Tina; Motamedi, Maryam

    2015-01-01

    Background. Heparin, used clinically as an anticoagulant, also has anti-inflammatory properties. The purpose of this systematic review was to provide a comprehensive review regarding the efficacy and safety of heparin and its derivatives as anti-inflammatory agents. Methods. We searched the following databases up to March 2012: Pub Med, Scopus, Web of Science, Ovid, Elsevier, and Google Scholar using combination of Mesh terms. Randomized Clinical Trials (RCTs) and trials with quasi-experimental design in clinical setting published in English were included. Quality assessments of RCTs were performed using Jadad score and Consolidated Standards of Reporting Trials (CONSORT) checklist. Results. A total of 280 relevant studies were reviewed and 57 studies met the inclusion criteria. Among them 48 studies were RCTs. About 65% of articles had score of 3 and higher according to Jadad score. Twelve studies had a quality score > 40% according to CONSORT items. Asthma (n = 7), inflammatory bowel disease (n = 5), cardiopulmonary bypass (n = 8), and cataract surgery (n = 6) were the most studied disease condition. Forty studies use unfractionated heparin (UFH) for intervention; the remaining studies use low molecular weight heparin (LMWH). Conclusion. Despite the conflicting results, heparin seems to be a safe and effective anti-inflammatory agent; although it is shown that heparin can decrease the level of inflammatory biomarkers and improves patient conditions, still more data from larger rigorously designed studies are needed to support use of heparin as an anti-inflammatory agent in clinical setting. However, because of the association between inflammation, atherogenesis, thrombogenesis, and cell proliferation, heparin and related compounds with pleiotropic effects may have greater therapeutic efficacy than compounds acting against a single target. PMID:26064103

  18. Anti-inflammatory activity studies on the stems and roots of Jasminum lanceolarium Roxb.

    PubMed

    Yan, Wen-xia; Zhang, Jian-hua; Zhang, Yi; Meng, Da-li; Yan, Dan

    2015-08-01

    Jasminum lanceolarium Roxb is an important traditional Chinese medicine. Its stems and roots have been used for the treatment of rheumatism and fever while the leaves are used as an anti-inflammatory agent to relieve pain. In order to support its traditional Chinese medicinal uses, five animal models were designed and the anti-inflammatory and analgesic properties of the 70% EtOH-H2O extracts of J. lanceolarium (EJL) were investigated. Meanwhile, biochemical parameters such as cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) in blood serum of rats exposed to acute (carrageenan) inflammation model were evaluated. At doses of 400 mg/kg, EJL exhibited higher anti-inflammation effect than that of indomethacin and better analgesic activity than that of aspirin (P<0.001). Furthermore, eleven isolated compounds including six lignanoids (1, 2, 6, 7, 8, and 11) and five iridoids (3, 4, 5, 9, and 10) were isolated from the active extracts and showed significant anti-inflammatory activities with the IC50 values of 1.76-5.22 mg/mL, respectively, when testing their inhibitory effects on phospholipase A2 in vitro. The results demonstrated that the possible anti-inflammatory mechanisms might be attributed to inhibit the hydrolysis of membrane phospholipids, production on both COX-2 and 5-LOX, and then finally inhibit the release of prostaglandins (PGs), which suggested that EJL had a non-selective inhibitory effect on the release or actions of these mediators, and might be a dual LOX-COX inhibitor for the treatment of inflammation from the natural resource. The studies on the animals and the inflammatory mediators, along with the bioactive compounds presumed that the existences of iridoids and lignanoids could be response for their bioactivities of the whole plants. PMID:26055344

  19. The anti-inflammatory effects of soluble epoxide hydrolase inhibitors are independent of leukocyte recruitment.

    PubMed

    Davis, Benjamin B; Liu, Jun-Yan; Tancredi, Daniel J; Wang, Lei; Simon, Scott I; Hammock, Bruce D; Pinkerton, Kent E

    2011-07-01

    Excess leukocyte recruitment to the lung plays a central role in the development or exacerbation of several lung inflammatory diseases including chronic obstructive pulmonary disease. Epoxyeicosatrienoic acids (EETs) are cytochrome P-450 metabolites of arachidonic acid reported to have multiple biological functions, including blocking of leukocyte recruitment to inflamed endothelium in cell culture through reduction of adhesion molecule expression. Inhibition of the EET regulatory enzyme, soluble epoxide hydrolase (sEH) also has been reported to have anti-inflammatory effects in vivo including reduced leukocyte recruitment to the lung. We tested the hypothesis that the in vivo anti-inflammatory effects of sEH inhibitors act through the same mechanisms as the in vitro anti-inflammatory effects of EETs in a rat model of acute inflammation following exposure to tobacco smoke. Contrary to previously published data, we found that sEH inhibition did not reduce tobacco smoke-induced leukocyte recruitment to the lung. Furthermore, sEH inhibition did not reduce tobacco smoke-induced adhesion molecule expression in the lung vasculature. Similarly, concentrations of EETs greater than or equal to their reported effective dose did not reduce TNF? induced expression of the adhesion molecules. These results suggest that the anti-inflammatory effects of sEH inhibitors are independent of leukocyte recruitment and EETs do not reduce the adhesion molecules responsible for leukocyte recruitment in vitro. This demonstrates that the widely held belief that sEH inhibition prevents leukocyte recruitment via EET prevention of adhesion molecule expression is not consistently reproducible. PMID:21683067

  20. Anti-inflammatory effects of a novel ricinoleic acid poloxamer gel system for transdermal delivery.

    PubMed

    Boddu, Sai H S; Alsaab, Hashem; Umar, Sadiq; Bonam, Sindhu Prabha; Gupta, Himanshu; Ahmed, Salahuddin

    2015-02-01

    Our previous study showed that the use of ricinoleic acid as an oil phase resulted in the formation of a stable pluronic lecithin organogel (PLO gel) with better thixotropic properties and higher permeation of ketoprofen than the isopropyl palmitate PLO gel. This study aims to evaluate and compare the in vitro and in vivo anti-inflammatory effects of the ricinoleic acid PLO gel system with isopropyl palmitate PLO gel. Ketoprofen was used as a model drug. In vitro anti-inflammatory activity and cell viability tests were performed in human rheumatoid arthritis synovial fibroblast cell line using a blank ricinoleic acid PLO gel and compared to that of the isopropyl palmitate PLO gel. In vivo anti-inflammatory activity of ricinoleic acid PLO gel containing 10% ketoprofen was evaluated and compared with the isopropyl palmitate PLO gel in a carrageenan-induced rat paw edema model. The results from the in vitro study showed that the blank ricinoleic acid PLO gel possessed significantly higher anti-inflammatory activity than isopropyl palmitate PLO gel at 1 mM concentration (p<0.05), while both the gel formulations had no significant cytotoxic activity. Further in vivo testing of the formulation showed that the ricinoleic acid PLO gel formulation was significantly more effective in reducing pain and edema when compared to the isopropyl palmitate PLO gel. In addition, the ricinoleic acid PLO gel formulation markedly inhibited the synthesis of prostaglandin E2. In conclusion, the efficacy of PLO gels used in pain management may be enhanced by using ricinoleic acid instead of isopropyl palmitate as an oil phase. PMID:25542985

  1. Precision attack on calcineurin in macrophages: a new anti-inflammatory weapon.

    PubMed

    Schultze, Joachim L

    2014-05-16

    Inflammation is a hallmark of many common diseases ranging from arthritis, atherosclerosis, or obesity to Alzheimer's disease and cancer. Identifying antiinflammatory mechanisms is therefore an important and timely task of modern biomedicine. In this issue of The EMBO Journal, a study conducted by Escolano and colleagues target a particular interaction site of calcineurin with NFAT in macrophages to elicit profound anti-inflammatory effects (Escolano et al, 2014). PMID:24674968

  2. Phytochemical screening and anti-inflammatory activity of Cnidoscolus quercifolius (Euphorbiaceae) in mice

    PubMed Central

    de Araújo Gomes, Leandra Macedo; de Andrade, Thayne Mayra; Silva, Juliane Cabral; de Lima, Julianeli Tolentino; Quintans-Junior, Lucindo José; da Silva Almeida, Jackson Roberto Guedes

    2014-01-01

    Background: Cnidoscolus quercifolius is a species popularly known as favela and faveleira, and belonging to the Caatinga biome (semi-arid vegetation, Brazil), where is used in folk medicine as an anti-inflammatory. Objective: The aim was to evaluate the anti-inflammatory effect of the ethanolic extract from barks (Cqb-EtOH) and leaves (Cql-EtOH) of C. quercifolius in mice using experimental models of inflammation. Materials and Methods: The preliminary phytochemical analysis of the ethanolic extract was performed. The activity was evaluated by paw edema induced by carrageenan and leukocytes migration to the peritoneal cavity induced by carrageenan methods. Results: A preliminary analysis of Cqb-EtOH revealed that it contained coumarins, flavonoids, monoterpenes/diterpenes and naphthoquinones, while the Cql-EtOH showed positive reaction to coumarins, anthracene derivatives, flavonoids, lignans and triterpenes/steroids. Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited significantly (P < 0.01) the increase in the edema volume after administration of carrageenan. In the peritonitis test, acute pretreatment with Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited the leukocyte migration. Conclusions: It can be concluded that extracts from the barks and leaves of C. quercifolius have anti-inflammatory activity, which supports the popular use of this plant to treat inflammation. Thus, extracts has significant anti-inflammatory properties, which are related probably to inhibition of release of mediators of the inflammatory process. PMID:25276074

  3. Anti-inflammatory activity of two classical formulations of Laghupanchamula in rats

    PubMed Central

    Ghildiyal, Shivani; Gautam, Manish K.; Joshi, Vinod K.; Goel, Raj K.

    2013-01-01

    Background: Laghupanchamula denotes combinations of roots of five herbs. However, in Ayurvedic classics besides four common herbs viz. Kantakari, Brihati, Shaliparni, and Prinshniparni, the fifth one is either Gokshura (Laghupanchamula with Gokshura LPG) or Eranda (Laghupanchamula with Eranda LPE), and both formulations have been documented to have shothahara (anti-inflammatory) action. Objectives: The present study was undertaken to compare the anti-inflammatory activity of 50% ethanolic extract of LPG (LPGE) and LPE (LPEE) in rats and safety in mice. Materials and Methods: LPGE and LPEE were given orally, administered either just before or 60 min before experiment on mice and for 7 days to rats. Paw edema was induced by carrageenan (acute) and formalin (sub-acute), whereas granuloma pouch (sub-acute) was induced by turpentine in rats. Results: Both LPGE and LPEE (1.0 g/kg) at 3 h after their administration showed inhibition of formalin-induced paw edema by 46.2% and 44.3% (P < 0.001) and carrageenan-induced paw edema by 53.9% and 60.4% (P < 0.001), respectively. After 7 days of treatment, both LPGE and LPEE showed 26.3% (P < 0.01) and 32.5% (P < 0.05) inhibition, respectively, against formalin-induced paw edema, and reduced weight of turpentine-induced granuloma pouch by 42.8% and 36.1% (P < 0.001), and volume of exudates by 31.2% and 36.2% (P < 0.001), respectively. No acute toxicity was observed in mice even with a 10.0-g/kg dose of both extracts. Conclusion: LPGE and LPEE significantly reduced acute and sub-acute inflammation, and showed effective and similar anti-inflammatory activity. They seemed to be safe, and use of both formulations in the Laghupanchamula for their anti-inflammatory activity is, thus, authenticated. PMID:23741158

  4. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

    PubMed Central

    2014-01-01

    Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-?B and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. Results In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-?B activation through p65 nuclear translocation via blocking I?B-? degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3?. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. Conclusions These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity. PMID:24962785

  5. Anti-Inflammatory and Antinociceptive Activities of a Hydroethanolic Extract of Tamarindus indica Leaves

    PubMed Central

    Bhadoriya, Santosh Singh; Mishra, Vijay; Raut, Sushil; Ganeshpurkar, Aditya; Jain, Sunil K.

    2012-01-01

    The present study aimed to investigate the anti-inflammatory and anti-nociceptive potential of a hydroethanolic extract of Tamarindus indica L. leaves (HTI) along with its possible mode of action. The anti-inflammatory activity of HTI was estimated by carrageenan-induced hind paw oedema in male Wistar albino rats. Furthermore, HTI was assessed to determine its effects on membrane stabilization. The antinociceptive action was determined by acetic acid-induced writhing, tail-flick, and the hot plate model. Oral administration of HTI at the dose of 500, 750, and 1000 mg/kg body weight produced significant (P< 0.01) anti-inflammatory as well as antinociceptive actions in a dose-dependent manner. Among all tested doses, 1000 mg/kg, p. o. reduced carrageenan-induced rat paw oedema at 1, 2, 3, and 4 h. Moreover, the 1000 mg/kg dose exhibited maximum percentage inhibition of acetic acid-induced writhing (48.9%), whereas standard drug diclofenac (25 mg/kg, p. o.) showed maximum inhibition (50.9%) of writhing. In the hot plate model, HTI (1000 mg/kg, orally) increased mean basal reaction time after 120 min (7.12±0.05 sec). In the tail flick model, HTI increased the maximum percentage of latency (36.06%), whereas the standard drug pethidine (4 mg/kg, intraperitoneally) showed maximum percentage of latency (43.85%) after 60 min. The findings of the present study supported anti-inflammatory and antinociceptive claims of T. indica as were mentioned in Indian traditional and folklore practices. PMID:23008815

  6. Experimental evaluation of analgesic, anti-inflammatory and anti-platelet potential of Dashamoola

    PubMed Central

    Parekar, Reshma R.; Bolegave, Somesh S.; Marathe, Padmaja A.; Rege, Nirmala N.

    2015-01-01

    Background: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. Objective: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. Materials and Methods: Wistar albino rats (180-200 g) and Swiss albino mice (20-25 g) of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice), Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice) and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey's test) and P < 0.05 was considered significant. Results: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01) less number of writhes. It showed significant (P < 0.001) anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001) and decrease in granuloma weight (P < 0.05) as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001). Conclusion: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin. PMID:25878458

  7. Anti-Inflammatory and Antinociceptive Activities of a Hydroethanolic Extract of Tamarindus indica Leaves.

    PubMed

    Bhadoriya, Santosh Singh; Mishra, Vijay; Raut, Sushil; Ganeshpurkar, Aditya; Jain, Sunil K

    2012-09-01

    The present study aimed to investigate the anti-inflammatory and anti-nociceptive potential of a hydroethanolic extract of Tamarindus indica L. leaves (HTI) along with its possible mode of action. The anti-inflammatory activity of HTI was estimated by carrageenan-induced hind paw oedema in male Wistar albino rats. Furthermore, HTI was assessed to determine its effects on membrane stabilization. The antinociceptive action was determined by acetic acid-induced writhing, tail-flick, and the hot plate model. Oral administration of HTI at the dose of 500, 750, and 1000 mg/kg body weight produced significant (P< 0.01) anti-inflammatory as well as antinociceptive actions in a dose-dependent manner. Among all tested doses, 1000 mg/kg, p. o. reduced carrageenan-induced rat paw oedema at 1, 2, 3, and 4 h. Moreover, the 1000 mg/kg dose exhibited maximum percentage inhibition of acetic acid-induced writhing (48.9%), whereas standard drug diclofenac (25 mg/kg, p. o.) showed maximum inhibition (50.9%) of writhing. In the hot plate model, HTI (1000 mg/kg, orally) increased mean basal reaction time after 120 min (7.12±0.05 sec). In the tail flick model, HTI increased the maximum percentage of latency (36.06%), whereas the standard drug pethidine (4 mg/kg, intraperitoneally) showed maximum percentage of latency (43.85%) after 60 min. The findings of the present study supported anti-inflammatory and antinociceptive claims of T. indica as were mentioned in Indian traditional and folklore practices. PMID:23008815

  8. Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation.

    PubMed

    Paris, Daniel; Beaulieu-Abdelahad, David; Abdullah, Laila; Bachmeier, Corbin; Ait-Ghezala, Ghania; Reed, Jon; Verma, Megha; Crawford, Fiona; Mullan, Michael

    2013-01-01

    Previous investigations have demonstrated the anti-inflammatory effects of cholinergic agonists, such as nicotine. In the present study, we investigated the potential anti-inflammatory activity of anatabine, a minor tobacco alkaloid also present in plants of the Solanacea family which displays a chemical structural similarity with nicotine. Our data show that anatabine prevents STAT3 and NF?B phosphorylation induced by lipopolysaccharide (LPS) or TNF-? in SH-SY5Y, HEK293, human microglia and human blood mononuclear cells. Using human whole blood, we found that anatabine prevents IL-1? production induced by LPS. We assessed anatabine's anti-inflammatory activity in vivo using an acute model of inflammation by challenging wild-type mice with LPS. We observed that a