These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Discovery of a Highly Potent Anti-inflammatory Epoxyisoprostane-Derived Lactone.  

PubMed

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

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

2014-12-17

2

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

PubMed

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

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

2013-01-01

3

CHF6001 I: A Novel Highly Potent and Selective Phosphodiesterase 4 Inhibitor with Robust Anti-Inflammatory Activity and Suitable for Topical Pulmonary Administration.  

PubMed

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

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

4

Structure and function of a potent lipopolysaccharide-binding antimicrobial and anti-inflammatory peptide.  

PubMed

Antimicrobial peptides (AMPs) play pivotal roles in the innate defense of vertebrates. A novel AMP (cathelicidin-PY) has been identified from the skin secretions of the frog Paa yunnanensis . Cathelicidin-PY has an amino acid sequence of RKCNFLCKLKEKLRTVITSHIDKVLRPQG. Nuclear magnetic resonance (NMR) spectroscopy analysis revealed that cathelicidin-PY adopts a tertiary structure with a mostly positively charged surface containing a helix (Thr15-Ser19). It possesses strong antimicrobial activity, low hemolytic activity, low cytotoxicity against RAW 264.7 cells, and strong anti-inflammatory activity. The action of antimicrobial activity of cathelicidin-PY is through the destruction of the cell membrane. Moreover, cathelicidin-PY exerts anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and inflammatory cytokines such as tumor necrosis factor (TNF-?), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Cathelicidin-PY inhibits the activation of Toll-like receptor 4 (TLR4) inflammatory response pathways induced by lipopolysaccharide (LPS). The NMR titration experiments indicated that cathelicidin-PY can bind to LPS. In conclusion, we have identified a novel potent peptide antibiotic with both antimicrobial and anti-inflammatory activities and laid the groundwork for future research and development. PMID:23594231

Wei, Lin; Yang, Juanjuan; He, Xiaoqin; Mo, Guoxiang; Hong, Jing; Yan, Xiuwen; Lin, Donghai; Lai, Ren

2013-05-01

5

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

PubMed Central

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

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

2014-01-01

6

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

PubMed Central

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

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

2012-01-01

7

Ethyl Acetate Extract of Artemisia anomala S. Moore Displays Potent Anti-Inflammatory Effect  

PubMed Central

Artemisia anomala S. Moore has been widely used in China to treat inflammatory diseases for hundreds of years. However, mechanisms associated with its anti-inflammatory effect are not clear. In this study, we prepared ethyl acetate, petroleum ether, n-BuOH, and aqueous extracts from ethanol extract of Artemisia anomala S. Moore. Comparing anti-inflammatory effects of these extracts, we found that ethyl acetate extract of this herb (EAFA) exhibited the strongest inhibitory effect on nitric oxide (NO) production in LPS/IFN?-stimulated RAW264.7 cells. EAFA suppressed the production of NO in a time- and dose-dependent manner without eliciting cytotoxicity to RAW264.7 cells. To understand the molecular mechanism underlying EAFA's anti-inflammatory effect, we showed that EAFA increased total cellular anti-oxidant capacity while reducing the amount of inducible nitric oxide synthase (iNOS) in stimulated RAW264.7 cells. EAFA also suppressed the expression of IL-1? and IL-6, whereas it elevates the level of heme oxygenase-1. These EAFA-induced events were apparently associated with NF-?B and MAPK signaling pathways because the DNA binding activity of p50/p65 was impaired and the activities of both ERK and JNK were decreased in EFEA-treated cells comparing to untreated cells. Our findings suggest that EAFA exerts its anti-inflammatory effect by inhibiting the expression of iNOS. PMID:24744815

Tan, Xi; Wang, Yuan-Lai; Yang, Xiao-Lu; Zhang, Dan-Dan

2014-01-01

8

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

PubMed

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

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

9

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

PubMed Central

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

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

10

Preclinical pharmacology profile of CS-706, a novel cyclooxygenase-2 selective inhibitor, with potent antinociceptive and anti-inflammatory effects.  

PubMed

We report here the preclinical anti-inflammatory profile of CS-706 [2-(4-ethoxyphenyl)-4-methyl-1-(4-sulfamoylphenyl)-1H-pyrrole], a novel cyclooxygenase-2 (COX-2) selective inhibitor. CS-706 selectively inhibited COX-2 in a human whole blood assay with an IC(50) of 0.31 microM, compared with an IC(50) of 2.2 microM for COX-1. The selectivity ratio of CS-706 was higher than those of the conventional non-steroidal anti-inflammatory drugs naproxen, indomethacin, and Diclofenac-Na, whereas it was lower than those of rofecoxib, valdecoxib and etoricoxib. It was similar to that of celecoxib. The pharmacokinetic profile of CS-706 showed rapid absorption and dose-proportional exposure after oral administration to rats. CS-706 inhibited prostaglandin E(2) production in inflamed tissue induced by yeast-injection in rats with potency similar to that of indomethacin. However, it inhibited gastric mucosal prostaglandin E(2) production in normal rats weakly compared with indomethacin. CS-706 ameliorated both yeast-induced inflammatory acute pain (ED(50)=0.0090 mg/kg) and adjuvant-induced chronic arthritic pain (ED(50)=0.30 mg/kg) in rats. CS-706 showed more potent antinociceptive activity than celecoxib and rofecoxib in these models. In an adjuvant-induced arthritic model in rats, CS-706 suppressed foot swelling prophylactically with an ID(50) of 0.10 mg/kg/day, and decreased foot swelling in the established arthritis therapeutically in a dose range of 0.040 to 1.0 mg/kg/day. Single administration of up to 100 mg/kg of CS-706 induced no significant gastric lesions in rats. In conclusion, CS-706 is a COX-2-selective inhibitor with a potent antinociceptive and anti-inflammatory activity and a gastric safety profile. PMID:17920584

Ushiyama, Shigeru; Yamada, Tomoko; Murakami, Yukiko; Kumakura, Sei-ichiro; Inoue, Shin-ichi; Suzuki, Keisuke; Nakao, Akira; Kawara, Akihiro; Kimura, Tomio

2008-01-01

11

High density lipoprotein mediates anti-inflammatory transcriptional reprogramming of macrophages via the transcriptional repressor ATF3  

PubMed Central

High Density Lipoprotein (HDL) mediates reverse cholesterol transport and it is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional repressor ATF3, as an HDL-inducible target gene in macrophages that down-regulates the expression of Toll-like receptor (TLR)-induced pro-inflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of novel HDL-based therapies. PMID:24317040

De Nardo, Dominic; Labzin, Larisa I.; Kono, Hajime; Seki, Reiko; Schmidt, Susanne V.; Beyer, Marc; Xu, Dakang; Zimmer, Sebastian; Lahrmann, Catharina; Schildberg, Frank A.; Vogelhuber, Johanna; Kraut, Michael; Ulas, Thomas; Kerksiek, Anja; Krebs, Wolfgang; Bode, Niklas; Grebe, Alena; Fitzgerald, Michael L.; Hernandez, Nicholas J.; Williams, Bryan; Knolle, Percy; Kneilling, Manfred; Röcken, Martin; Lütjohann, Dieter; Wright, Samuel D.; Schultze, Joachim L.; Latz, Eicke

2014-01-01

12

Thiazolyl\\/oxazolyl formazanyl indoles as potent anti-inflammatory agents  

Microsoft Academic Search

A series of 3-(2?-substituted indolidene aminothiazol-4?-yl)-2-(4-chlorophenyl) indoles (3a–3d), 3-(2?-substituted indolidene amino oxazol-4?-yl)-2-(4-chlorophenyl) indoles (3a?–3d?) and 3-[2?-(1?-substituted phenyl-3?-substituted indolyl formazan-4?-yl) thiazol-4?-yl]-2-(4-chlorophenyl) indoles (4a–4h), 3-[2?-(1?-substituted phenyl-3?-substituted indolyl formazan-4?-yl) oxazol-4?-yl]-2-(4-chlorophenyl) indoles (4a?–4h?) were synthesized and evaluated for their anti-inflammatory activity against carrageenan induced oedema in albino rats at a dose of 50mg\\/kg p.o. The structure of all these compounds were established on the

Nisha Singh; Sudhir Kumar Bhati; Ashok Kumar

2008-01-01

13

Arzanol, a Potent mPGES-1 Inhibitor: Novel Anti-Inflammatory Agent  

PubMed Central

Arzanol is a novel phloroglucinol ?-pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NF?B activation, HIV replication in T cells, releases of IL-1?, IL-6, IL-8, and TNF-?, and biosynthesis of PGE2 by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects. PMID:24198734

Kothavade, Pankaj S.; Nagmoti, Dnyaneshwar M.; Bulani, Vipin D.; Juvekar, Archana R.

2013-01-01

14

Arzanol, a potent mPGES-1 inhibitor: novel anti-inflammatory agent.  

PubMed

Arzanol is a novel phloroglucinol ? -pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NF ?B activation, HIV replication in T cells, releases of IL-1 ? , IL-6, IL-8, and TNF-? , and biosynthesis of PGE? by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects. PMID:24198734

Kothavade, Pankaj S; Nagmoti, Dnyaneshwar M; Bulani, Vipin D; Juvekar, Archana R

2013-01-01

15

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

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

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

2012-01-01

16

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

PubMed

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

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

2013-01-15

17

Biochemical, cellular, and anti-inflammatory properties of a potent, selective, orally bioavailable benzamide inhibitor of Rho kinase activity.  

PubMed

Rho kinase, is the most widely studied downstream effector of the small Rho GTPase RhoA. Two Rho kinase isoforms have been described and are frequently referred to in the literature as ROCK1 and ROCK2. The RhoA-Rho kinase pathway has been implicated in the recruitment of cellular infiltrates to disease loci in a number of preclinical animal models of inflammatory disease. In this study, we used biochemical enzyme assays and a cellular target biomarker assay to define PF-4950834 [N-methyl-3-{[(4-pyridin-4-ylbenzoyl)amino]methyl}benzamide] as an ATP-competitive, selective Rho kinase inhibitor. We further used PF-4950834 to study the role of Rho kinase activation in lymphocyte and neutrophil migration in addition to the endothelial cell-mediated expression of adhesion molecules and chemokines, which are essential for leukocyte recruitment. The inhibitor blocked stromal cell-derived factor-1alpha-mediated chemotaxis of T lymphocytes in vitro and the synthesis of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in activated human endothelial cells in vitro. The secretion of chemokines interleukin-8 and monocyte chemoattractant protein-1 was also inhibited in activated endothelial cells. In addition, when dosed orally, the compound potently inhibited neutrophil migration in a carrageenan-induced acute inflammation model. In summary, we have used a pharmacologic approach to link Rho kinase activation to multiple phenotypes that can contribute to leukocyte infiltration. Inhibition of this pathway therefore could be strongly anti-inflammatory and provide therapeutic benefit in chronic inflammatory diseases. PMID:20228155

Rajagopalan, Lakshman E; Davies, Michael S; Kahn, Larry E; Kornmeier, Christine M; Shimada, Hideaki; Steiner, Toni A; Zweifel, Ben S; Wendling, Jay M; Payne, Maria A; Loeffler, Richard F; Case, Brenda L; Norton, Monica B; Parikh, Mihir D; Nemirovskiy, Olga V; Mourey, Robert J; Masferrer, Jaime L; Misko, Thomas P; Kolodziej, Stephen A

2010-06-01

18

New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice.  

PubMed

Myrrhanol A, a new triterpene isolated from guggul (Balsamodendron or Commiphora mukul Hook.)-gum resin, displays a potent anti-inflammatory effect on exudative pouch fluid, angiogenesis, and granuloma weights in adjuvant-induced air-pouch granuloma of mice. Its effects were more marked than those of hydrocortisone and the 50% aqueous methanolic extract of the crude drug. Myrrhanol A is a plausible candidate for a potent anti-inflammatory agent. PMID:11327606

Kimura, I; Yoshikawa, M; Kobayashi, S; Sugihara, Y; Suzuki, M; Oominami, H; Murakami, T; Matsuda, H; Doiphode, V V

2001-04-23

19

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

PubMed Central

Lipoxins are bioactive eicosanoids that are immunomodulators. In human myeloid cells, lipoxin (LX) A4 actions are mediated by interaction with a G protein–coupled receptor. To explore functions of LXA4 and aspirin-triggered 5(S),6(R),15(R)-trihydroxy-7,9,13-trans-11-cis–eicosatetraenoic acid (15-epi-LXA4) in vivo, we cloned and characterized a mouse LXA4 receptor (LXA4R). When expressed in Chinese hamster ovary cells, the mouse LXA4R showed specific binding to [3H]LXA4 (Kd ? 1.5 nM), and with LXA4 activated GTP hydrolysis. Mouse LXA4R mRNA was most abundant in neutrophils. In addition to LXA4 and 15-epi-LXA4, bioactive LX stable analogues competed with both [3H]LXA4 and [3H]leukotriene D4 (LTD4)– specific binding in vitro to neutrophils and endothelial cells, respectively. Topical application of LXA4 analogues and novel aspirin-triggered 15-epi-LXA4 stable analogues to mouse ears markedly inhibited neutrophil infiltration in vivo as assessed by both light microscopy and reduced myeloperoxidase activity in skin biopsies. The 15(R)-16-phenoxy-17,18, 19,20-tetranorLXA4 methyl ester (15-epi-16-phenoxy-LXA4), an analogue of aspirin triggered 15-epi-LXA4, and 15(S)-16-phenoxy-17,18,19,20-tetranor-LXA4 methyl ester (16-phenoxy-LXA4) were each as potent as equimolar applications of the anti-inflammatory, dexamethasone. Thus, we identified murine LXA4R, which is highly expressed on murine neutrophils, and showed that both LXA4 and 15-epi-LXA4 stable analogues inhibit neutrophil infiltration in the mouse ear model of inflammation. These findings provide direct in vivo evidence for an anti-inflammatory action for both aspirin-triggered LXA4 and LXA4 stable analogues and their site of action in vivo. PMID:9151906

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

1997-01-01

20

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

PubMed

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

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

2014-11-01

21

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

PubMed

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

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

2013-08-15

22

Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-?-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.  

PubMed

The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 ?g/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-? (TNF-?) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-I?B-?, reducing the degradation of sequestered nuclear factor kappa B (NF-?B) in the cytoplasm, and inhibited the translocation of NF-?B/p65 to the nucleus, the transcription of TNF-? mRNA and the production of TNF-? in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-? production. PMID:24365491

Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

2014-02-01

23

Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone  

PubMed Central

Background Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures. Results Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17?-hydroxy-2-(hydroxy-methyl)-17?-methyl-5?-androstan-1-en-3-one (2), 2?,17?-di(hydroxyl-methyl)-5?-androstan-3?,17?-diol (3), 17?-methyl-5?-androstan-2?,3?,17?-triol (4), 17?-hydroxy-2-(hydroxymethyl)-17?-methyl-androst-1,4-dien-3-one (5), 17?-hydroxy-2?-(hydroxy-methyl)-17?-methyl-5?-androstan-3-one (6), and 2?-(hydroxymethyl)-17?-methyl-5?-androstan-3?-17?-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2–5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1–7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 ?g/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 ?g/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay. Conclusion Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs. PMID:23237028

2012-01-01

24

An anti-inflammatory principle from cactus  

Microsoft Academic Search

In previous studies, the ethanol extract of cactus (Opuntia ficus-indica) showed potent anti-inflammatory action. In the present study, following fractionation of the methanol extract of cactus stems guided by adjuvant-induced chronic inflammation model in mice, an active anti-inflammatory principle has been isolated and identified as ?-sitosterol.

Eun-Hee Park; Ja-Hoon Kahng; Sang Hyun Lee; Kuk-Hyun Shin

2001-01-01

25

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

PubMed

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

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

2008-04-01

26

Synthesis and biological activity of NOSH-naproxen (AVT-219) and NOSH-sulindac (AVT-18A) as potent anti-inflammatory agents with chemotherapeutic potential  

PubMed Central

Nitric oxide- (NO) and hydrogen sulfide- (H2S) releasing naproxen (NOSH-naproxen) and NO and H2S-releasing sulindac (NOSH-sulindac) were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. These cell lines are of adenomatous (colon, pancreas), epithelial (breast), and lymphocytic (leukemia) origin. Using HT-29 human colon cancer cells, NOSH-naproxen and NOSH-sulindac increased apoptosis, and inhibited proliferation. NOSH-naproxen caused a G0/G1 whereas NOSH-sulindac caused a G2/M block in the cell cycle. Both compounds exhibited significant anti-inflammatory properties, using the carrageenan rat paw edema model. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-naproxen was approximately 8000-fold more potent than the sum of its parts in inhibiting cell growth. Our data suggest that these compounds merit further investigation as potential anti-cancer agents. PMID:24273639

Kodela, Ravinder; Chattopadhyay, Mitali; Kashfi, Khosrow

2013-01-01

27

Surface plasmon resonance studies and biochemical evaluation of a potent peptide inhibitor against cyclooxygenase-2 as an anti-inflammatory agent.  

PubMed

Cyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation [D.L. Dewitt, W.L. Smith, Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence, Proc. Natl. Acad. Sci. USA 85 (1988) 1412-1416, 1]. It exists mainly in two isoforms COX-1 and COX-2 [A. Raz, A. Wyche, N. Siegel, P. Needleman, Regulation of fibroblast cyclooxygenase synthesis by interleukin-1, J. Biol. Chem. 263 (1988) 3022-3028, 2]. The conventional non-steroidal anti-inflammatory drugs (NSAIDs) have adverse gastrointestinal side-effects, because they inhibit both isoforms [T.D. Warner, F. Guiliano, I. Vojnovic, A. Bukasa, J.A. Mitchell, J.P. Vane, Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis, Proc. Natl. Acad. Sci. USA 96 (1999) 7563-7568, 3; L.J. Marnett, A.S. Kalgutkar, Cyclooxygenase 2 inhibitors: discovery, selectivity and the future, Trends Pharmacol. Sci. 20 (1999) 465-469, 4; J.R. Vane, NSAIDs, Cox-2 inhibitors, and the gut, Lancet 346 (1995) 1105-1106, 5]. Therefore drugs which selectively inhibit COX-2, known as coxibs were developed. Recent reports on the harmful cardiovascular and renovascular side-effects of the anti-inflammatory drugs have led to the quest for a novel class of COX-2 selective inhibitors. Keeping this in mind, we have used the X-ray crystal structures of the complexes of the COX-1 and COX-2 with the known inhibitors for a rational, structure based approach to design a small peptide, which is potent inhibitor for COX-2. The peptides have been checked experimentally by in-vitro kinetic studies using surface plasmon resonance (SPR) and other biochemical methods. We have identified a tripeptide inhibitor which is a potential lead for a new class of COX-2 inhibitor. The dissociation constant (K(D)) determined for COX-2 with peptide WCS is 1.90x10(-10)M, the kinetic constant (K(i)) determined by spectrophotometry is 4.85x10(-9)M and the IC(50) value is 1.5x10(-8)M by ELISA test. PMID:17640617

Somvanshi, Rishi K; Kumar, Ashwini; Kant, Shashi; Gupta, Deepti; Singh, S Bhaskar; Das, Utpal; Srinivasan, Alagiri; Singh, Tej P; Dey, Sharmistha

2007-09-14

28

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

PubMed Central

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

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

2013-01-01

29

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

PubMed

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

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

2006-01-01

30

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

PubMed Central

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

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

2013-01-01

31

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

PubMed

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

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

2014-03-01

32

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

PubMed Central

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

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

33

Antihyperglycemic and Anti-Inflammatory Effects of Standardized Curcuma xanthorrhiza Roxb. Extract and Its Active Compound Xanthorrhizol in High-Fat Diet-Induced Obese Mice  

PubMed Central

Xanthorrhizol, a natural compound isolated from Curcuma xanthorrhiza Roxb. (Java turmeric), has been reported to possess antioxidant and anticancer properties; however, its effects on metabolic disorders remain unknown. The aim of the present study was to evaluate the effects of xanthorrhizol (XAN) and C. xanthorrhiza extract (CXE) with standardized XAN on hyperglycemia and inflammatory markers in high-fat diet- (HFD-) induced obese mice. Treatment with XAN (10 or 25?mg/kg/day) or CXE (50 or 100?mg/kg/day) significantly decreased fasting and postprandial blood glucose levels in HFD-induced obese mice. XAN and CXE treatments also lowered insulin, glucose, free fatty acid (FFA), and triglyceride (TG) levels in serum. Epididymal fat pad and adipocyte size were decreased by high doses of XAN (26.6% and 20.1%) and CXE (25.8% and 22.5%), respectively. XAN and CXE treatment also suppressed the development of fatty liver by decreasing liver fat accumulation. Moreover, XAN and CXE significantly inhibited production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6), interleukin-1? (IL-1?), and C-reactive protein (CRP) in adipose tissue (27.8–82.7%), liver (43.9–84.7%), and muscle (65.2–92.5%). Overall, these results suggest that XAN and CXE, with their antihyperglycemic and anti-inflammatory activities, might be used as potent antidiabetic agents for the treatment of type 2 diabetes. PMID:25053966

2014-01-01

34

Anti-Inflammatory Diet  

MedlinePLUS

... anti-inflammatory essen- tial fats. Organic free-range chicken tend to be lower in antibiotics and are fed a vegetable/grain based diet which tends to offer cleaner sources of protein. • Spices/herbs – Seasonings such as garlic, ginger and ...

35

The anti-inflammatory effects of a high-frequency oligodeoxynucleotide from the genomic DNA of Lactobacillus casei.  

PubMed

Genomic DNA has been identified as an anti-inflammatory component of Lactobacillus species, the effects of which are mediated through toll-like receptor (TLR) 9. In this study, we identified 14 novel anti-inflammatory oligodeoxynucleotide (ODN) from the genomic DNA of Lactobacillus casei by measuring their effects on the secretion of interleukin (IL)-8 (CXCL8) in the human epithelial colorectal adenocarcinoma cell line Caco-2 cells. The ODN TTTTGCCG strongly decreased IL-8 secretion. In the genomic DNA of Lactobacillus species, the frequency of TTTTGCCG was highest in the genomic DNA of L. casei and similar among strains of L. casei. Decreases in inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions in macrophage-like differentiated THP-1 cells confirmed the anti-inflammatory effect of TTTTGCCG. Furthermore, oral administration of TTTTGCCG ameliorated dextran sodium sulfate (DSS)-induced murine colitis and DSS-induced increased expression of inflammatory factor mRNAs, such as macrophage inflammatory protein (MIP)-2 (CXCL2), iNOS, and COX-2. The anti-inflammatory effect of TTTTGCCG was mainly regulated by an increase in heat shock protein (Hsp) 70 expression in the epithelium. TLR9 and Hsp90 may primarily mediate the anti-inflammatory effect of TTTTGCCG on Hsp70 signaling. PMID:25193776

Hiramatsu, Yukihiro; Satho, Tomomitsu; Hyakutake, Mika; Irie, Keiichi; Mishima, Kenichi; Miake, Fumio; Kashige, Nobuhiro

2014-09-01

36

Anti-inflammatory ingredients.  

PubMed

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

Wu, Jessica

2008-07-01

37

Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q'eqchi' Maya traditional medicine.  

PubMed

The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q'eqchi' Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotanical investigation of the uses of N. lobata by the Q'eqchi' Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiterpene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 ?g/mL reduced LPS-stimulated TNF-? production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9?-hydroxy-8?-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 ?M) than the positive control parthenolide (IC50=4.79 ?M). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. PMID:23747054

Walshe-Roussel, Brendan; Choueiri, Christine; Saleem, Ammar; Asim, Muhammd; Caal, Federico; Cal, Victor; Rojas, Marco Otarola; Pesek, Todd; Durst, Tony; Arnason, John Thor

2013-08-01

38

High-performance thin layer chromatographic analysis of anti-inflammatory triterpenoids from Boswellia serrata Roxb.  

PubMed

A rapid and simple high-performance thin layer chromatographic (HPTLC) method was developed for the simultaneous quantitative estimation of the biologically active triterpenoids beta-boswellic acid, 3-O-acetyl-beta-boswellic acid, 11-keto-beta-boswellic acid and 3-O-acetyl-11-keto-beta-boswellic acid from the gum resin of Boswellia serrata. The assay combines the isolation and separation of boswellic acid derivatives on silica gel 60F254-HPTLC plates with spot visualisation and scanning at 250 nm. Methanol was found to be the most appropriate solvent for the exhaustive extraction of boswellic acid derivatives. PMID:11793815

Krohn, K; Rao, M S; Raman, N V; Khalilullah, M

2001-01-01

39

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

PubMed Central

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

2013-01-01

40

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

PubMed Central

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

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

2014-01-01

41

Anti-inflammatory activity and pharmacokinetic profile of a new parenteral formulation of nimesulide.  

PubMed

Nimesulide, a selective COX-2 inhibitor, exerts potent anti-inflammatory and analgesic effects when administered orally, rectally or topically. The present study was designed to evaluate the anti-inflammatory activity of a new parenteral formulation of nimesulide and to correlate it with the pharmacokinetic profile. Nimesulide was administered intramuscularly at increasing doses of 1. 5, 3, 6, 12.5 and 25 mg kg-1 which produced dose-dependent anti-inflammatory effects in the carrageenan-induced rat paw edema. The anti-inflammatory activity of nimesulide was greater than that of diclofenac which was administered at identical doses though the difference was not statistically significant. Peak anti-inflammatory effects with nimesulide were observed between 2 and 3 h post-treatment which correlates well with the tmax of 115 min. The plasma concentration of nimesulide at different time points was assayed using HPLC after administration at a dose of 25 mg kg-1. Peak plasma concentration (Cmax) was 23 microgram ml-1 while t1/2 was derived as 4.2 h. Area Under Curve (AUC(0-6 h)) was calculated as 83. 31 microgram ml-1 h-1. No toxicity or adverse effects were noted at the doses administered. The present study demonstrates that nimesulide administered intramuscularly may be superior to other routes of administration when fast onset of action is required with high plasma concentration. PMID:10072704

Gupta, S K; Bhardwaj, R K; Tyagi, P; Sengupta, S; Velpandian, T

1999-02-01

42

Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro.  

PubMed

The aggregation of alpha-synuclein (alphaS) in the brain has been implicated as a critical step in the development of Lewy body diseases (LBD) [Parkinson's disease (PD)/dementia with Lewy bodies (DLB)] and multiple system atrophy (MSA). The involvement of neuroinflammation and microglial activation has been emphasized in the pathogenesis of PD. Recent epidemiological studies have revealed that therapeutic use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing PD. Here, we examined the effects of NSAIDs, such as ibuprofen, aspirin, acetaminophen, meclofenamic acid sodium salt, sulindac sulfide, ketoprofen, flurbiprofen, diclofenac sodium salt, naproxen, and indomethacin, on the formation and destabilization of alphaS fibrils (falphaS) at pH 7.5 and 37 degrees C in vitro, using fluorescence spectroscopy with thioflavin S and electron microscopy. All examined NSAIDs, except for naproxen and indomethacin, inhibited the formation of falphaS in a dose-dependent manner. Moreover, these molecules dose-dependently destabilized preformed falphaS. The overall activity was in the order: ibuprofen approximately aspirin approximately acetaminophen approximately meclofenamic acid sodium salt approximately sulindac sulfide>ketoprofen approximately flurbiprofen approximately diclofenac sodium salt>naproxen approximately indomethacin. These findings indicate that NSAIDs could be key molecules for the development of therapeutic or preventive agents for LBD and MSA. PMID:18164319

Hirohata, Mie; Ono, Kenjiro; Morinaga, Akiyoshi; Yamada, Masahito

2008-03-01

43

Effect of Eluent pH on the Ionic and Molecular Forms of the Non-Steroidal Anti-Inflammatory Agents in Reversed-Phase High-Performance Liquid Chromatography  

Microsoft Academic Search

High-performance liquid chromatographic conditions for the best separation of some non-steroidal anti-inflammatory agents were described. The dependence of eluent pH on the ionic (protonated) and molecular (non-protonated) forms of analysed compounds have been investigated. This paper is the study of the retention behavior of some anti-inflammatory agents depending of the eluent pH.Some derivatives of phenol (acetaminophen, aspirin, salicylamide, phenacetin and

E. Nivaud-Guernet; M. Guernet; D. Ivanov?; M. Medenica

1994-01-01

44

Natural products and anti-inflammatory activity.  

PubMed

The aim of this review paper was to summarise some commonly available natural products and their anti-inflammatory activity. We have collected data from MEDLINE, Current Contents and scientific journals, which included 92 publications. There are numerous natural products detailed in this literature; however we have summarized a few of the most commonly available and potent ones. In this paper, the natural products with anti-inflammatory activity including curcumin, parthenolide, cucurbitacins, 1,8-cineole, pseudopterosins, lyprinol, bromelain, flavonoids, saponins, marine sponge natural products and Boswellia serrata gum resin were reviewed. Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Further studies are being conducted to investigate the mechanism of action, metabolism, safety and long term side effect of these natural products, as well as interactions between these natural products with food and drug components. PMID:16672197

Yuan, Gaofeng; Wahlqvist, Mark L; He, Guoqing; Yang, Min; Li, Duo

2006-01-01

45

Anti-inflammatory activity of diterpene alkaloids from Aconitum baikalense.  

PubMed

We compared anti-inflammatory activity of individual diterpene alkaloids isolated from Aconitum baikalense (napelline, songorine, hypaconitine, mesaconitine, 12-epinapelline N-oxide) under conditions of acute inflammation of different genesis. The tested substances showed high antiexudative activity comparable with that of sodium diclofenac. Unlike nonsteroidal anti-inflammatory drugs, diterpene alkaloids exerted no ulcerogenic effect. PMID:24770754

Nesterova, Yu V; Povetieva, T N; Suslov, N I; Zyuz'kov, G N; Aksinenko, S G; Pushkarskii, S V; Krapivin, A V

2014-03-01

46

Differential expression of pro-inflammatory and anti-inflammatory cytokines during experimental infection with low or high virulence bovine viral diarrhea virus in beef calves.  

PubMed

The objective was to compare the mRNA expression of pro-inflammatory (TNF-?, IL-1?, IFN-?, IL-2, IL-12, IL-15) and anti-inflammatory (IL-4, IL-10, TGF-?) cytokines, after experimental infection with low or high virulence noncytopathic (ncp) bovine viral diarrhea virus (BVDV). Thirty BVDV-naïve, beef calves were intranasally inoculated with low (LV; n=10, SD-1) or high (HV; n=10, 1373) virulence ncp BVDV or with BVDV-free cell culture medium (Control, n=10). Calves were euthanized on day 5 post-inoculation, and tracheo-bronchial lymph node and spleen samples were collected for mRNA expression through quantitative-RT-PCR. mRNA levels of pro-inflammatory (TNF-?, IL-1?, IL-2, IFN-?) and anti-inflammatory (IL-4 and IL-10) cytokines were up-regulated in tracheo-bronchial lymph nodes of HV, but not in LV, compared to the control group (P<0.05). IL-12 mRNA level was up-regulated in tracheo-bronchial lymph nodes of both LV and HV groups (P ? 0.05). A significant up-regulation of IL-15 mRNA was observed in tracheo-bronchial lymph nodes for LV calves (P<0.002), but not for HV calves. Experimental inoculation with BVDV-2 1373 stimulated significant mRNA expression of pro-inflammatory and anti-inflammatory cytokines. In contrast, inoculation with BVDV-1a SD-1 only resulted in up-regulation of IL-12 and IL-15 mRNA, which is associated with activation of macrophages and NK cells during innate immune response. PMID:24461321

Palomares, Roberto A; Brock, Kenny V; Walz, Paul H

2014-02-15

47

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

PubMed Central

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

Alajmi, Mohamed F.; Alam, Perwez

2014-01-01

48

Pharmacological potential of Populus nigra extract as antioxidant, anti-inflammatory, cardiovascular and hepatoprotective agent  

PubMed Central

Objective To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract. Methods Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema. Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections. Vasorelaxant effect was estimated in endothelium-intact and -rubbed rings of porcine coronary arteries precontracted with high concentration of U46619. Results The results showed a moderate antioxidant activity (40%), but potent anti-inflammatory activity (49.9%) on carrageenan-induced mice paw edema, and also as revealed by histopathologic examination, complete protection against AlCl3-induced hepatic toxicity. Relaxant effects of the same extract on vascular preparation from porcine aorta precontracted with high concentration of U46619 were considerable at 10?1 g/L, and comparable (P>0.05) between endothelium-intact (67.74%, IC50=0.04 mg/mL) and -rubbed (72.72%, IC50=0.075 mg/mL) aortic rings. Conclusions The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca2+ influx. PMID:23998009

Debbache-Benaida, Nadjet; Atmani-Kilani, Dina; Schini-Keirth, Valérie Barbara; Djebbli, Nouredine; Atmani, Djebbar

2013-01-01

49

Structural insights into the interaction between a potent anti-inflammatory protein, viral CC chemokine inhibitor (vCCI), and the human CC chemokine, Eotaxin-1.  

PubMed

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 poxvirus-encoded protein viral CC chemokine inhibitor (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? (macrophage inflammatory protein-1?) complex indicated that vCCI uses negatively charged residues in ?-sheet II to interact with positively charged residues in the MIP-1? N terminus, 20s region and 40s 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), a 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-1. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1 (monocyte chemoattractant protein-1), MIP-1?, and RANTES (regulated on activation normal T cell expressed and secreted), were determined as 1.1, 1.2, and 0.22 nm, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and multiple CC chemokines. PMID:24482230

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

2014-03-01

50

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

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.

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

2014-01-30

51

Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity.  

PubMed

Decoctions prepared from the bark of Uncaria tomentosa (cat's claw) are widely used in the traditional Peruvian medicine for the treatment of several diseases, in particular as a potent anti-inflammatory agent. Therefore, the main purpose of this study was to determine if the well-known anti-inflammatory activity of cat's claw decoction was related with its reactivity with the oxidant species generated in the inflammatory process and to establish a relationship between such antioxidant ability and its phenolic composition. We observed that the decoction prepared according to the traditional Peruvian medicine presented a potent radical scavenger activity, as suggested by its high capacity to reduce the free radical diphenylpicrylhydrazyl, and by its reaction with superoxide anion, peroxyl and hydroxyl radicals as well as with the oxidant species, hydrogen peroxide and hypochlorous acid. It also protected membrane lipids against peroxidation induced by the iron/ascorbate system, as evaluated by the formation of thiobarbituric acid-reactive substances (TBARs). The decoction phenolic profile was established by chromatographic analysis (HPLC/DAD and TLC) revealing essentially the presence of proanthocyanidins (oligomeric procyanidins) and phenolic acids, mainly caffeic acid. Thus, our results provide evidence for an antioxidant mechanism underlying the anti-inflammatory activity of cat's claw and support some of the biological effects of proanthocyanidins, more exactly its antioxidant and radical scavenging activities. PMID:15649515

Gonçalves, Cristina; Dinis, Teresa; Batista, Maria Teresa

2005-01-01

52

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

PubMed

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

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

2012-06-01

53

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

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

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

2014-03-21

54

Anti-inflammatory asterosaponins from the starfish Astropecten monacanthus.  

PubMed

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

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

2013-09-27

55

Anti-inflammatory Agents: Present and Future  

PubMed Central

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

Dinarello, Charles A.

2012-01-01

56

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

PubMed Central

Evaluation of abundantly available agro-industrial by-products for their bioactive compounds and biological activities is beneficial in particular for the food and pharmaceutical industries. In this study, rapeseed meal, cottonseed meal and soybean meal were investigated for the presence of bioactive compounds and antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities. Methanolic extracts of rapeseed meal showed significantly (P < 0.01) higher phenolics and flavonoids contents; and significantly (P < 0.01) higher DPPH and nitric oxide free radical scavenging activities when compared to that of cottonseed meal and soybean meal extracts. Ferric thiocyanate and thiobarbituric acid tests results showed rapeseed meal with the highest antioxidant activity (P < 0.01) followed by BHT, cotton seed meal and soybean meal. Rapeseed meal extract in xanthine oxidase and tyrosinase inhibitory assays showed the lowest IC50 values followed by cottonseed and soybean meals. Anti-inflammatory assay using IFN-?/LPS stimulated RAW 264.7 cells indicated rapeseed meal is a potent source of anti-inflammatory agent. Correlation analysis showed that phenolics and flavonoids were highly correlated to both antioxidant and anti-inflammatory activities. Rapeseed meal was found to be promising as a natural source of bioactive compounds with high antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities in contrast to cotton and soybean meals. PMID:22272095

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

2011-01-01

57

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

Microsoft Academic Search

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

C. Bodet; F. Chandad; D. Grenier

2006-01-01

58

Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents  

PubMed Central

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

Bala, Suman; Sharma, Neha; Saini, Vipin

2014-01-01

59

The anti-inflammatory effects of sanguinarine and its modulation of inflammatory mediators from peritoneal macrophages.  

PubMed

The quaternary ammonium salt, sanguinarine (SANG), is of great practical and research interest because of its pronounced, widespread physiological effects, which promote anti-microbial and anti-inflammatory responses in experimental animals. Sanguinarine was originally shown to possess anti-inflammatory properties and it has been used to treat various inflammatory diseases. To gain insight into the anti-inflammatory effect of sanguinarine and its mechanisms of action, we used animal models of acute and chronic inflammation and lipopolysaccharide (LPS)-induced murine peritoneal macrophages to examine the anti-inflammatory function of sanguinarine. Sanguinarine displayed significant anti-inflammatory effects both in vitro and in vivo. Our findings further demonstrated that sanguinarine potently inhibited the expression of inflammatory mediators and inflammation in general. Additionally, our results demonstrated that sanguinarine inhibited the activation of mitogen-activated protein kinase (MAPK), which altered inflammatory mediator synthesis and release in vitro. This study extends our understanding of the anti-inflammatory activity of sanguinarine in acute and chronic inflammation. Furthermore, our findings provide clarification of the molecular mechanisms underlying the anti-inflammatory activity of sanguinarine, supporting the naturopathic use of sanguinarine for the treatment of various human inflammatory diseases. PMID:22705062

Niu, Xiaofeng; Fan, Ting; Li, Weifeng; Xing, Wei; Huang, Huimin

2012-08-15

60

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

PubMed Central

Aims and objectives: The purpose of this study was to evaluate and compare the anti-inflammatory activity of the aqueous root bark extract of Aegle marmelos (Bilwa) in experimental acute and chronic inflammatory animal models. Materials and Methods: Aqueous extract of root bark of Bilwa was prepared and tested for anti-inflammatory activity in albino rats weighing 150-280 grams. The animals were randomly divided into 3 groups of 6 each; one group served as control and other two groups received indomethacin and Bilwa orally 1 hour prior to experimentation. The in vivo anti-inflammatory activity was studied using the acute (Carrageenan induced paw edema) and chronic (Cotton pellet induced granuloma) animal models. Anti-inflammatory activity was expressed as Percent inhibition (PI). Statistical analysis was performed using One-way analysis of variance (ANOVA) followed by Scheffe's post hoc test. P < 0.05 was considered statistically significant. Results: The PI with indomethacin and Bilwa in carrageenan induced paw edema were 52.7% and 46% and in cotton pellet induced granuloma were 24.7% and 9.2% respectively. Indomethacin showed highly significant anti-inflammatory activity in both the models. However, Bilwa showed highly significant activity in acute model and but a trend of anti-inflammatory activity in chronic model studied. Conclusions: As Bilwa showed significant anti-inflammatory activity in the models studied, it can be a promising anti-inflammatory agent. PMID:21844992

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

2011-01-01

61

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

SciTech Connect

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.

Liu Junyan [Department of Entomology and Cancer Center, University of California, Davis, CA 95616 (United States); Qiu Hong [Division of Cardiovascular Medicine, University of California, Davis, CA 95616 (United States); Morisseau, Christophe; Hwang, Sung Hee; Tsai, Hsing-Ju; Ulu, Arzu [Department of Entomology and Cancer Center, University of California, Davis, CA 95616 (United States); Chiamvimonvat, Nipavan [Division of Cardiovascular Medicine, University of California, Davis, CA 95616 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology and Cancer Center, University of California, Davis, CA 95616 (United States)

2011-09-01

62

Anti-Inflammatory Agents for Cancer Therapy  

PubMed Central

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

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

2010-01-01

63

Indigenous New Zealand honeys exhibit multiple anti-inflammatory activities.  

PubMed

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

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

2012-06-01

64

Structures and mechanism for the design of highly potent glucocorticoids.  

PubMed

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

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

65

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

PubMed

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

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

66

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

PubMed Central

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

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

67

Synthesis, analgesic, anti-inflammatory and anti-ulcerogenic activities of certain novel Schiff's bases as fenamate isosteres.  

PubMed

A series of certain novel Schiff bases as fenamate isosteres (VI:a-k) were synthesized to locate analgesic, anti-inflammatory agent with minimal ulcerogenic potential. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis as well as IR, and NMR and mass spectroscopic data. All the compounds were evaluated for their anti-inflammatory activity by carrageenan induced paw oedema method. The compounds possessing good anti-inflammatory activity were further tested for analgesic, ulcerogenic, lipid peroxidation potentials and liver toxicity. Compounds (VI-c), (VI-f), (VI-h) and (VI-i) showed the best anti-inflammatory and significant analgesic activities at doses comparable to that of the standard drug Indomethacin. However, compounds (VI-c) and (VI-f) could be considered the most potent anti-inflammatory and analgesic molecules with maximum reduction in gastro-intestinal ulceration with no hepatocyte necrosis or liver degeneration. PMID:25522819

Alafeefy, Ahmed M; Bakht, Mohammed A; Ganaie, Majid A; Ansarie, Mohd N; El-Sayed, Nahed N; Awaad, Amani S

2015-01-15

68

Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of Polygonatum verticillatum  

PubMed Central

Background The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders. Methods The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode’s solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules. Results In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102?±?0.19 ?g/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and ?-sitosterol. Conclusions These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation. PMID:23895558

2013-01-01

69

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

PubMed

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

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

2010-10-01

70

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

PubMed Central

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

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

2013-01-01

71

Identification of 14,20-dihydroxy-docosahexaenoic acid as a novel anti-inflammatory metabolite.  

PubMed

Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as D-series resolvins, protectin and maresin. Here, we analysed the lipids in inflammatory exudates using liquid chromatography-tandem mass spectrometry and identified a novel DHA metabolite, 14,20-dihydroxy-DHA (14,20-diHDHA) and showed that it is biosynthesized by eosinophils through the 12/15-lipoxygenase pathway. The chemical structure of the dominant 14,20-diHDHA isomer, which is endogenously biosynthesized by eosinophils, was identified as 14S,20R-diHDHA using chemically synthesized stereoisomers. Nanogram doses of 14,20-diHDHA displayed a potent anti-inflammatory action by limiting neutrophil infiltration in zymosan-induced peritonitis. The in vivo formation and potent anti-inflammatory action of 14,20-diHDHA may contribute to the protective effects of DHA. PMID:25012818

Yokokura, Yoshiyuki; Isobe, Yosuke; Matsueda, Shinnosuke; Iwamoto, Ryo; Goto, Tomomi; Yoshioka, Takeshi; Urabe, Daisuke; Inoue, Masayuki; Arai, Hiroyuki; Arita, Makoto

2014-12-01

72

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats.  

PubMed

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-?) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-? expression and inhibited the nuclear transcription factor-kappa B (NF-?B) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-?), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1?) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-? pathway. PMID:24848621

Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

2014-08-15

73

Oxpholipin 11D: An Anti-Inflammatory Peptide That Binds Cholesterol and Oxidized Phospholipids  

PubMed Central

Background Many Gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. Methodology/Results Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14-residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable ?-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features. Conclusion Given the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and other Oxpholipins may have therapeutic potential. PMID:20418958

Ruchala, Piotr; Navab, Mohamad; Jung, Chun-Ling; Hama-Levy, Susan; Micewicz, Ewa D.; Luong, Hai; Reyles, Jonathan E.; Sharma, Shantanu; Waring, Alan J.; Fogelman, Alan M.; Lehrer, Robert I.

2010-01-01

74

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

PubMed

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

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

2014-04-01

75

Anti-Inflammatory and Pro-Resolving Lipid Mediators  

PubMed Central

The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that non-steroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held to be a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution possessing potent anti-inflammatory and pro-resolving actions. A lipid mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3-polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates in addition to the lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. These new chemical mediator families were coined resolvins and protectins, given their potent bioactions. In this annual review, we present recent advances on the biosynthesis and stereospecific actions of these new pro-resolving mediators, which have also proven to be organ protective and anti-fibrotic. PMID:18233953

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

2009-01-01

76

ANTI-INFLAMMATORY ACTIVITY OF DODONAEA VISCOSE  

PubMed Central

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

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

1998-01-01

77

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

PubMed Central

Background Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) originates from Papua Island, Indonesia and grows in tropical areas. The different parts of the fruit of P. macrocarpa were evaluated for antioxidant, anti-inflammatory, and cytotoxic activities. Methods Phaleria macrocarpa fruit were divided into pericarp, mesocarp and seed. All parts of the fruit were reflux extracted with methanol. The antioxidant activity of the extracts were characterized in various in vitro model systems such as FTC, TBA, DPPH radical, reducing power and NO radical. Anti-inflammatory assays were done by using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-? and cytotoxic activities were determined by using several cancer cell lines and one normal cell line Results The results showed that different parts (pericarp, mesocarp, and seed) of Phaleria macrocarpa fruit contain various amount of total phenolic (59.2 ± 0.04, 60.5 ± 0.17, 47.7 ± 1.04 mg gallic acid equivalent/g DW) and flavonoid compounds (161.3 ± 1.58, 131.7 ± 1.66, 35.9 ± 2.47 mg rutin equivalent/g DW). Pericarp and mesocarp showed high antioxidant activities by using DPPH (71.97%, 62.41%), ferric reducing antioxidant power (92.35%, 78.78%) and NO scavenging activity (65.68%, 53.45%). Ferric thiocyanate and thiobarbituric acid tests showed appreciable antioxidant activity in the percentage hydroperoxides inhibitory activity from pericarp and mesocarp in the last day of the assay. Similarly, the pericarp and mesocarp inhibited inducible nitric oxide synthesis with values of 63.4 ± 1.4% and 69.5 ± 1.4% in macrophage RAW 264.7 cell lines induced by LPS/IFN-? indicating their notable anti-inflammatory potential. Cytotoxic activities against HT-29, MCF-7, HeLa and Chang cell lines were observed in all parts. Conclusions These results indicated the possible application of P. macrocarpa fruit as a source of bioactive compounds, potent as an antioxidant, anti inflammatory and cytotoxic agents. PMID:22070850

2011-01-01

78

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

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

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

79

Photoelectron spectroscopy of non-steroidal anti-inflammatory drugs  

NASA Astrophysics Data System (ADS)

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.

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

2013-08-01

80

Investigation of the anti-inflammatory properties of hydroxypyridinones.  

PubMed Central

Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the chelators competed successfully for iron with apotransferrin, and some removed up to 34% of iron from ferritin. The best anti-inflammatory effects were achieved with the most hydrophilic chelators and those which chelated iron most avidly. Activity was dependent on dose. The route of administration was also an important factor with lower affinity chelators. This work introduces a range of simple bidentate iron chelators, which under certain conditions exceed desferrioxamine in their iron scavenging abilities, and some of which, in this simple animal model, approach indomethacin in their anti-inflammatory capabilities. PMID:2730166

Hewitt, S D; Hider, R C; Sarpong, P; Morris, C J; Blake, D R

1989-01-01

81

Orthogonal array designs for the optimization of liquid-liquid-liquid microextraction of nonsteroidal anti-inflammatory drugs combined with high-performance liquid chromatography-ultraviolet detection.  

PubMed

Orthogonal array designs (OADs) were applied for the first time to optimize liquid-liquid-liquid microextraction (LLLME) conditions for the analysis of three nonsteroidal anti-inflammatory drug residues (2-(4-chlorophenoxy)-2-methylpropionic acid, ketoprofen, and naproxen) in wastewater samples. Six relevant factors were investigated: type of organic solvent, composition of donor phase and acceptor phase, stirring speed, extraction time and salt concentration. In the first stage, mixed-level orthogonal array design, an OA16 (4(1) x 2(12)) matrix was employed to study the effect of six factors, by which the effect of each factor was estimated using individual contributions as response functions. Based on the results of the first stage, 1-octanol was chosen as organic solvent for extraction. The other five factors were selected for further optimization using an OA16 (4(5)) matrix and a 4 x 4 table to locate more exact levels for each variable. The relative standard deviations for the reproducibility of optimized LLLME varied from 6.2 to 7.1%. The coefficients of determination for calibration curves were higher than 0.9950. The method detection limits for drugs spiked in ultrapure water were in the range of 0.03-0.3 ng/mL. The final optimized conditions were applied to the analysis of drug residues in three wastewater samples in Singapore. PMID:16199224

Wu, Jingming; Lee, Hian Kee

2005-10-28

82

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

PubMed Central

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

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

2014-01-01

83

Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms  

Microsoft Academic Search

Chronic inflammation is a key feature of vascular disease states such as atherosclerosis. Multiple clinical studies have shown that a class of medications termed statins lower cardiovascular morbidity and mortality. Originally developed to lower serum cholesterol, increasing evidence suggests that these medications have potent anti-inflammatory effects that contribute to their beneficial effects in patients. Here, we discuss the clinical and

Mukesh K. Jain; Paul M. Ridker

2005-01-01

84

The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats  

Microsoft Academic Search

We recently demonstrated that bee venom (BV) injection into the Zusanli acupoint produced a significantly more potent anti-inflammatory and antinociceptive effect than injection into a non-acupoint in a Freund's adjuvant induced rheumatoid arthritis (RA) model. However, the precise BV constituents responsible for these antinociceptive and\\/or anti-inflammatory effects are not fully understood. In order to investigate the possible role of the

Young Bae Kwon; Hye Jung Lee; Ho Jae Han; Woung Chon Mar; Sung Keel Kang; Ok Byung Yoon; Alvin J. Beitz; Jang Hern Lee

2002-01-01

85

Anti-inflammatory activity of extracts from fruits, herbs and spices  

Microsoft Academic Search

Inflammation plays an important role in various diseases with high prevalence within populations such as rheumatoid arthritis, atherosclerosis and asthma. Here we demonstrate the anti-inflammatory activity of various fruits, herbs and spices in a lipopolysaccharide-stimulated macrophage model. These compounds acted by reduction of pro-inflammatory interleukin (IL)-6 or tumour necrosis factor (TNF)-alpha production, enhancement of anti-inflammatory IL-10 production, or reduction of

Monika Mueller; Stefanie Hobiger; Alois Jungbauer

2010-01-01

86

Evaluation of anti-inflammatory activity of Calotropis gigantea (AKANDA) in various biological system.  

PubMed

To evaluate the effect of Calotropis G in various experimental animal models. The anti-inflammatory activity was evaluated using carrageenin-induced kaolin -induced rat paw oedema for acute and cotton-pellet granuloma, adjuvant-induced arthritis model for chronic inflammation. Antipyretic activity was carried out using yeast induced pyresis method. Phenylquinone--induced writhing method in mice was used for analgesic activity. Test compounds exhibited variable anti-inflammatory activity and peak activity of the test compounds were reached at 2 h. Alkaloid fraction possesses comparatively high initial anti-inflammatory activity. The residual anti-inflammatory activity of alkaloid fraction of Calotropis G suggest either a greater protein binding nature of the compound there by providing a slow released pool of active drug molecule in the system or non available of possible bioactive metabolites to retain the activity profile relation. PMID:17203820

Adak, Manoranjan; Gupta, Joyanta Kumar

2006-09-01

87

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

PubMed

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

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

1989-01-01

88

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

PubMed Central

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

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

2014-01-01

89

Ethanesulfohydroxamic acid ester prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs): synthesis, nitric oxide and nitroxyl release, cyclooxygenase inhibition, anti-inflammatory, and ulcerogenicity index studies.  

PubMed

The carboxylic acid group of the anti-inflammatory (AI) drugs indo-methacin, (S)-naproxen and ibuprofen was covalently linked via a two-carbon ethyl spacer to a sulfohydroxamic acid moiety (CH(2)CH(2)SO(2)NHOH) to furnish a group of hybrid ester prodrugs that release nitric oxide (NO) and nitroxyl (HNO). Biological data acquired for this hitherto unknown class of ethanesulfohydroxamic acid ester prodrugs showed (i) all compounds exhibited superior NO, but similar HNO, release properties relative to arylsulfohydroxamic acids, (ii) the (S)-naproxen and ibuprofen prodrug esters are more potent AI agents than their parent NSAID, (iii) the indomethacin prodrug ester, in contrast to indomethacin which is highly ulcerogenic, showed no visible stomach lesions [ulcer index (UI) = 0 for a 80 ?mol/kg oral dose] while retaining potent AI activity, and iv) that the indomethacin prodrug ester, unlike indomethacin which is an ulcerogenic selective COX-1 inhibitor, is a selective COX-2 inhibitor (COX-2 selectivity index = 184) devoid of ulcerogenicity that is attributed to its high COX-2 SI and/or ability to release cytoprotective NO. PMID:21280601

Huang, Zhangjian; Velázquez, Carlos A; Abdellatif, Khaled R A; Chowdhury, Morshed A; Reisz, Julie A; DuMond, Jenna F; King, S Bruce; Knaus, Edward E

2011-03-10

90

Statins as anti-inflammatory agents  

Microsoft Academic Search

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in cardiovascular disease have generally been attributed to their cholesterol-lowering property. However, an increasing number of in vitro and in vivo studies indicate that statins have direct anti-inflammatory effects that are not mediated by their hypocholesterolemic activity. In this article, the HMG-CoA-reductase-dependent and -independent mechanisms by which statins might

Gabriele Weitz-Schmidt

2002-01-01

91

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

PubMed Central

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

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

2012-01-01

92

Flumizole, a new nonsteroidal anti-inflammatory agent.  

PubMed

Flumizole is a potent anti-inflammatory agent in animal models with an inhibitory activity severalfold that of indomethacin in rat foot edema and prostaglandin synthetase tests. The drug was well absorbed from the GI tract when administered in the solution used in pharmacological assays. However, markedly poorer absorption of the solid form of this poorly water-soluble agent led to the development of a flumizole dispersion with polyethylene glycol 6000. The solid dispersion exhibited an increased dissolution rate in simulated gastric fluid and improved absorption properties in dogs relative to unformulated flumizole. Studies with a capsule formulation of the solid dispersion in human volunteers were indicative of good drug absorption. Plasma levels of flumizole were rapidly achieved and declined with a short half-life (2-7 hr) in rats, dogs, and humans. PMID:810570

Wiseman, E H; McIlhenny, H M; Bettis, J W

1975-09-01

93

Erdosteine: antitussive and anti-inflammatory effects.  

PubMed

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

Dal Negro, Roberto W

2008-01-01

94

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

PubMed

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

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

2011-11-01

95

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

PubMed

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

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

2012-06-01

96

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

PubMed

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

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

2007-05-30

97

Anti-Inflammatory Effects of Epoxyeicosatrienoic Acids  

PubMed Central

Epoxyeicosatrienoic acids (EETs) are generated by the activity of both selective and also more general cytochrome p450 (CYP) enzymes on arachidonic acid and inactivated largely by soluble epoxide hydrolase (sEH), which converts them to their corresponding dihydroxyeicosatrienoic acids (DHETs). EETs have been shown to have a diverse range of effects on the vasculature including relaxation of vascular tone, cellular proliferation, and angiogenesis as well as the migration of smooth muscle cells. This paper will highlight the growing evidence that EETs also mediate a number of anti-inflammatory effects in the cardiovascular system. In particular, numerous studies have demonstrated that potentiation of EET activity using different methods can inhibit inflammatory gene expression and signalling pathways in endothelial cells and monocytes and in models of cardiovascular diseases. The mechanisms by which EETs mediate their effects are largely unknown but may include direct binding to peroxisome proliferator-activated receptors (PPARs), G-protein coupled receptors (GPCRs), or transient receptor potential (TRP) channels, which initiate anti-inflammatory signalling cascades. PMID:22848834

Thomson, Scott J.; Askari, Ara; Bishop-Bailey, David

2012-01-01

98

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

PubMed

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

Singh, Bharat; Sharma, Ram Avtar

2013-03-15

99

Loteprednol etabonate ophthalmic suspension 0.5 %: efficacy and safety for postoperative anti-inflammatory use.  

PubMed

Topical corticosteroids are routinely used as postoperative ocular anti-inflammatory drugs; however, adverse effects such as increased intraocular pressure (IOP) are observed with their use. While older corticosteroids such as dexamethasone and prednisolone acetate offer good anti-inflammatory efficacy, clinically significant increases in IOP (?10 mmHg) are often associated with their use. Loteprednol etabonate, a novel C-20 ester-based corticosteroid, was retrometabolically designed to offer potent anti-inflammatory efficacy but with decreased impact on IOP. After exerting its therapeutic effects on the site of action, loteprednol etabonate is rapidly converted to inactive metabolites, resulting in fewer adverse effects. Randomized controlled studies have demonstrated the clinical efficacy and safety of loteprednol etabonate ophthalmic suspension 0.5 % for the treatment of postoperative inflammation in post-cataract patients with few patients, if any, exhibiting clinically significant increases (?10 mmHg) in IOP. Furthermore, safety studies demonstrated a minimal effect of loteprednol etabonate on IOP with long-term use or in steroid responders with a much lower propensity to increase IOP relative to prednisolone acetate or dexamethasone. The anti-inflammatory treatment effect of loteprednol etabonate appears to be similar to that of rimexolone and difluprednate with less impact on IOP compared to difluprednate, although confirmatory comparative studies are needed. The available clinical data suggest that loteprednol etabonate is an efficacious and safe corticosteroid for the treatment of postoperative inflammation. PMID:22707339

Amon, Michael; Busin, Massimo

2012-10-01

100

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

Microsoft Academic Search

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

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

1996-01-01

101

Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease  

NASA Astrophysics Data System (ADS)

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.

Tang, Jun

102

Novel pyrazolopyrimidine derivatives targeting COXs and iNOS enzymes; design, synthesis and biological evaluation as potential anti-inflammatory agents.  

PubMed

A novel set of 4-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidine and 5-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated as potential anti-inflammatory agents. The newly prepared compounds were assessed through the examination of their in vitro inhibition of four targets; cyclooxygenases subtypes (COX-1 and COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-?B). Compounds 8a, 10c and 13c were the most potent and selective ligands against COX-2 with inhibition percentages of 79.6%, 78.7% and 78.9% at a concentration of 2 ?M respectively, while compound 13c significantly inhibited both COX subtypes. On the other hand, fourteen compounds showed high iNOS inhibitory activities with IC50 values in the range of 0.22-8.5?M where the urea derivative 11 was the most active compound with IC50 value of 0.22 ?M. Most of the tested compounds were found to be devoid of inhibitory activity against NF-kB. Moreover, almost all compounds were not cytotoxic, (up to 25 ?g/ml), against a panel of normal and cancer cell lines. The in silico docking results were in agreement with the in vitro inhibitory activities against COXs and iNOS enzymes. The results of in vivo anti-inflammatory and antinociceptive studies were consistent with that of in vitro studies which confirmed that compounds 8a, 10c and 13c have significant anti-inflammatory and analgesic activities comparable to that of the control, ketorolac. Taken together, dual inhibition of COXs and iNOS with novel pyrazolopyrimidine derivatives is a valid strategy for the development of anti-inflammatory/analgesic agents with the probability of fewer side effects. PMID:24907682

Abdelazeem, Ahmed H; Abdelatef, Shaimaa A; El-Saadi, Mohammed T; Omar, Hany A; Khan, Shabana I; McCurdy, Christopher R; El-Moghazy, Samir M

2014-10-01

103

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

PubMed Central

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

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

2014-01-01

104

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

PubMed

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

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

2014-10-01

105

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

PubMed

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

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

2012-04-01

106

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

PubMed

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

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

2011-06-01

107

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

PubMed Central

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

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

108

Heme oxygenase-1 and anti-inflammatory M2 macrophages.  

PubMed

Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting enzymatic step of heme degradation and produces carbon monoxide, free iron, and biliverdin. HO-1, a stress-inducible protein, is induced by various oxidative and inflammatory signals. Consequently, HO-1 expression has been regarded as an adaptive cellular response against inflammatory response and oxidative injury. Although several transcriptional factors and signaling cascades are involved in HO-1 regulation, the two main pathways of Nrf2/Bach1 system and IL-10/HO-1 axis exist in monocyte/macrophage. Macrophages are broadly divisible into two groups: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. More recently, several novel macrophage subsets have been identified including Mhem, Mox, and M4 macrophages. Of these, M2 macrophages, Mhem, and Mox are HO-1 highly expressing macrophages. HO-1 has been recognized as having major immunomodulatory and anti-inflammatory properties, which have been demonstrated in HO-1 deficient mice and human cases of genetic HO-1 deficiency. However, the mechanism underlying the immunomodulatory actions of HO-1 remains poorly defined. This review specifically addresses macrophage polarization. The present current evidence indicates that HO-1 induction mediated by multiple pathways can drive the phenotypic shift to M2 macrophages and suggests that HO-1 induction in macrophages is a potential therapeutic approach to immunomodulation in widely diverse human diseases. PMID:25241054

Naito, Yuji; Takagi, Tomohisa; Higashimura, Yasuki

2014-12-15

109

Anti-inflammatory effects of resolvin-D1 on human corneal epithelial cells: in vitro study  

PubMed Central

Background This study evaluated the anti-inflammatory effects of Resolvin-D1 (RV-D1) and its mechanism of action in human corneal epithelial (HCE) cells. Methods HCE cells were incubated with different concentrations of RV-D1 for different time periods. Oleic acid (OA) and Dexamethasone (DM) served as negative and positive controls, respectively. Cells were stimulated with polyriboinosinic:polyribocytidylic acids (poly I:C). The protein contents and mRNA expression levels of Tumor necrosis factor-? (TNF-?), Interleukin (IL)-6, IL-1? and IL-8 were evaluated with multiplex fluorescent bead immunoassay (FBI) and real time-PCR, respectively. In addition, the expression of inhibitory factor-?B? (I-?B?) was evaluated with real time-PCR. Results The protein level of pro-inflammatory cytokines TNF-?, IL-6, IL-1? and IL-8 significantly increased after stimulation with Poly I:C. RV-D1 treatment at concentration of 1 ?M decreased the protein level of TNF-? to 20.76?±?9.3% (P??0.05) and IL-8 to 51.15?±?13.01% (P?highly significant dose response curve was demonstrated for RV-D1 treated HCE cells for TNF-? and IL-1?. DM treatment decreased the protein content for all of the pro-inflammatory cytokines, similar results were demonstrated at the mRNA level. The anti-inflammatory effects of RV-D1 were similar to those of DM for TNF-?, IL-6 and IL-8. Conclusions RV-D1 may serve as a potent anti-inflammatory agent in ocular surface inflammation, as evaluated in cultured HCE cells. The anti-inflammatory effects of RV-D1 were comparable to those of DM, and were mediated through nuclear factor kappa B (NF-?B) signal transduction. PMID:24580770

2014-01-01

110

Anti-inflammatory therapy for diabetic retinopathy  

PubMed Central

Diabetic retinopathy (DR) is one of the most common complications of diabetes. This devastating disease is a leading cause of blindness in people of working age in industrialized countries and affects the daily lives of millions of people. Despite tight glycemic control, blood pressure control, and lipid-lowering therapy, the number of DR patients keeps growing and therapeutic approaches are limited. Moreover, there are significant limitations and side-effects for the current therapies. Thus, there is a great need for development of new strategies for prevention and treatment of DR. Studies have shown that DR has prominent features of chronic, subclinical inflammation. This review will focus on the role of inflammation in DR and summarize the progress of studies of anti-inflammatory strategies for DR. PMID:21554091

Zhang, Wenbo; Liu, Hua; Rojas, Modesto; Caldwell, Robert W.; Caldwell, Ruth B.

2013-01-01

111

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

Microsoft Academic Search

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

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

2000-01-01

112

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

PubMed Central

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

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

2012-01-01

113

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

NASA Astrophysics Data System (ADS)

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.

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

114

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

PubMed Central

Background Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries. Methods and Findings Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7–58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%. Conclusions Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs. Please see later in the article for the Editors' Summary PMID:23424288

McGettigan, Patricia; Henry, David

2013-01-01

115

Evaluation of Phytochemical Screening and Anti Inflammatory Activity of Leaves and Stem of Mikania scandens (L.) Wild  

PubMed Central

Background: The greatest disadvantage in the presently available potent synthetic anti-inflammatory drugs lies in their toxicity and reappearance of symptoms after discontinuation. Hence, people are returning to the natural products with the hope of safety and security. Several species of Mikania have been reported to have anti-inflammatory properties. Aim: The present study aims to assess the anti-inflammatory activity of the ethanolic extract of the leaves and stem of Mikania scandens in vivo and in vitro. Materials and Methods: The in vitro bioassay consisted of assaying the effect of the extracts against denaturation of protein (egg albumin) and measuring the absorbance. In vivo anti-inflammatory activity was checked by measuring the percentage inhibition of carrageenan-induced rat paw edema after oral administration of the extracts to male Wistar rats. Results: The plant extracts revealed the presence of tannins, alkaloids, steroids and flavonoids in both the leaf and stem extracts. The in vitro study of leaf extracts of M. scandens demonstrated that at 16000 ?g/ml concentration a better anti-inflammatory activity was exhibited which is more than the stem extracts. Similarly in the in vivo study, carrageenan induced inflammation was significantly antagonized by M. scandens leaf extract, with inhibition of 50% at 1000 mg/kg. Conclusion: The ethanolic extract of both leaf and stem of M. scandens showed potent anti-inflammatory activity. In comparison the leaf extract found to be more potent in both the conditions in vivo and in vitro, comparing with the standard drug diclofenac sodium and traditional control rumalaya perhaps due to the presence of phytochemicals like alkaloids and flavonoids in the plant. PMID:25221699

Banerjee, S; Chanda, A; Adhikari, A; Das, AK; Biswas, S

2014-01-01

116

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

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

Es'haghi, Zarrin; Esmaeili-Shahri, Effat

2014-10-01

117

Anti-inflammatory, spasmolytic and diuretic effects of a commercially available Solidago gigantea Herb. extract.  

PubMed

The evaluation of a commercially available Solidago gigantea Herb. extract (Urol mono) revealed pronounced anti-inflammatory properties in the rat with respect to a reduction of the carrageenin-induced rat paw oedema. A direct comparison with diclofenac-Na (3 mg/kg b.w. p.o.) revealed that a high dose of Solidago gigantea Herb. extract possesses the same anti-inflammatory efficacy as diclofenac-Na. In addition, the Solidago gigantea Herb. extract exhibited moderate spasmolytic and diuretic properties. PMID:7710440

Leuschner, J

1995-02-01

118

Reduction of glucose intolerance with high fat feeding is associated with anti-inflammatory effects of thioredoxin 1 overexpression in mice  

PubMed Central

Aging is associated with reduced ability to maintain normal glucose homeostasis. It has been suggested that an age-associated increase in chronic pro-inflammatory state could drive this reduction in glucoregulatory function. Thioredoxins (Trx) are oxido-reductase enzymes that play an important role in the regulation of oxidative stress and inflammation. In this study, we tested whether overexpression of Trx1 in mice [Tg(TRX1)+/0] could protect from glucose metabolism dysfunction caused by high fat diet feeding. Body weight and fat mass gains with high fat feeding were similar in Tg(TRX1)+/0 and wild-type mice; however, high fat diet induced glucose intolerance was reduced in Tg(TRX1)+/0 mice relative to wild-type mice. In addition, expression of the pro-inflammatory cytokine TNF-? was reduced in adipose tissue of Tg(TRX1)+/0 mice compared to wild-type mice. These findings suggest that activation of thioredoxins may be a potential therapeutic target for maintenance of glucose metabolism with obesity or aging. PMID:22953037

Salmon, Adam B.; Flores, Lisa C.; Li, Yan; Van Remmen, Holly; Richardson, Arlan; Ikeno, Yuji

2012-01-01

119

Investigation of the Anti-Inflammatory Effects of Safranal on High-Fat Diet and Multiple Low-Dose Streptozotocin Induced Type 2 Diabetes Rat Model.  

PubMed

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

Hazman, Omer; Oval?, Serhat

2014-11-20

120

Anti-Leishmanial, Anti-Inflammatory and Antimicrobial Activities of Phenolic Derivatives from Tibouchina paratropica.  

PubMed

A new phenolic derivative, 2,8-dihydroxy-7H-furo[2,3-f]chromen-7-one (1), together with isoquercitrin (2), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti-parasitic activity against Leishmania donovani (IC50 ?=?0.809?µg/mL). In addition, an 85% reduction in the secretion of the pro-inflammatory cytokine IL-6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1, but no effect on the anti-inflammatory IL-10 was observed. Compound 2 showed neither anti-parasitic nor anti-inflammatory properties. In addition, no cytotoxic activities were observed against the human-derived macrophage THP-1 cells. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25417600

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

2014-11-24

121

Design, synthesis, characterization and in vitro and in vivo anti-inflammatory evaluation of novel pyrazole-based chalcones.  

PubMed

Abstract A series of novel pyrazole-based chalcones have been designed, synthesized from 1-methyl-5-(2,4,6-trimethoxyphenyl)-1H-pyrazole (6). The structures of regioisomers 6 and 7 were determined by 2D (1)H-(1)H COSY, (1)H-(13)C HSQC and (1)H-(13)C HMBC experiments. The newly synthesized compounds were tested for their inhibitory activity against COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Moreover, they were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model for acute inflammation and cotton pellet-induced granuloma model for chronic inflammation. All the synthesized compounds showed potential to demonstrate anti-inflammatory activities, of particular interest compounds 10i, 10e, 10f, and 10h were found to be potent anti-inflammatory agents. PMID:24666306

Chavan, Hemant V; Adsul, Laxman K; Kotmale, Amol S; Dhakane, Valmik D; Thakare, Vishnu N; Bandgar, Babasaheb P

2015-02-01

122

Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats  

PubMed Central

Background Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional Chinese medicinal plant, is used to treat some infectious diseases and it may have uses as a healthy food and applications in cosmetics and as an ornamental groundcover. The ethanol extract of the flowering aerial parts of L. japonica (LJEE) was investigated for its healing efficiency in a rat excision wound model. Methods Excision wounds were inflicted upon three groups of eight rats each. Healing was assessed by the rate of wound contraction in skin wound sites in rats treated with simple ointment base, 10% (w/w) LJEE ointment, or the reference standard drug, 0.2% (w/w) nitrofurazone ointment. The effects of LJEE on the contents of hydroxyproline and hexosamine during healing were estimated. The antimicrobial activity of LJEE against microorganisms was also assessed. The in vivo anti-inflammatory activity of LJEE was investigated to understand the mechanism of wound healing. Results LJEE exhibited significant antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared with 10% (w/w) LJEE exhibited potent wound healing capacity as evidenced by the wound contraction in the excision wound model. The contents of hydroxyproline and hexosamine also correlated with the observed healing pattern. These findings were supported by the histopathological characteristics of healed wound sections, as greater tissue regeneration, more fibroblasts, and angiogenesis were observed in the 10% (w/w) LJEE ointment-treated group. The results also indicated that LJEE possesses potent anti-inflammatory activity, as it enhanced the production of anti-inflammatory cytokines that suppress proinflammatory cytokine production. Conclusions The results suggest that the antimicrobial and anti-inflammatory activities of LJEE act synergistically to accelerate wound repair. PMID:23173654

2012-01-01

123

Identification of anti-inflammatory and other biological activities of 3-carboxamide, 3-carbohydrazide and ester derivatives of gatifloxacin  

PubMed Central

Background Seventeen 1,4-dihydroquinoline-3-carboxamide and 1,4-dihydroquinoline-3-carbohydrazide derivatives of gatifloxacin have been prepared with a facile one step synthesis aiming to improve antibacterial, antifungal and immunological activities. The methodology allows the introduction of a variety of substituents such as amines, alcohol, phenol, amides and alkyl halides into the core structure of gatifloxacin. Results The analog N-(3-aminophenyl)-1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide has been identified as a potentially excellent anti-inflammatory agent, which exhibited highly potent effects on the oxidative burst activity of whole blood phagocytes (IC50 <12.5 ?g mL-1), neutrophils (IC50 <0.1 ?g mL-1) and macrophages phagocytes (IC50 <3.1 ?g mL-1) as well as potent T-cell proliferation inhibitory effect (IC50 3.7 ?g mL-1) while having comparable antibacterial activity to gatifloxacin. Another analog, 1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-N-phenyl-1,4-dihydroquinoline-3-carbohydrazide has tremendous T-cell proliferation inhibitory effect IC50 <3.1 ?g mL-1 as compared to prednisolone, whereas, 3,5-dihydroxyphenyl1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate and 2-hydroxyphenyl-1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate envision good inhibitory activity on T-cells proliferation (IC50 6.8 & 8.8 ?g mL-1 respectively). Conclusions The structural modification at carboxylic group has resulted in improved anti-inflammatory activities with comparable antibacterial activity to gatifloxacin. We believe that C3 structural modifications of gatifloxacin are definitely important in bringing major immunomodulatory changes in these compounds. PMID:23316796

2013-01-01

124

A neutrophil multitarget functional bioassay to detect anti-inflammatory natural products.  

PubMed

A multitarget functional bioassay was optimized as a method for detecting substances interacting with the inflammatory process of activated neutrophil granulocytes, mainly to release elastase detected by p-nitroanilide (pNA) formation. Using this bioassay, 100 fractionated extracts of 96 plants were screened, with results presented in a manner that links recorded biological activity to phylogenetic information. The plants were selected to represent a major part of the angiosperms, with emphasis on medicinal plants, Swedish anti-inflammatory plants, and plants known to contain peptides. Of the tested extracts, 41% inhibited pNA formation more than 60%, and 3% stimulated formation. The extract of Digitalis purpurea enhanced pNA formation, and digitoxin, the active compound, was isolated and identified. Plant extracts that exhibited potent nonselective inhibition (>80% inhibition) were evaluated further for direct inhibition of isolated elastase and trypsin enzyme. The inhibitory effect of most tested extracts on the isolated enzyme elastase was similar to that of PAF- and fMLP-induced pNA formation. Compared to trypsin, inhibition of elastase by extracts of Rubus idaeus and Tabernaemontana dichotoma was significantly higher (80% and 99%, respectively). Inhibition of trypsin by the extract of Reseda luteola was high (97%). Orders such as Lamiales and Brassicales were shown to include a comparably high proportion of plants with inhibitory extracts. PMID:11809061

Johansson, Senia; Göransson, Ulf; Luijendijk, Teus; Backlund, Anders; Claeson, Per; Bohlin, Lars

2002-01-01

125

Anti-inflammatory activity of Chinese medicinal vine plants.  

PubMed

Anti-inflammatory activities of ethanol extracts from nine vine plants used in traditional Chinese medicine to treat inflammatory conditions were evaluated against a panel of key enzymes relating to inflammation. The enzymes included cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), phospholipase A(2) (PLA(2)), 5-lipoxygenase (5-LO) and 12-lipoxygenase (12-LO). The vine plants studied were: the stem of Spatholobus suberectus Dunn, the stem of Trachelospermum jasminoides Lem., the root from Tripterygium wilfordii Hook. f., the stem of Sinomenium acutum Rehder and Wilson, the stem of Piper kadsura (Choisy) Ohwi, the stem of Polygonum multiflorum Thunb., the root and stem from Tinospora sagittata Gagnep., the root of Tinospora sinensis (Lour.) Merrill, and the stem of Clematis chinensis Osbeck. All of the plant extracts showed inhibitory activities against at least one of the enzymes in various percentages depending upon the concentrations. The extract from S. suberectus was found to be active against all enzymes except COX-2. Its IC(50) values were 158, 54, 31 and 35 microg/ml in COX-1, PLA(2), 5-LO and 12-LO assays, respectively. T. jasminoides showed potent inhibitory activities against both COX-1 (IC(50) 35 microg/ml) and PLA(2) (IC(50) 33 microg/ml). The most potent COX-1, COX-2 and 5-LO inhibition was observed in the extract of T. wilfordii with the IC(50) values of 27, 125 and 22 microg/ml, respectively. The findings of this study may partly explain the use of these vine plants in traditional Chinese medicine for the treatment of inflammatory conditions. PMID:12576203

Li, Rachel W; David Lin, G; Myers, Stephen P; Leach, David N

2003-03-01

126

Cajucarinolide and isocajucarinolide: anti-inflammatory diterpenes from Croton cajucara.  

PubMed

Cajucarinolide and isocajucarinolide, two new clerodane diterpenes, have been isolated from the cortices of Croton cajucara (Euphorbiaceae). These compounds possess anti-inflammatory activity and inhibit bee venom phospholipase A2 in vitro. PMID:1484896

Ichihara, Y; Takeya, K; Hitotsuyanagi, Y; Morita, H; Okuyama, S; Suganuma, M; Fujiki, H; Motidome, M; Itokawa, H

1992-12-01

127

Anti-Inflammatory Activity of Chitooligosaccharides in Vivo  

PubMed Central

All the reports to date on the anti-inflammatory activity of chitooligosaccharides (COS) are mostly based on in vitro methods. In this work, the anti-inflammatory activity of two COS mixtures is characterized in vivo (using balb/c mice), following the carrageenan-induced paw edema method. This is a widely accepted animal model of acute inflammation to evaluate the anti-inflammatory effect of drugs. Our data suggest that COS possess anti-inflammatory activity, which is dependent on dose and, at higher doses, also on the molecular weight. A single dose of 500 mg/kg b.w. weight may be suitable to treat acute inflammation cases; however, further studies are needed to ascertain the effect upon longer inflammation periods as well as studies upon the bioavailability of these compounds. PMID:20631868

Fernandes, João C.; Spindola, Humberto; de Sousa, Vanessa; Santos-Silva, Alice; Pintado, Manuela E.; Malcata, Francisco Xavier; Carvalho, João E.

2010-01-01

128

Anti-Inflammatory Activity of Delonix regia (Boj. Ex. Hook)  

PubMed Central

The present work was to evaluate the anti-inflammatory activity of Delonix regia leaves (Family: Caesalpiniaceae). The powder of Delonix regia leaves was subjected to extraction with ethanol in soxhlet extractor. The ethanol extract after preliminary phytochemical investigation showed the presence of sterols, triterpenoids, phenolic compounds and flavonoids. The anti-inflammatory activity was studied using carrageenan-induced rat paw edema and cotton pellet granuloma at a three different doses (100, 200, and 400?mg/kg b.w. p.o.) of ethanol extract. The ethanol extract of Delonix regia leaves was exhibited significant anti-inflammatory activity at the dose of 400?mg/kg in both models when compared with control group. Indomethacin (10?mg/kg b.w. p.o) was also shown significant anti-inflammatory activity in both models. PMID:22110490

Shewale, Vaishali D.; Deshmukh, Tushar A.; Patil, Liladhar S.; Patil, Vijay R.

2012-01-01

129

Synthesis and biological evaluation studies of novel quinazolinone derivatives as antibacterial and anti-inflammatory agents  

PubMed Central

Some novel 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones bearing sulfonamide derivatives (4–11) were synthesized in good yields and evaluated for their possible antibacterial, anti-inflammatory activities and acute toxicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Their antibacterial activities were evaluated by the agar well diffusion method while their anti-inflammatory activities were evaluated by the carrageenan-induced hind paw edema test. All the tested compounds showed considerable antibacterial activities and high to moderate anti-inflammatory activities that last for 12 h compared to ibuprofen. All the tested compounds showed no toxic symptoms or mortality rates 24 h post-administration at tested anti-inflammatory doses. In addition, LD50 for all tested compounds was higher than that for ibuprofen implying their good safety margin. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs. PMID:24648828

F. Zayed, Mohamed; H. Hassan, Memy

2013-01-01

130

Evaluation of the antioxidant, anti-inflammatory, and anticancer activities of Euphorbia hirta ethanolic extract.  

PubMed

This study evaluated the chemical composition, antioxidant, anti-inflammatory and anticancer activities of a Euphorbia hirta L. extract. The antioxidant activities of whole E. hirta ethanol extract were determined by electron spin resonance spectrophotometric analysis of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl, and alkyl radical levels and by using an online high-performance liquid chromatography (HPLC)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. The E. hirta ethanol extract (0.5 mg/mL) exhibited DPPH-scavenging activity of 61.19% ± 0.22%, while the positive control (0.5 mg/mL ascorbic acid) had 100% ± 0.22% activity. The concentration of the extract required to trap 50% of DPPH (IC50) was 0.205 mg/mL. Online HPLC analysis of the extract also showed strong antioxidant activity. The anti-inflammatory activity of the E. hirta extract was assessed in lipopolysaccharide-induced RAW 264.7 macrophages. The anti-inflammatory activity was highest in the presence of 200 µg/mL E. hirta extract, and nitric oxide production was decreased significantly (p < 0.05). The extract also showed selective anticancer activity at a concentration of 100 µg/mL (p < 0.05). These results indicated that E. hirta may warrant further investigation for the development of antioxidant, anti-inflammatory, and anticancer herbal medications. PMID:25225720

Sharma, Neelesh; Samarakoon, Kalpa W; Gyawali, Rajendra; Park, Yang-Ho; Lee, Sung-Jin; Oh, Sung Jong; Lee, Tae-Hoon; Jeong, Dong Kee

2014-01-01

131

Analgesic and anti-inflammatory activities of Trigonella foenum-graecum (seed) extract.  

PubMed

Analgesic and anti-inflammatory effects were examined in a partially purified fraction (MTH) of the Trigonella foenum-graecum seed extract. The analgesic effects of graded doses of fraction (MTH in 10-40 mg/kg p.o.) were evaluated in mice against acetic acid induced writhing (chemically induced pain) and hot-plate method (thermally induced pain). The analgesia produced by MTH was compared with the standard analgesics pentazocine (PTZ, 5 mg/kg p.o.) and diclofenac sodium (DIS, 5 mg/kg p.o.). Acute anti-inflammatory activity of fraction (MTH) was also evaluated in carrageenan-induced rat paw edema model at the doses 10 and 20 mg/kg i.p. and compared with diclofenac sodium (5 mg/kg i.p.). In comparison to control group MTH showed highly significant, dose dependent analgesic activity against thermally as well as chemically induced pain (p < 0.001). MTH at the dose of 40 mg/kg has shown significant analgesic activity (p < 0.001) as compared to diclofenac sodium and pentazocine at the doses employed. In comparison to control, MTH at the employed doses produced marked acute anti-inflammatory activity in rats (p <0.001). The results suggest that the water soluble fraction (MTH) of herbal origin has significant analgesic and anti-inflammatory potential as reflected by the parameters investigated. Further investigations are, however, necessary to explore mechanism(s) of action involved in these pharmacological activities. PMID:19051589

Vyas, Savita; Agrawal, Rajendra Prasad; Solanki, Pooja; Trivedi, Piyush

2008-01-01

132

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

PubMed Central

GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized. PMID:9792333

van der Velden, V H

1998-01-01

133

Anti-inflammatory effects of Dendrobium nobile derived phenanthrenes in LPS-stimulated murine macrophages.  

PubMed

Dendrobium nobile belongs to the Orchidaceae family and is one of the medicinal herbs used in traditional Chinese medicine as a therapeutic agent for gastrointestinal and cardiovascular diseases. In this study, we separated three phenanthrenes (ephemeranthol A (EA), 1,5,7-trimethoxyphenanthren-2-ol (TP), dehydroorchinol (DO)) from D. nobile, and compared their anti-inflammatory activities. TP is a new phenanthrene compound and its structure was determined from (1)H, (13)C NMR and HR-ESI-MS data. To analyze the anti-inflammatory activities of the phenanthrenes, Raw 264.7 cells were used, since they are immature-macrophages and easily matured by LPS stimulation. EA and DO showed anti-inflammatory activities in the activated Raw 264.7 cells. That is, we showed that EA is a potent inhibitor of the production of nitric oxide and pro-inflammatory cytokines. The inhibitory activities of phenanthrenes were found to be caused by blockage of NF-?B activation and the phosphorylation of MAP kinases in the macrophages. These results are expected to serve as a guide for future studies on the ability of phenanthrenes to inhibit acute and chronic inflammatory diseases. PMID:25370607

Kim, Jeong Hwa; Oh, Su-Yeon; Han, Sang-Bae; Uddin, Golam Mezbah; Kim, Chul Young; Lee, Jae Kwon

2014-11-01

134

Natural compound cudraflavone B shows promising anti-inflammatory properties in vitro.  

PubMed

Cudraflavone B (1) is a prenylated flavonoid found in large amounts in the roots of Morus alba, a plant used as a herbal remedy for its reputed anti-inflammatory properties. The present study shows that this compound causes a significant inhibition of inflammatory mediators in selected in vitro models. Thus, 1 was identified as a potent inhibitor of tumor necrosis factor ? (TNF?) gene expression and secretion by blocking the translocation of nuclear factor ?B (NF-?B) from the cytoplasm to the nucleus in macrophages derived from a THP-1 human monocyte cell line. The NF-?B activity reduction resulted in the inhibition of cyclooxygenase 2 (COX-2) gene expression. Compound 1 acts as a COX-2 and COX-1 inhibitor with higher selectivity toward COX-2 than indomethacin. Pretreatment of cells by 1 shifted the peak in an regulatory gene zinc-finger protein 36 (ZFP36) expression assay. This natural product has noticeable anti-inflammatory properties, suggesting that 1 potentially could be used for development as a nonsteroidal anti-inflammatory drug lead. PMID:21319773

Hošek, Jan; Bartos, Milan; Chudík, Stanislav; Dall'Acqua, Stefano; Innocenti, Gabbriella; Kartal, Murat; Kokoška, Ladislav; Kollár, Peter; Kutil, Zsófia; Landa, P?emysl; Marek, Radek; Závalová, Veronika; Žemli?ka, Milan; Šmejkal, Karel

2011-04-25

135

Anti-inflammatory alkaloids from the stems of Picrasma quassioides BENNET.  

PubMed

During further chemical and biological investigations of Picrasma quassioides BENNET, four new bis-?-carboline alkaloids, quassidines E-H (1-4), and three new ?-carboline alkaloids, canthin-16-one-14-butyric acid (5), 3-(1,1-dimethoxylmethyl)-?-carboline (6), and 6,12-dimethoxy-3-formyl-?-carboline (7), were isolated from its anti-inflammatory CHCl(3)-soluble fraction. Structures of new compounds were elucidated and characterized by MS and NMR analysis. A plausible biogenetic pathway for quassidine E (1), the first bis-?-carboline alkaloid in which a canthin-6-one moiety and a ?-carboline moiety were connected together by a single carbon-carbon bond from the nature, was proposed. Quassidines E-G (1-3) showed potent inhibitory activity on the production of nitric oxide (NO), tumor necrosis factor ? (TNF-?), or interleukin 6 (IL-6) in mouse monocyte-macrophage RAW264.7 cells stimulated by lipopolysaccharide (LPS). Analysis of anti-inflammatory activity of all ?-carboline and bis-?-carboline alkaloids from P. quassioides showed that the carbonyl groups or double carbon-carbon bonds at C-14 for ?-carbolines and C-14' for bis-?-carbolines were bioactive groups for their in vitro anti-inflammatory activity. Structure-activity relationship of these compounds on inhibitory activity of the three inflammatory cytokines was discussed. PMID:21372418

Jiao, Wei-Hua; Gao, Hao; Zhao, Feng; Lin, Hou-Wen; Pan, Yu-Min; Zhou, Guang-Xiong; Yao, Xin-Sheng

2011-01-01

136

Screening of Ficus religiosa leaves fractions for analgesic and anti-inflammatory activities  

PubMed Central

Objective: To evaluate the different fractions of dried leaves of Ficus religiosa Linn for analgesic and anti-inflammatory activity using different models of pain and inflammation Materials and Methods: The analgesic activity of F. religiosa carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. Five different fractions (FRI, FRII, FRIII, FRIV and FRV) of F. religiosa at the dose level of 20 and 40 mg/kg, p.o were tested. Results: The fraction FRI (40 mg/kg, p.o.) and FRIII (40 mg/kg, p.o) were found to be more effective (P<0.01) in preventing carrageenan induced rat paw edema, cotton pellet granuloma formation, and acetic acid induced writhing compared to the other fractions. FRI (20 mg/kg, p.o.) and FRIII (20 mg/kg, p.o.) were also found to be more effective in increasing latency period in tail flick method. Conclusion: Out of five different fractions of F. religiosa leaves tested, FRI and FRIII possess potent analgesic and anti-inflammatory activities against different models of inflammation and pain. PMID:22144770

Gulecha, Vishal; Sivakumar, T; Upaganlawar, Aman; Mahajan, Manoj; Upasani, Chandrashekhar

2011-01-01

137

Antioxidant, Antinociceptive and Anti-inflammatory Activities of Ethanolic Extract of Leaves of Alocasia indica (Schott.).  

PubMed

Extracts obtained from the leaves of various Alocasia species have been used in India as folk remedy for the treatment of various inflammatory ailments including rheumatism and bruise. The ethanolic extract of leaves of Alocasia indica Schott. was evaluated by using different in vitro antioxidant models of screening like scavenging of 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical. The antinociceptive activity was tested by acetic acid-induced writhing response, hot plate method, and tail flick method in albino rats. The anti-inflammatory potential of gels of ethanolic extract has been determined by using carrageenan-induced paw edema assay, formalin-induced paw edema assay, arachidonic acid-induced ear edema assay, and xylene-induced ear edema assay. The extract showed remarkable antioxidant activity in all models, comparable to the standard reference drug ascorbic acid. The ethanolic extract of Alocasia indica and its gels produced dose-dependent antinociceptive and anti-inflammatory activity, respectively. This finding suggests that ethanolic extract of A. indica possess potent antinociceptive and anti-inflammatory activity possibly due to its free radical scavenging properties. PMID:21264115

Mulla, Wa; Kuchekar, Sb; Thorat, Vs; Chopade, Ar; Kuchekar, Bs

2010-04-01

138

Nonsteroidal anti-inflammatory agents: Species differences in pharmacodynamics  

Microsoft Academic Search

The disposition kinetics and systemic availability of nonsteroidal anti-inflammatory (NSAI) agents as well as their antipyretic and anti-nociceptive properties are reviewed in different species. The anti-inflammatory versus bradykinin, serotonin and kaolin oedema activities of aspirin (ASA), phenylbutazone (PBZ) and indomethacin (IDM) explain their large use in veterinary medicine. The low analgesic effect versus NO3Ag arthritis, radiant heat and tail pressure

Y. Ruckebusch; P. L. Toutain

1983-01-01

139

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

PubMed Central

The aim of this study was to determine the in vitro anti-inflammatory effect of hot water extract from Cordyceps militaris fruiting bodies (CMWE) on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production, tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) release in RAW 264.7 cells. The treatment of macrophages with various concentrations of hot CMWE significantly reduced LPS-induced production as well as NO, TNF-? and IL-6 secretion in a concentration-dependent manner. These results suggest that CMWE have potent inhibitory effects on the production of these inflammatory mediators. PMID:23956624

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

140

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

PubMed Central

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

Cianciolo, George J.; Pizzo, Salvatore V.

2012-01-01

141

Evaluation of anti-inflammatory, analgesic, and antipyretic activities of the ethanol extract from Murdannia loriformis (Hassk.) Rolla Rao et Kammathy  

PubMed Central

Introduction: Murdannia loriformis (hassk) Rolla Roa et Kammathy, family Commelinaceae, is used by Chinese practitioners as a remedy for cancer in an early stage, and also for treating other diseases including colds, throat infections, pneumonia, diabetes mellitus, flu and inflammation. Although anticancer as well as other pharmacological effects of M. loriformis have been reported, its anti-inflammatory and other activities related to inflammation are still limited. Methods: The anti-inflammatory activity was evaluated using carrageenan- and arachidonic acid-induced paw edema in rats, and cotton pellet-induced granuloma formation in rats. The analgesic and antipyretic activities were determined by formalin test in mice and yeast-induced hyperthermia in rats, respectively. Results: The ethanol extract of the aerial part of M. loriformis exhibited anti-inflammatory activity on the rat paw edema induced by carrageenan and arachidonic acid. It also showed an inhibitory effect on the granuloma and the transudative formation of the rat implanted with cotton pellets as well as lowered the elevated serum alkaline phosphatase activity to normal level. It exerted potent analgesic effect on both the early and late phase of formalin test as well as the antipyretic effect on yeast-induced hyperthermic rats. The oral single high dose of the extract of 5,000 mg/Kg did not produce death or any abnormalities or changes of the internal organs of rats during 14 days of the observed period. Conclusion: The results obtained from this study support the use of the plant in traditional medicine for inflammatory ailments. PMID:25671174

Kunnaja, Phraepakaporn; Wongpalee, Somsakul Pop; Panthong, Ampai

2014-01-01

142

Furan fatty acid as an anti-inflammatory component from the green-lipped mussel Perna canaliculus  

PubMed Central

A lipid extract of Perna canaliculus (New Zealand green-lipped mussel) has reportedly displayed anti-inflammatory effects in animal models and in human controlled studies. However, the anti-inflammatory lipid components have not been investigated in detail due to the instability of the lipid extract, which has made the identification of the distinct active components a formidable task. Considering the instability of the active component, we carefully fractionated a lipid extract of Perna canaliculus (Lyprinol) and detected furan fatty acids (F-acids). These naturally but rarely detected fatty acids show potent radical-scavenging ability and are essential constituents of plants and algae. Based on these data, it has been proposed that F-acids could be potential antioxidants, which may contribute to the protective properties of fish and fish oil diets against chronic inflammatory diseases. However, to date, in vivo data to support the hypothesis have not been obtained, presumably due to the limited availability of F-acids. To confirm the in vivo anti-inflammatory effect of F-acids in comparison with that of eicosapentaenoic acid (EPA), we developed a semisynthetic preparation and examined its anti-inflammatory activity in a rat model of adjuvant-induced arthritis. Indeed, the F-acid ethyl ester exhibited more potent anti-inflammatory activity than that of the EPA ethyl ester. We report on the in vivo activity of F-acids, confirming that the lipid extract of the green-lipped mussel includes an unstable fatty acid that is more effective than EPA. PMID:21972415

Wakimoto, Toshiyuki; Kondo, Hikaru; Nii, Hirohiko; Kimura, Kaori; Egami, Yoko; Oka, Yusuke; Yoshida, Masae; Kida, Eri; Ye, Yiping; Akahoshi, Saeko; Asakawa, Tomohiro; Matsumura, Koichi; Ishida, Hitoshi; Nukaya, Haruo; Tsuji, Kuniro; Kan, Toshiyuki; Abe, Ikuro

2011-01-01

143

Melanocortins and the cholinergic anti-inflammatory pathway.  

PubMed

Experimental evidence indicates that small concentrations of inflammatory molecules produced by damaged tissues activate afferent signals through ascending vagus nerve fibers, that act as the sensory arm of an "inflammatory reflex". The subsequent activation of vagal efferent fibers, which represent the motor arm of the inflammatory reflex, rapidly leads to acetylcholine release in organs of the reticuloendothelial system. Acetylcholine interacts with ?7 subunit-containing nicotinic receptors in tissue macrophages and other immune cells and rapidly inhibits the synthesis/release of tumor necrosis factor-? and other inflammatory cytokines. This neural anti-inflammatory response called "cholinergic anti-inflammatory pathway" is fast and integrated through the central nervous system. Preclinical studies are in progress, with the aim to develop therapeutic agents able to activate the cholinergic anti-inflammatory pathway. Melanocortin peptides bearing the adrenocorticotropin/?-melanocyte-stimulating hormone sequences exert a protective and life-saving effect in animals and humans in conditions of circulatory shock. These neuropeptides are likewise protective in other severe hypoxic conditions, such as prolonged respiratory arrest, myocardial ischemia, renal ischemia and ischemic stroke, as well as in experimental heart transplantation. Moreover, experimental evidence indicates that melanocortins reverse circulatory shock, prevent myocardial ischemia/reperfusion damage and exert neuroprotection against ischemic stroke through activation of the cholinergic anti-inflammatory pathway. This action occurs via stimulation of brain melanocortin MC3/MC4 receptors. Investigations that determine the molecular mechanisms of the cholinergic anti-inflammatory pathway activation could help design of superselective activators of this pathway. PMID:21222261

Giuliani, Daniela; Ottani, Alessandra; Altavilla, Domenica; Bazzani, Carla; Squadrito, Francesco; Guarini, Salvatore

2010-01-01

144

The cholinergic anti-inflammatory pathway: a critical review.  

PubMed

From a critical review of the evidence on the cholinergic anti-inflammatory pathway and its mode of action, the following conclusions were reached. (1) Both local and systemic inflammation may be suppressed by electrical stimulation of the peripheral cut end of either vagus. (2) The spleen mediates most of the systemic inflammatory response (measured by TNF-? production) to systemic endotoxin and is also the site where that response is suppressed by vagal stimulation. (3) The anti-inflammatory effect of vagal stimulation depends on the presence of noradrenaline-containing nerve terminals in the spleen. (4) There is no disynaptic connection from the vagus to the spleen via the splenic sympathetic nerve: vagal stimulation does not drive action potentials in the splenic nerve. (5) Acetylcholine-synthesizing T lymphocytes provide an essential non-neural link in the anti-inflammatory pathway from vagus to spleen. (6) Alpha-7 subunit-containing nicotinic receptors are essential for the vagal anti-inflammatory action: their critical location is uncertain, but is suggested here to be on splenic sympathetic nerve terminals. (7) The vagal anti-inflammatory pathway can be activated electrically or pharmacologically, but it is not the efferent arm of the inflammatory reflex response to endotoxemia. PMID:24411268

Martelli, D; McKinley, M J; McAllen, R M

2014-05-01

145

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

PubMed

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

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

2013-03-01

146

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

PubMed Central

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

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

2014-01-01

147

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

PubMed Central

The protein-enriched extracts of housefly larvae were segregated by gel-filtration chromatography (GFC) and then anti-inflammatory activity screening in RAW264.7 (induced by LPS) was carried out. After acquire the anti-inflammatory effective parts, its anti-atherosclerotic properties in vivo were then evaluated. Results showed that the anti-inflammatory effective parts of housefly larvae were low-molecular-weight parts. After treated with the effective parts oral gavaged for 4 weeks, the atherosclerotic lesions of the mouse were significantly decreased. The inflammatory and lipid parameters were also reduced (except HDL which was increased). Western blot analysis demonstrated that the effective parts exerted potent inhibitory effect on expression of p65 in nucleus and cytoplasm. The results of immunofluorescence microscopy analysis also showed that the expressions of p65 both in cytoplasm and nucleus were significantly reduced. The hypothesis that the anti-inflammatory effective parts of housefly larvae possessed anti-atherosclerosis activity in mouse and the possible mechanism could be associated with the inhibition of expression and nuclear transfer of NF-?B p65 could be derived. PMID:23554828

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

2013-01-01

148

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

Microsoft Academic Search

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

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

2003-01-01

149

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

PubMed Central

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

2014-01-01

150

Tetra- and pentacyclic triterpene acids from the ancient anti-inflammatory remedy frankincense as inhibitors of microsomal prostaglandin E(2) synthase-1.  

PubMed

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

Verhoff, Moritz; Seitz, Stefanie; Paul, Michael; Noha, Stefan M; Jauch, Johann; Schuster, Daniela; Werz, Oliver

2014-06-27

151

Anti-inflammatory properties of drugs from saffron crocus.  

PubMed

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

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

2012-01-01

152

Biological evaluation of Phellinus linteus-fermented broths as anti-inflammatory agents.  

PubMed

Phellinus linteus and its constituent hispolon induce potent anti-inflammatory activity in macrophages. Efficient production of the effective constituent and the biological function of P. linteus in the regulation of innate sensing have rarely been investigated. The aim of this study was to efficiently manufacture P. linteus-fermented broth containing the effective constituent, hispolon, and evaluate its immunoregulatory functions in macrophages. Four distinct fermented broths (PL1-4) and the medium dialyzate (MD) were prepared to screen suitable culture conditions for the mycelial growth of P. linteus. The P. linteus-fermented broth exhibited a dose-responsive inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production by murine macrophages. In addition, the P. linteus-fermented broths suppressed macrophage LPS-mediated nuclear factor (NF)-?B activity and tumor necrosis factor (TNF)-?. Among the tested samples from P. linteus, PL4 contained vast amounts of hispolon and showed the greatest anti-inflammatory activity in both the RAW264.7 cells and murine primary peritoneal exudate macrophages (PEMs). This study demonstrates that the purification of the effective constituent from P. linteus-fermented broth may enable the production of a potent therapeutic agent for anti-inflammation in macrophages. PMID:24503424

Lin, Chun-Jung; Lien, Hsiu-Man; Chang, Hsiao-Yun; Huang, Chao-Lu; Liu, Jau-Jin; Chang, Yun-Chieh; Chen, Chia-Chang; Lai, Chih-Ho

2014-07-01

153

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

Microsoft Academic Search

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

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

1997-01-01

154

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

PubMed

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

Hong, Yun-Jung; Yang, Ki-Sook

2013-08-01

155

Screening of the topical anti-inflammatory activity of some Central American plants.  

PubMed

Hexane, chloroform and methanol extracts of seven herbal drugs used in the folk medicine of Central America against skin disorders (Aristolochia trilobata leaves and bark, Bursera simaruba bark, Hamelia patens leaves, Piper amalago leaves, and Syngonium podophyllum leaves and bark) were evaluated for their topical anti-inflammatory activity against the Croton oil-induced ear oedema in mice. Most of the extracts induced a dose-dependent oedema reduction. The chloroform extract of almost all the drugs exhibited interesting activities with ID(50) values ranging between 108 and 498 micro g/cm(2), comparable to that of indomethacin (93 micro g/cm(2)). Therefore, the tested plants are promising sources of principles with high anti-inflammatory activity. PMID:12065153

Sosa, S; Balick, M J; Arvigo, R; Esposito, R G; Pizza, C; Altinier, G; Tubaro, Aurelia

2002-07-01

156

Anti-inflammatory and antinociceptive potential of Maclura pomifera (Rafin.) Schneider fruit extracts and its major isoflavonoids, scandenone and auriculasin.  

PubMed

The aqueous, ethanolic and chloroform extracts and two prenylated isoflavones: scandenone (I) and auriculasin (II), isolated from the fruits of Maclura pomifera (Rafin.) Schneider, were investigated for their in vivo anti-inflammatory and antinociceptive activity. For the anti-inflammatory activity, both carrageenan-induced hind paw edema and 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema models and for the antinociceptive activity, p-benzoquinone-induced abdominal constriction test were used. Scandenone, the chloroform and the ethanolic extracts were shown to possess antinociceptive activity and anti-inflammatory activity on carrageenan-induced hind paw edema model at 100 mg/kg dose. The same compound and the extract were also found to be highly active in (TPA)-induced mouse ear edema model whereas auriculasin and the H(2)O extract showed to be inactive in all of the assays. PMID:16600547

Kupeli, Esra; Orhan, Ilkay; Toker, Gulnur; Yesilada, Erdem

2006-09-19

157

Analgesic and anti-inflammatory studies of cyclopeptide alkaloid fraction of leaves of Ziziyphus nummularia.  

PubMed

Ziziyphus nummularia (family: Rhamnaceae) is a thorny small bush, grows in abundance in the grazing lands of the arid areas of Rajasthan, India. It is an important ethnomedicinal plant of the Thar Desert; local inhabitants use every part of the plant as medicine. Kernels are prescribed in pregnancy as soporific, antiemetic and for relieving abdominal pain. The insect gall is powered and given orally with water to cure bone fracture. Crushed root is applied on the paining shoulder of the bullock. The decoction of leaves is used for the treatment of cough and cold; leaves are also regarded as diaphoretic and prescribed in typhoid. Paste of leaves is used for healing of cuts, boils and cutaneous disease. It is widely used in pain and inflammatory conditions. Z. nummularia contains a unique group of alkaloids known as cyclopeptide alkaloids, in continuation of our work carried out on the leaves of Z. nummularia , present study was initiated to explore antiinflammatory and analgesic potential of cyclopeptide alkaloids isolated from the leaves of Z. nummularia (IFZN). Anti-inflammatory activity was tested against rat paw oedema, mouse peritonitis and cotton pellet granuloma. For screening of analgesic activity, acetic acid induced writhing, tail flick and hot plate test were performed. IFZN 30 mg/kg shows the anti-oedematogenic effect against paw oedema induced by carrageenan, dextran, serotonin and histamine; IFZN 20 and 30 mg/kg were found to have highly significant anti-nociceptive effects. Result of pharmacological studies indicated that IFZN is a potent and efficacious analgesic agent. The analgesic activity of IFZN is mediated by the peripheral as well as central pathways. PMID:24235873

Goyal, Manoj; Ghosh, Manik; Nagori, B P; Sasmal, D

2013-10-01

158

Analgesic and anti-inflammatory studies of cyclopeptide alkaloid fraction of leaves of Ziziyphus nummularia  

PubMed Central

Ziziyphus nummularia (family: Rhamnaceae) is a thorny small bush, grows in abundance in the grazing lands of the arid areas of Rajasthan, India. It is an important ethnomedicinal plant of the Thar Desert; local inhabitants use every part of the plant as medicine. Kernels are prescribed in pregnancy as soporific, antiemetic and for relieving abdominal pain. The insect gall is powered and given orally with water to cure bone fracture. Crushed root is applied on the paining shoulder of the bullock. The decoction of leaves is used for the treatment of cough and cold; leaves are also regarded as diaphoretic and prescribed in typhoid. Paste of leaves is used for healing of cuts, boils and cutaneous disease. It is widely used in pain and inflammatory conditions. Z. nummularia contains a unique group of alkaloids known as cyclopeptide alkaloids, in continuation of our work carried out on the leaves of Z. nummularia, present study was initiated to explore antiinflammatory and analgesic potential of cyclopeptide alkaloids isolated from the leaves of Z. nummularia (IFZN). Anti-inflammatory activity was tested against rat paw oedema, mouse peritonitis and cotton pellet granuloma. For screening of analgesic activity, acetic acid induced writhing, tail flick and hot plate test were performed. IFZN 30 mg/kg shows the anti-oedematogenic effect against paw oedema induced by carrageenan, dextran, serotonin and histamine; IFZN 20 and 30 mg/kg were found to have highly significant anti-nociceptive effects. Result of pharmacological studies indicated that IFZN is a potent and efficacious analgesic agent. The analgesic activity of IFZN is mediated by the peripheral as well as central pathways. PMID:24235873

Goyal, Manoj; Ghosh, Manik; Nagori, B.P.; Sasmal, D.

2013-01-01

159

Evaluation of analgesic, antipyretic and anti-inflammatory activity on Cordia dichotoma G. Forst. Leaf  

PubMed Central

Background: Cordia dichotoma G. Forst. is an important medicinal plant of family Boraginaceae. Traditionally, its leaves are used to treat fever, headache, and joint pain but its medicinal activities have not been proven by research. Objective: To evaluate the analgesic, anti-inflammatory, and antipyretic activity of C. dichotoma G. Forst. leaf extract. Material and Methods: The various extracts of leaf powder were prepared by using soxhlet apparatus. The methanol extract was selected for pharmacological study. To evaluate analgesic activity, Eddy's hot plate method, to study anti-inflammatory activity, carageenan-induced rat paw edema method, and to study antipyretic activity, yeast-induced pyrexia method was used. SD female rats (180-200 g) were used for the study. Results: In all three tests, the methanol extract high dose (400 mg/kg) was found to be highly significant as compared to standard drug. Conclusion: This study proved the traditional uses of plant leaves and concluded the analgesic, anti-inflammatory, and antipyretic activity of the leaf methanol extract. PMID:25598647

Gupta, Richa; Kaur, Jagjit

2015-01-01

160

Type I Interferons as Anti-Inflammatory Mediators  

NSDL National Science Digital Library

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

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

2007-12-11

161

Anti-Inflammatory Properties of C-Peptide  

PubMed Central

C-peptide, historically considered a biologically inactive peptide, has been shown to exert insulin-independent biological effects on a number of cells proving itself as a bioactive peptide with anti-inflammatory properties. Type 1 diabetic patients typically lack C-peptide, and are at increased risk of developing both micro- and macrovascular complications, which account for significant morbidity and mortality in this population. Inflammatory mechanisms play a pivotal role in vascular disease. Inflammation and hyperglycemia are major components in the development of vascular dysfunction in type 1 diabetes. The anti-inflammatory properties of C-peptide discovered to date are at the level of the vascular endothelium, and vascular smooth muscle cells exposed to a variety of insults. Additionally, C-peptide has shown anti-inflammatory properties in models of endotoxic shock and type 1 diabetes-associated encephalopathy. Given the anti-inflammatory properties of C-peptide, one may speculate dual hormone replacement therapy with both insulin and C-peptide in patients with type 1 diabetes may be warranted in the future to decrease morbidity and mortality in this population. PMID:20039006

Haidet, Jaime; Cifarelli, Vincenza; Trucco, Massimo; Luppi, Patrizia

2009-01-01

162

Glycosaminoglycan analogs as a novel anti-inflammatory strategy  

PubMed Central

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

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

2012-01-01

163

Anti-inflammatory and side effects of cyclooxygenase inhibitors  

Microsoft Academic Search

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs in inflammatory diseases, since they are effec- tive in management of pain, fever, redness, edema arising as a consequence of inflammatory mediator release. Studies have shown that both therapeutic and side effects of NSAIDs are dependent on cyclooxygenase (COX) inhibition. COX isoforms have been named constitutive (COX-1) and inducible (COX-2).

Halis Süleyman; Berna Demircan; Yalçin Karagöz

164

Anti-inflammatory drugs and their mechanism of action  

Microsoft Academic Search

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their therapeutic activities through inhibition of cyclooxygenase (COX), the enzyme that makes prostaglandins (PGs). They share, to a greater or lesser degree, the same side effects, including gastric and renal toxicity. Recent research has shown that there are at least two COX isoenzymes. COX-1 is constitutive and makes PGs that protect the stomach and kidney

J. R. Vane; R. M. Botting

1998-01-01

165

Anti-inflammatory activity of mycelial extracts from medicinal mushrooms.  

PubMed

Medicinal mushrooms have been essential components of traditional Chinese herbal medicines for thousands of years, and they protect against diverse health-related conditions. The components responsible for their anti-inflammatory activity have yet to be fully studied. This study investigates the anti-inflammatory activity of n-hexane, chloroform, ethyl acetate, and methanol extracts of mycelia in submerged culture from 5 commercially available medicinal mushrooms, namely Cephalosporium sinensis, Cordyceps mortierella, Hericium erinaceus, Ganoderma lucidum, and Armillaria mellea. MTT colorimetric assay was applied to measure the cytotoxic effects of different extracts. Their anti-inflammatory activities were evaluated via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) in murine macrophage-like cell line RAW264.7 cells. Of the 20 extracts, n-hexane, chloroform, ethyl acetate, and methanol extracts from C. sinensis, C. mortierella, and G. lucidum; chloroform extracts from H. erinaceus and A. mellea; and ethyl acetate extracts from A. mellea at nontoxic concentrations (<300 ?g/mL) dose-dependently inhibited LPS-induced NO production. Among them, the chloroform extract from G. lucidum was the most effective inhibitor, with the lowest half maximal inhibitory concentration (64.09 ± 6.29 ?g/mL) of the LPS-induced NO production. These results indicate that extracts from medicinal mushrooms exhibited anti-inflammatory activity that might be attributable to the inhibition of NO generation and can therefore be considered a useful therapeutic and preventive approach to various inflammation-related diseases. PMID:25271860

Geng, Yan; Zhu, Shuiling; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Zheng-Hong

2014-01-01

166

Systems Biology based studies on anti-inflammatory compounds  

Microsoft Academic Search

The introduction of the ‘omics’ techniques (transcriptomics, proteomics, and metabolomics) and systems biology, has caused fundamental changes in the drug discovery process and many other fields in the life science area. In this thesis we explored the possibilities to apply these holistic technologies to investigate the effects of known and potential anti-inflammatory compounds on macrophages. For this purpose we made

Kitty Catharina Maria Verhoeckx

2005-01-01

167

Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis.  

PubMed

Recent clinical trials of the gum resin of Boswellia serrata have shown promising results in patients with ulcerative colitis. The objective of this study was to determine whether a semisynthetic form of acetyl-11-keto-beta-boswellic acid (sAKBA), the most potent anti-inflammatory component of the resin, also confers protection in experimental murine colitis induced by dextran sodium sulfate (DSS) to compare its effects with those standard medications of ulcerative colitis like steroids and to examine whether leukocyte-endothelial cell adhesion is a major target of action of sAKBA. Clinical measurements of disease activity and histology were used to assess disease progression, and intravital microscopy was employed to monitor the adhesion of leukocytes and platelets in postcapillary venules of the inflamed colon. sAKBA treatment significantly blunted disease activity as assessed both grossly and by histology. Similarly, the recruitment of adherent leukocytes and platelets into inflamed colonic venules was profoundly reduced in mice treated with sAKBA. Because previous studies in the DSS model have shown that P-selectin mediates these blood cell-endothelial cell interactions, the expression of P-selectin in the colonic microcirculation was monitored using the dual-radiolabeled antibody technique. The treatment of established colitis with sAKBA largely prevented the P-selectin upregulation normally associated with DSS colitis. All of the protective responses observed with sAKBA were comparable to that realized in mice treated with a corticosteroid. Our findings demonstrated an anti-inflammatory effect of sAKBA and indicated that P-selectin-mediated recruitment of inflammatory cells is a major site of action for this novel anti-inflammatory agent. PMID:16423918

Anthoni, C; Laukoetter, M G; Rijcken, E; Vowinkel, T; Mennigen, R; Müller, S; Senninger, N; Russell, J; Jauch, J; Bergmann, J; Granger, D N; Krieglstein, C F

2006-06-01

168

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

PubMed Central

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

Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

2014-01-01

169

Mechanisms of Action of Ig Preparations: Immunomodulatory and Anti-Inflammatory Effects  

PubMed Central

Primary immunodeficiency (PID) disorders that predispose patients to recurrent infections require immunoglobulin (Ig) replacement therapy. Ig replacement therapy has been stated as beneficial, although the optimal IgG trough level to be maintained over time in order to minimize infectious risk has not been established. The most common route of administration of Ig has been intravenously, although there are different options, one of them being the subcutaneous route. Ig replacement therapy has been a life-saving treatment for patients suffering from primary and secondary antibody immunodeficiency. The key role of regular Ig replacement in patients with antibody deficiencies is related to the ability to provide specific antibodies that could not be produced by these patients as demonstrated by the reduction of severe infections such as meningitis and pneumonia. The therapeutic benefits of Ig may also be due to an active role in various anti-inflammatory and immunomodulatory activities, which may complicate the clinical picture of PID. Anti-inflammatory activities are seen more generally when intravenous Ig is administered at high dose. The immunomodulatory and anti-inflammatory activities are important not only in the treatment of autoimmune diseases but also in patients suffering from immunodeficiency. PMID:25628625

Matucci, Andrea; Maggi, Enrico; Vultaggio, Alessandra

2015-01-01

170

Analgesic and anti-inflammatory property of the methanol extract from Ligustrum morrisonense leaves in rodents.  

PubMed

Ligustrum morrisonense Kaneh and Sasaki (abbreviated as LM), an endemic Ligustrum plant in Taiwan, is similar to Ligustrum lucidum, which is usually used for curing hepatic and inflammatory disorders. The aim of this study was to evaluate the analgesic and anti-inflammatory properties of LM by chemical-induced algesia and carrageenan-induced inflammation in rodents. Its triterpenoid contents were measured by using high performance liquid chromatography-photodiode array detector. LM leaf extracts effectively inhibited writhing responses induced by 1% acetic acid and biphasic-licking responses caused by 1% formalin. LM leaf extract also reduced the edema induced by 1% carrageenan. Furthermore, LM leaf extract reduced the abdominal Evan's blue extravasations caused by lipopolysaccharide (LPS), serotonin, histamine and bradykinin. LM leaf extract has higher contents of amyrin and lupeol among six assayed triterpenoid compounds. In conclusion, LM is a potential analgesic and anti-inflammatory Ligustrum plant, and its anti-inflammatory effects are partially related to decreasing microvascular permeability via inflammatory mediators and inhibiting cyclooxygenase-2 activity. PMID:21476210

Wu, Chi-Rei; Lin, Wen-Hsin; Lin, Yung-Ta; Wen, Chi-Luan; Ching, Hui; Lin, Li-Wei

2011-01-01

171

Validated RP-HPLC and HPTLC methods for determination of anti-inflammatory bis-indole alkaloid in Desmodium gangeticum.  

PubMed

Here, two simple and accurate methods, namely high-performance liquid chromatography and high-performance thin-layer chromatography for the detection of gangenoid, an anti-inflammatory alkaloid, in a well-known Indian medicinal plant Desmodium gangeticum, are described. The proposed methods were successfully used for the estimation of gangenoid in D. gangeticum root. PMID:24079376

Yadav, Akhilesh K; Gupta, Madan M

2014-01-01

172

In vivo anti-inflammatory and antinociceptive activity of the crude extract and fractions from Rosa canina L. fruits.  

PubMed

The aqueous and ethanol extracts of Rosa canina L. (Rosaceae) fruits and the fractions prepared from the latter were investigated for their anti-inflammatory and antinociceptive activities in several in vivo experimental models. The ethanolic extract was shown to possess significant inhibitory activity against inflammatory models (i.e., carrageenan-induced and PGE(1)-induced hind paw edema models, as well as on acetic acid-induced increase in a capillary permeability model) and on a pain model based on the inhibition of p-benzoquinone-induced writhing in mice. Hexane, chloroform, ethylacetate, n-butanol and the remaining water fractions were obtained through bioassay-guided fractionation. Ethylacetate and n-butanol fractions displayed potent anti-inflammatory and antinociceptive activities at a dose of 919 mg/kg without inducing acute toxicity. Further attempts to isolate and define the active constituent(s) were inconclusive, possibly due to the synergistic interaction of components in the extract. PMID:17482395

Deliorman Orhan, Didem; Hartevio?lu, Ali; Küpeli, Esra; Yesilada, Erdem

2007-06-13

173

Anti-inflammatory effect of Momordica charantia in sepsis mice.  

PubMed

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

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

2014-01-01

174

[Diclofenac: update on tolerableness and spinal anti-inflammatory action.  

PubMed

The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs in the control of postoperative pain. In choosing the NSAID to be used, it is essential to assess the most favorable risk/benefit ratio according to a careful assessment of intrinsic and extrinsic risk factors and cardiovascular, gastrointestinal, renal and metabolic patient comorbidities. Diclofenac dose of 150 mg/die is the NSAID that has wider literature that attests its efficacy and tolerability. Due to its high lipid solubility, it is one of the few NSAIDs that are able to cross the blood-brain barrier, with an action principally directed towards COX-2. Over time, several studies have been conducted to evaluate the side effects of NSAIDs. Regarding Diclofenac's cardiovascular and gastrointestinal tolerability, recent studies indicate that the relative risk and absolute risk of complications of Diclofenac are similar to COXIB and inferior to other NSAIDs. Important feature of Diclofenac is that, unlike other NSAIDs, it does not interfere with the cardio-protective effect of acetyl-salicylic acid. Diclofenac potassium is instead indicated for use as an analgesic in headache and as an antipyretic in influenza-like symptoms. Studies with the aim of investigating the intestinal damage exacerbated by proton pump inhibitors drugs, when associated with NSAIDs, state that at least in part, they aggravate the intestinal damage induced by NSAIDs due to significant changes in intestinal microbial populations. The reference dose of Diclofenac used in all randomized controlled trials is 150 mg/die; this controlled release dosage allows to decrease the number of daily administrations, ensuring a better patient compliance, especially if elderly and/or in polytherapy. PMID:25078485

Sandri, A

2014-08-01

175

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

PubMed Central

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

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

2014-01-01

176

Arzanol, a prenylated heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo.  

PubMed

Based on its capacity to inhibit in vitro HIV-1 replication in T cells and the release of pro-inflammatory cytokines in monocytes, the prenylated heterodimeric phloroglucinyl ?-pyrone arzanol was identified as the major anti-inflammatory and anti-viral constituent from Helichrysum italicum. We have now investigated the activity of arzanol on the biosynthesis of pro-inflammatory eicosanoids, evaluating its anti-inflammatory efficacy in vitro and in vivo. Arzanol inhibited 5-lipoxygenase (EC 7.13.11.34) activity and related leukotriene formation in neutrophils, as well as the activity of cyclooxygenase (COX)-1 (EC 1.14.99.1) and the formation of COX-2-derived prostaglandin (PG)E(2)in vitro (IC(50)=2.3-9?M). Detailed studies revealed that arzanol primarily inhibits microsomal PGE(2) synthase (mPGES)-1 (EC 5.3.99.3, IC(50)=0.4?M) rather than COX-2. In fact, arzanol could block COX-2/mPGES-1-mediated PGE(2) biosynthesis in lipopolysaccharide-stimulated human monocytes and human whole blood, but not the concomitant COX-2-derived biosynthesis of thromboxane B(2) or of 6-keto PGF(1?), and the expression of COX-2 or mPGES-1 protein was not affected. Arzanol potently suppressed the inflammatory response of the carrageenan-induced pleurisy in rats (3.6mg/kg, i.p.), with significantly reduced levels of PGE(2) in the pleural exudates. Taken together, our data show that arzanol potently inhibits the biosynthesis of pro-inflammatory lipid mediators like PGE(2)in vitro and in vivo, providing a mechanistic rationale for the anti-inflammatory activity of H. italicum, and a rationale for further pre-clinical evaluation of this novel anti-inflammatory lead. PMID:20933508

Bauer, Julia; Koeberle, Andreas; Dehm, Friederike; Pollastro, Federica; Appendino, Giovanni; Northoff, Hinnak; Rossi, Antonietta; Sautebin, Lidia; Werz, Oliver

2011-01-15

177

Chemical composition and anti-inflammatory activities of the essential oils from Acacia mearnsii de Wild.  

PubMed

The volatile oils of the leaves and the stem bark of Acacia mearnsii de Wild obtained by hydro-distillation were analysed by gas chromatography-mass spectrometry. A total of 20, 38, 29 and 38 components accounted for 93.8%, 92.1%, 78.5% and 90.9% of the total oils of the fresh, dry leaves and fresh, dry stem bark, respectively. The major components of the oil were octadecyl alcohol (25.5%) and phytol (10.5%); cis-verbenol (29.5%); phytol (10.1%) and phytol (23.4%) for the fresh leaves, dried leaves, fresh stem, dry stem bark, respectively. Oral administration of essential oils at a dose of 2% showed significant (p < 0.05) anti-inflammatory properties in the albumin-induced test model in rats. Oils from the fresh leaves and dry stems inhibited inflammation beyond 4 h post treatment. The potent anti-inflammatory activity of essential oils of A. mearnsii hereby confirmed its traditional use in treating various inflammatory diseases. PMID:25422136

Avoseh, Opeyemi N; Oyedeji, Ope-Oluwa O; Aremu, Kayode; Nkeh-Chungag, Benedicta N; Songca, Sandile P; Oluwafemi, Samuel O; Oyedeji, Adebola O

2014-11-25

178

Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.  

PubMed

Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines-this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor ?-light-chain-enhancer of activated B cells ?B (NF-?B) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-?B pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke. PMID:25549058

Zhang, Linjie; Yang, Li

2015-01-01

179

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

PubMed Central

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

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

2009-01-01

180

Topical anti-inflammatory effect of tirucallol, a triterpene isolated from Euphorbia lactea latex.  

PubMed

Latex from Euphorbia lactea (Euphorbiaceae), a native Dominican medicinal plant, is claimed to be useful in the treatment of inflammation. Topical application of tirucallol, a tetracyclic triterpene isolated from Euphorbia lacteal latex, suppressed ear edema in the mouse model in a dose-dependent manner, as well as affecting the influx of polymorphonuclear cells in response to topical application of 12-O-tetradecanoylphorbol-acetate (TPA) in the mouse ear. In addition, the effect of tirucallol, on some macrophage functions was analyzed in vitro. Non-toxic concentrations of tirucallol potently inhibited nitrite production in lipopolysaccharide-stimulated macrophages. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression although tirucallol slightly affected to prostaglandin E(2) (PGE(2)) generation. The results of the study revealed that tirucallol (0.3%), present in Euphorbia lactea latex, exerts a topical anti-inflammatory effect in vivo, via a mechanism of action related to the neutrophil migration. On the other hand, it can be deduced that the mechanism of the anti-inflammatory activity of this triterpene is related to the control of the production of NO and its effect on the expression of iNOS. PMID:19577446

Fernandez-Arche, A; Saenz, M T; Arroyo, M; de la Puerta, R; Garcia, M D

2010-02-01

181

The anti-inflammatory effects of soluble epoxide hydrolase inhibitors are independent of leukocyte recruitment q  

E-print Network

The anti-inflammatory effects of soluble epoxide hydrolase inhibitors are independent of leukocyte 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

Simon, Scott I.

182

Neural inhibition of inflammation: the cholinergic anti-inflammatory pathway.  

PubMed

The innate immune system is activated by infection and injury to release pro-inflammatory cytokines, which activate macrophages and neutrophils and modulate specific cellular responses. The magnitude of the cytokine response is critical, because a deficient response may result in secondary infections, while an excessive response may be more injurious than the original insult. We recently described a neural pathway, termed the "cholinergic anti-inflammatory pathway", that reflexively monitors and adjusts the inflammatory response by inhibiting pro-inflammatory cytokine synthesis. Efferent signals in the vagus nerve provide a direct mechanism for neural regulation of the immune response that is rapid, localized, and integrated. Vagus nerve stimulation inhibits the release of TNF, HMGB1, and other cytokines, and protects against endotoxemia and ischemia-reperfusion injury. This newly identified physiological mechanism of maintaining immunological homeostasis suggests that novel therapeutics may effectively modulate inflammatory responses by activating the cholinergic anti-inflammatory pathway. PMID:14733730

Czura, Christopher J; Friedman, Steven G; Tracey, Kevin J

2003-01-01

183

Evidence for anti-inflammatory effects of exercise in CKD.  

PubMed

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

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

2014-09-01

184

Anti-inflammatory properties of kefir and its polysaccharide extract  

Microsoft Academic Search

Kefir is a fermented beverage originating form the Caucasian regions composed of a number of bacteria and yeasts living together\\u000a in polysaccharide grains secreted by them. Kefir can be considered a probiotic source as it presents anti-bacterial, anti-mycotic,\\u000a anti-neoplasic and immunomodulatory properties. Aiming to appraise a possible anti-inflammatory effect of kefir we conducted\\u000a cotton-induced granuloma and paw oedema assays in

K. L. Rodrigues; J. C. T. Carvalho; J. M. Schneedorf

2005-01-01

185

Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia  

Microsoft Academic Search

Aims: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in hypercholesterolemic subjects. Methods and results: In 33 asymptomatic men with total cholesterol

Jacek Musial; Anetta Undas; Piotr Gajewski; Milosz Jankowski; Wojciech Sydor; Andrzej Szczeklik

2001-01-01

186

Recent considerations in nonsteroidal anti-inflammatory drug gastropathy  

Microsoft Academic Search

Conservative calculations estimate that approximately 107,000 patients are hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone. The figures for all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated. The Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) Post-Marketing Surveillance

Gurkirpal Singh

1998-01-01

187

Anti-inflammatory cyclohexenyl chalcone derivatives in Boesenbergia pandurata.  

PubMed

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

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

2002-01-01

188

Anti-inflammatory activity of traditional Chinese medicinal herbs  

PubMed Central

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

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

2011-01-01

189

UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect  

PubMed Central

Background To explain observed differences during SPF determination using either an in vivo or in vitro method, we hypothesized on the presence of ingredients having anti-inflammatory properties. Methodology/Principal Findings To research our hypothesis, we studied the 21 UV filters both available on the market and authorized by European regulations and subjected these filters to the phorbol-myristate-acetate test using mice. We then catalogued the 13 filters demonstrating a significant anti-inflammatory effect with edema inhibition percentages of more than 70%. The filters are: diethylhexyl butamido triazone (92%), benzophenone-5 and titanium dioxide (90%), benzophenone-3 (83%), octocrylène and isoamyl p-methoxycinnamate (82%), PEG-25 PABA and homosalate (80%), octyl triazone and phenylbenzimidazole sulfonic acid (78%), octyl dimethyl PABA (75%), bis-ethylhexyloxyphenol methoxyphenyl triazine and diethylamino hydroxybenzoyl hexylbenzoate (70%). These filters were tested at various concentrations, including their maximum authorized dose. We detected a dose-response relationship. Conclusions/Significance The anti-inflammatory effect of a sunscreen ingredient may affect the in vivo SPF value. PMID:23284607

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

2012-01-01

190

Anti-Inflammatory Activity and Composition of Senecio salignus Kunth  

PubMed Central

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

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

2013-01-01

191

Anti-inflammatory effects of South American Tanacetum vulgare.  

PubMed

In recent years the role of phenolic compounds and sesquiterpene lactones, particularly parthenolide, in the anti-migraine and anti-inflammatory effects of Tanacetum parthenium (Asteraceae) has attracted much attention. However, the closely-related cosmopolitan species T. vulgare has remained outside the mainstream of research in this field. After treating the aerial parts of T. vulgare with dichloromethane and methanol, and applying conventional column and thin-layer chromatographic techniques, it was possible to isolate from the moderately lipophilic fractions the principles responsible for the anti-inflammatory activity of this plant against the mouse-ear oedema induced by 12-O-tetradecanoylphorbol 13-acetate. These were identified by ultraviolet and nuclear magnetic resonance spectroscopy as parthenolide (93% oedema inhibition at 0.5 mg/ear, ID50 (dose of drug inhibiting the oedema by 50%) = 0.18 micromol/ear) and the methoxyflavones jaceosidin (80% oedema inhibition at 0.5 mg/ear, ID50 = 0.50 micromol/ear), eupatorin, chrysoeriol and diosmetin. Because in molar terms the potency of parthenolide was nearly three times greater than that of the most active of the flavones and because it is obtained from the plant in considerably larger amounts, the flavonoids must only be partially responsible, and to a minor extent, for the observed in-vivo anti-inflammatory local effect. PMID:9811170

Schinella, G R; Giner, R M; Recio, M C; Mordujovich de Buschiazzo, P; Ríos, J L; Máñez, S

1998-09-01

192

ANTI-INFLAMMATORY ACTIVITY OF MIRABILIS JALAPA LINN. LEAVES  

PubMed Central

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

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

2010-01-01

193

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

NASA Astrophysics Data System (ADS)

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.

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

2014-09-01

194

New N-pyridinyl(methyl)-N1-substituted-3-indolepropanamides acting as topical and systemic anti-inflammatory agents.  

PubMed

N-Pyridinyl(methyl)-N1-substituted-3-indolepropanamides (17-32) were prepared starting from the corresponding acids and screened for their anti-inflammatory activity. Pharmacomodulation was carried out on the indole and amidic nitrogens by incorporation of substituents associated with higher potency in previously synthesized related 3-indolepropanamides series. In the inhibition of topical inflammation determined by reduction of ear thickness in the acute PMA mouse ear swelling test, high levels of activity (ID50 approximately 0.030 mMol kg(-1)) were noticed for the five propanamides 17, 21, 22, 27 and 31. A comparative study showed the positive influence of a methyl group at the indole nitrogen in the 4-pyridinyl sub-series (1 --> 21) and of a 4-fluorobenzyl group in the 3-pyridinylmethyl sub-series (19 --> 31), at least after oral administration. After topical application, although compounds 17, 21, 22, 27 and 31 exerted significant (50%) ear edema inhibition at 2 x 50 microg/ear, they remained less potent than 24,29 and 30 (almost 70% inhibition). Among these eight amides, only 17, 21, 22 and 27 showed a significant activity in the carrageenan rat paw aedema model at 0.2 mMol kg(-1). Finally, although less active than the N-(4-pyridinyl) amide 21, the N-4,6-dimethyl-2-pyridinyl derivatives 17 and 27 were devoid of the toxic effects observed with 21 and to a lesser extent with 22. PMID:12943205

Gallard, Anthony; Duflos, Muriel; Nourrisson, Marie-Renee; Le Baut, Guillaume; Grimaud, Nicole; Petit, Jean Yves

2003-04-01

195

Design, synthesis, docking and anti-inflammatory evaluation of novel series of benzofuran based prodrugs.  

PubMed

Several new benzofuran derivatives were synthesized, via appropriate synthetic route as anti-inflammatory agents. The anti-inflammatory activity of the prepared compounds was evaluated using carrageenan rat model. Among the synthesized compounds, some compounds showed comparable anti-inflammatory activity to nimesulide, the standard drug taken for anti-inflammatory studies. Docking study of the prepared compounds was performed for the study of interaction of molecules with the active site of COX-2. Preliminary biological studies and docking gave an interesting insight, into the validity of employing benzofuran analogues as good anti-inflammatory agent. PMID:24745964

Yadav, Pratima; Singh, Praveen; Tewari, Ashish Kumar

2014-05-15

196

Metallothionein as an Anti-Inflammatory Mediator  

PubMed Central

The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT) is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions. PMID:19436762

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

2009-01-01

197

Anti-inflammatory compounds from the aerial parts of Aceriphyllum rossii.  

PubMed

A new megastigmane glycoside, galloyl linarionoside A (1), together with 13 known compounds (2-14) were isolated from the aerial parts of Aceriphyllum rossii ENGLER. (Saxifragaceae). The chemical structures of the isolated compounds were established mainly by using nuclear magnetic resonance spectra, mass spectrometry, and modified Mosher's method. Among the isolates, compounds 4, 5, 6 and 7 showed potent inhibitory activity against the lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells with IC50 values of 12.5, 9.5, 10.5 and 9.3 µM, respectively. The anti-inflammatory effect of compound 7 was accompanied by dose-dependent decreases in the production of inducible nitric oxide synthase and cyclooxygenase-2 proteins not in the inhibitor kappa B (I?B)-dependent nuclear factor-kappa B activation. PMID:24492589

Trang, Tran Thi Thu; Cuong, To Dao; Hung, Tran Manh; Kim, Jeong Ah; Lee, Jeong Hyung; Woo, Mi Hee; Choi, Jae Sue; Lee, Hyeong Kyu; Min, Byung Sun

2014-01-01

198

Melittin-glutathione S-transferase fusion protein exhibits anti-inflammatory properties and minimal toxicity.  

PubMed

Although potent, proteins often require chemical modification for therapeutic use. Immunogenicity, difficult synthesis, and scale-up of these modifications are all engineering obstacles that stand in the way of expanding the use of these therapeutics. Melittin, a peptide derived from bee venom, has been shown to modulate inflammation. Although potentially therapeutic, the native peptide causes cell lysis and toxicity significantly hindering therapeutic application. Based upon the knowledge of the pore formation mechanism, we examined the toxicity and therapeutic effect of a melittin fusion protein with glutathione-S-transferase. The fusion of melittin and glutathione S-transferase results in diminished toxicity of the peptide and retained anti-inflammatory properties at doses that exceed toxic concentration of native melittin. Our results suggest that fusion proteins, particularly those of glutathione-S-transferase, may be facile modifications to control protein activity. PMID:25240321

Rayahin, Jamie E; Buhrman, Jason S; Gemeinhart, Richard A

2014-12-18

199

Antioxidant and anti-inflammatory activities of selected medicinal plants and fungi containing phenolic and flavonoid compounds  

PubMed Central

Background This study aims to determine the relationship between the antioxidant and anti-inflammatory activities of the thirteen herbs and two fungi extracts, and their total phenolic and flavonoid contents. Methods Antioxidant activities were evaluated by four assays: an antioxidant activity assay using Saccharomyces cerevisiae, a DPPH ((2, 2-diphenyl-1-picrylhydrazyl) assay to assess free radical scavenging, an assay assessing ferrous ions or iron (II) chelating ability, and a ferric reducing antioxidant power (FRAP) assay. Total phenolic and flavonoid contents were determined using the Folin-Ciocalteu and aluminium chloride methods, respectively. Anti-inflammatory activities were determined by measuring the inhibition of nitric oxide and TNF-? production in lipopolysaccharide- and interferon-?-activated J774A.1 macrophages. Their cytotoxicities against macrophages were determined by MTT assay. Results A positive linear correlation between antioxidant activities and the total phenolic and flavonoid content of the plant extracts was found. The plant extracts with high phenolic and flavonoid content also exhibited significant anti-inflammatory activity with good cell viability. Conclusion The selected herbs could be a rich source of antioxidants and free radical scavenging compounds. The levels of phenolic and flavonoid compounds were correlated with the antioxidant and anti-inflammatory activities of the extracts from the herbs. PMID:23176585

2012-01-01

200

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

PubMed

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

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

201

Synthesis and anti-inflammatory activity of new arylidene-thiazolidine-2,4-diones as PPARgamma ligands.  

PubMed

Eight new 5-arylidene-3-benzyl-thiazolidine-2,4-diones with halide groups on their benzyl rings were synthesized and assayed in vivo to investigate their anti-inflammatory activities. These compounds showed considerable biological efficacy when compared to rosiglitazone, a potent and well-known agonist of PPARgamma, which was used as a reference drug. This suggests that the substituted 5-arylidene and 3-benzylidene groups play important roles in the anti-inflammatory properties of this class of compounds. Docking studies with these compounds indicated that they exhibit specific interactions with key residues located in the site of the PPARgamma structure, which corroborates the hypothesis that these molecules are potential ligands of PPARgamma. In addition, competition binding assays showed that four of these compounds bound directly to the ligand-binding domain of PPARgamma, with reduced affinity when compared to rosiglitazone. An important trend was observed between the docking scores and the anti-inflammatory activities of this set of molecules. The analysis of the docking results, which takes into account the hydrophilic and hydrophobic interactions between the ligands and the target, explained why the 3-(2-bromo-benzyl)-5-(4-methanesulfonyl-benzylidene)-thiazolidine-2,4-dione compound had the best activity and the best docking score. Almost all of the stronger hydrophilic interactions occurred between the substituted 5-arylidene group of this compound and the residues of the binding site. PMID:20471839

Barros, Cleiton Diniz; Amato, Angélica Amorim; de Oliveira, Tiago Bento; Iannini, Karime Bicas Rocha; Silva, Anekécia Lauro da; Silva, Teresinha Gonçalves da; Leite, Elisa Soares; Hernandes, Marcelo Zaldini; Alves de Lima, Maria do Carmo; Galdino, Suely Lins; Neves, Francisco de Assis Rocha; Pitta, Ivan da Rocha

2010-06-01

202

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

PubMed Central

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

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

2013-01-01

203

Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway  

PubMed Central

The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-?, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signalregulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, 8.79 × 105 M-1. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK. [BMB Reports 2013; 46(12): 594-599] PMID:24195792

Lee, Eunjung; Jeong, Ki-Woong; Shin, Areum; Jin, Bonghwan; Jnawali, Hum Nath; Jun, Bong-Hyun; Lee, Jee-Young; Heo, Yong-Seok; Kim, Yangmee

2013-01-01

204

Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway.  

PubMed

The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-?, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, 8.79 × 10(5) M(-1). Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK. PMID:24195792

Lee, Eunjung; Jeong, Ki-Woong; Shin, Areum; Jin, Bonghwan; Jnawali, Hum Nath; Jun, Bong-Hyun; Lee, Jee-Young; Heo, Yong-Seok; Kim, Yangmee

2013-12-01

205

Anti-inflammatory properties of BHUx, a polyherbal formulation to prevent atherosclerosis.  

PubMed

BHUx is a polyherbal formulation consisting of water-soluble fractions of five medicinal plants (Commiphora mukul, Terminalia arjuna, Boswellia serrata, Semecarpus anacardium and Strychnos nux vomica). The present study was undertaken to evaluate its antioxidant and antiinflammatory effects. BHUx, standardized by HPLC fingerprinting and filtered through 0.2 microm filter paper, was employed for different studies under in vivo and in vitro conditions. Under in vivo conditions, BHUx significantly reduced inflammation in the carrageenan-induced rat paw oedema model of inflammation, suggesting its anti-inflammatory properties. In order to test the mechanism of action of BHUx, further in vitro studies were undertaken on cumene-hydroperoxide-induced lipid peroxidation (CHP) in liver homogenate, LPS-induced NO production in peritoneal macrophages and on key enzymes of arachidonic acid cascade, involved in the mediation of inflammation. Under the conditions, BHUx showed concentration-dependent inhibition of CHP-induced lipid peroxidation in liver homogenate, suggesting its antioxidant properties. Similarly the potent anti-inflammatory effects of BHUx are evident by (a) preferential inhibition of COX-2 (IC50 for COX-2 = 80 microg/ml and IC50 for COX-1 = 169 microg/ml), (b) low ratios in the IC50 values of COX-2/COX-1 (0.47), (c) decreased production of NO in LPS-induced peritoneal macrophages and (d) inhibition of 5-LOX (IC50 = 795 microg/ml). BHUx also showed a preference for inhibiting 15-lipoxygenase (IC50 = 44 microg/ml), a key enzyme implicated in LDL oxidation. These studies suggest that BHUx is acting mainly at three levels, i.e., as a potent natural antioxidant, by reduction of key inflammatory mediators of arachidonic acid cascade and by preventing 15-LOX-mediated LDL oxidations, to prevent atherosclerosis. PMID:15265316

Tripathi, Yamini B; Reddy, M Mallikarjuna; Pandey, R S; Subhashini, J; Tiwari, O P; Singh, B K; Reddanna, P

2004-01-01

206

Transdermal microemulsions of Boswellia carterii Bird: formulation, characterization and in vivo evaluation of anti-inflammatory activity.  

PubMed

Abstract Context: Boswellia species are trees (family: Bruseraceae) found in India, Northern Africa and the Middle East. Objective: This study aims at formulating low dose biologically active fraction from the oleogum resin of Boswellia carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti-inflammatory efficacy. Materials and methods: The bioactive fraction of the oleogum resin of BC was tested for solubility in different components. The most efficient were selected for constructing phase diagrams for ME preparation. The bioactive fraction was assayed by high performance liquid chromatography for 3-acetyl-11-keto-?-boswellic acid (AKBA), at 210?nm. The bioactive fraction was incorporated in 6?MEs. ME systems were evaluated for drug content and optimized systems were tested for characterization, permeation, skin irritancy and in vivo evaluation of anti-inflammatory activity. Results and Discussion: Two systems were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio, with oil content 7.78 and 17.5%, respectively. The systems showed high encapsulation efficiency >83%, small droplet size <100?nm, and suitable pH for topical application. Permeation parameters for ME1 were higher compared to ME4. Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory activity versus the standard TD anti-inflammatory piroxicam. Conclusions: Optimized TD BC MEs could be used as a safe, effective and long acting alternative to oral anti-inflammatories, providing higher and prolonged efficacy and better patient compliance. PMID:24725029

Mostafa, Dina Mahmoud; Ammar, Nagwa Mohammed; Basha, Mona; Hussein, Rehab Ali; El Awdan, Sally; Awad, Gamal

2014-04-14

207

A review of the molecular aspects of melatonin's anti-inflammatory actions: recent insights and new perspectives.  

PubMed

Melatonin is a highly evolutionary conserved endogenous molecule that is mainly produced by the pineal gland, but also by other nonendocrine organs, of most mammals including man. In the recent years, a variety of anti-inflammatory and antioxidant effects have been observed when melatonin is applied exogenously under both in vivo and in vitro conditions. A number of studies suggest that this indole may exert its anti-inflammatory effects through the regulation of different molecular pathways. It has been documented that melatonin inhibits the expression of the isoforms of inducible nitric oxide synthase and cyclooxygenase and limits the production of excessive amounts of nitric oxide, prostanoids, and leukotrienes, as well as other mediators of the inflammatory process such as cytokines, chemokines, and adhesion molecules. Melatonin's anti-inflammatory effects are related to the modulation of a number of transcription factors such as nuclear factor kappa B, hypoxia-inducible factor, nuclear factor erythroid 2-related factor 2, and others. Melatonin's effects on the DNA-binding capacity of transcription factors may be regulated through the inhibition of protein kinases involved in signal transduction, such as mitogen-activated protein kinases. This review summarizes recent research data focusing on the modulation of the expression of different inflammatory mediators by melatonin and the effects on cell signaling pathways responsible for the indole's anti-inflammatory activity. Although there are a numerous published reports that have analyzed melatonin's anti-inflammatory properties, further studies are necessary to elucidate its complex regulatory mechanisms in different cellular types and tissues. PMID:22725668

Mauriz, José L; Collado, Pilar S; Veneroso, Christiano; Reiter, Russel J; González-Gallego, Javier

2013-01-01

208

Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway.  

PubMed

Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) reduced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1?, interleukin-6 and tumor necrosis factor-? in brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-?B) inhibition. These observations were inhibited by the alpha7 nicotinic acetylcholine receptor (?7nAchR) antagonist ?-bungarotoxin (?-BGT). In addition, puerarin pretreatment increased the expression of ?7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory response. Our results also indicated that the anti-inflammatory effect of puerarin may partly be mediated through the activation of the cholinergic anti-inflammatory pathway. PMID:25206641

Liu, Xiaojie; Mei, Zhigang; Qian, Jingping; Zeng, Yongbao; Wang, Mingzhi

2013-12-01

209

Biogenic synthesis, purification, and chemical characterization of anti-inflammatory resolvins derived from docosapentaenoic acid (DPAn-6).  

PubMed

Enzymatically oxygenated derivatives of the omega-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

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

2009-05-29

210

Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti-inflammatory drugs.  

PubMed

The effect of several nitric oxide releasing-non-steroidal anti-inflammatory drugs (NO-NSAID) and nitroprednisolone on blood vessel relaxation in vitro and in vivo was studied. Nitroflurbiprofen (NOF; EC(50), 688.8+/-93.8 microM), nitroaspirin (NOA; EC(50), 57.9+/-6.5 microM), nitroparacetamol (NOPARA; EC(50), 71.5+/-14.6 microM) and nitroprednisolone (EC(50), 15.1+/-1.4 microM) caused concentration-related relaxation of noradrenaline (NA)-contracted rat aortic rings. All NO releasing compounds tested were approximately three orders of magnitude less potent than sodium nitroprusside (SNP, EC(50), 35.7+/-3.5 nM). The vasorelaxant effect of NOF and NOPARA in the rat aorta was potentiated by zaprinast (5 microM) and reduced by ODQ (5 microM). Flurbiprofen and paracetamol (100 microM) caused minimal (<10%) relaxation of the rat aorta and did not affect the response to SNP. The effect of NOF was unchanged in the presence of L-NAME (100 microM; EC(30), 181.8+/-35.1 microM cf. EC(30), 125.1+/-17.0 microM, P>0.05) but increased by removal of the endothelium (EC(30), 164.3+/-26.3 microM cf. EC(50), 688.8+/-93.8 microM, P<0.05). NOF (0.1 - 50 microM) produced a small but not concentration-related vasodilation of the NA-preconstricted (i.e. "high tone") perfused rat mesentery preparation (cf. SNP, EC(30), 4.4+/-0.7 microM). In contrast, NOF (1 - 100 microM) produced concentration-related vasodilation of the "high tone" perfused rat kidney with an EC(50) of 33.1+/-4.4 microM. Neither NOF (74 mg kg(-1), i.p.) nor NOA (91.9 mg kg(-1), i.p.) nor equimolar doses of flurbiprofen (50 mg kg(-1), i.p.) or aspirin (50 mg kg(-1), i.p.) affected mean arterial blood pressure (MAP) or heart rate (HR) of pentobarbitone-anaesthetized rats over a 1 h period. NO-NSAID relax blood vessels in vitro by an NO-dependent mechanism. The absolute vasorelaxant effect of NO releasing drug varies greatly with the choice of compound and between blood vessel preparations. PMID:11487511

Keeble, J; Al-Swayeh, O A; Moore, P K

2001-08-01

211

Anti-inflammatory and anticancer activity of ergoflavin isolated from an endophytic fungus.  

PubMed

Biodiversity is a major resource for identification of new molecules with specific therapeutic activities. To identify such an active resource, high throughput screening (HTS) of the extracts prepared from such diversity are examined on specific functional assays. Based on such HTS studies and bioactivity-based fractionation, we have isolated ergoflavin, a pigment from an endophytic fungus, growing on the leaves of an Indian medicinal plant Mimosops elengi (bakul). We report here the isolation, structure elucidation, and biological properties of this compound, which showed good anti-inflammatory and anticancer activities. PMID:19479845

Deshmukh, Sunil Kumar; Mishra, Prabhu Dutt; Kulkarni-Almeida, Asha; Verekar, Shilpa; Sahoo, Manas Ranjan; Periyasamy, Giridharan; Goswami, Hitesh; Khanna, Amit; Balakrishnan, Arun; Vishwakarma, Ram

2009-05-01

212

5-Arylidene-2-imino-4-thiazolidinones: Design and synthesis of novel anti-inflammatory agents  

Microsoft Academic Search

The synthesis and pharmacological activity of 5-arylidene-2-imino-4-thiazolidinones (3a–8a) are described. All derivatives exhibited significant activity levels in models of acute inflammation such as carrageenan-induced paw and pleurisy edema in rats. In particular, 5-(3-methoxyphenylidene)-2-phenylimino-3-propyl-4-thiazolidinone (3a) displayed high levels of carrageenan-induced paw edema inhibition comparable to those of indomethacin. In addition the ability of such a new class of anti-inflammatory agents to

Rosaria Ottanà; Rosanna Maccari; Maria Letizia Barreca; Giuseppe Bruno; Archimede Rotondo; Antonietta Rossi; Giuseppa Chiricosta; Rosanna Di Paola; Lidia Sautebin; Salvatore Cuzzocrea; Maria Gabriella Vigorita

2005-01-01

213

Oenothein B's contribution to the anti-inflammatory and antioxidant activity of Epilobium sp.  

PubMed

Willow herb tea or preparation are available and relatively popular in the European market, and claimed to be effective inter alia because of their anti-inflammatory activity. The present study is therefore aimed at comparing the anti-inflammatory and antioxidant activity of extracts of the three most popular Epilobium species (E. angustifolium, E. hirsutum and E. parviflorum) and at juxtaposing this activity against the dominating compounds from the following extracts: oenothein B (OeB), quercetin-3-O-glucuronide and myricetin-3-O-rhamnoside. The phytochemical analysis of the extracts has shown that OeB quantities vary between 20% and 35%, while flavonoids content does not exceed 2%. All extracts have inhibited the activity of hyaluronidase and lipoxygenase with IC?? around 5 ?g/ml and 25 ?g/ml. The inhibition of hyaluronidase is related with the presence of OeB, a strong inhibitor of this enzyme (IC??) 1.1 ?M). Additionally, the extracts inhibited myeloperoxidase (MPO) release from stimulated neutrophils. OeB inhibited MPO release similarly to the anti-inflammatory drug indomethacin with IC?? 7.7 ?M and 15.4 ?M, respectively. Tested extracts significantly reduced the production of reactive oxygen species (ROS) from f-MLP and PMA induced neutrophils with IC?? 5 ?g/ml and 25 ?g/ml, respectively. The flavonoids content seems to exert little influence on extracts' activity, contrary to OeB, whose high concentration explains the activity of extract obtained from Epilobium. Tested currently marketed Epilobium preparations are often wrongly assigned, but we should stress that the level of OeB in all tested herbs was high and always exceeded 2% in raw material. PMID:21112753

Kiss, Anna K; Bazylko, Agnieszka; Filipek, Agnieszka; Granica, Sebastian; Jaszewska, Edyta; Kiarszys, Urszula; Ko?mider, Anita; Piwowarski, Jakub

2011-05-15

214

Induction of anti-inflammatory cytokine expression by IPNV in persistent infection.  

PubMed

Infectious Pancreatic Necrosis Virus (IPNV) is the agent of a well-characterized acute disease that produces a systemic infection and high mortality in farmed fish species but also persistent infection in surviving fish after outbreaks. Because viral persistence of susceptible mammal hosts appears to be associated with the modulation of anti-inflammatory cytokine expression, in this study we examined the expression levels of key pro- and anti-inflammatory cytokines in kidney and spleen of trout, as well as humoral immune response (IgM and IgT) during experimental persistent viral infection and in the acute phase of infection as a comparison. IPNV infection in rainbow trout resulted in a distinct profile of cytokine expression depending on the type of infection, acute or persistent. Levels of early pro-inflammatory cytokines, IL-1? and IL-8, did not increase in the head kidney of the fish with persistent asymptomatic infection but increased in some of the symptomatic infected fish. The antiviral cytokine IFN? was not significantly induced in any of the infected fish groups. The level of expression of the Th1-related cytokine IL-12 was significantly higher in trout with persistent asymptomatic infection than in symptomatic fish. This was also accompanied by an increase in IFN?. The anti-inflammatory cytokines IL-10 and TGF-?1 had distinct expression profiles. While IL-10 expression increased in all infected fish, TGF-?1 was only up-regulated in fish with persistent infection. All infected fish had significantly lower total IgM levels than the non-infected fish whereas IgT levels did not change. Specific and neutralizing antibodies against IPNV were not observed in acute and persistent infection except in the group of fish with the lowest degree of clinical signs. Interestingly, the lack of humoral immune response could be associated with the high expression of anti-inflammatory cytokines, which might inhibit antibody production. The balance between pro-inflammatory Th1 type cytokines and the regulatory cytokines could explain the high percentage of survival and the resolution of the inflammatory response in the IPNV-infected fish but also the establishment of viral persistence. PMID:25193394

Reyes-Cerpa, Sebastián; Reyes-López, Felipe; Toro-Ascuy, Daniela; Montero, Ruth; Maisey, Kevin; Acuña-Castillo, Claudio; Sunyer, J Oriol; Parra, David; Sandino, Ana María; Imarai, Mónica

2014-12-01

215

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

PubMed

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

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

2013-11-01

216

Anti-inflammatory and antioxidant properties of a new arylidene-thiazolidinedione in macrophages.  

PubMed

Thiazolidinediones (TZDs) are a class of drugs used for treatment of type 2 diabetes. However, the therapy with currently available TDZs (e.g. rosiglitazone) is associated with important side effects, such as edema and weight gain, suggesting that the investigation of alternative TZDs with better pharmacological properties is warranted. In this study, we investigated both anti-inflammatory and antioxidant properties of a new chemically modified TZD, the arylidene-thiazolidinedione 5-(4-methanesulfonyl-benzylidene)-3-(4-nitrobenzyl)-thiazolidine-2,4-dione (SF23), and compared the results to those obtained with rosiglitazone. We found that our SF23 displays a weaker affinity for PPAR?, up-regulating in a lower magnitude the expression of both PPAR? and CD36 compared to rosiglitazone. In lipopolysaccharide (LPS)-stimulated macrophages, SF23 decreased nitrite production and attenuated the mRNA expression of both iNOS and COX-2. These anti-inflammatory effects were comparable to those obtained with rosiglitazone. Interestingly, SF23, but not rosiglitazone, prevented LPS-induced mitochondrial membrane hyperpolarization, apoptosis, reactive oxygen species (ROS) generation, and the expression of NADPH oxidase subunits, Nox1 and Nox2. In addition, in macrophages from Nrf2?/? mice, SF23 protected against LPSinduced cellular death and ROS production, whereas rosiglitazone was only able to protect normal Nrf2?/? cells against oxidative injury, suggesting that, unlike rosiglitazone, the antioxidant activity of SF23 might be Nrf2-independent. Finally, in macrophages exposed to high concentrations of glucose, SF23 induced significant increases in the mRNA expression of glucose transporters, insulin receptor substrate and mitoNEET. Altogether, our data indicate that our new chemically modified TDZ displays similar anti-inflammatory properties, but superior antioxidant effects on the LPS-stimulated macrophages compared to rosiglitazone. PMID:21728966

Faine, L A; Rudnicki, M; César, F A; Heras, B L; Boscá, L; Souza, E S; Hernandes, M Z; Galdino, S L; Lima, M C A; Pitta, I R; Abdalla, D S P

2011-01-01

217

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

PubMed Central

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

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

2014-01-01

218

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

PubMed

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

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

2014-02-01

219

Novel Anti-inflammatory Activity of Epoxyazadiradione against Macrophage Migration Inhibitory Factor  

PubMed Central

Macrophage migration inhibitory factor (MIF) is responsible for proinflammatory reactions in various infectious and non-infectious diseases. We have investigated the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid purified from neem (Azadirachta indica) fruits, against MIF. Epoxyazadiradione inhibited the tautomerase activity of MIF of both human (huMIF) and malaria parasites (Plasmodium falciparum (PfMIF) and Plasmodium yoelii (PyMIF)) non-competitively in a reversible fashion (Ki, 2.11–5.23 ?m). Epoxyazadiradione also significantly inhibited MIF (huMIF, PyMIF, and PfMIF)-mediated proinflammatory activities in RAW 264.7 cells. It prevented MIF-induced macrophage chemotactic migration, NF-?B translocation to the nucleus, up-regulation of inducible nitric-oxide synthase, and nitric oxide production in RAW 264.7 cells. Epoxyazadiradione not only exhibited anti-inflammatory activity in vitro but also in vivo. We tested the anti-inflammatory activity of epoxyazadiradione in vivo after co-administering LPS and MIF in mice to mimic the disease state of sepsis or bacterial infection. Epoxyazadiradione prevented the release of proinflammatory cytokines such as IL-1?, IL-1?, IL-6, and TNF-? when LPS and PyMIF were co-administered to BALB/c mice. The molecular basis of interaction of epoxyazadiradione with MIFs was explored with the help of computational chemistry tools and a biological knowledgebase. Docking simulation indicated that the binding was highly specific and allosteric in nature. The well known MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) inhibited huMIF but not MIF of parasitic origin. In contrast, epoxyazadiradione inhibited both huMIF and plasmodial MIF, thus bearing an immense therapeutic potential against proinflammatory reactions induced by MIF of both malaria parasites and human. PMID:22645149

Alam, Athar; Haldar, Saikat; Thulasiram, Hirekodathakallu V.; Kumar, Rahul; Goyal, Manish; Iqbal, Mohd Shameel; Pal, Chinmay; Dey, Sumanta; Bindu, Samik; Sarkar, Souvik; Pal, Uttam; Maiti, Nakul C.; Bandyopadhyay, Uday

2012-01-01

220

Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents.  

PubMed

Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappaB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappaB response element. A549-NF-kappaB cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappaB. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappaB inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 microM. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappaB, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going. PMID:19674895

Zeng, Kui; Thompson, Karin Emmons; Yates, Charles R; Miller, Duane D

2009-09-15

221

Natural anti-inflammatory agents for pain relief  

PubMed Central

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

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

2010-01-01

222

Anti-inflammatory and immunosuppressive drugs and reproduction  

PubMed Central

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

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

2006-01-01

223

Calcium Fructoborate—Potential Anti-inflammatory Agent  

Microsoft Academic Search

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

Romulus Ion Scorei; Petre Rotaru

224

Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema  

PubMed Central

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

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

2013-01-01

225

Antinociceptive and anti-inflammatory activities of Cuscuta chinensis seeds in mice.  

PubMed

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the ?-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CC MeOH ) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20-500 mg/kg of CC MeOH significantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CC MeOH (100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after ?-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CC MeOH may be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CC MeOH also decreased IL-1?, IL-6, NF-?B, TNF-?, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CC MeOH in vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases. PMID:24467546

Liao, Jung-Chun; Chang, Wen-Te; Lee, Meng-Shiou; Chiu, Yung-Jia; Chao, Wei-Kai; Lin, Ying-Chih; Lin, Ming-Kuem; Peng, Wen-Huang

2014-01-01

226

Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract.  

PubMed

A standardized willow bark extract (STW 33-I) has been examined to clarify its possible mechanism of action as an anti-inflammatory agent. Various facets have been investigated in two inflammation models: the 6-day air pouch model in rats, representing the acute state and the adjuvant induced arthritis representing the chronic one. Parameters included leukocytic infiltration, levels of cytokines and prostanoids in blood, and effects on cyclo-oxygenase (COX)-1 and/or COX-2 enzymes as well as effects involving free radical production. The effect of the extract was compared at two dose levels with comparable anti-inflammatory doses of acetylsalicylic acid (CAS 50-78-2, ASA) as a non-selective COX inhibitor, and celecoxib (CAS 169590-42-5) as a selective COX-2 inhibitor. On a mg/kg basis, the extract was at least as effective as ASA in reducing inflammatory exudates and in inhibiting leukocytic infiltration as well as in preventing the rise in cytokines, and was more effective than ASA in suppressing leukotrienes, but equally effective in suppressing prostaglandins. On COX-2, STW 33-I was more effective than ASA. The present findings show that STW 33-I significantly raises GSH (reduced glutathione) levels, an effect which helps to limit lipid peroxidation. The extract was more potent than either ASA or celecoxib. Higher doses of the extract also reduced malondialdehyde levels and raised shows definite superiority to either ASA or celecoxib in protecting the body against oxidative stress. It is therefore evident that STW 33-I is at least as active as ASA on all the parameters of inflammatory mediators measured, when both are given on a similar mg/kg dose. Considering, however, that the extract contains only 24% salicin (molecular weight 286.2), while ASA has a molecular weight of 180.3, it follows that on a molar basis of salicin vs salicylate, the extract contains less than a sixth of the amount of salicin as the amount of salicylate in ASA. Thus it appears that STW 33-I with its lower "salicin" content than an equivalent dose of ASA, is at least as active as ASA on the measured parameters, a fact that leads one to speculate that other constituents of the extract contribute to its overall activity. The presence of polyphenols in STW 33-I probably plays a significant role in enhancing its free radical scavenging properties. The fact that STW 33-I was superior to ASA in this respect would suggest that the extract may have a better anti-inflammatory effect than ASA on a weight to weight basis, with possibly less side effects. PMID:16366042

Khayyal, Mohamed T; El-Ghazaly, Mona A; Abdallah, Dalal M; Okpanyi, Samuel N; Kelber, Olaf; Weiser, Dieter

2005-01-01

227

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

PubMed Central

Information about the anti-inflammatory activity and metabolism of ?-mangostin (?-MG), the most abundant xanthone in mangosteen fruit, in human cells is limited. On the basis of available literature, we hypothesized that ?-MG will inhibit the secretion of pro-inflammatory mediators by control and activated macrophage-like THP-1, hepatic HepG2, enterocyte-like Caco-2, and colon HT-29 human cell lines, as well as primary human monocyte-derived macrophages (MDM), and that such activity would be influenced by the extent of metabolism of the xanthone. ?-MG attenuated TNF-? and IL-8 secretion by the various cell lines but increased TNF-? output by both quiescent and LPS-treated MDM. The relative amounts of free and phase II metabolites of ?-MG and other xanthones present in media 24 h after addition of ?-MG was shown to vary by cell type and inflammatory insult. Increased transport of xanthones and their metabolites across Caco-2 cell monolayers suggests enhanced absorption during an inflammatory episode. The anti-inflammatory activities of xanthones and their metabolites in different tissues merit consideration. PMID:23578285

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

2013-01-01

228

Anti-inflammatory properties of exenatide in human pancreatic islets.  

PubMed

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

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

2012-01-01

229

Analgesic, anti-inflammatory, and antipyretic effects of Ixora coccinea.  

PubMed

Abstract Background: The present study was carried out to explore the potential of the ethanol extract of Ixora coccinea L. (IC) leaves as analgesic, anti-inflammatory and antipyretic agents using the hot-plate, acetic acid-induced writhing, carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests in rodents. Methods: The extract was prepared by soaking the dried powdered leaves of IC in ethanol for 2 days. The filtrate thus obtained by filtration and evaporation was considered as a stock solution and was used in all experimental models. Results: Oral administration of IC (250 and 500 mg/kg) significantly (p<0.05) increased the reaction time in the hot-plate test. Ixora coccinea (250 and 500 mg/kg) produced 56.14% and 63.16% inhibition (p<0.05) in acetic acid-induced writhing. It also (250 and 500 mg/kg) produced significant (p<0.05) inhibition of paw edema pronounced at 6 h after carrageenan injection. Intraperitoneal administration of IC (250 and 500 mg/kg) lowered the body temperature in brewer's yeast-induced hyperthermia. Conclusions: Based on the findings, it may be concluded that the IC leaves possessed analgesic, anti-inflammatory, and antipyretic activities. Phytochemical constituents of IC leaves such as flavonoids, tannins, and triterpenes in ethanol extract could be correlated with its observed biological activities. PMID:24468614

Ali Adnan, Md Syed; Al-Amin, Md Mamun; Nasir Uddin, Mir Muhammad; Shohel, M; Bhattacharjee, Rajib; Hannan, J M A; Das, Biplab Kumar

2014-01-27

230

Dexamethasone increases ROS production and T cell suppressive capacity by anti-inflammatory macrophages.  

PubMed

Macrophages have been demonstrated to suppress T cell responses by producing reactive oxygen species (ROS) leading to the subsequent induction of T regulatory cells in a ROS-dependent manner. Macrophages may therefore be instrumental in downregulating T cell responses in situations of exacerbated immune responses. Here we investigated the effect of immunosuppressive drugs on ROS production by macrophage subsets and the subsequent effects on T cell activation. Macrophage types 1 and 2 were differentiated with GM-CSF or M-CSF, in presence or absence of dexamethasone, cyclosporine A, FK506, rapamycin, or mycophenolic acid. The ROS producing capacity of fully differentiated Mph was highest in anti-inflammatory Mph2 and not affected by exposure to immunosuppressive drugs. However, presence of rapamycin during Mph2 differentiation decreased the ROS production of these cells. In contrast, other immunosuppressive drugs, with dexamethasone being the most potent, increased the ROS producing capacity of Mph2. Intriguingly although the ROS producing ability of Mph1 was unaffected, dexamethasone strongly increased the ROS producing capabilities of dendritic cells. Both at the mRNA and protein level we found that dexamethasone enhanced the expression of NOX2 protein p47(phox). Functionally, dexamethasone further enhanced the capacity of Mph2 to suppress T cell mediated IFN-? and IL-4 production. In vivo, only in rats with normal ROS production (congenic DA.Ncf1(E3/E3)) it was observed that dexamethasone injection resulted in long-lasting upregulation of ROS production by macrophages and induced higher levels of Treg in a ROS-dependent manner. In conclusion, we show that the anti-inflammatory drug dexamethasone increases the ROS producing capacity of macrophages. PMID:22047959

Kraaij, Marina D; van der Kooij, Sandra W; Reinders, Marlies E J; Koekkoek, Karin; Rabelink, Ton J; van Kooten, Cees; Gelderman, Kyra A

2011-12-01

231

Differential effects of non-steroidal anti-inflammatory drugs on mitochondrial dysfunction during oxidative stress.  

PubMed

We investigated the effects of several non-steroidal anti-inflammatory drugs on swelling related properties of mitochondria, with an emphasis on compounds that are marketed and utilized topically in the eye (nepafenac, ketorolac, diclofenac, bromfenac), and compared these to the effects of amfenac (a metabolite of nepafenac) and to celecoxib (active principle of Celebrex). With the exception of the last compound, none of the drugs promote swelling of normal mitochondria that are well energized by succinate oxidation. However, swelling is seen when the mitochondria are under an oxidative stress due to the presence of t-butylhydroperoxide. When used at 200 microM the order of potency is celecoxib > bromfenac > diclofenac > ketorolac > amfenac > nepafenac approximately equal to 0. Again with the exception of celecoxib, this swelling is not seen when mitochondria are depleted of endogenous Ca(2+) and is accelerated when exogenous Ca(2+) is provided. Sr(2+) does not substitute for exogenous Ca(2+) and prevents swelling in the presence of endogenous Ca(2+) only. The same is true for ruthenium red (inhibitor of the Ca(2+) uniporter), for cyclosporin A (inhibitor of the mitochondrial permeability transition), and for a 3.4 kDa polyethylene glycol (polymer that cancels the force which drives swelling following the permeability transition). It is concluded that several non-steroidal anti-inflammatory drugs promote the mitochondrial permeability transition under conditions of oxidative stress and in a Ca(2+) dependent fashion, whereas celecoxib functions by another mechanism. Potency of those compounds that promote the transition varies widely with bromfenac being the most potent and nepafenac having almost no effect. The mitochondrial dysfunction which is caused by the transition may underlie side effects that are produced by some of these compounds. PMID:19810214

Lal, Nirupama; Kumar, Jitendra; Erdahl, Warren E; Pfeiffer, Douglas R; Gadd, Martha E; Graff, Gustav; Yanni, John M

2009-10-01

232

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

PubMed

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

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

2013-01-01

233

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

PubMed Central

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

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

234

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

PubMed Central

BACKGROUND AND PURPOSE Lysophosphatidylcholines (lysoPCs) with polyunsaturated acyl chains are known to exert anti-inflammatory actions. 15-Lipoxygeanation is crucial for anti-inflammatory action of polyunsaturated acylated lysoPCs. Here, the anti-inflammatory actions of 1-(15-hydroxyeicosapentaenoyl)-lysoPC (15-HEPE-lysoPC) and its derivatives were examined in a mechanistic analysis. EXPERIMENTAL APPROACH Anti-inflammatory actions of 15-HEPE-lysoPC in zymosan A-induced peritonitis of mice were examined by measuring plasma leakage and leucocyte infiltration, and determining levels of lipid mediators or cytokines. KEY RESULTS When each lysoPC, administered i.v., was assessed for its ability to suppress zymosan A-induced plasma leakage, 15-HEPE-lysoPC was found to be more potent than 1-(15-hydroperoxyeicosapentaenoyl)-lysoPC or 1-eicosapentaenoyl-lysoPC. Separately, i.p. administration of 15-HEPE-lysoPC markedly inhibited plasma leakage, in contrast to 15-HEPE, which had only a small effect. 15-HEPE-lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation of LTC4 and LTB4, 5-lipoxygenation products, as well as the levels of pro-inflammatory cytokines. The time-course study indicated that 15-HEPE-lysoPC might participate in both the early inflammatory phase and resolution phase. Additionally, 15-HEPE-lysoPC administration caused a partial suppression of LTC4-induced plasma leakage and LTB4-induced leucocyte infiltration. In the metabolism study, peritoneal exudate was shown to contain lysoPC-hydrolysing activity, crucial for anti-inflammatory activity, and a system capable of generating lipoxin A from 15-hydroxy eicosanoid precursor. CONCLUSIONS AND IMPLICATIONS 15-HEPE-lysoPC, a precursor for 15-HEPE in target cells, induced anti-inflammatory actions by inhibiting the formation of pro-inflammatory leukotrienes and cytokines, and by enhancing the formation of lipoxin A. 15-HEPE-lysoPC might be one of many potent anti-inflammatory lipids in vivo. PMID:21091644

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

2011-01-01

235

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

PubMed Central

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

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

2014-01-01

236

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

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

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

2014-08-01

237

HMGB1-Binding Heptamer Confers Anti-Inflammatory Effects in Primary Microglia Culture  

PubMed Central

High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In the postischemic brain, HMGB1 is massively released during NMDA-induced acute damage and triggers inflammatory processes. In a previous study, we demonstrated that intranasally delivered HMGB1 binding heptamer peptide (HBHP; HMSKPVQ) affords robust neuroprotective effects in the ischemic brain after middle cerebral artery occlusion (MCAO, 60 minutes). In the present study, we investigated HBHP-induced anti-inflammatory effects on microglia activation. In LPS-treated primary microglia culture, HMGB1 was rapidly released and accumulated in culture media. Furthermore, LPS-conditioned media collected from primary microglia cultures (LCM) activated naïve microglia and markedly induced NO and proinflammatory cytokines. However, the suppression of HMGB1 by siRNA-HMGB1, HMGB1 A box, or anti-HMGB1 antibody significantly attenuated LCM-induced microglial activation, suggesting that HMGB1 plays a critical role in this process. A pull-down assay using biotin-labeled HBHP showed that HBHP binds directly to HMGB1 (more specifically to HMGB1 A box) in LCM. In addition, HBHP consistently inhibited LCM-induced microglial activation and suppressed the inductions of iNOS and proinflammatory cytokines. Together these results suggest that HBHP confers anti-inflammatory effects in activated microglia cultures by forming a complex with HMGB1. PMID:24465145

Kim, Il-Doo

2013-01-01

238

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

PubMed Central

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

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

239

Purification and anti-inflammatory action of tripeptide from salmon pectoral fin byproduct protein hydrolysate.  

PubMed

In this study, the anti-inflammatory peptide from salmon pectoral fin byproduct protein hydrolysate by pepsin hydrolysis, was purified and identified using Sephadex G-25 gel permeation chromatography, high performance liquid chromatography and time-of-flight liquid chromatography/tandem mass spectrometry (TOF LC/MS/MS). The purified anti-inflammatory peptide was identified to be a tripeptide (PAY). Lipopolysaccharide treatment significantly (p<0.05) stimulated the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW264.7 cells. However, PAY treatment significantly (p<0.05) inhibited the production of NO by 63.80% and PGE2 by 45.33%. Western blotting analysis revealed that PAY significantly (p<0.05) suppressed the protein expression of inducible nitric oxide synthase and cyclooxygenase-2, which are responsible for the production of NO and PGE2. Additionally, PAY treatment also significantly (p<0.05) attenuated the production of pro-inflammatory cytokines, including tumour necrosis factor-?, interleukin-6 and -1?. PMID:25172694

Ahn, Chang-Bum; Cho, Young-Sook; Je, Jae-Young

2015-02-01

240

Thymoquinone Poly(lactide-co-glycolide) Nanoparticles Exhibit Enhanced Anti-proliferative, Anti-inflammatory, and Chemosensitization Potential  

PubMed Central

Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy confirmed particle diameter ranged between 150–200 nm. Electrophoretic gel shift mobility assay showed that TQ nanoparticles (NP) were more active than TQ in inhibiting NF-?B activation and in suppressing the expression of cyclin D1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), markers of cell proliferation, metastasis and angiogenesis, respectively. TQ-NP was also more potent than TQ in suppressing proliferation of colon cancer, breast cancer, prostate cancer, and multiple myeloma cells. Esterase staining for plasma membrane integrity revealed that TQ-NP was more potent than TQ in sensitizing leukemic cells to TNF- and paclitaxel-induced apoptosis. Overall our results demonstrate that encapsulation of TQ into nanoparticles enhances its anti-proliferative, anti-inflammatory, and chemosensitizing effects. PMID:20105430

Ravindran, Jayaraj; Nair, Hareesh B; Sung, Bokyung; Prasad, Sahdeo; Tekmal, Rajeshwar R.; Aggarwal, Bharat B.

2010-01-01

241

Anti-inflammatory and antifibrotic effects of methyl palmitate  

SciTech Connect

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

El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com

2011-08-01

242

Novel tight-binding inhibitory factor-kappaB kinase (IKK-2) inhibitors demonstrate target-specific anti-inflammatory activities in cellular assays and following oral and local delivery in an in vivo model of airway inflammation.  

PubMed

Nuclear factor-kappaB (NF-kappaB) is one of the major families of transcription factors activated during the inflammatory response in asthma and chronic obstructive pulmonary disease. Inhibitory factor-kappaB kinase 2 (IKK-2) has been shown to play a pivotal role in cytokine-induced NF-kappaB activation in airway epithelium and in disease-relevant cells. Nevertheless, the potential toxicity of specific IKK-2 inhibitors may be unacceptable for oral delivery in chronic obstructive pulmonary disease. Therefore, local delivery to the lungs is an attractive alternative that warrants further exploration. Here, we describe potent and selective small-molecule IKK-2 inhibitors [8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide (PHA-408) and 8-(2-(3,4-bis(hydroxymethyl)-3,4-dimethylpyrrolidin-1-yl)-5-chloroisonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo-[g]indazole-3-carboxamide (PF-184)] that are competitive for ATP have slow off-rates from IKK-2 and display broad in vitro anti-inflammatory activities resulting from NF-kappaB pathway inhibition. Notably, PF-184 has been designed to have high systemic clearance, which limits systemic exposure and maximizes the effects locally in the airways. We used an inhaled lipopolysaccharide-induced rat model of neutrophilia to address whether inhibiting NF-kappaB activation locally within the airways would show anti-inflammatory effects in the absence of systemic exposure. PHA-408, a low-clearance compound previously shown to be efficacious orally in a rodent model of arthritis, dose-dependently attenuated inhaled lipopolysaccharide-induced cell infiltration and cytokine production. Interestingly, PF-184 produced comparable dose-dependent anti-inflammatory activity by intratracheal administration and was as efficacious as intratracheally administered fluticasone propionate (fluticasone). Together, these results support the potential therapeutic utility of IKK-2 inhibition in inflammatory pulmonary diseases and demonstrate anti-inflammatory efficacy of an inhaled IKK-2 inhibitor in a rat airway model of neutrophilia. PMID:19478133

Sommers, Cynthia D; Thompson, Janice M; Guzova, Julia A; Bonar, Sheri L; Rader, Randall K; Mathialagan, Sumathy; Venkatraman, Neetu; Holway, Vicky Walker; Kahn, Larry E; Hu, George; Garner, Debra S; Huang, Horng-Chih; Chiang, Po-Chang; Schindler, John F; Hu, Yiding; Meyer, Debra M; Kishore, Nandini N

2009-08-01

243

Structural basis for both pro- and anti-inflammatory response induced by mannose-specific legume lectin from Cymbosema roseum  

Microsoft Academic Search

Legume lectins, despite high sequence homology, express diverse biological activities that vary in potency and efficacy. In studies reported here, the mannose-specific lectin from Cymbosema roseum (CRLI), which binds N-glycoproteins, shows both pro-inflammatory effects when administered by local injection and anti-inflammatory effects when by systemic injection. Protein sequencing was obtained by Tandem Mass Spectrometry and the crystal structure was solved

Bruno A. M. Rocha; Plinio Delatorre; Taianá M. Oliveira; Raquel G. Benevides; Alana F. Pires; Albertina A. S. Sousa; Luis A. G. Souza; Ana Maria S. Assreuy; Henri Debray; Walter F. de Azevedo; Alexandre H. Sampaio; Benildo S. Cavada

2011-01-01

244

Investigation of the Anti-Inflammatory Potential of Aloe vera Gel (97.5%) in the Ultraviolet Erythema Test  

Microsoft Academic Search

Background:Aloe vera is a natural product that is frequently used in soothing skin care products such as aftersun lotions. In the present study we aimed to explore the anti-inflammatory potential of a highly concentrated A. vera gel in the UV erythema test in vivo. Methods: 40 volunteers with skin types II and III were included in the randomized, double-blind, placebo-controlled,

J. Reuter; A. Jocher; J. Stump; B. Grossjohann; G. Franke; C. M. Schempp

2008-01-01

245

Anti-inflammatory and cytotoxic activities of five Veronica species.  

PubMed

Biological activities of five Veronica species (Scrophulariaceae), V. cymbalaria, V. hederifolia, V. pectinata var. glandulosa, V. persica and V. polita were studied for their anti-inflammatory and cytotoxic activities. Their methanol extracts showed both the inhibitory activity of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages and cytotoxic activity against KB epidermoid carcinoma and B16 melanoma. When the methanol extracts were fractionated between water and chloroform, water fractions significantly inhibited NO production without any cytotoxicity, while chloroform fractions showed cytotoxicity dose-dependently. When the radical scavenging activity was determined using 2,2-diphenyl-1-picryl-hydrazyl (DPPH), water fractions of the five Veronica species scavenged free radicals effectively, suggesting that the inhibitory effect of this species on NO production was due to their radical scavenging activity. On the other hand, chloroform fractions of Veronica species except for V. cymbalaria showed similar cytotoxic activity against KB and B16 melanoma cells. PMID:11995929

Harput, U Sebnem; Saracoglu, Iclal; Inoue, Makoto; Ogihara, Yukio

2002-04-01

246

Anti-inflammatory activity of flavonoids from Eupatorium arnottianum.  

PubMed

Three anti-inflammatory compounds: nepetin, jaceosidin and hispidulin have been isolated and identified from Eupatorium arnottianum Griseb. dichloromethane extract. Nepetin reduced the TPA mouse ear edema by 46.9% and jaceosidin by 23.2% (1mg/ear). Both compounds inhibited the NF kappaB induction by 91 and 77%, respectively. Furthermore phytochemical analysis of the ethanol extract has led to the identification of eriodictyol, hyperoside, rutin, caffeic and chlorogenic acids. All these compounds are reported for the first time in this species. The finding of topical antiinflammatory activity exerted by Eupatorium arnottianum extract and the identification of active principles could support the use of this plant for the treatment of inflammatory affections. PMID:17570627

Clavin, M; Gorzalczany, S; Macho, A; Muñoz, E; Ferraro, G; Acevedo, C; Martino, V

2007-07-25

247

Anti-inflammatory strategies for the treatment of sepsis.  

PubMed

Sepsis leads to an overwhelming inflammatory response of the host and is usually accompanied by well-known clinical symptoms (fever, tachycardia, leukocytosis, and so on) and the accompanying systemic inflammatory response syndrome (SIRS). Accordingly, most efforts to develop treatment strategies for sepsis have focused on those designed to counteract overactivation of the inflammatory system. Despite intensive research into identifying targets in sepsis, most of the resulting clinical trials have been based on experimental data and have resulted in no beneficial effects (i.e., survival). Recombinant activated protein C (APC) represents the first treatment that has led to restricted approval for use in sepsis in the USA and worldwide. This article reviews approaches to anti-inflammatory treatment in sepsis and provides an outlook into ongoing clinical trials as well as new treatments that have not yet been evaluated in the clinical setting. PMID:12662146

Riedemann, Niels C; Ward, Peter A

2003-04-01

248

Antioxidant and Anti-Inflammatory Activities of Barettin  

PubMed Central

In this paper, we present novel bioactivity for barettin isolated from the marine sponge Geodia barretti. We found that barettin showed strong antioxidant activity in biochemical assays as well as in a lipid peroxidation cell assay. A de-brominated synthetic analogue of barettin did not show the same activity in the antioxidant cell assay, indicating that bromine is important for cellular activity. Barettin was also able to inhibit the secretion of the inflammatory cytokines IL-1? and TNF? from LPS-stimulated THP-1 cells. This combination of anti-inflammatory and antioxidant activities could indicate that barettin has an atheroprotective effect and may therefore be an interesting product to prevent development of atherosclerosis. PMID:23880935

Lind, Karianne F.; Hansen, Espen; Østerud, Bjarne; Eilertsen, Karl-Erik; Bayer, Annette; Engqvist, Magnus; Leszczak, Kinga; Jørgensen, Trond Ø.; Andersen, Jeanette H.

2013-01-01

249

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

PubMed

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

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

250

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

PubMed Central

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

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

2013-01-01

251

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

PubMed

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

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

252

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

PubMed Central

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

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

253

Anti-Inflammatory and Antipyretic Activities of Hygrophila spinosa T. Anders Leaves (Acanthaceae)  

Microsoft Academic Search

Purpose: Hygrophila spinosa T. Anders (Acanthaceae) is commonly used in the traditional system of medicine for the treatment of inflammation, pain, jaundice, rheumatism, arthritis, anaemia, etc. In the present study, we investigated the anti-inflammatory and antipyretic activities of the petroleum ether, chloroform, alcoholic and aqueous extracts of the leaf of this plant. Methods: The anti-inflammatory activity of the various extracts

Arjun Patra; Shivesh Jha; P. Narasimha Murthy; Pronobesh Chattopadhyay; Ghanshyam Panigrahi; Devdeep Roy

254

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...

255

Neurobiology of Aging, in press Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia  

E-print Network

decline, and dementia Marie-Laure Ancelin, PhD.a,b,§,* , Isabelle Carrière, PhD.a,b,§ , Catherine Helmer persons. Cognitive performance, clinical diagnosis of dementia, and anti-inflammatory use were evaluated of incident dementia over 7 years. Nonsteroidal anti- inflammatory drug use was not significantly associated

Paris-Sud XI, Université de

256

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.) ...

257

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

PubMed

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

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

2012-01-01

258

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

PubMed Central

Background The main aim of this study is to evaluate the antioxidant and anti-inflammatory properties of forty four traditional Chinese medicinal herbal extracts and to examine these activities in relation to their antioxidant content. Methods The antioxidant activities were investigated using DPPH radical scavenging method and yeast model. The anti-inflammatory properties of the herbal extracts were evaluated by measuring their ability to inhibit the production of nitric oxide and TNF-? in RAW 264.7 macrophages activated by LPS and IFN- ?, respectively. The cytotoxic effects of the herbal extracts were determined by Alomar Blue assay by measuring cell viability. In order to understand the variation of antioxidant activities of herbal extracts with their antioxidant contents, the total phenolics, total flavonoids and trace metal (Mg, Mn, Cu, Zn, Se and Mo) quantities were estimated and a correlation analysis was carried out. Results Results of this study show that significant levels of phenolics, flavonoids and trace metal contents were found in Ligustrum lucidum, Paeonia suffuticosa, Salvia miltiorrhiza, Sanguisorba officinalis, Spatholobus suberectus, Tussilago farfara and Uncaria rhyncophylla, which correlated well with their antioxidant and anti-inflammatory activities. Some of the plants displayed high antioxidant and anti-inflammatory activities but contained low levels of phenolics and flavonoids. Interestingly, these plants contained significant levels of trace metals (such as Zn, Mg and Se) which are likely to be responsible for their activities. Conclusions The results indicate that the phenolics, flavonoids and trace metals play an important role in the antioxidant activities of medicinal plants. Many of the plants studied here have been identified as potential sources of new antioxidant compounds. PMID:23038995

2012-01-01

259

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

PubMed Central

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

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

2014-01-01

260

Comparison of piroxicam pharmacokinetics and anti-inflammatory effect in rats after intra-articular and intramuscular administration.  

PubMed

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

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

2014-05-01

261

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

SciTech Connect

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.

He, Xiao-dong; Tobo, Masayuki; Mogi, Chihiro; Nakakura, Takashi; Komachi, Mayumi; Murata, Naoya; Takano, Mutsumi; Tomura, Hideaki; Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)] [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Okajima, Fumikazu, E-mail: fokajima@showa.gunma-u.ac.jp [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)] [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

2011-12-02

262

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

PubMed Central

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

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

2011-01-01

263

N-butanol Extract from Melilotus Suaveolens Ledeb Affects Pro- and Anti-Inflammatory Cytokines and Mediators  

PubMed Central

Melilotus suaveolens Ledeb is a traditional medicinal plant for treating inflammation-related disease. This explores the inner anti-inflammatory mechanism of n-butanol extract from M. suaveolens Ledeb. Inflammatory cellular model was established by lipopolysaccharide intervention on RAW264.7 cell line. Levels of secreted cytokines TNF-?, IL-1?, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-?, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, activation of NF-?B and ingredients in the extract were assayed by ELISA, real time quantitative PCR, western blot, immunocytochemical test and HPLC fingerprint test, respectively. As a result, the extract could not only markedly reduce the production of pro-inflammatory mediators to different extents by blocking NF-?B activation but also promote the release of anti-inflammatory mediator HO-1 significantly. Each 1 g extract contained 0.023531 mg coumarin and another two high polar ingredients, probably saponins. It can be concluded that the extract has similar effects on antagonizing pro-inflammatory mediators and cytokines like Dexamethasone, and has effects on promoting the production of anti-inflammatory mediators. PMID:18955281

Zhao, Lei; Tao, Jun-Yan; Jin, Feng; Pang, Ran; Dong, Ji-Hua

2010-01-01

264

Antibacterial Activities and In Vitro Anti-Inflammatory (Membrane Stability) Properties of Methanolic Extracts of Gardenia coronaria Leaves  

PubMed Central

This work is carried out with Gardenia coronaria leaves that belong to the family Rubiaceae, which is a small-to-medium-sized but tall, deciduous tree, 7.6–9?m high on an average. Leaves are used for the treatment of rheumatic pain and bronchitis. The leaf of the plant consists of coronalolide, coronalolic acid, coronalolide methyl ester, ethyl coronalolate acetate triterpenes (secocycloartanes), and so forth. Methanol extract from the leaves of Gardenia coronaria was completely screened for membrane stability and antibacterial activity. The lower concentrations of Methanolic leaf extract of Gardenia coronaria gave good antimicrobial and anti-inflammatory activity, but higher concentrations gave relatively more projecting antibacterial activity in vitro as compared with Kanamycin. The crude drug's anti-inflammatory effects were compared with those of Aspirin as positive control. The Methanolic extracts of Gardenia coronaria leaves possessed a broad spectrum antibacterial activity against a variety of both Gram-negative and Gram-positive organisms like Streptococcus agalactiae, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, Shigella sonnei, Shigella boydii, and Proteus mirabilis, with a zone of inhibition from 10 to 16?mm. The extract also showed good membrane stability to be considered as having significant anti-inflammatory action. PMID:24695677

Jainul, Mohammed Abdullah; Faruq, Kazi Omar; Islam, Atiqul

2014-01-01

265

Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents  

PubMed Central

Sepsis, a typically acute inflammatory disease, is the biggest cause of death in ICU (intensive care unit). Novel anti-inflammatory alternatives are still in urgent need. In this study, we designed and synthesized 30 indole-2-one and 7-aza-2-oxindole derivatives based on the skeleton of tenidap, and their anti-inflammatory activity was determined by evaluating the inhibitory potency against lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-? and interleukin (IL)-6 release in RAW264.7 macrophages. Quantitative SAR (structure–activity relationship) analysis revealed that a high molecular polarizability and low lipid/water partition coefficient (ALogP) in indole-2-one are beneficial for anti-inflammatory activity. Moreover, compounds 7i and 8e inhibited the expression of TNF-?, IL-6, COX-2, PGES, and iNOS in LPS-stimulated macrophages, and 7i exhibited a significant protection from LPS-induced septic death in mouse models. These data present a series of new indole-2-one compounds with potential therapeutic effects in acute inflammatory diseases. PMID:25378906

Chen, Gaozhi; Jiang, Lili; Dong, Lili; Wang, Zhe; Xu, Fengli; Ding, Ting; Fu, Lili; Fang, Qilu; Liu, Zhiguo; Shan, Xiaoou; Liang, Guang

2014-01-01

266

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

PubMed Central

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

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

2012-01-01

267

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

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

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

2014-01-01

268

Anti-inflammatory, gastroprotective, free-radical-scavenging, and antimicrobial activities of hawthorn berries ethanol extract.  

PubMed

Hawthorn [Crataegus monogyna Jacq. and Crataegus oxyacantha L.; sin. Crataegus laevigata (Poiret) DC., Rosaceae] leaves, flowers, and berries are used in traditional medicine in the treatment of chronic heart failure, high blood pressure, arrhythmia, and various digestive ailments, as well as geriatric and antiarteriosclerosis remedies. According to European Pharmacopoeia 6.0, hawthorn berries consist of the dried false fruits of these two species or their mixture. The present study was carried out to test free-radical-scavenging, anti-inflammatory, gastroprotective, and antimicrobial activities of hawthorn berries ethanol extract. Phenolic compounds represented 3.54%, expressed as gallic acid equivalents. Determination of total flavonoid aglycones content yielded 0.18%. The percentage of hyperoside, as the main flavonol component, was 0.14%. With respect to procyanidins content, the obtained value was 0.44%. DPPH radical-scavenging capacity of the extract was concentration-dependent, with EC50 value of 52.04 microg/mL (calculation based on the total phenolic compounds content in the extract). Oral administration of investigated extract caused dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. The obtained anti-inflammatory effect was 20.8, 23.0, and 36.3% for the extract doses of 50, 100, and 200 mg/kg, respectively. In comparison to indomethacin, given in a dose producing 50% reduction of rat paw edema, the extract given in the highest tested dose (200 mg/kg) showed 72.4% of its activity. Gastroprotective activity of the extract was investigated using an ethanol-induced acute stress ulcer in rats with ranitidine as a reference drug. Hawthorn extract produced dose-dependent gastroprotective activity (3.8 +/- 2.1, 1.9 +/- 1.7, and 0.7 +/- 0.5 for doses of 50, 100, and 200 mg/kg, respectively), with the efficacy comparable to that of the reference drug. Antimicrobial testing of the extract revealed its moderate bactericidal activity, especially against gram-positive bacteria Micrococcus flavus, Bacillus subtilis, and Lysteria monocytogenes, with no effect on Candida albicans. All active components identified in the extract might be responsible for activities observed. PMID:18698794

Tadi?, Vanja M; Dobri?, Silva; Markovi?, Goran M; Dordevi?, Sofija M; Arsi?, Ivana A; Menkovi?, Nebojsa R; Stevi?, Tanja

2008-09-10

269

Sulphurous thermal water increases the release of the anti-inflammatory cytokine IL-10 and modulates antioxidant enzyme activity.  

PubMed

The beneficial effects of hot springs have been known for centuries and treatments with sulphurous thermal waters are recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects of the therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements. Here, the effects of an S-based compound (NaSH) and of a specific sulphurous thermal water characterized by additional ions such as sodium chloride, bromine and iodine (STW) were investigated in terms of cytokine release and anti-oxidant enzyme activity in primary human monocytes and in saliva from 50 airway disease patients subjected to thermal treatments. In vitro, NaSH efficiently blocked the induction of pro-inflammatory cytokines and counterbalanced the formation of ROS. Despite STW not recapitulating these results, possibly due to the low concentration of S-based compounds reached at the minimum non-toxic dilution, we found that it enhanced the release of IL-10, a potent anti-inflammatory cytokine. Notably, higher levels of IL-10 were also observed in patients' saliva following STW treatment and this increase correlated positively with salivary catalase activity (r2 = 0.19, *p less than 0.01). To our knowledge, these results represent the first evidence suggesting that S-based compounds and STW may prove useful in facing chronic inflammatory and age-related illness due to combined anti-inflammatory and anti-oxidant properties. PMID:24067460

Prandelli, C; Parola, C; Buizza, L; Delbarba, A; Marziano, M; Salvi, V; Zacchi, V; Memo, M; Sozzani, S; Calza, S; Uberti, D; Bosisio, D

2013-01-01

270

Anti-Inflammatory and PPAR Transactivational Effects of Oleanane-Type Triterpenoid Saponins from the Roots of Pulsatilla koreana  

PubMed Central

In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-?B inhibitory activity of the isolated compounds was measured in TNF?-treated HepG2 cells using a luciferase reporter system. Compounds 19–23 inhibited TNF?-stimulated NF-?B activation in a dose-dependent manner, with IC50 values ranging from 0.75–8.30 ?M. Compounds 19 and 20 also inhibited the TNF?-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7–11 and 19–23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with EC50 values ranging from 0.9–10.8 ?M. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents. PMID:25143813

Li, Wei; Yan, Xi Tao; Sun, Ya Nan; Ngan, Thi Thanh; Shim, Sang Hee; Kim, Young Ho

2014-01-01

271

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

PubMed Central

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

Hwang, Joon-Ho; Lim, Sang-Bin

2014-01-01

272

?-Amyrone, a specific inhibitor of cyclooxygenase-2, exhibits anti-inflammatory effects in vitro and in vivo of mice.  

PubMed

The whole plant of Sedum lineare Thunb has been used as traditional folk medicines for the treatment of sore throat, persistent hepatitis, jaundice and dysentery. ?-Amyrone (13(18)-Oleanen-3-one), a pentacyclic triterpene compound from S. lineare Thunb, was found to possess a potent anti-inflammatory effect in different inflammation model animals. Pretreatment with ?-Amyrone (i.p.) inhibited the ear edema in xylene-induced mouse ear edema. ?-Amyrone also decreased the level of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and leukocyte numbers in acetic acid-induced peritonitis in vivo. To clarify the possible mechanism of ?-Amyrone, we investigated the effect of ?-Amyrone in lipopolysaccharide (LPS) induced peritoneal macrophages. The data indicated that ?-Amyrone notably inhibited IL-6, TNF-? and NO production. In addition, the result showed that ?-Amyrone may control the cyclooxygenase-2 (COX-2) regulation and not the cyclooxygenase-1 (COX-1) at protein levels. These results suggest that ?-Amyrone is a bioactive agent which possesses anti-inflammatory effects, which may be relevant to the regulation of COX-2. PMID:24813716

Niu, Xiaofeng; Yao, Huan; Li, Weifeng; Mu, Qingli; Li, Huani; Hu, Hua; Li, Yongmei; Huang, Huimin

2014-07-01

273

Anti-inflammatory activities of methanol extracts from various seaweed species.  

PubMed

Thirty-seven species of common seaweeds from the coast of Korea were screened for anti-inflammatory activity Methanol extracts of the seaweeds were tested against mouse ear edema and erythema induced by phorbol myristate acetate. At 40 mg ml(-1) of extract, edema was strongly suppressed by the seaweeds Undaria pinnatifida and Ulva linza, with relative inhibition of 85 and 84%, respectively These two seaweeds also showed the greatest suppression of erythema, with inhibition of 78 and 70%, respectively IC50 values of U. pinnatifida were 10, 15, and 18 mg ml(-1) when inflammation symptoms of edema, erythema, and blood flow, respectively were measured. The IC50 of U. linza was 20, 26, and 31 mg ml(-1) when edema, erythema, and blood flow, respectively, were measured. A linear correlation among inhibition rates of edema, erythema, and blood flow was observed with high confidence. PMID:19195382

Khan, Mohammed N A; Choi, Jae Suk; Lee, Min Chul; Kim, Eliya; Nam, Taek Jeong; Fujii, Hitoshi; Hong, Yong Ki

2008-07-01

274

Effect of phonophoresis on skin permeation of commercial anti-inflammatory gels: sodium diclofenac and ketoprofen.  

PubMed

This study evaluated the use of ultrasound in combination with the commercial anti-inflammatory drugs ketoprofen and sodium diclofenac, according to the parameters used in physiotherapy. Ketoprofen and sodium diclofenac were used in the Franz diffusion cell model adapted to an ultrasound transducer in three conditions: no ultrasound, one application of ultrasound and two applications of ultrasound. High-performance liquid chromatography was used to quantify the total amount of drug permeating skin per unit area, as well as flux and latency. The results showed that for ketoprofen, the amount of drug permeating skin and flux increased with two ultrasound applications. Permeation of sodium diclofenac decreased in the presence of ultrasound. Ultrasound parameters and drug properties must be considered in the use of phonophoresis. PMID:23820249

Souza, Jaqueline; Meira, Alianise; Volpato, Nadia Maria; Mayorga, Paulo; Gottfried, Carmem

2013-09-01

275

Characterizing the Metabolic Fingerprint and Anti-inflammatory Activity of Hypericum gentianoides  

PubMed Central

In this paper we characterize the metabolic fingerprint and first reported anti-inflammatory activity of Hypericum gentianoides. H. gentianoides has a history of medical use by Native Americans, but it has been studied very little for biological activity. High-performance liquid chromatography (HPLC) and liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) analyses of a methanol extract show that H. gentianoides contains a family of over nine related compounds that have retention times, mass spectra, and a distinctive UV absorption spectra characteristic of certain acyl-phloroglucinols. These metabolites are abundant relative to other secondary products present in H. gentianoides, accounting for approximately 0.2 g per gram of dry plant tissue. H. gentianoides methanol extracts and a specific semipreparative HPLC fraction from these extracts containing the putative acyl-phloroglucinols reduce prostaglandin E2 synthesis in mammalian macrophages. PMID:18512936

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

2009-01-01

276

Assessment of intestinal permeability changes induced by nonsteroidal anti-inflammatory drugs in the rat.  

PubMed

Intestinal permeability was investigated as an alternative to intestinal ulceration for measuring nonsteroidal anti-inflammatory drug (NSAID) gut damage in the rat and developed as a method for routine measurement. NSAID dose-response curves produced using the two indices of damage showed that intestinal permeability is as sensitive and reproducible as ulceration, although changes could not be detected before visible ulceration occurred. Lactulose, [51Cr]-EDTA and [14C]-carboxyinulin were compared as possible in vivo markers of rat intestinal permeability. Measurement of [51Cr]-EDTA permeation was found to be the most sensitive and reproducible method. Dose-response curves produced by measuring [51Cr]-EDTA permeation were used to compare the potency of the two NSAIDs piroxicam and (S+) ibuprofen; piroxicam was found to be 10 times more potent in increasing intestinal permeability than (S+)-ibuprofen. These studies show that intestinal permeability measurement is a useful alternative to other methods of assessing NSAID adverse effect and is easily and rapidly performed. PMID:7496048

Ford, J; Martin, S W; Houston, J B

1995-09-01

277

Anti-inflammatory activities of cecropin a and its mechanism of action.  

PubMed

Cecropin A is a novel 37-residue cecropin-like antimicrobial peptide isolated from the cecropia moth, Hyalophora cecropia. We have demonstrated that cecropin A is an antibacterial agent and have investigated its mode of action. In this study, we show that cecropin A has potent antimicrobial activity against 2 multidrug resistant organisms-Acinetobacter baumanii and-Pseudomonas aeruginosa. Interactions between cecropin A and membrane phospholipids were studied using tryptophan blue shift experiments. Cecropin A has a strong interaction with bacterial cell mimetic membranes. These results imply that cecropin A has selectivity for bacterial cells. To address the potential the rapeutic efficacy of cecropin A, its anti-inflammatory activities and mode of action in mouse macrophage-derived RAW264.7 cells stimulated with lipopolysaccharide (LPS) were examined. Cecropin A suppressed nitrite production, mTNF-?, mIL-1?, mMIP-1, and mMIP-2 cytokine release in LPS-stimulated RAW264.7 cells. Furthermore, cecropin A inhibited intracellular cell signaling via the ERK, JNK, and p38 MAPK pathway, leading to the prevention of COX-2 expression in LPS-stimulated RAW264.7 cells. These results strongly suggest that cecropin A should be investigated as a potential agent for the prevention and treatment of inflammatory diseases. PMID:25319409

Lee, Eunjung; Shin, Areum; Kim, Yangmee

2015-01-01

278

Cytotoxic and anti-inflammatory constituents from the seeds of Descurainia sophia.  

PubMed

A new sinapoyl glycoside, 1,3-di-O-sinapoyl-?-D-glucopyranose (1) along with 13 known compounds, including, sinapoyl glycosides (2 and 3), cardenolide glycoside (4), flavonoids (5-10), lignan (11), phenolic acids (12 and 13), and phytosterol (14), were isolated from the seeds of Descurainia sophia by chromatographic separation methods. The structures of 1-14 were determined by the interpretation of spectroscopic data as well as by comparison of that data with previously reported values. Compounds 2, 3, 5, 6, and 11 were identified in and isolated from this plant for the first time in this study. All isolates were evaluated for in vitro cytotoxic activities against seven human cancer cell lines and for in vitro anti-inflammatory potential using LPS-stimulated RAW264.7 murine macrophages. Compound 4 showed potent cytotoxicity (IC50 values ranging from 0.034 to 0.596 ?M) against all human cancer cell lines tested and was identified as the main active cytotoxic constituent of this plant. Compound 8 (ED50 = 5.45 ?M) and 11 (ED50 = 10.02 ?M) exerted dose-dependent inhibitory effects on NO production in LPS-stimulated RAW264.7 cells. PMID:23435946

Lee, You Jin; Kim, No Soo; Kim, Haejin; Yi, Jin-Mu; Oh, Se-Mi; Bang, Ok-Sun; Lee, Jun

2013-05-01

279

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

PubMed Central

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

2014-01-01

280

Anti-inflammatory Effects of Baicalin, Baicalein, and Wogonin In Vitro and In Vivo.  

PubMed

Here, three structurally related polyphenols found in the Chinese herb Huang Qui, namely baicalin, baicalein, and wogonin, were examined for its effects on inflammatory responses by monitoring the effects of baicalin, baicalein, and wogonin on lipopolysaccharide (LPS)-mediated vascular inflammatory responses. We found that each compound inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to human endothelial cells. Each compound induced potent inhibition of phorbol-12-myristate 13-acetate and LPS-induced endothelial cell protein C receptor shedding. It also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore, each compound suppressed the production of tumor necrosis factor-? or interleukin-6 and the activation of nuclear factor-?B or extracellular regulated kinases 1/2 by LPS. Moreover, treatment with each compound resulted in reduced LPS-induced lethal endotoxemia. These results suggest that baicalin, baicalein, and wogonin posses anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. PMID:25249339

Lee, Wonhwa; Ku, Sae-Kwang; Bae, Jong-Sup

2015-02-01

281

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

PubMed

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

Kazemi, M

2015-03-01

282

Flavonol glycosides from Muehlenbeckia platyclada and their anti-inflammatory activity.  

PubMed

A new flavonol, morin-3-O-alpha-rhamnopyranoside (1), along with four known flavonols, kaempferol 3-O-alpha-rhamnopyranoside (2), kaempferol 3-O-beta-glucopyranoside (3), quercetin 3-O-alpha-rhamnopyranoside (4) and (+)-catechin (5), were isolated from the methanolic extract of Muehlenbeckia platyclada. The structures of these compounds were determined on the basis of chemical and spectroscopic evidence, as well as acid hydrolysis of the original glycoside. Isolates were evaluated for inhibition of generation of superoxide anion, and inhibition of release of neutrophil elastase. Compound 2 showed moderate inhibition of superoxide anion generation with an IC(50) value of 6.11+/-0.86 microg/ml; 1, 3 and 5 inhibited neutrophil elastase release with IC(50) values of 3.82+/-0.80, 8.61+/-1.38 and 4.37+/-0.72 microg/ml, respectively, and were 15-fold more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in this anti-inflammatory assay. PMID:19252320

Yen, Chiao-Ting; Hsieh, Pei-Wen; Hwang, Tsong-Long; Lan, Yu-Hsuan; Chang, Fang-Rong; Wu, Yang-Chang

2009-03-01

283

Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice  

PubMed Central

Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13?/? mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury. PMID:22915644

De Meyer, Simon F.; Savchenko, Alexander S.; Haas, Michael S.; Schatzberg, Daphne; Carroll, Michael C.; Schiviz, Alexandra; Dietrich, Barbara; Rottensteiner, Hanspeter; Scheiflinger, Friedrich

2012-01-01

284

Multiple pathways are responsible for Anti-inflammatory and Cardiovascular activities of Hordeum vulgare L.  

PubMed

Background Hordeum vulgare L. (HV or barley) is used by traditional healers to treat various inflammatory and cardiovascular diseases, without the knowledge of pharmacologic rationale behind its actions. This study was designed to explore the potential scientific mechanism(s) that could explain the use of Hordeum vulgare in traditional medicine as a treatment for various inflammatory and cardiovascular diseases.MethodsA crude extract and its three fractions were prepared from HV and screened for the inhibition of platelet aggregation and various metabolites of cyclooxygenase (COX), lipoxygenase (LOX) pathways of arachidonic acid (AA) metabolism as well as for its effects on certain antioxidant enzymes. Platelet aggregation was monitored using turbidometric principle, AA metabolism through radioimmunoassay and antioxidant enzymes by commercial kits using spectrophotometer.ResultsResults show that HV exhibited activities against all human platelet agonists used except adenine diphosphate, and inhibited both COX and LOX pathways of AA metabolism. It also elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). However, these activities were distributed in various fractions of HV. Aqueous fraction was most potent in elevating SOD activity; chloroform fraction had concentrated compounds responsible for COX inhibition while n-hexane seems to possess compounds responsible for LOX inhibition as well as the only fraction enhancing the activity of GPx.ConclusionsThese results suggest the likely mechanisms responsible for observed anti-inflammatory and cardiovascular effects of HV in traditional medicine. PMID:25428431

Gul, Saima; Ahmed, Sagheer; Kifli, Nurolaini; Uddin, Qazi; Batool Tahir, Nafisa; Hussain, Abrar; Jaafar, Hawa; Moga, Marius; Zia-Ul-Haq, Muhammad

2014-11-26

285

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

PubMed

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

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

286

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

PubMed

A certain number of filters have notable anti-inflammatory properties with percentage inhibition of PMA-induced edema in mice at over 70%. The question arose as to whether this effect was likely to continue after UV irradiation. It can be noted that 7 filters retain an equivalent anti-inflammatory effect before and after 2h of irradiation in a Suntest device (650 W/m(2)). For 9 filters, the anti-inflammatory effect decreases and for 5 filters, the anti-inflammatory effect increases. Various behaviors should be noted. 3 groups of substances can be distinguished: such as phenylbenzimidazole sulfonic acid which loses its anti-inflammatory character after irradiation (the percentage inhibition falls from 80 to 44%), oxybenzone which retains a constant anti-inflammatory character (89% inhibition before and after irradiation and also octyl methoxycinnamate which becomes very anti-inflammatory (with a percentage inhibition of 93%). The same phenomenon is observed in the case of commercial products. This should be made known as it can have a considerable impact on the results which are displayed on the packaging of sun products. PMID:23639290

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

2013-08-16

287

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety  

PubMed Central

Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis. PMID:21753867

Roth, Sanford H

2011-01-01

288

Anti-Inflammatory Components from the Root of Solanum erianthum  

PubMed Central

Two new norsesquiterpenoids, solanerianones A and B (1–2), together with nine known compounds, including four sesquiterpenoids, (?)-solavetivone (3), (+)-anhydro-?-rotunol (4), solafuranone (5), lycifuranone A (6); one alkaloid, N-trans-feruloyltyramine (7); one fatty acid, palmitic acid (8); one phenylalkanoid, acetovanillone (9), and two steroids, ?-sitosterol (10) and stigmasterol (11) were isolated from the n-hexane-soluble part of the roots of Solanum erianthum. Their structures were elucidated on the basis of physical and spectroscopic data analyses. The anti-inflammatory activity of these isolates was monitored by nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells. The cytotoxicity towards human lung squamous carcinoma (CH27), human hepatocellular carcinoma (Hep 3B), human oral squamous carcinoma (HSC-3) and human melanoma (M21) cell lines was also screened by using an MTT assay. Of the compounds tested, 3 exhibited the strongest NO inhibition with the average maximum inhibition (Emax) at 100 ?M and median inhibitory concentration (IC50) values of 98.23% ± 0.08% and 65.54 ± 0.18 ?M, respectively. None of compounds (1–9) was found to possess cytotoxic activity against human cancer cell lines at concentrations up to 30 ?M. PMID:23771024

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

2013-01-01

289

Nucleic acid-binding polymers as anti-inflammatory agents  

PubMed Central

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

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

2011-01-01

290

Cannabinoid-like anti-inflammatory compounds from flax fiber.  

PubMed

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

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

2012-09-01

291

Anti-inflammatory studies on Adenanthera pavonina seed extract.  

PubMed

A methanol extract of the seeds of Adenanthera pavonina was evaluated for pharmacological effects in animal models. The extract (50-200 mg/kg) produced statistically significant (P < 0.05) inhibition of the carrageenan-induced paw oedema in the rat, as well as the acetic-acid-induced vascular permeability in mice. At doses of 100 and 200 mg/kg, pleurisy induced with carrageenan was also inhibited. The extract (50-200 mg/kg) exhibited a dose-dependent and significant (P < 0.05) analgesic activity in the acetic-induced writhing in mice. In addition, both early and late phases of the formalin-induced paw licking in mice was inhibited by the extract. Acute toxicity studies revealed that the extract produced reduced motor activity. The LD50 value of the extract was found to be 1.36 g/kg. This study demonstrated the anti-inflammatory and analgesic effects of A. pavonina extract. PMID:15265320

Olajide, Olumayokun A; Echianu, Chinonye A; Adedapo, Aduragbemi D A; Makinde, Janet M

2004-01-01

292

Chondroprotective and anti-inflammatory effects of sesamin.  

PubMed

Osteoarthritis (OA) is a major disability of elderly people. Sesamin is the main compound in Sesamun indicum Linn., and it has an anti-inflammatory effect by specifically inhibiting ?5-desaturase in polyunsaturated fatty acid biosynthesis. The chondroprotective effects of sesamin were thus studied in a porcine cartilage explant induced with interleukin-1beta (IL-1?) and in a papain-induced osteoarthritis rat model. With the porcine cartilage explant, IL-1? induced release of sulfated-glycosaminoglycan (s-GAG) and hydroxyproline release, and this induction was significantly inhibited by sesamin. This ability to inhibit these processes might be due to its ability to decrease expression of MMP-1, -3 and -13, which can degrade both PGs and type II collagen, both at the mRNA and protein levels. Interestingly, activation of MMP-3 might also be inhibited by sesamin. Moreover, in human articular chondrocytes (HACs), some pathways of IL-1? signal transduction were inhibited by sesamin: p38 and JNK. In the papain-induced OA rat model, sesamin treatment reversed the following pathological changes in OA cartilage: reduced disorganization of chondrocytes in cartilage, increased cartilage thickness, and decreased type II collagen and PGs loss. Sesamin alone might increase formation of type II collagen and PGs in the cartilage tissue of control rats. These results demonstrate that sesamin efficiently suppressed the pathological processes in an OA model. Thus, sesamin could be a potential therapeutic strategy for treatment of OA. PMID:22704650

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

2012-08-01

293

Membranous nephropathy and nonsteroidal anti-inflammatory agents.  

PubMed

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

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

2013-11-01

294

Anti-inflammatory drimane sesquiterpene lactones from an Aspergillus species.  

PubMed

IFN-? inducible protein 10 (IP-10, CXCL10) is a 10 kDa chemokine, which is secreted from various cell types after exposure to pro-inflammatory stimuli. This chemokine is a ligand for the CXCR3 receptor and regulates immune responses by activating and recruiting leukocytes such as T cells, eosinophils, monocytes, and NK cells to sites of inflammation. Altered expression of CXCL10 has been associated with chronic inflammatory and infectious diseases and therefore CXCL10 represents a promising target for the development of new anti-inflammatory drugs. In a search for inhibitors of CXCL10 promoter activity, three structurally related drimane sesquiterpene lactones (compounds 1-3) were isolated from fermentations of an Aspergillus species. Compounds 1 and 2 inhibited the IFN-?/TNF-?/IL-1? induced CXCL10 promoter activity in transiently transfected human DLD-1 colon carcinoma cells in a dose-dependent manner with IC50 values of 12.4 ?M for 1 and 55 ?M for 2, whereas 3 was devoid of any biological activity. Moreover, compounds 1 and 2 reduced CXCL10 mRNA levels and synthesis in IFN-?/TNF-?/IL-1? stimulated DLD-1 cells. PMID:24792812

Felix, Silke; Sandjo, Louis P; Opatz, Till; Erkel, Gerhard

2014-06-01

295

Generation and Dietary Modulation of Anti-Inflammatory Electrophilic Omega-3 Fatty Acid Derivatives  

PubMed Central

Dietary ?-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic ?,?-unsaturated ketone derivatives of the ?-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-?B-driven gene expression. Herein, the endogenous generation of ?-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30–55 years of age with a reported EPA+DHA consumption of ?300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n?=?24) or identical appearing soybean oil (control condition, n?=?21). Participants and laboratory technicians remained blinded to treatment assignments. Results 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions The endogenous detection of these electrophilic ?-3 fatty acid ketone derivatives supports the precept that the benefit of ?-3 PUFA-rich diets can be attributed to the generation of electrophilic oxygenated metabolites that transduce anti-inflammatory actions rather than the suppression of pro-inflammatory AA metabolites. Trial Registration ClinicalTrials.gov NCT00663871 PMID:24736647

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

2014-01-01

296

Anti - inflammatory and sedative - hypnotic activity of the methanolic extract of the leaves of mentha arvensis.  

PubMed

Mentha arvensis Linn, a plant used as traditional medicine and in perfumery, has now been explored for its pharmacological activities as an anti-inflammatory and also as sedativehypnotic plant drug. The methanolic extract of the leaves after being processed, was taken for the pharmacological study. Anti-inflammatory activity was carried out on albino rats. Further, the activity was compared to that of a standard anti-inflammatory drug - nimesulide and the percent inhibition of oedema determined. The sedative hypnotic activity, when carried out on mice, showed the potentiation of pentobarbitone induced sleeping time. The data of average recovery time was analyzed to show the standard deviation from the mean. PMID:22557118

Verma, S M; Arora, H; Dubey, R

2003-10-01

297

Synthesis of novel phosphorylated guanidine derivatives from cyanamide and their anti-inflammatory activity.  

PubMed

A series of novel guanidine derivatives were synthesized in three steps and their anti-inflammatory activities in vitro and in vivo evaluated. 2-Aminopyridin-3-ol (1) was reacted with thiophosphoryl chloride (2) to give a monochloride (3). It was further reacted with cyanamide to afford the corresponding cyanamine (4), which was subsequently reacted with different heterocyclic amines to form the title compounds (5a-l). The substituent in the guanidine function affected the potency of anti-inflammatory activity. The compounds having benzothiazole, fluorophenyl, and piperazinyl moieties enhanced the anti-inflammatory activity. PMID:23302584

Katla, Venkata Ramana; Syed, Rasheed; Kuruva, Chandra Sekhar; Kuntrapakam, Hema Kumar; Chamarthi, Naga Raju

2013-01-01

298

A Strong Anti-Inflammatory Signature Revealed by Liver Transcription Profiling of Tmprss6?/? Mice  

PubMed Central

Control of systemic iron homeostasis is interconnected with the inflammatory response through the key iron regulator, the antimicrobial peptide hepcidin. We have previously shown that mice with iron deficiency anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficient-high hepcidin Tmprss6 KO mice. The transcriptional response associated with chronic hepcidin overexpression due to genetic inactivation of Tmprss6 is unknown. By using whole genome transcription profiling of the liver and analysis of spleen immune-related genes we identified several functional pathways differentially expressed in Tmprss6 KO mice, compared to IDA animals and thus irrespective of the iron status. In the effort of defining genes potentially targets of Tmprss6 we analyzed liver gene expression changes according to the genotype and independently of treatment. Tmprss6 inactivation causes down-regulation of liver pathways connected to immune and inflammatory response as well as spleen genes related to macrophage activation and inflammatory cytokines production. The anti-inflammatory status of Tmprss6 KO animals was confirmed by the down-regulation of pathways related to immunity, stress response and intracellular signaling in both liver and spleen after LPS treatment. Opposite to Tmprss6 KO mice, Hfe?/? mice are characterized by iron overload with inappropriately low hepcidin levels. Liver expression profiling of Hfe?/? deficient versus iron loaded mice show the opposite expression of some of the genes modulated by the loss of Tmprss6. Altogether our results confirm the anti-inflammatory status of Tmprss6 KO mice and identify new potential target pathways/genes of Tmprss6. PMID:23922777

Riba, Michela; Rausa, Marco; Sorosina, Melissa; Cittaro, Davide; Garcia Manteiga, Jose Manuel; Nai, Antonella; Pagani, Alessia; Martinelli-Boneschi, Filippo; Stupka, Elia; Camaschella, Clara; Silvestri, Laura

2013-01-01

299

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

PubMed Central

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

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

2014-01-01

300

Utility of published guidelines on the use of nonsteroidal anti-inflammatory drugs in the elderly.  

PubMed

Canadian Consensus guidelines regarding appropriate use of nonsteroidal anti-inflammatory drugs (NSAID) were recently published. This study was done to evaluate the application of these guidelines on NSAID practice patterns in frail elderly patients referred to a specialist Geriatric Assessment Clinic. A retrospective chart review was undertaken of referrals who were currently prescribed NSAIDs. Data were captured on age, sex, weight, diagnoses, medications and dosages, indication for NSAID treatment, lying BP (as assessed in the clinic) and recent serum creatinine result. Creatinine clearance was subsequently calculated use the Cockcroft-Gault equation. Complete data were available on 107 patients (68% women, average age 80.6 years). Thirty percent were on a traditional NSAID, the remainder were on a Coxib. Concomitant aspirin was prescribed in 37%. Cytoprotection was being used in 38% and did not increase appreciably in patients with additional risk factors for GI toxicity, i.e., concomitant aspirin usage (35%), and history of GI toxicity (48%). Sixty-seven were taking anti-hypertensive medications, although more than two thirds of these patients were uncontrolled. Newly diagnosed hypertension was present in 19.6%. Calculated creatinine clearance revealed moderate to severe renal impairment in 79% of subjects, although serum creatinine was only elevated in 18%. In total, 70% of subjects were found to have relative or absolute risk factors for NSAID therapy. Given the high prevalence of potential contraindications to anti-inflammatory drug usage in this study, we advocate the dissemination and application of these guidelines in geriatric patients in an attempt to reduce potential morbidity and mortality. PMID:18607671

Juby, Angela G; Davis, Paul

2008-09-01

301

Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action.  

PubMed

Shock waves (SW), defined as a sequence of single sonic pulses characterised by high peak pressure (100 MPa), a fast rise in pressure (< 10 ns) and a short lifecycle (10 micros), are conveyed by an appropriate generator to a specific target area at an energy density ranging from 0.03 to 0.11 mJ/mm(2). Extracorporeal SW (ESW) therapy was first used on patients in 1980 to break up kidney stones. During the last ten years, this technique has been successfully employed in orthopaedic diseases such as pseudoarthosis, tendinitis, calcarea of the shoulder, epicondylitis, plantar fasciitis and several inflammatory tendon diseases. In particular, treatment of the tendon and muscle tissues was found to induce a long-time tissue regeneration effect in addition to having a more immediate anthalgic and anti-inflammatory outcome. In keeping with this, an increase in neoangiogenesis in the tendons of dogs was observed after 4-8 weeks of ESW treatment. Furthermore, clinical observations indicate an immediate increase in blood flow around the treated area. Nevertheless, the biochemical mechanisms underlying these effects have yet to be fully elucidated. In the present review, we briefly detail the physical properties of ESW and clinical cases treated with this therapy. We then go on to describe the possible molecular mechanism that triggers the anti-inflammatory action of ESW, focusing on the possibility that ESW may modulate endogenous nitric oxide (NO) production either under normal or inflammatory conditions. Data on the rapid enhancement of endothelial NO synthase (eNOS) activity in ESW-treated cells suggest that increased NO levels and the subsequent suppression of NF-kappaB activation may account, at least in part, for the clinically beneficial action on tissue inflammation. PMID:19601786

Mariotto, Sofia; de Prati, Alessandra Carcereri; Cavalieri, Elisabetta; Amelio, Ernesto; Marlinghaus, Ernst; Suzuki, Hisanori

2009-01-01

302

Probucol plus cilostazol attenuate hypercholesterolemia?induced exacerbationin ischemic brain injury via anti-inflammatory effects.  

PubMed

Probucol, a lipid-lowering agent with anti-oxidant properties, is involved in protection against atherosclerosis, while cilostazol, an antiplatelet agent, has diverse neuroprotective properties. In this study, we investigated the anti-inflammatory effects of probucol and cilostazol on focal cerebral ischemia with hypercholesterolemia. Apolipoprotein E (ApoE) knockout (KO) mice were fed a high-fat diet (HFD) with or without 0.3% probucol and/or 0.2% cilostazol for 10 weeks. To assess the protective effects of the combined therapy of probucol and cilostazol on ischemic injury, the mice received 40 min of middle cerebral artery occlusion (MCAO). Infarct volumes, neurobehavioral deficits and neuroinflammatory mediators were subsequently evaluated 48 h after reperfusion. Probucol alone and probucol plus cilostazol significantly decreased total- and low-density lipoprotein (LDL)-cholesterol in ApoE KO with HFD. MCAO resulted in significantly larger infarct volumes in ApoE KO mice provided with HFD compared to those fed a regular diet, although these volumes were significantly reduced in the probucol plus cilostazol group. Consistent with a smaller infarct size, probucol alone and the combined treatment of probucol and cilostazol improved neurological and motor function. In addition, probucol alone and probucol plus cilostazol decreased MCP-1 expression and CD11b and GFAP immuno-reactivity in the ischemic cortex. These findings suggested that the inhibitory effects of probucol plus cilostazol in MCP-1 expression in the ischemic brain with hypercholesterolemia allowed the identification of one of the mechanisms responsible for anti-inflammatory action. Probucol plus cilostazol may therefore serve as a therapeutic strategy for reducing the impact of stroke in hypercholesterolemic subjects. PMID:25017431

Kim, Ji Hyun; Hong, Ki Whan; Bae, Sun Sik; Shin, Yong-Il; Choi, Byung Tae; Shin, Hwa Kyoung

2014-09-01

303

VBP15: preclinical characterization of a novel anti-inflammatory delta 9,11 steroid.  

PubMed

?9,11 modifications of glucocorticoids (21-aminosteroids) have been developed as drugs for protection against cell damage (lipid peroxidation; lazaroids) and inhibition of neovascularization (anecortave). Part of the rationale for developing these compounds has been the loss of glucocorticoid receptor binding due to the ?9,11 modification, thus avoiding many immunosuppressive activities and deleterious side effect profiles associated with binding to glucocorticoid and mineralocorticoid receptors. We recently demonstrated that anecortave acetate and its 21-hydroxy analog (VBP1) do, in fact, show glucocorticoid and mineralocorticoid receptor binding activities, with potent translocation of the glucocorticoid receptor to the cell nucleus. We concluded that ?9,11 steroids showed novel anti-inflammatory properties, retaining NF-?B inhibition, but losing deleterious glucocorticoid side effect profiles. Evidence for this was developed in pre-clinical trials of chronic muscle inflammation. Here, we describe a drug development program aimed at optimizing the ?9,11 chemistry. Twenty ?9,11 derivatives were tested in in vitro screens for NF-?B inhibition and GR translocation to the nucleus, and low cell toxicity. VBP15 was selected as the lead compound due to potent NF-?B inhibition and GR translocation similar to prednisone and dexamethasone, lack of transactivation properties, and good bioavailability. Phamacokinetics were similar to traditional glucocorticoid drugs with terminal half-life of 0.35 h (mice), 0.58 h (rats), 5.42 h (dogs), and bioavailability of 74.5% (mice), and 53.2% (dogs). Metabolic stability showed ?80% remaining at 1 h of VBP6 and VBP15 in human, dog, and monkey liver microsomes. Solubility, permeability and plasma protein binding were within acceptable limits. VBP15 moderately induced CYP3A4 across the three human hepatocyte donors (24-42%), similar to other steroids. VBP15 is currently under development for treatment of Duchenne muscular dystrophy. PMID:23498916

Reeves, Erica K M; Hoffman, Eric P; Nagaraju, Kanneboyina; Damsker, Jesse M; McCall, John M

2013-04-15

304

In vitro and ex vivo pharmacodynamics of selected non-steroidal anti-inflammatory drugs in equine whole blood.  

PubMed

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenases (COX), and the inhibition of COX-2 rather than COX-1 can limit the onset of NSAID-related adverse effects. The pharmacodynamic properties of eltenac, naproxen, tepoxalin, SC-560 and NS 398 in healthy horses were investigated using an in vitro whole blood assay. To predict COX selectivity in clinical use, eltenac and naproxen were also studied ex vivo after intravenous administration. SC-560 acted as a selective COX-1 inhibitor, tepoxalin as a dual inhibitor with potent activity against COX-1, and NS 398 as a preferential COX-2 inhibitor. Eltenac was a preferential COX-2 inhibitor in vitro but un-selective in the ex vivo study. Naproxen maintained its non-selectivity both in vitro and ex vivo. These findings have demonstrated that in vitro studies may not accurately predict in vivo NSAID selectivity for COX and should be confirmed using an ex vivo whole blood assay. PMID:21565533

Cuniberti, B; Odore, R; Barbero, R; Cagnardi, P; Badino, P; Girardi, C; Re, G

2012-03-01

305

Anti-inflammatory and anti-nociceptive activities of two new triterpenoids from Adiantum capillus-veneris Linn.  

PubMed

Two new triterpenoids characterised as 30-normethyl fernen-22-one (capillirone, 1) and hopan-3?-ol (capillirol B, 2), along with two known triterpenoids, 4-?-hydroxyfilican-3-one and 3-?,4-?-dihydroxyfilicane, have been isolated from the ethanolic extract of the fronds of Adiantum capillus-veneris Linn. (Adiantaceae). Compounds 1 and 3 showed significant anti-inflammatory activity with 33.07% (p < 0.01) and 42.30% (p < 0.001) inhibition as compared to indomethacin that exhibited 60.00% (p < 0.001) inhibition after 3 h in the carrageenan-induced hind paw oedema method. Compound 3 showed potent anti-nociceptive activity with 42.37% inhibition as compared to indomethacin that showed 45.34% inhibition in the writhing test. PMID:23972143

Haider, Saqlain; Kharbanda, Chetna; Alam, Mohammad Sarwar; Hamid, Hinna; Ali, Mohammad; Alam, Mahboob; Nazreen, Syed; Ali, Yakub

2013-01-01

306

Experimental evaluation of analgesic and anti-inflammatory potential of Oyster mushroom Pleurotus florida  

PubMed Central

Background: Edible mushrooms have been used as flavorful foods and as health nutritional supplements for several centuries. A number of bioactive molecules have been identified in numerous mushroom species Objective: To evaluate the analgesic and anti-inflammatory potential of Oyster Mushroom Pleurotus florida using various experimental models in Wistar rats. Materials and Methods: Acute toxicity studies were performed whereby dose of 250 mg/ kg and 500 mg/kg was selected for present study, Analgesic activity was determined using hot plate method, tail flick method, acetic acid induced writhing and formalin induced pain in rats, while carrageenan was used to induce inflammation and anti-inflammatory studies were performed. Results: HEE showed significant (P < 0.01) analgesic and anti-inflammatory response against all experimental models. Conclusion: These studies conclude that Pleurotus florida possesses analgesic and anti- inflammatory potential which might be due to presence of myochemicals like flavonoids, phenolics and polysaccharides. PMID:23543896

Ganeshpurkar, Aditya; Rai, Gopal

2013-01-01

307

Anticancer, Anti-Inflammatory, and Analgesic Activities of Synthesized 2-(Substituted phenoxy) Acetamide Derivatives  

PubMed Central

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

Pal, Dilipkumar; Hegde, Rahul Rama; Hashim, Syed Riaz

2014-01-01

308

Kaurenic acid: An in vivo experimental study of its anti-inflammatory and antipyretic effects  

PubMed Central

Objective: This study was designed to investigate the anti-inflammatory and antipyretic effects of kaurenic acid (KA), a tetracyclic diterpenoid carboxylic acid, using in vivo experimental animal models. Material and Methods: The anti-inflammatory activity of KA was evaluated in rats, using egg albumin-induced paw edema (acute test) and Freund’s complete adjuvant-induced paw edema (subacute test), whereas the antipyretic effect was studied in rabbits by peptone-induced pyresis. Acute and subacute toxicity of KA were analyzed in NMRI mice. Results: KA showed anti-inflammatory and antipyretic properties, and the effect caused was significantly dose-related (P < 0.001) in both cases. The mean lethal doses of KA were 439.2 and 344.6 mg/kg for acute and subacute toxicity, respectively. Conclusion: On the basis of these findings, it may be inferred that KA has an anti-inflammatory and antipyretic potential. PMID:21206621

Sosa-Sequera, Miriam C.; Suárez, Omar; Daló, Nelson L.

2010-01-01

309

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...

310

Ion exchange chromatographic separation and isolation of oligosaccharides of intact low-molecular-weight heparin for the determination of their anticoagulant and anti-inflammatory properties.  

PubMed

It is well known that enoxaparin, a widely used anticoagulant and low-molecular-weight heparin containing a large number of oligosaccharides, possesses anti-inflammatory activity. Whilst enoxaparin has shown promising results in various inflammatory disorders, some of its oligosaccharides have anti-inflammatory properties and others increase the risk of bleeding due to their anticoagulant effects. The aim of this study was to develop an effective ion exchange chromatographic (IC) technique which allows the separation, isolation and, consequently, the identification of different oligosaccharides of enoxaparin with or without anticoagulant activity. The developed method utilises a semi-preparative CarboPac PA100 (9?×?250 mm) ion exchange column with sodium chloride gradient elution and UV detection at 232 nm. The method successfully resolved enoxaparin into more than 30 different peaks. IC-derived oligosaccharides with high, moderate, low or no anticoagulant activity were identified using an anti-factor Xa assay. The anti-inflammatory activity of selected oligosaccharides was investigated using the Griess assay. Using this technique, the oligosaccharides of enoxaparin with low or no anticoagulant activity, whilst exhibiting significant anti-inflammatory activity, could be fractionated. This technique can provide a platform to identify the oligosaccharides which are devoid of significant anticoagulant activity and are responsible for the therapeutic effects of enoxaparin that have been observed in various inflammatory conditions. PMID:23712644

Shastri, Madhur D; Johns, Cameron; Hutchinson, Joseph P; Khandagale, Manish; Patel, Rahul P

2013-07-01

311

Hollow fiber liquid-phase microextraction and determination of nonsteroidal anti-inflammatories by capillary electrophoresis and sulfonamides by HPLC in human urine.  

PubMed

In this paper two applications of three-phase HF-LPME for the determination of pharmaceuticals in human urine are proposed: a capillary electrophoresis with a photodiode array detection method for the analysis of seven nonsteroidal anti-inflammatory drugs (NSAIDs) and a high-performance liquid chromatographic with photo diode array and fluorescence detection method for the determination of four sulfonamides and their corresponding N(4)-acetyl-metabolites. Q3/2 Accurel® polypropylene hollow fibers were used for both procedures. Dihexyl ether was used as the supported liquid membrane for the determination of anti-inflammatories and 1-octanol for sulfonamides. An aqueous solution (pH 12) was used in both procedures as the acceptor phase and as the donor phase an aqueous solution (pH 2), and a 2 M Na(2)SO(4) aqueous solution (pH 4) was used for the determination of the anti-inflammatories and sulfonamides. The detection limits obtained were between 0.25 (naproxen) and 0.86 ng/mL (aceclofenac) for the determination of anti-inflammatories and 7 × 10(-4) (sulfamethoxazole) and 0.048 ng/mL (N(4)-acetyl-sulfamethazine) for sulfonamides. The method was successfully applied to the determination of the analytes in human urine. PMID:22753263

Villar Navarro, M; Ramos Payán, M; Fernández-Torres, R; Bello López, M A

2013-02-01

312

Evaluation of In Vitro Anti-Inflammatory Activities and Protective Effect of Fermented Preparations of Rhizoma Atractylodis Macrocephalae on Intestinal Barrier Function against Lipopolysaccharide Insult  

PubMed Central

Lipopolysaccharide (LPS), a potent inducer of systemic inflammatory responses, is known to cause impairment of intestinal barrier function. Here, we evaluated the in vitro protective effect of an unfermented formulation of Rhizoma Atractylodis Macrocephalae (RAM), a traditional Chinese herbal medicine widely used in the treatment of many digestive and gastrointestinal disorders, and two fermented preparations of RAM, designated as FRAM-1 (prepared in Luria-Bertani broth) and FRAM-2 (prepared in glucose), on intestinal epithelial cells (IECs) against LPS insult. In general, fermented formulations, especially FRAM-2, but not unfermented RAM, exerted an appreciable protective effect on IECs against LPS-induced perturbation of membrane resistance and permeability. Both fermented formulations exhibited appreciable anti-inflammatory activities in terms of their ability to inhibit LPS-induced gene expression and induced production of a number of key inflammatory mediators and cytokines in RAW 264.7 macrophage cells. However, in most cases, FRAM-2 exhibited stronger anti-inflammatory effects than FRAM-1. Our findings also suggest that suppression of nuclear factor-?? (NF-??) activity might be one of the possible mechanisms by which the fermented RAM exerts its anti-inflammatory effects. Collectively, our results highlight the benefits of using fermented products of RAM to protect against LPS-induced inflammatory insult and impairment in intestinal barrier function. PMID:23573125

Bose, Shambhunath; Kim, Hojun

2013-01-01

313

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

PubMed Central

The aqueous and methanol extracts from the dry bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae)—evaluated orally at the doses of 300 and 600?mg/kg against pain induced by acetic acid, formalin, pressure and against inflammation induced by carrageenan, histamine, serotonin and formalin in mice and rats, showed a dose dependant inhibition of pain and inflammation with a maximum effect of 56.38%, 73.06% and 42.79% produced by the aqueous extract, respectively on pain induced by acetic acid, formalin and pressure while the methanol extract at the same dose respectively inhibited these models of pain by 62.70%, 84.54% and 47.70%. The oral administration of aqueous and methanol extracts caused significant anti-inflammatory activity on paw oedema induced by histamine, serotonin and formalin. The present results show that the bulbils of Dioscorea bulbifera var sativa possess potent analgesic and anti-inflammatory activities. These activities may results from the inhibition of inflammatory mediators such as histamine, serotonin and prostaglandins. Thus, the analgesic activity of the bulbils of Dioscorea bulbifera may be at least partially linked to its anti-inflammatory activity. PMID:20953397

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

2011-01-01

314

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

PubMed Central

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

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

315

Cellular and molecular mechanisms of anti-inflammatory effect of Aflapin: a novel Boswellia serrata extract  

Microsoft Academic Search

There is significant number of evidences suggesting the anti-inflammatory properties of gum resin extracts of Boswellia serrata containing 3-O-acetyl-11-keto-?-boswellic acid (AKBA) and their promising potential as therapeutic interventions against inflammatory diseases\\u000a such as osteoarthritis (OA). Unfortunately, the poor bioavailability of AKBA following oral administration might limit the\\u000a anti-inflammatory efficacy of standardized Boswellia extract(s). To address this issue, we describe a

Krishanu Sengupta; Jayaprakash N. Kolla; Alluri V. Krishnaraju; Nandini Yalamanchili; Chirravuri V. Rao; Trimurtulu Golakoti; Smriti Raychaudhuri; Siba P. Raychaudhuri

2011-01-01

316

Effect of Anti-inflammatory Medications on Neuropathological Findings in Alzheimer Disease  

Microsoft Academic Search

Background: There has been no analysis of brain tis- sue from longitudinally observed, cognitively tested pa- tients to validate whether anti-inflammatory medica- tions protect against the pathological changes of Alzheimer disease. Objective: To investigate the role of anti-inflammatory medications in alleviating the pathological features of Alz- heimer disease. Design and Main Outcome Measures: A 5-year post- mortem tissue collection was

Glenda M. Halliday; Claire E. Shepherd; Heather McCann; Wayne G. J. Reid; David A. Grayson; G. Anthony Broe; Jillian J. Kril

2000-01-01

317

Anti-inflammatory and analgesic activity of Alkanna bracteosa and Alkanna tricophila  

Microsoft Academic Search

Alkanna bracteosa and Alkanna tricophila, Boraginaceae, have been reported to be useful for their anti-inflammatory and wound-healing effects in traditional medicine. Methanol extracts of A. bracteosa and A. tricophila were evaluated for their potential analgesic and anti-inflammatory properties. Alkanna bracteosa was observed to produce a maximum of 42% reduction of hind paw licking in acute as well as 68% alleviation

Saber Zare Mahmoudi; Mohammad Seyedabadi; Hamid Reza Monsef Esfahani; Yaghoub Amanzadeh; Seyed Nasser Ostad

2011-01-01

318

Anti-inflammatory and analgesic activity of Alkanna bracteosa and Alkanna tricophila  

Microsoft Academic Search

Alkanna bracteosa and Alkanna tricophila, Boraginaceae, have been reported to be useful for their anti-inflammatory and wound-healing effects in traditional medicine. Methanol extracts of A. bracteosa and A. tricophila were evaluated for their potential analgesic and anti-inflammatory properties. Alkanna bracteosa was observed to produce a maximum of 42% reduction of hind paw licking in acute as well as 68% alleviation

Saber Zare Mahmoudi; Mohammad Seyedabadi; Hamid Reza Monsef Esfahani; Yaghoub Amanzadeh; Seyed Nasser Ostad

2012-01-01

319

Anti-Inflammatory and Antinociceptive Effects of Mitragyna speciosa Korth Methanolic Extract  

Microsoft Academic Search

Objectives: To determine the anti-inflammatory and antinociceptive activities of Mitragyna speciosa Korth methanol extract in rodents. Materials and Methods: Anti-inflammatory activity was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma tests in rats. Antinociceptive activity was measured using the writhing test and the hot plate test in mice, and the formalin test in rats. All drugs and extracts were

W. M. Shaik Mossadeq; M. R. Sulaiman; T. A. Tengku Mohamad; H. S. Chiong; Z. A. Zakaria; M. L. Jabit; M. T. H. Baharuldin; D. A. Israf

2009-01-01

320

Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.  

PubMed

An aqeuous extract of Lobaria pulmonaria (L.) Hoffm., from which a tea is prepared and consumed as treatment for various diseases in northeastern Turkey, was tested for its anti-inflammatory and antiulcerogenic effects in rats. The carrageenan-induced paw edema, cotton pellet granuloma and indomethacin-induced gastric damage models were used to determine these effects. The extract exhibited moderate anti-inflammatory and strong antiulcerogenic activities. PMID:13678242

Süleyman, H; Odabasoglu, F; Aslan, A; Cakir, A; Karagoz, Y; Gocer, F; Halici, M; Bayir, Y

2003-01-01

321

Nonsteroidal anti-inflammatory-induced pseudoporphyria: is there an alternative drug?  

PubMed

Drug-induced pseudoporphyria cutanea tarda has been attributed to many different medications including several nonsteroidal anti-inflammatory drugs (NSAIDs). Often the patients taking these anti-inflammatory medications became part of a treatment dilemma when one of the drugs is deemed the cause of a blistering disease. We present a prototypical case of NSAID-induced pseudoporphyria cutanea tarda and suggest alternative NSAIDs that may be safely used in these patients. PMID:10228751

Checketts, S R; Morrison, K A; Baughman, R D

1999-04-01

322

Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin  

Microsoft Academic Search

Flavonoids are widely distributed in many fruits and plants, and it has been shown that most flavonoids have anti-inflammatory activity; however, the mechanisms of how the flavonoids exhibit their anti-inflammatory activity have not been clarified. We therefore focus on flavonoids Apigenin, Luteolin and Fisetin because of their related structure. We found that these compounds significantly inhibited TNF?-induced NF-?B transcriptional activation;

Megumi Funakoshi-Tago; Kei Nakamura; Kenji Tago; Tadahiko Mashino; Tadashi Kasahara

2011-01-01

323

Evaluation of anti-inflammatory activity of selected medicinal plants of Khyber Pakhtunkhwa, Pakistan.  

PubMed

In present study, the anti-inflammatory potential of three medicinal plants, Xanthium strumarium, Achyranthes aspera and Duchesnea indica were evaluated, using both in vitro and in vivo assays. Carrageenan induced hind paw edema model was used to carry out the in vivo anti-inflammatory activity, while for in vitro screening lipoxygenase inhibition assay was used. Crude extract of all the selected plants depicted significant (plt;0.001) anti-inflammatory activity, at late phase of inflammation. Achyranthes aspera also showed considerable anti-inflammatory activity (47%) at relatively lower concentration (200 mg/ml), at the initial phase of inflammation. Similarly the ethyl acetate fraction of all the selected plants showed significant lipoxygenase inhibition activity when compared with the standard drug (Baicalein). The results obtained from both in vitro and in vivo anti-inflammatory activity suggest that the ethyl acetate fraction of the crude extract of all the selected plants can be used for the isolation of new lead compounds with better anti-inflammatory activity. PMID:24577927

Khuda, Fazli; Iqbal, Zafar; Khan, Ayub; Zakiullah; Shah, Yasar; Ahmad, Lateef; Nasir, Fazli; Hassan, Muhammad; Ismail; Shah, Waheed Ali

2014-03-01

324

Antimicrobial, Antiparasitic, Anti-Inflammatory, and Cytotoxic Activities of Lopezia racemosa  

PubMed Central

The present study investigates the potential benefits of the Mexican medicinal plant Lopezia racemosa (Onagraceae). Extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Extracts and fractions were tested against a panel of nine bacterial and four fungal species. The antiparasitic activity was tested against Leishmania donovani, whereas the anti-inflammatory activity of the compounds was determined by measuring the secretion of interleukin-6 from human-derived macrophages. The same macrophage cell line was used to investigate the cytotoxicity of the compounds. Various extracts and fractions showed antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. The hexanic fraction HF 11-14b was the most interesting fraction with antimicrobial, and anti-inflammatory activities. The benefit of L. racemosa as a traditional medicinal plant was confirmed as shown by its antibacterial, antifungal and anti-inflammatory activities. To the best of our knowledge, this is the first study reporting the biological activities of L. racemosa, including antiparasitic and anti-inflammatory activities. PMID:23843731

Cruz Paredes, Carla; Bolívar Balbás, Paulina; Juárez, Zaida Nelly; Sánchez Arreola, Eugenio; Hernández, Luis Ricardo

2013-01-01

325

A Comparative Study of Sodium Houttuyfonate and 2-Undecanone for Their in Vitro and in Vivo Anti-Inflammatory Activities and Stabilities  

PubMed Central

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

Chen, Jing; Wang, Wenqing; Shi, Chunyang; Fang, Jianguo

2014-01-01

326

A comparative study of sodium houttuyfonate and 2-undecanone for their in vitro and in vivo anti-inflammatory activities and stabilities.  

PubMed

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

Chen, Jing; Wang, Wenqing; Shi, Chunyang; Fang, Jianguo

2014-01-01

327

ACCELERATED COMMUNICATION Di(2-ethylhexyl) phthalate Is a Highly Potent Agonist for the  

E-print Network

ACCELERATED COMMUNICATION Di(2-ethylhexyl) phthalate Is a Highly Potent Agonist for the Human the common plasticizer, di(2- ethylhexyl) phthalate (DEHP), as a highly potent and uniquely selective agonist

Omiecinski, Curtis

328

Potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice  

PubMed Central

Introduction Endothelins are involved in tissue inflammation, pain, edema and cell migration. Our genome-wide microarray analysis revealed that endothelin-1 (ET-1) and endothelin-2 (ET-2) showed a marked up-regulation in dorsal root ganglia during the acute phase of arthritis. We therefore examined the effects of endothelin receptor antagonists on the development of arthritis and inflammatory pain in monoarthritic mice. Methods Gene expression was examined in lumbar dorsal root ganglia two days after induction of antigen-induced arthritis (AIA) using mRNA microarray analysis. Effects of drug treatment were determined by repeated assessment of joint swelling, pain-related behavior, and histopathological manifestations during AIA. Results Daily oral administration of the mixed ETA and ETB endothelin receptor antagonist bosentan significantly attenuated knee joint swelling and inflammation to an extent that was comparable to dexamethasone. In addition, bosentan reduced inflammatory mechanical hyperalgesia. Chronic bosentan administration also inhibited joint swelling and protected against inflammation and joint destruction during AIA flare-up reactions. In contrast, the ETA-selective antagonist ambrisentan failed to promote any detectable antiinflammatory or antinociceptive activity. Conclusions Thus, the present study reveals a pivotal role for the endothelin system in the development of arthritis and arthritic pain. We show that endothelin receptor antagonists can effectively control inflammation, pain and joint destruction during the course of arthritis. Our findings suggest that the antiinflammatory and antinociceptive effects of bosentan are predominantly mediated via the ETB receptor. PMID:21689431

2011-01-01

329

Substituted phenyl groups improve the pharmacokinetic profile and anti-inflammatory effect of urea-based soluble epoxide hydrolase inhibitors in murine models  

PubMed Central

Soluble epoxide hydrolase inhibitors (sEHIs) are anti-inflammatory, analgesic, anti-hypertensive, cardio- and renal-protective in multiple animal models. However, the earlier adamantyl-containing urea-based inhibitors are rapidly metabolized. Therefore, new potent inhibitors with the adamantyl group replaced by a substituted phenyl group were synthesized to presumptively offer better pharmacokinetic (PK) properties.. Here we describe the improved PK profile of these inhibitors and the anti-inflammatory effect of the most promising one in a murine model. The PK profiles of inhibitors were determined following p.o. administration and serial bleeding in mice. The anti-inflammatory effect of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea(TPPU), the most promising inhibitor among the five sEHIs tested, was investigated in a lipopolysaccharide (LPS)-challenged murine model. The earlier broadly-used adamantyl-containing sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), was used for comparison. Compared with the earlier adamantyl-containing urea-based inhibitors, substituted phenyl-containing urea-based inhibitors afford more favorable PK properties, such as higher Cmaxs, larger AUCs and longer t1/2s, which, as expected, show more stable metabolic stability. Moreover, oral administration of TPPU dramatically reversed the shifts caused by LPS-challenge in plasma levels of inflammatory cytokines, epoxides and corresponding diols, which is more potent than t-AUCB. The substituted phenyl-containing sEHIs are more metabolically stable than those with adamantyl group, resulting in more potent efficacy in vivo. This indicates a new strategy for development of sEHIs for further study toward clinical trials. PMID:23291046

Liu, Jun-Yan; Lin, Yan-Ping; Qiu, Hong; Morisseau, Christophe; Rose, Tristan E.; Hwang, Sung Hee; Chiamvimonvat, Nipavan; Hammock, Bruce D.

2013-01-01

330

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

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

Moreira, Daniel Medeiros; da Silva, Roberto Leo; Vieira, Jefferson Luís; Fattah, Tammuz; Lueneberg, Maria Emilia; Gottschall, Carlos Antonio Mascia

2014-11-01

331

Overuse of prescription and OTC non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis and osteoarthritis.  

PubMed

Non-steroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to have significant cardiovascular and gastrointestinal toxicity; high dose of intake and concomitant use of multiple compounds or corticosteroids are factors that increase the risk of NSAID toxicity. In this paper we described our experience on NSAIDs misuse (both prescribing and OTC formulations), particularly relevant in the setting of rheumatoid arthritis (39.5 percent of patients) and osteoarthritis (47 percent of patients). We also evaluated causes underlying NSAIDs misuse (e.g. not satisfactory pain control, other painful conditions, etc). PMID:23527735

Cavagna, L; Caporali, R; Trifiro, G; Arcoraci, V; Rossi, S; Montecucco, C

2013-01-01

332

Genetic polymorphisms in anti-inflammatory cytokine signaling and the prevalence of gastric precancerous lesions in Venezuela  

Microsoft Academic Search

Objectives  The aim of the study was to assess the effects of genetic polymorphisms in anti-inflammatory mediators, i.e., IL10, IL4 and IL4R on the prevalence of gastric precancerous lesions and their interactions with other environmental factors.\\u000a \\u000a \\u000a \\u000a Methods  The study population consisted of 2,033 Venezuelan subjects known to have extremely high Helicobacter Pylori (HP) infection rates. The odds ratios (OR) and 95% confidence

Ikuko Kato; Federico Canzian; Silvia Franceschi; Martyn Plummer; Leen-Jan van Doorn; Yanhui Lu; Lydie Gioia-Patricola; Jorge Vivas; Gladys Lopez; Richard K. Severson; Ann G. Schwartz; Nubia Muñoz

2006-01-01

333

Endoplasmic Reticulum Stress Mediates the Anti-Inflammatory Effect of Ethyl Pyruvate in Endothelial Cells  

PubMed Central

Ethyl pyruvate (EP) is a simple aliphatic ester of the metabolic intermediate pyruvate that has been demonstrated to be a potent anti-inflammatory agent in a variety of in vivo and in vitro model systems. However, the protective effects and mechanisms underlying the actions of EP against endothelial cell (EC) inflammatory injury are not fully understood. Previous studies have confirmed that endoplasmic reticulum stress (ERS) plays an important role in regulating the pathological process of EC inflammation. In this study, our aim was to explore the effects of EP on tumor necrosis factor-? (TNF-?)-induced inflammatory injury in human umbilical vein endothelial cells (HUVECs) and to explore the role of ERS in this process. TNF-? treatment not only significantly increased the adhesion of monocytes to HUVECs and inflammatory cytokine (sICAM1, sE-selectin, MCP-1 and IL-8) production in cell culture supernatants but it also increased ICAM and MMP9 protein expression in HUVECs. TNF-? also effectively increased the ERS-related molecules in HUVECs (GRP78, ATF4, caspase12 and p-PERK). EP treatment effectively reversed the effects of the TNF-?-induced adhesion of monocytes on HUVECs, inflammatory cytokines and ERS-related molecules. Furthermore, thapsigargin (THA, an ERS inducer) attenuated the protective effects of EP against TNF-?-induced inflammatory injury and ERS. The PERK siRNA treatment not only inhibited ERS-related molecules but also mimicked the protective effects of EP to decrease TNF-?-induced inflammatory injury. In summary, we have demonstrated for the first time that EP can effectively reduce vascular endothelial inflammation and that this effect at least in part depends on the attenuation of ERS. PMID:25470819

Yi, Wei; Yang, Yang; Zhao, Dajun; Yang, Honggang; Geng, Ting; Xing, Jianzhou; Zhang, Yu; Tan, Songtao; Yi, Dinghua

2014-01-01

334

Toll-like receptors as a target of food-derived anti-inflammatory compounds.  

PubMed

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

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

2014-11-21

335

Anti-Inflammatory Impact of Minocycline in a Mouse Model of Tauopathy  

PubMed Central

Alzheimer's disease (AD) is characterized by the extracellular deposition of ?-amyloid in senile plaques, the intraneuronal accumulation of hyperphosphorylated tau aggregates as neurofibrillary tangles, and progressive neuronal loss leading to the onset of dementia. Increasing evidence suggests that neuroinflammatory processes contribute to the progression of AD. Minocycline is a semi-synthetic tetracycline derivative commonly used in the treatment of acne. Many studies have revealed that minocycline also has potent anti-inflammatory actions that are neuroprotective in rodent models of Huntington's disease, Parkinson's disease and motor neuron disease. Recently, we demonstrated that minocycline reduces the development of abnormal tau species in the htau mouse model of Alzheimer's disease. We have now extended these findings by examining the impact of minocycline on inflammatory processes in htau mice. Immunohistochemical analysis revealed that minocycline treatment resulted in fewer activated astrocytes in several cortical regions of htau mice, but did not affect astrocytosis in the hippocampus. We found htau mice have significantly elevated amounts of several cortical pro-inflammatory cytokines. In addition, we find that minocycline treatment significantly reduced the amounts of several inflammatory factors, including monocyte chemoattractant proteins 1 and 5, interleukins -6 and -10, eotaxin, and I-309. Furthermore, the reduced amounts of these cytokines significantly correlated with the amount of tau phosphorylated at Ser396/404 in the cortex of htau mice. These results may reveal new cytokine targets of minocycline that could be associated with its inhibition of tau pathology development in vivo. It is possible that further investigation of the role of these cytokines in neurodegenerative processes may identify novel therapeutic targets for Alzheimer's disease and related disorders. PMID:21423446

Garwood, Claire J.; Cooper, Jonathan D.; Hanger, Diane P.; Noble, Wendy

2010-01-01

336

Plant-based hydrocarbon esters from Tragia involucrata possess antimicrobial and anti-inflammatory activities.  

PubMed

Antimicrobial and anti-inflammatory activities of hydrocarbon esters obtained from Tragia involucrata were evaluated by disk-diffusion (250 µg/ml), and broth-dilution (500-7.8 µg/ml), methods against bacteria. Among the compounds, shellsol showed the most potent activity against Burkholderia pseudomallei (KHW), Aeromonas hydrophila, Staphylococcus aureus, Bacillus subtilis, Streptococcus pyogenes, Klebsiella pneumoniae, Proteus mirabilis, and Streptococcus pneumoniae. Interestingly, vinyl hexylether was active against food-spoilage bacteria (Bacillus cereus and Proteus vulgaris), 2, 4-methyl hexane also exerted antimicrobial activity against K. pneumoniae, S. pyogenes, B. pseudomallei, Alcaligens viscolactis, and Pseudomonas aeruginosa. 2-methylnonane and 2, 6-dimethyl heptane showed only weak activity. For example, shellsol showed bacteriostatic effect (MIC of 7.8 µg/ml) against A. hydrophila, vinyl hexylether (MIC of 15.6 µg/ml) against P. mirabilis, and 2, 4-methyl hexane (MIC of 31.25 µg/ml) on B. pseudomallei. Cytotoxic effects of compounds were assayed in human skin and monkey kidney cells (62.5-2000 µg/ml) by an XTT assay. The vinyl hexylether, 2, 4-dimethyl hexane and shellsol did not show any toxicity up to 1000 µg/ml concentrations. The 2-methylnonane and 2, 6-dimethyl heptane induced morphological changes (e.g. cell disintegration and lysis) of both cell types at a 2000 µg/ml. The vinyl hexylether, 2, 4-dimethyl hexane and shellsol were devoid of toxic effects; however, 2-methylnonane induced weight loss and severe necrosis as evidenced by histopathological and serum biochemical analysis in rats. Interestingly, shellsol showed the maximum inhibition of carrageenan-induced, paw oedema in rats. In conclusion, findings of this study clearly indicate that biologically active hydrocarbon esters, such as shellsol, vinyl hexylether, and 2, 4-dimethyl hexane isolated from T. involucrata, may effectively control the growth of certain food-borne and food-spoilage pathogens. PMID:23713670

Samy, Ramar Perumal; Sethi, Gautam; Chow, Vincent T K; Stiles, Bradley G

2013-04-01

337

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

PubMed Central

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

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

2008-01-01

338

Synthesis of N-arylidene-2-(2-Phenoxyphenyl) Acetohydrazides as Anti-Inflammatory Agents  

PubMed Central

Diclofenac sodium has been used for its anti-inflammatory actions for about 28 years, but since all the non-steroidal anti-inflammatory drugs (NSAIDs) suffer from the lethal gastro intestinal (GI) toxicities, diclofenac sodium is not an exception. The free –COOH group is thought to be responsible for the GI toxicity associated with all traditional NSAIDs. In the present research, the main motto was to develop new chemical entities as potential anti-inflammatory agents with no GI toxicities. A new type of 2-(2-phenoxyphenyl) acetohydrazide possessing N-arylidene substituents, was synthesized for evaluation as anti-inflammatory agents. The starting material 2-(2-Phenoxyphenyl) acetohydrazide was synthesized from 2-phenoxybenzoic acid in several steps according to the previous published method. Various substituted arylidene-2-phenoxynicotinic acid hydrazide derivatives were synthesized by the reaction of hydrazide 17 with selected aldehydes and screened for their potential anti-inflammatory activity. The structure of synthesized compounds was confirmed by different nuclear magnetic resonance technique, Fourier transform infrared spectroscopy (FTIR) and Mass-spectrometry data format. Qualitative structure-activity relationship data, acquired using the carrageenan-induced rat paw edema assay, showed that this group of arylidene-2-phenoxybenzoic acid hydrazides exhibit anti-inflammatory activity with significant reduction of rat paw edema (17-58% reduction in inflammation at different time intervals) in comparison with control group and a moderate to good activity range in comparison with diclofenac as the reference drug. Compounds 9a, 9d and 9e exhibited the most prominent and consistent anti-inflammatory activity. The compound, N-(4-Chlorobenzylidene)-2-(2-phenoxyphenyl) acetohydrazide (9d), exhibited the most in-vivo activity (32-58% reduction in inflammation) compared to the reference drug diclofenac (35-74% reduction in inflammation) in a carrageenan induced rat paw-edema assay. PMID:24250367

Shekarchi, Maral; Navidpour, Latifeh; Rajabi Khorami, Afshin; shekarchi, Mahtab; Partoazar, Alireza; Shafaroodi, Hamed; Rahmanipour, Narges; Shafiee, Abbas; Shekarchi, Maryam

2011-01-01

339

Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens.  

PubMed

Different species of the Scrophularia genus (Scrophulariaceae) have been reported to have bacteriostatic and anti-inflammatory properties. In previous studies the anti-inflammatory and antibacterial activity of different extracts from Scrophularia frutescens were investigated and p-coumaric, caffeic, ferulic gentisic, protocatechuic, syringic and isovanillic acids were isolated and identified. In this work the anti-inflammatory activity of these compounds, administered orally, has been studied against carrageenan-induced rat paw oedema and, administered topically, against tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema. The compounds' myeloperoxidase activity in inflamed ear was also investigated. Some of the phenolic acids were remarkably active in the TPA test (protocatechuic 71.59% inhibition, P < 0.001; syringic 74.43%, P < 0.001; ferulic 71.02% P < 0.001) and all significantly inhibited mouse ear oedema. They were only moderately active, or were without activity, in the carrageenan test. These results imply that the phenolic acids assayed are more effective topically than as oral anti-inflammatory agents and that their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue. This study has also enabled us to make some observations on the possible relationship between the chemical structure and anti-inflammatory activity of the compounds assayed. PMID:9821668

Fernández, M A; Sáenz, M T; García, M D

1998-10-01

340

Anti-inflammatory sesquiterpene lactones from Lychnophora trichocarpha Spreng. (Brazilian Arnica).  

PubMed

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

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

341

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

PubMed

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

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

2014-01-01

342

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

PubMed

Leea macrophylla (Leeaceae) is a wild edible plant with ethomedicinal importance as anti-inflammatory agent. However, no systematic studies on its anti-inflammatory activity and mechanisms have been reported. Present study was undertaken to evaluate anti-inflammatory activity of methanol extract of L. macrophylla leaves. Phytochemical investigation revealed presence of sterols, triterpenoids and ascorbic acid in extract. Methanol extract inhibited lipopolysaccharide stimulated production of inflammatory mediators viz. prostaglandin E2, tumor necrotic factor-?, interleukin-6 and interleukin-1? in vitro in mouse peritoneal macrophages. Additionally, the in vivo anti-inflammatory activity of this extract was evaluated by using carrageenan induced paw edema and cotton pellet granuloma assays in experimental rats. Oral administration of extract (100 and 200 mg/kg) exhibited dose dependant inhibition of carrageenan induced inflammation (p<0.05) and the reduction of the granuloma tissue formation (p<0.05-0.01). The extract (100 and 200 mg/kg, orally) exhibited significant central and peripheral analgesic activity in hot-plate test (p<0.01) and acetic acid induced writhing test (p<0.05-0.01) respectively in experimental mice. Treatment with extract (100 and 200 mg/kg, orally) significantly reduced the yeast provoked elevated body temperature (p<0.05-0.01) in experimental rats. These results confirmed the traditional anti-inflammatory indication of L. macrophylla leaves. PMID:23831308

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

2013-09-01

343

Anti-inflammatory Activity and Mechanism of Surfactin in Lipopolysaccharide-Activated Macrophages.  

PubMed

Surfactin is primarily produced by Bacillus natto TK-1 and is one of the most powerful biosurfactants. It consists of a heptapeptide interlinked with a ?-hydroxy fatty acid. Because of its special structure, surfactin shows broad biological effects, including anti-tumour, anti-microbial and anti-mycoplasma activities. It also has potential anti-inflammatory activity; however, the anti-inflammatory mechanism of surfactin has not been explored. In this study, we investigated the anti-inflammatory mechanism of surfactin in lipopolysaccharide (LPS)-stimulated macrophages. Surfactin exhibited an anti-inflammatory effect without cytotoxicity at certain concentrations, and the lipopolysaccharide (LPS)-stimulated cells appeared normal after surfactin treatment. Surfactin significantly inhibited the increased expression of IFN-?, IL-6, iNOS and nitric oxide (NO). TLR4 is the critical receptor for LPS; therefore, the TLR4 signal transduction pathway is the primary pathway that mediates LPS-induced inflammation. The results show that surfactin downregulated the LPS-induced TLR4 protein expression of macrophages and indicated that the surfactin-mediated signal pathway was involved in with TLR4. The subsequent studies demonstrated that surfactin exhibited anti-inflammatory effects by attenuating the activation of nuclear factor-?B (NF-?B), which is involved in the nuclear factor-?B (NF-?B) cell signalling pathways. These results suggest that surfactin may be a new therapeutic agent for inflammation. PMID:25331175

Zhang, Yuanyuan; Liu, Chuan; Dong, Bin; Ma, Xiaolei; Hou, Lihua; Cao, Xiaohong; Wang, Chunling

2014-10-21

344

In vitro anti-inflammatory and antioxidant potential of Si-Miao-San, its modifications and pure compounds.  

PubMed

The ancient Chinese prescription Si-Miao-San (SMS), which is widely used for the treatment of various diseases, e.g. rheumatic disorders, has been modified (m1SMS, m2SMS). The purpose of this study was to investigate the anti-inflammatory, antioxidant, and anti-tyrosinase effects of Si-Miao-San, of its two modifications, the component herbs, and its main pure ingredients. In vitro tyrosinase, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and lipid peroxidation (LPO) assays were carried out in order to determine the inhibitory potential of the samples. The traditionally applied decoctions as well as their fractions (n-hexane, DCM, n-BuOH) were tested for their activities in concentrations of 100 microg/mL and 400 microg/mL, and the pure compounds in a range 6.25 microg/mL to 100 microg/mL. In conclusion, the decoction of m2SMS exhibited strong antioxidant activity in the DPPH assay, while the decoction of the classical SMS formulation showed low activity. The present results have shown the modifications to be more efficient scavengers of free radicals, such as superoxide and peroxide radicals. In addition, the decoctions of the two modifications have been shown to be more potent tyrosinase inhibitors. These formulas may thus be used as antiinflammatory and anti-aging prescriptions, as they may help to prevent cell damage. This study clearly establishes the two modifications of Si-Miao-San as valuable sources of natural antioxidants and anti-inflammatory agents, and also as candidates in the search for modem pharmaceuticals. PMID:24079188

Lower-Nedza, Agnieszka D; Kuess, Carmen; Zhao, Haiyu; Bian, Baolin; Brantner, Adelheid H

2013-08-01

345

Anti-inflammatory effects of hepatocyte growth factor on the vicious cycle of macrophages and adipocytes.  

PubMed

The paracrine loop involving inflammatory cytokines between adipocytes and macrophages establishes a vicious cycle that aggravates pro-inflammatory changes in adipose tissue. The serum level of hepatocyte growth factor (HGF) is increased in metabolic syndrome, but whether HGF is beneficial or detrimental in inflammatory conditions is unclear. We previously reported that HGF has strong anti-inflammatory effects. We therefore hypothesized that HGF may inhibit chronic inflammation in adipose tissue by inhibiting the vicious cycle between adipocytes and macrophages. We stimulated the macrophage cell line RAW264 with HGF and evaluated pro-inflammatory cytokines. Coculturing differentiated 3T3-L1 adipocytes with RAW264 results in marked upregulation of pro-inflammatory cytokines. We examined whether HGF suppresses the upregulation of pro-inflammatory cytokines in this coculture system. Cardiac-specific HGF transgenic mice (HGF-Tg) were crossed with ApoE KO (knockout) mice, to yield ApoE KO/HGF-Tg mice, which were treated with a high-fat diet (HFD) and received angiotensin (Ang) II. The phenotypes of ApoE KO and ApoE KO/HGF-Tg mice were compared. Treatment with HGF reduced the expression of pro-inflammatory cytokine genes (Tumor necrosis factor-?, monocyte chemoattractant protein-1 and interleukin-6) in RAW264 and the coculture system. The anti-inflammatory effects of HGF were also confirmed in in vivo studies. Macrophage infiltration in epididymal adipose and fatty liver was reduced in ApoE KO/HGF-Tg. Adipocyte diameter was reduced in ApoE KO/HGF-Tg, and the serum adiponectin level was upregulated. These beneficial effects in ApoE KO/HGF-Tg mice under HFD and Ang II infusion were abrogated by an anti-HGF neutralizing antibody. These results suggest that HGF inhibits the vicious cycle of adipocytes and macrophages through the inhibition of macrophage-mediated pro-inflammatory cytokines and upregulation of adiponectin in adipocytes. These favorable effects may suppress chronic inflammation in adipose tissue. PMID:24621470

Kusunoki, Hiroshi; Taniyama, Yoshiaki; Otsu, Rei; Rakugi, Hiromi; Morishita, Ryuichi

2014-06-01

346

Characterization of anti-inflammatory compounds using transcriptomics, proteomics, and metabolomics in combination with multivariate data analysis  

Microsoft Academic Search

The discovery of new anti-inflammatory drugs is often based on an interaction with a specific target, although other pathways often play a primary or secondary role. Anti-inflammatory drugs can be categorized into classes, based on their mechanism of action. In this article we investigate the possibility to characterize novel anti-inflammatory compounds by three holistic methods. For this purpose, we make

Kitty C. M. Verhoeckx; Sabina Bijlsma; Sonja Jespersen; Raymond Ramaker; Elwin R. Verheij; Renger F. Witkamp; Jan van der Greef; Richard J. T. Rodenburg

2004-01-01

347

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

PubMed Central

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

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

2015-01-01

348

In vitro anti-inflammatory activity of phenolic rich extracts from white and red common beans.  

PubMed

According to epidemiological evidence, diets rich in fruits and vegetables can reduce the incidence of several chronic diseases that share an inflammatory component. These protective effects are attributed, in part, to the occurrence of different antioxidant components, mainly phenolic compounds. Our aim was to characterise phenolic composition, and to determine antioxidant and anti-inflammatory activities of phenolic rich extracts obtained from two kinds of common beans, white kidney beans (WKB) and round purple beans (RPB). Phenolic acids were the predominant component in WKB extracts, whereas RPB extracts presented higher concentrations of phenolic compounds, mainly catechin derivatives, proanthocyanidins and catechin glucoside. In addition, RPB extracts showed higher antioxidant capacity and higher anti-inflammatory activity by the reduction of NO production and cytokine mRNA expression of LPS stimulated macrophages. These results suggest that common bean extracts may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion. PMID:24837943

García-Lafuente, Ana; Moro, Carlos; Manchón, Noelia; Gonzalo-Ruiz, Alicia; Villares, Ana; Guillamón, Eva; Rostagno, Mauricio; Mateo-Vivaracho, Laura

2014-10-15

349

Anti-inflammatory and antinociceptive properties of dantrolene sodium in rats and mice.  

PubMed

Our study aimed at examining the possible anti-inflammatory and antinociceptive effects of dantrolene sodium in rats and mice. The anti-inflammatory effect of dantrolene sodium (2.5, 5 and 10 mg kg (-1)) was investigated and compared with diclofenac sodium (5 mg kg (-1)) using the formalin-, histamine-, and carrageenan-induced paw oedema and cotton pellet granuloma tests. Analgesic effects of dantrolene sodium were evaluated and compared with metamizol (200 mg kg (-1)) in acetic acid-induced writhing and formalin-induced paw licking tests. It was found that dantrolene sodium significantly diminished the nociceptive response in mice, showing at the same time considerable anti-inflammatory properties in rats. PMID:12162945

Büyükokuro?lu, Mehmet Emin

2002-06-01

350

Anti-inflammatory activity of two varieties of Pippali (Piper longum Linn.)  

PubMed Central

The present study has beenundertaken to evaluate the anti-inflammatory activity of two varieties of Pippali in acute and sub-acute experimental models of inflammation in albino rats. Four different market samples of each variety of Pippali were procured from different regions of India. The samples collected from South India which have given more extractive values were selected for screening of anti-inflammatory activity. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 200 mg/kg and the activity was compared with standard anti-inflammatory drugs in both models. Among the two different test samples studied, it was found that Chhoti variety of Pippali suppressed inflammation of both acute and sub acute phase, while Badi variety of Pippali only of acute phase. Thus for the therapeutic utility, Chhoti variety of Pippali may be considered over the Badi variety. PMID:23559810

Kumari, Mamta; Ashok, B. K.; Ravishankar, B.; Pandya, Tarulata N.; Acharya, Rabinarayan

2012-01-01

351

Anti-inflammatory activity of two varieties of Pippali (Piper longum Linn.).  

PubMed

The present study has beenundertaken to evaluate the anti-inflammatory activity of two varieties of Pippali in acute and sub-acute experimental models of inflammation in albino rats. Four different market samples of each variety of Pippali were procured from different regions of India. The samples collected from South India which have given more extractive values were selected for screening of anti-inflammatory activity. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 200 mg/kg and the activity was compared with standard anti-inflammatory drugs in both models. Among the two different test samples studied, it was found that Chhoti variety of Pippali suppressed inflammation of both acute and sub acute phase, while Badi variety of Pippali only of acute phase. Thus for the therapeutic utility, Chhoti variety of Pippali may be considered over the Badi variety. PMID:23559810

Kumari, Mamta; Ashok, B K; Ravishankar, B; Pandya, Tarulata N; Acharya, Rabinarayan

2012-04-01

352

Evaluation of Caesalpinia pulcherrima Linn. for anti-inflammatory and antiulcer activities  

PubMed Central

Objective: To evaluate the ethanolic and aqueous extracts of aerial parts of Caesalpinia pulcherrima (Linn.) Sw. for anti-inflammatory and antiulcer activities. Materials and Methods: Anti-inflammatory action of the ethanolic and aqueous extracts of C. pulcherrima (100 and 200 mg/kg b.w.) (CPE and CPA) were evaluated by cotton pellet granuloma models. Pylorus ligation and aspirin induced ulcer models were employed for evaluating antiulcer activity for both the extracts. Ulcerogenic potential of CP was also evaluated. Result: The ethanolic and aqueous extracts of C. pulcherrima significantly decreased (P<0.01) the granuloma tissue development. CPE and CPA at both the doses exhibited significant (P<0.01) antiulcer activity by decreasing the ulcer score in both the ulcer models and it was not ulcerogenic. Conclusion: The ethanolic and aqueous extracts of aerial parts of C. pulcherrima (CPE and CPA) possess significant anti-inflammatory and antiulcer activities. PMID:21572651

Sharma, Vivek; Rajani, G.P.

2011-01-01

353

3-Aminothiophene-2-acylhydrazones: non-toxic, analgesic and anti-inflammatory lead-candidates.  

PubMed

Different chemotypes are described as anti-inflammatory. Among them the N-acylhydrazones (NAH) are highlighted by their privileged structure nature, being present in several anti-inflammatory drug-candidates. In this paper a series of functionalized 3-aminothiophene-2-acylhydrazone derivatives 5a-i were designed, synthesized and bioassayed. These new derivatives showed great anti-inflammatory and analgesic potency and efficacy. Compounds 5a and 5d stand out in this respect, and were also active in CFA-induced arthritis in rats. After daily treatment for seven days with 5a and 5d (50 µmol/Kg), by oral administration, these compounds were not renal or hepatotoxic nor immunosuppressive. Compounds 5a and 5d also displayed good drug-scores and low risk toxicity calculated in silico using the program OSIRIS Property Explorer. PMID:24955640

da Silva, Yolanda Karla Cupertino; Reyes, Christian Tadeo Moreno; Rivera, Gildardo; Alves, Marina Amaral; Barreiro, Eliezer J; Moreira, Magna Suzana Alexandre; Lima, Lídia Moreira

2014-01-01

354

Maresin Biosynthesis and Identification of Maresin 2, a New Anti-Inflammatory and Pro-Resolving Mediator from Human Macrophages  

PubMed Central

Maresins are a new family of anti-inflammatory and pro-resolving lipid mediators biosynthesized from docosahexaenoic acid (DHA) by macrophages. Here we identified a novel pro-resolving product, 13R,14S-dihydroxy-docosahexaenoic acid (13R,14S-diHDHA), produced by human macrophages. PCR mapping of 12-lipoxygenase (12-LOX) mRNA sequence in human macrophages and platelet showed that they are identical. This human 12-LOX mRNA and enzyme are expressed in monocyte-derived cell lineage, and enzyme expression levels increase with maturation to macrophages or dendritic cells. Recombinant human 12-LOX gave essentially equivalent catalytic efficiency (kcat/KM) with arachidonic acid (AA) and DHA as substrates. Lipid mediator metabololipidomics demonstrated that human macrophages produce a novel bioactive product 13,14-dihydroxy-docosahexaenoic acid in addition to maresin-1, 7R,14S-dihydroxy-4Z,8E,10E,12Z,16Z,19Z-docosahexaenoic acid (MaR1). Co-incubations with human recombinant 12-LOX and soluble epoxide hydrolase (sEH) demonstrated that biosynthesis of 13,14-dihydroxy-docosahexaenoic acid (13,14-diHDHA) involves the 13S,14S-epoxy-maresin intermediate produced from DHA by 12-LOX, followed by conversion via soluble epoxide hydrolase (sEH). This new 13,14-diHDHA displayed potent anti-inflammatory and pro-resolving actions, and at 1 ng reduced neutrophil infiltration in mouse peritonitis by ?40% and at 10 pM enhanced human macrophage phagocytosis of zymosan by ?90%. However, MaR1 proved more potent than the 13R,14S-diHDHA at enhancing efferocytosis with human macrophages. Taken together, the present findings demonstrate that macrophages produced a novel bioactive product identified in the maresin metabolome as 13R,14S-dihydroxy-docosahexaenoic acid, from DHA via conversion by human 12-LOX followed by sEH. Given its potent bioactions, we coined 13R,14S-diHDHA maresin 2 (MaR2). PMID:25036362

Deng, Bin; Wang, Chin-Wei; Arnardottir, Hildur H.; Li, Yongsheng; Cheng, Chien-Yee Cindy; Dalli, Jesmond; Serhan, Charles N.

2014-01-01

355

Nonsteroidal Anti-inflammatory Drugs, Proton Pump Inhibitors, and Gastrointestinal Injury: Contrasting Interactions in the Stomach and Small Intestine.  

PubMed

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

Marlicz, Wojciech; Loniewski, Igor; Grimes, David S; Quigley, Eamonn M

2014-12-01

356

Flavonols enhanced production of anti-inflammatory substance(s) by Bifidobacterium adolescentis: prebiotic actions of galangin, quercetin, and fisetin.  

PubMed

The gut microbiota is capable of the bioconversion of flavonoids whereas influences of probiotic anaerobes on the bioactivities of flavonoids and vice versa are still unclear. Here, we investigated functional interactions with respect to the anti-inflammatory activity between flavonols and probiotic bacteria. Ten enteric (6 probiotic and 4 indigenous) bacteria were incubated with flavonols (galangin, kaempferol, quercetin, myricetin, and fisetin) under anaerobic conditions, and the supernatants were assessed for their effects on nitric oxide (NO) production in lipopolysaccaride-stimulated RAW264 cells. Although the conditioned medium from the flavonol mono-culture and almost all of the tested co-cultures failed to inhibit NO production, the medium from the Bifidobacterium adolescentis/flavonols (galangin, quercetin, and fisetin) co-culture highly suppressed NO production. This activity increased during the 1-6 H incubation in a time-dependent manner and was not observed in the co-culture using heat-inactivated B. adolescentis. Interestingly, when the B. adolescentis cell number was increased, the supernatant from the mono-culture of the bacteria showed NO suppression, suggesting that B. adolescentis may produce NO suppressant(s), and flavonols may have a promoting effect. These findings indicate that flavonols have a prebiotic-like effect on the anti-inflammatory activity of B. adolescentis. PMID:23554103

Kawabata, Kyuichi; Sugiyama, Yuta; Sakano, Taiken; Ohigashi, Hajime

2013-01-01

357

Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation  

PubMed Central

A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways. PMID:24454992

Wagner, Anika Eva; Terschluesen, Anna Maria; Rimbach, Gerald

2013-01-01

358

ABT-963 [2-(3,4-difluoro-phenyl)-4-(3-hydroxy-3-methyl-butoxy)-5-(4-methanesulfonyl-phenyl)-2H-pyridazin-3-one], a highly potent and selective disubstituted pyridazinone cyclooxgenase-2 inhibitor.  

PubMed

Nonsteriodal anti-inflammatory drugs (NSAIDs) are efficacious for the treatment of pain associated with inflammatory disease. Clinical experience with marketed selective cyclooxygenase-2 (COX-2) inhibitors (celecoxib, rofecoxib, and valdecoxib) has confirmed the utility of these agents in the treatment of inflammatory pain with an improved gastrointestinal safety profile relative to NSAID comparators. These COX-2 inhibitors belong to the same structural class. Each contains a core heterocyclic ring with two appropriately substituted phenyl rings appended to adjacent atoms. Here, we report the identification of vicinally disubstituted pyridazinones as potent and selective COX-2 inhibitors. The lead compound in the series, ABT-963 [2-(3,4-difluoro-phenyl)-4-(3-hydroxy-3-methyl-butoxy)-5-(4-methanesulfonyl-phenyl)-2H-pyridazin-3-one], has excellent selectivity (ratio of 276, COX-2/COX-1) in human whole blood, improved aqueous solubility compared with celecoxib and rofecoxib, high oral anti-inflammatory potency in vivo, and gastric safety in the animal studies. After oral administration, ABT-963 reduced prostaglandin E2 production in the rat carrageenan air pouch model (ED50 of 0.4 mg/kg) and reduced the edema in the carrageenan induced paw edema model with an ED30 of 1.9 mg/kg. ABT-963 dose dependently reduced nociception in the carrageenan hyperalgesia model (ED50 of 3.1 mg/kg). After 14 days of dosing in the adjuvant arthritis model, ABT-963 had an ED(50) of 1.0 mg/kg in reducing the swelling of the hind paws. Magnetic resonance imaging examination of the diseased paws in the adjuvant model showed that ABT-963 significantly reduced bone loss and soft tissue destruction. ABT-963 is a highly selective COX-2 inhibitor that may have utility in the treatment of the pain and inflammation associated with arthritis. PMID:15277581

Harris, Richard R; Black, Lawrence; Surapaneni, Sekhar; Kolasa, Teodozyj; Majest, Sandra; Namovic, Marian T; Grayson, George; Komater, Victoria; Wilcox, Denise; King, Linda; Marsh, Kennan; Jarvis, Michael F; Nuss, Merrill; Nellans, Hugh; Pruesser, Lee; Reinhart, Glenn A; Cox, Bryan; Jacobson, Peer; Stewart, Andrew; Coghlan, Michael; Carter, George; Bell, Randy L

2004-12-01

359

Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns.  

PubMed

The human newborn infant is susceptible to gut inflammatory disorders. In particular, growth-restricted infants or infants born prematurely may develop a severe form of intestinal inflammation known as necrotizing enterocolitis (NEC), which has a high mortality. Milk provides a multitude of proteins with anti-inflammatory properties and in this review we gather together some recent significant advances regarding the isolation and proteomic identification of these minor constituents of both human and bovine milk. We introduce the process of inflammation, with a focus on the immature gut, and describe how a multitude of milk proteins act against the inflammatory process according to both in vitro and in vivo studies. We highlight the effects of milk proteins such as caseins, and of whey proteins such as alpha-lactalbumin, beta-lactoglobulin, lactoferrin, osteopontin, immunoglobulins, trefoil factors, lactoperoxidase, superoxide dismutase, platelet-activating factor acetylhydrolase, alkaline phosphatase, and growth factors (TGF-?, IGF-I and IGF-II, EGF, HB-EGF). The effects of milk fat globule proteins, such as TLR-2, TLR-4, sCD14 and MFG-E8/lactadherin, are also discussed. Finally, we indicate how milk proteins could be useful for the prophylaxis and therapy of intestinal inflammation in infants and children. PMID:23660296

Chatterton, Dereck E W; Nguyen, Duc Ninh; Bering, Stine Brandt; Sangild, Per Torp

2013-08-01

360

Structural studies of an anti-inflammatory lectin from Canavalia boliviana seeds in complex with dimannosides.  

PubMed

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

Bezerra, Gustavo Arruda; Viertlmayr, Roland; 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

361

Isolation and tandem mass fragmentations of an anti-inflammatory compound from Aralia elata.  

PubMed

One-step isolation of a saponin from Aralia elata was undertaken using high-speed countercurrent chromatography coupled with evaporative light scattering detection. A triterpenoid saponin, elatoside F, was purified with 96.8% purity using a two-phase-system comprising chloroform-methanol-water-isopropanol. The yield was 35.0 mg from 348.2 mg of the enriched saponin fraction. In vitro anti-inflammatory study demonstrated that elatoside F inhibited lipopolysaccharide-induced nitric oxide production, as well as nuclear factor kappaB activation, in a dose-dependent manner. Two types of mass ionization technique were compared on elatoside F to investigate characteristic fragmentation patterns. MALDI-TOF tandem mass spectrometric fragmentation patterns of sodiated ions provided structural information on glycosidic cleavages and on extensive cross-ring cleavages. Electrospray ionization multiple-stage tandem mass fragmentation of both sodiated and lithiated ions could provide information on glycosidic cleavages. All observed tandem mass fragmentation spectra provided valuable elatoside F structural information when unknown samples from crude extracts are under screening by mass spectrometry. PMID:19557359

Lee, Ju Hyeon; Ha, Young Wan; Jeong, Choon Sik; Kim, Yeong Shik; Park, Youmie

2009-06-01

362

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review.  

PubMed

Reduced levels of HDL cholesterol (HDL-C) are a strong independent predictor of coronary artery disease (CAD) risk. The major anti-atherogenic function of HDL is to mediate reverse cholesterol transport. This response is highly dependent on apoA-I and apoE, protein components of HDL. Randomized clinical trials have assessed effects of several classes of drugs on plasma cholesterol levels in CAD patients. Agents including cholestyramine, fibrates, niacin, and statins significantly lower LDL cholesterol (LDL-C) and induce modest increases in HDL-C, but tolerance issues and undesirable side effects are common. Additionally, residual risk may be present in patients with persistently low HDL-C and other complications despite a reduction in LDL-C. These observations have fueled interest in the development of new pharmacotherapies that positively impact circulating lipoproteins. The goal of this review is to discuss the therapeutic potential of synthetic apolipoprotein mimetic peptides. These include apoA-I mimetic peptides that have undergone initial clinical assessment. We also discuss newer apoE mimetics that mediate the clearance of atherogenic lipids from the circulation and possess anti-inflammatory properties. One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials. PMID:25157031

White, C Roger; Garber, David W; Anantharamaiah, G M

2014-10-01

363

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

PubMed Central

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

Asplund, Maria; Boehler, Christian; Stieglitz, Thomas

2014-01-01

364

Anti-Inflammatory Effects of the Chinese Herbal Formula Sini Tang in Myocardial Infarction Rats  

PubMed Central

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

Liu, Jiangang; Peter, Karoline; Shi, Dazhuo; Zhang, Lei; Dong, Guoju; Zhang, Dawu; Breiteneder, Heimo; Bauer, Rudolf; Ma, Yan

2014-01-01

365

Anti-inflammatory effects of the chinese herbal formula sini tang in myocardial infarction rats.  

PubMed

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

Liu, Jiangang; Peter, Karoline; Shi, Dazhuo; Zhang, Lei; Dong, Guoju; Zhang, Dawu; Breiteneder, Heimo; Bauer, Rudolf; Jakowitsch, Johannes; Ma, Yan

2014-01-01

366

Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials  

PubMed Central

Existing drugs are slow to eradicate Mycobacterium tuberculosis (Mtb) in patients and have failed to control tuberculosis globally. One reason may be that host conditions impair Mtb’s replication, reducing its sensitivity to most antiinfectives. We devised a high-throughput screen for compounds that kill Mtb when its replication has been halted by reactive nitrogen intermediates (RNIs), acid, hypoxia, and a fatty acid carbon source. At concentrations routinely achieved in human blood, oxyphenbutazone (OPB), an inexpensive anti-inflammatory drug, was selectively mycobactericidal to nonreplicating (NR) Mtb. Its cidal activity depended on mild acid and was augmented by RNIs and fatty acid. Acid and RNIs fostered OPB’s 4-hydroxylation. The resultant 4-butyl-4-hydroxy-1-(4-hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione (4-OH-OPB) killed both replicating and NR Mtb, including Mtb resistant to standard drugs. 4-OH-OPB depleted flavins and formed covalent adducts with N-acetyl-cysteine and mycothiol. 4-OH-OPB killed Mtb synergistically with oxidants and several antituberculosis drugs. Thus, conditions that block Mtb’s replication modify OPB and enhance its cidal action. Modified OPB kills both replicating and NR Mtb and sensitizes both to host-derived and medicinal antimycobacterial agents. PMID:23012453

Gold, Ben; Pingle, Maneesh; Brickner, Steven J.; Shah, Nilesh; Roberts, Julia; Rundell, Mark; Bracken, W. Clay; Warrier, Thulasi; Somersan, Selin; Venugopal, Aditya; Darby, Crystal; Jiang, Xiuju; Warren, J. David; Fernandez, Joseph; Ouerfelli, Ouathek; Nuermberger, Eric L.; Cunningham-Bussel, Amy; Rath, Poonam; Chidawanyika, Tamutenda; Deng, Haiteng; Realubit, Ronald; Glickman, J. Fraser; Nathan, Carl F.

2012-01-01

367

Synthesis and biological evaluation of a novel baicalein glycoside as an anti-inflammatory agent.  

PubMed

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

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

368

Interactions between non-steroidal anti-inflammatory drugs and lipid membranes  

NASA Astrophysics Data System (ADS)

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.

Boggara, Mohan; Krishnamoorti, Ramanan

2008-03-01

369

Anti-inflammatory effects of black rice, cyanidin-3-O-beta-D-glycoside, and its metabolites, cyanidin and protocatechuic acid.  

PubMed

The anti-inflammatory effects of cyanidin-3-O-beta-D-glycoside (C3G), a major constituent of black rice (BR), and its metabolites, cyanidin and protocatechuic acid (PA), were assessed in lipopolysaccharide (LPS)-induced RAW 264.7 cells and carrageenan-induced inflammation in air pouches in BALB/c mice. BR, C3G and its metabolites suppressed the production of the proinflammatory cytokines, TNF-alpha and IL-1 beta, and the inflammatory mediators, NO and prostaglandin E2 (PGE2), as well as the gene expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. These agents also inhibited the phosphorylation of I kappaB-alpha, the nuclear translocation of NF-kappaB, and the activation of mitogen-activated protein kinases. Furthermore, these agents significantly inhibited the leukocyte number and the levels of TNF-alpha, PGE2, and protein in the exudates of the air pouch in carrageenan-treated mice, as well as COX-2 expression and NF-kappaB activation. Among the test agents, PA most potently inhibited these inflammatory mediators in vivo and in vitro. Based on these findings, if BR is orally administered, its main constituent, C3G, may be metabolized to cyanidin and/or PA, which express potent anti-inflammatory effects by regulating NF-kappaB and MAPK activation. PMID:20669401

Min, Sung-Won; Ryu, Su-Noh; Kim, Dong-Hyun

2010-08-01

370

Analgesic and anti-inflammatory activities of the sesquiterpene fraction from Annona reticulata L. bark.  

PubMed

The sesquiterpene fraction of Annona reticulata bark was studied by GC/MS. Three major components were identified: copaene (35.40%), patchoulane (13.49%) and 1H-cycloprop(e)azulene (22.77%). The fraction was also screened for its analgesic and anti-inflammatory activities. The sesquiterpene fraction at doses 12.5 and 25?mg?kg?¹ and the unsaponified petroleum ether extract at a dose of 50?mg?kg?¹ exhibited significant central as well as peripheral analgesic and anti-inflammatory activities. These activities were comparable with the standard drugs used in the respective experiments. PMID:22007723

Chavan, Machindra J; Wakte, Pravin S; Shinde, Devanand B

2012-01-01

371

Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.  

PubMed

A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies. PMID:20800934

Balakumar, C; Lamba, P; Kishore, D Pran; Narayana, B Lakshmi; Rao, K Venkat; Rajwinder, K; Rao, A Raghuram; Shireesha, B; Narsaiah, B

2010-11-01

372

A novel treatment of central serous chorioretinopathy with topical anti-inflammatory therapy.  

PubMed

A 45-year-old Caucasian female with diagnosis of central serous chorioretinopathy (CSCR) did not improve on conventional observational approach. She was not willing to proceed with photocoagulation or photodynamic therapy. An unconventional approach of topical anti-inflammatory (ketorolac, dexamethasone and hydrocortisone) preparation was prescribed. The course of her CSCR responded well on this unconventional treatment, but relapsed on cessation or tapering of treatment. After 18 weeks of treatment with a gradual taper, her condition resolved. The present case highlights an alternative but unconventional treatment of CSCR with prolonged use of anti-inflammatories. PMID:22949003

Chong, Chee-Foong; Yang, David; Pham, Thuan Q; Liu, Henry

2012-01-01

373

Synthesis and anti-inflammatory activity of the major metabolites of imrecoxib.  

PubMed

We have developed a novel and moderately selective COX-2 inhibitor, imrecoxib, as a new anti-inflammatory drug. We describe herein the preparation of the major metabolites M2 and M4 of imrecoxib, as well as the in vitro and in vivo activities of the two compounds. The results showed that both M2 and M4 are potential COXs inhibitors with a moderate COX-1/COX-2 selectivity, and their anti-inflammatory activity in vivo was equal to or slightly higher than the clinical celecoxib. PMID:19286379

Feng, Zhiqiang; Chu, Fengming; Guo, Zongru; Sun, Piaoyang

2009-04-15

374

Anti-inflammatory Effect of Bumblebee Alcohol Extracts in CFA-Induced Rat Edema  

PubMed Central

In this study, we prepared alcohol extracts of the larva, pupa, queen, and cocoon (clony) of B. ignitus, B. terrestris, and B. h. sapporoensis, and tested the anti-inflammatory activity of the extracts by using a rat model of adjuvant-induced edema. The extracts derived from the queen of B. ignitus, the queen of B. terrestris, and the cocoon of B. ignitus decreased hind paw edema after 1 day of i.p. administration. These extracts also induced vasorelaxation and NO production in calf pulmonary artery endothelial cells. These results suggest that bumblebee alcohol extracts has anti-inflammatory and vasorelaxant properties. PMID:24278617

Han, Jea Woong; Yoon, Hyung Joo; Hwang, Jae Sam; Young, Yun Eun

2012-01-01

375

Analgesic and anti-inflammatory properties of Thespesia populnea leaf extracts.  

PubMed

Analgesic and anti-inflammatory activities of the aqueous and ethanol extracts of Thespesia populnea Soland. ex. Correa (Malvaceae) leaves were evaluated in animal models. Orally-administered aqueous and ethanol extracts (100, 200 and 400?mg?kg?¹ bw) showed significant analgesic activity in chemical-, mechanical- and thermally-induced pain test models in mice. The extracts also reduced paw oedema induced by carrageenan in rats. The results obtained in this study suggest that Thespesia populnea extracts have analgesic and anti-inflammatory properties. PMID:21916770

Ilavarasan, R; Mohideen, S; Venkataraman, S

2012-01-01

376

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

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

Shaaban, Omaima G.; Rizk, Ola H.; Bayad, Aida E.; El-Ashmawy, Ibrahim M.

2013-01-01

377

In vitro screening of the action of non-steroidal anti-inflammatory drugs on hypochlorous acid-induced hyaluronan degradation  

Microsoft Academic Search

The antioxidative effect of two non-steroidal anti-inflammatory drugs was studied in vitro by measuring the kinetics of degradation of high-molecular weight hyaluronan (HA) in a system comprising hypochlorous acid + CuCl2 + ascorbic acid using a Brookfield rotational viscometer equipped with a Teflon cup and spindle of coaxial cylindrical geometry. The changes in HA chemical structure were investigated by chemiluminometry.

Monika Stankovská; Juergen Arnhold; Jozef Rychlý; Holger Spalteholz; Peter Gemeiner; Ladislav Šoltés

2007-01-01

378

Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents  

PubMed Central

Summary A high-yielding general synthesis of imidazophosphor ester based tetrazolo[1,5-b]pyridazines is described. A conjugated reaction between 3,6-diazidopyridazine and different types of phosphonyl carbanion reagents followed by intramolecular cyclization afforded the target products, by using sodium ethanolate solution as a reaction medium. Among the products, five compounds, at a dose of 50 mg per kilogram body weight, showed a notable antinociceptive and anti-inflammatory activity without toxic side-effects. PMID:24062835

Ganoub, Neven A; Sabry, Eman

2013-01-01

379

Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima.  

PubMed

Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC(50) values of 5.30 ± 0.21 and 13.12 ± 0.64 ?M, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC(50) values of 23.52 ± 1.37 and 69.85 ± 4.11 ?M, respectively. PMID:23200246

Thao, Nguyen Phuong; Nam, Nguyen Hoai; Cuong, Nguyen Xuan; Quang, Tran Hong; Tung, Pham The; Dat, Le Duc; Chae, Doobyeong; Kim, Sohyun; Koh, Young-Sang; Kiem, Phan Van; Minh, Chau Van; Kim, Young Ho

2013-01-01

380

Anti-Inflammatory Components of the Starfish Astropecten polyacanthus  

PubMed Central

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor ? (TNF-?)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 ?M. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 ?M, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 ?M, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 ?M) and 6 (IC50 = 79.05 ± 2.05 ?M) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 ?M) and 4 (IC50 = 16.73 ± 0.25 ?M) moderately inhibited the production of TNF-? and IL-6, respectively. PMID:23945602

Thao, Nguyen Phuong; Cuong, Nguyen Xuan; Luyen, Bui Thi Thuy; Quang, Tran Hong; Hanh, Tran Thi Hong; Kim, Sohyun; Koh, Young-Sang; Nam, Nguyen Hoai; Kiem, Phan Van; Minh, Chau Van; Kim, Young Ho

2013-01-01

381

Anti-inflammatory components of the starfish Astropecten polyacanthus.  

PubMed

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor ? (TNF-?)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 ?M. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 ?M, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 ?M, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 ?M) and 6 (IC50 = 79.05 ± 2.05 ?M) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 ?M) and 4 (IC50 = 16.73 ± 0.25 ?M) moderately inhibited the production of TNF-? and IL-6, respectively. PMID:23945602

Thao, Nguyen Phuong; Cuong, Nguyen Xuan; Luyen, Bui Thi Thuy; Quang, Tran Hong; Hanh, Tran Thi Hong; Kim, Sohyun; Koh, Young-Sang; Nam, Nguyen Hoai; Van Kiem, Phan; Van Minh, Chau; Kim, Young Ho

2013-08-01

382

Phenylacetic acids and the structurally related non-steroidal anti-inflammatory drug diclofenac bind to specific gamma-hydroxybutyric acid sites in rat brain.  

PubMed

Gamma-Hydroxybutyric acid (GHB) is a proposed neurotransmitter or neuromodulator with a yet unresolved mechanism of action. GHB binds to both specific high-affinity GHB binding sites and to gamma-aminobutyric acid subtype B (GABA(B)) receptors in the brain. To separate specific GHB effects from GABA(B) receptor effects, it is imperative to develop GHB selective and potent compounds. We generated the compound, 4-(biphen-4-yl)-4-hydroxybutyric acid, which is the 4-hydroxyl analogue of the non-steroidal anti-inflammatory drug (NSAID) fenbufen (referred to as gamma-hydroxyfenbufen). When measured in a rat brain homogenate [(3)H]NCS-382 binding assay, gamma-hydroxyfenbufen inhibited [(3)H]NCS-382 binding with a 10-fold higher affinity than GHB (K(i) 0.44 microM), thus establishing it as a novel lead structure. The active metabolite of fenbufen, 4-biphenylacetic acid inhibited [(3)H]NCS-382 binding with a twofold higher affinity than GHB. Measuring the affinities of structurally related NSAIDs for the [(3)H]NCS-382 site identified diclofenac, a clinically relevant NSAID (Voltaren, Diclon) of the phenylacetic acid (PAA) type, as a GHB ligand (K(i) value of 5.1 microM). Other non-NSAID PAAs also exhibited affinities similar to GHB. Our data raise the interesting possibility that the widely used over-the-counter drug compound, diclofenac, might affect GHB binding at relevant clinical dosages. Furthermore, the identification of PAAs as GHB ligands supplies new information about the structural preferences of the GHB ligand-binding site. PMID:19645815

Wellendorph, Petrine; Høg, Signe; Skonberg, Christian; Bräuner-Osborne, Hans

2009-04-01

383

Org 214007-0: A Novel Non-Steroidal Selective Glucocorticoid Receptor Modulator with Full Anti-Inflammatory Properties and Improved Therapeutic Index  

PubMed Central

Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects. PMID:23152771

Laskewitz, Anke J.; Dijkema, Rein; van der Maaden, Hans M.; Smit, Martin J.; Plate, Ralf; Conti, Paolo G. M.; Jans, Christan G. J. M.; Timmers, C. Marco; van Boeckel, Constant A. A.; Lusher, Scott J.; McGuire, Ross; van Schaik, Rene C.; de Vlieg, Jacob; Smeets, Ruben L.; Hofstra, Claudia L.; Boots, Annemieke M. H.; van Duin, Marcel; Ingelse, Benno A.; Schoonen, Willem G. E. J.; Grefhorst, Aldo; van Dijk, Theo H.; Kuipers, Folkert; Dokter, Wim H. A.

2012-01-01

384

The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease  

Microsoft Academic Search

Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory