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1

Tricyclic Compounds Containing Non-enolizable Cyano Enones. A Novel Class of Highly Potent Anti-inflammatory and Cytoprotective Agents=  

PubMed Central

Forty-four novel tricycles containing non-enolizable cyano enones (TCEs) were designed and synthesized on the basis of a semisynthetic pentacyclic triterpenoid, bardoxolone methyl, which is currently being developed in Phase II clinical trials for the treatment of severe chronic kidney disease in diabetic patients. Most of the TCEs having two different kinds of non-enolizable cyano enones in rings A and C are highly potent suppressors of induction of inducible nitric oxide synthase stimulated with interferon-?, and highly potent inducers of the cytoprotective enzymes heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Among these compounds, (±)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile ((±)-31) is the most potent in these bioassays in our pool of drug candidates including semisynthetic triterpenoids and synthetic tricycles. These facts strongly suggest that an essential factor for potency is not a triterpenoid skeleton, but the cyano enone functionality. Notably, TCE 31 reduces hepatic tumorigenesis induced with aflatoxin in rats. Further preclinical studies and detailed mechanism studies on 31 are in progress.

Honda, Tadashi; Yoshizawa, Hidenori; Sundararajan, Chitra; David, Emilie; Lajoie, Marc J.; Favaloro, Frank G.; Janosik, Tomasz; Su, Xiaobo; Honda, Yukiko; Roebuck, Bill D.; Gribble, Gordon W.

2011-01-01

2

Discovery of GW870086: a potent anti-inflammatory steroid with a unique pharmacological profile  

PubMed Central

Background and Purpose Glucocorticoids are highly effective therapies for a range of inflammatory diseases. Advances in the understanding of the diverse molecular mechanisms underpinning glucocorticoid action suggest that anti-inflammatory molecules with reduced side effect liabilities can be discovered. Here we set out to explore whether modification of the 17? position of the steroid nucleus could generate molecules with a unique pharmacological profile and to determine whether such molecules would retain anti-inflammatory activity. Experimental Approach The pharmacological properties of GW870086 were compared with fluticasone propionate (FP) using a range of cellular and in vivo model systems, including extensive gene expression profiling. Key Results GW870086 repressed inflammatory cytokine release from lung epithelial cells in a similar manner to FP but antagonized the effect of dexamethasone on MMTV-driven reporter gene transactivation. GW870086 had a strong effect on the expression of some glucocorticoid-regulated genes (such as PTGS2), while having minimal impact on the expression of other known target genes (such as SGK). GW870086 retained the ability to strengthen tight junctions in epithelial cell culture but, unlike FP, was unable to protect the culture from elastase-mediated damage. In murine models of irritant-induced contact dermatitis and ovalbumin-induced allergic inflammation, GW870086 showed comparable anti-inflammatory efficacy to FP. Conclusion and Implications GW870086 is a potent anti-inflammatory compound with a unique ability to regulate only a subset of those genes that are normally affected by classical glucocorticoids. It has the potential to become a new topical steroid with a different safety profile to existing therapies.

Uings, I J; Needham, D; Matthews, J; Haase, M; Austin, R; Angell, D; Leavens, K; Holt, J; Biggadike, K; Farrow, S N

2013-01-01

3

Cu(II) complex of an estradiol derivative with potent anti-inflammatory properties.  

PubMed

In the present study, the A-ring of estradiol was converted to an acetylsalicylic structure which was further complexed with Cu(II). The aim was to combine the anti-inflammatory properties of estrogens with those of Cu(II) complexes. Key intermediate of the synthesis was 2-formyl-estradiol (2) which was prepared in quantitative yield through reaction of the phenoxymagnesium bromide of estradiol with formaldehyde in the presence of HMPA. For a successful reaction, an excess of ethylmagnesium bromide was required, and the mechanism is discussed. The target complex 5 exhibited potent anti-inflammatory properties, comparable to those of indomethacin, in the carrageenan-induced rat paw edema. This biological activity was not due either to the steroidal ligand or to the complexed Cu(II) alone. PMID:1793357

Spyriounis, D M; Rekka, E; Demopoulos, V J; Kourounakis, P N

1991-09-01

4

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

PubMed Central

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

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

2012-01-01

5

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

6

Stereocontrolled Total Synthesis of the Potent Anti-inflammatory and Pro-resolving Lipid Mediator Resolvin D3 and its Aspirin-Triggered 17R-Epimer  

PubMed Central

The first total synthesis of stereochemically pure resolvin D3 and aspirin-triggered resolvin D3 is reported. These enzymatic metabolites of docosahexaenoic acid (DHA) have potent anti-inflammatory and pro-resolving actions. The convergent synthetic strategy is based on enantiomerically pure starting materials and it is highly stereocontrolled.

Winkler, Jeremy W.; Uddin, Jasim; Serhan, Charles N.

2013-01-01

7

GPR120 is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-Inflammatory and Insulin Sensitizing Effects  

PubMed Central

SUMMARY Omega-3 fatty acids (?-3 FAs), DHA and EPA, exert anti-inflammatory effects, but the mechanisms are poorly understood. Here we show that the G protein-coupled receptor 120 (GPR120) functions as an ?-3 FA receptor/sensor. Stimulation of GPR120 with ?-3 FAs or a chemical agonist causes broad anti-inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal macrophages. All of these effects are abrogated by GPR120 knockdown. Since chronic macrophage-mediated tissue inflammation is a key mechanism for insulin resistance in obesity, we fed obese WT and GPR120 knockout mice a high fat diet with or without ?-3 FA supplementation. The ?-3 FA treatment inhibited inflammation and enhanced systemic insulin sensitivity in WT mice, but was without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional ?-3 FA receptor/sensor and mediates potent insulin sensitizing and anti-diabetic effects in vivo by repressing macrophage-induced tissue inflammation.

Oh, Da Young; Talukdar, Saswata; Bae, Eun Ju; Imamura, Takeshi; Morinaga, Hidetaka; Fan, WuQiang; Li, Pingping; Lu, Wendell J.; Watkins, Steven M.; Olefsky, Jerrold M.

2010-01-01

8

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

PubMed

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 basis of elemental and spectral (IR, (1)H NMR and mass spectral data) studies. All the compounds of this series show moderate to good activity. The most active compound of this series 3-(2'-methyl indolidene aminothiazol-4'-yl)-2-(4-chlorophenyl) indole (3b) is found to be the most potent and has shown higher percent of inhibition of oedema, lower ulcerogenic liability and acute toxicity than the reference drug phenyl butazone. PMID:18289736

Singh, Nisha; Bhati, Sudhir Kumar; Kumar, Ashok

2008-11-01

9

Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.  

PubMed

Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules. PMID:20161797

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

2010-01-01

10

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

PubMed Central

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

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

2010-01-01

11

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.

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

2014-01-01

12

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

PubMed

High-density lipoprotein (HDL) mediates reverse cholesterol transport and 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 regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory 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 new 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 R G; Knolle, Percy; Kneilling, Manfred; Röcken, Martin; Lütjohann, Dieter; Wright, Samuel D; Schultze, Joachim L; Latz, Eicke

2014-02-01

13

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.

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; Rocken, Martin; Lutjohann, Dieter; Wright, Samuel D.; Schultze, Joachim L.; Latz, Eicke

2014-01-01

14

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

PubMed Central

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

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

2010-01-01

15

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

16

Group IIA secretory PLA2 inhibition by ursolic acid: a potent anti-inflammatory molecule.  

PubMed

Ursolic acid (3beta-hydroxy-urs-12-en-28-oic acid) isolated from many medicinal plants has diverse pharmacologically important properties, including strong anti-inflammatory activity. However its interaction with pro-inflammatory PLA2 is not known. Ursolic acid inhibited secretory PLA2 (sPLA2) enzymes purified from Vipera russelli, Naja naja venom and human pleural fluid and synovial fluid. IC50 values determined for these enzymes ranged from 12 to 18 microM. Group II secretory PLA2 from both venoms & human inflammatory source were found to be sensitive to inhibition in comparison with group I cobra venom sPLA2. Variation in Ca2+ concentration from 2.5-15 mM did not alter the level of inhibition. Similarly sPLA2 inhibition by ursolic acid is independent of substrate concentration. Ursolic acid interacts with purified venom sPLA2 enzymes and enhances relative fluorescence intensity in a dose dependent manner. In the presence of ursolic acid apparent shift in the far UV-CD spectra of sPLA2 was observed, indicating a direct interaction with the enzyme and formation of enzyme-ursolic acid complex. This complex results in irreversible inhibition of sPLA2 as evident by dialysis study. Inhibition of sPLA2 induced mouse paw edema and indirect hemolytic activity confirmed its sPLA2 inhibitory activity in vivo and in situ respectively. These studies revealed that the strong anti-inflammatory activity of ursolic acid is by inhibiting sPLA2 enzymes. PMID:17456043

Nataraju, A; Raghavendra Gowda, C D; Rajesh, R; Vishwanath, B S

2007-01-01

17

Design and Synthesis of Potent N-Acylethanolamine-hydrolyzing Acid Amidase (NAAA) Inhibitor as Anti-Inflammatory Compounds  

PubMed Central

N-acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme involved in biological deactivation of N-palmitoylethanolamide (PEA), which exerts anti-inflammatory and analgesic effects through the activation of nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-?). To develop selective and potent NAAA inhibitors, we designed and synthesized a series of derivatives of 1-pentadecanyl-carbonyl pyrrolidine (compound 1), a general amidase inhibitor. Structure activity relationship (SAR) studies have identified a compound 16, 1-(2-Biphenyl-4-yl)ethyl-carbonyl pyrrolidine, which has shown the highest inhibition on NAAA activity (IC50?=?2.12±0.41 µM) and is characterized as a reversible and competitive NAAA inhibitor. Computational docking analysis and mutagenesis study revealed that compound 16 interacted with Asparagine 209 (Asn209) residue flanking the catalytic pocket of NAAA so as to block the substrate entrance. In vitro pharmacological studies demonstrated that compound 16 dose-dependently reduced mRNA expression levels of iNOS and IL-6, along with an increase of intracellular PEA levels, in mouse macrophages with lipopolysaccharides (LPS) induced inflammation. Our study discovered a novel NAAA inhibitor, compound 16, that could serve as a potential anti-inflammatory agent.

Chen, Ling; Zhu, Chenggang; Huang, Rui; Zheng, Xiao; Qiu, Yan; Fu, Jin

2012-01-01

18

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.

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

2012-01-01

19

TOPICAL ANTIHISTAMINES DISPLAY POTENT ANTI-INFLAMMATORY ACTIVITY LINKED IN PART TO ENHANCED PERMEABILITY BARRIER FUNCTION  

PubMed Central

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

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

2012-01-01

20

Synthesis and pharmacological evaluation of novel limonin derivatives as anti-inflammatory and analgesic agents with high water solubility.  

PubMed

A novel series of water-soluble derivatives of limonin were synthesized by introducing various tertiary amines onto the C (7)-position of limonin. Ten target compounds were characterized and screened for their anti-inflammatory and analgesic activity in vivo. Compound 3c exhibited the strongest analgesic and anti-inflammatory activity among the limonin and its derivatives tested; its analgesic activity is more potent than that of aspirin and its anti-inflammatory activity is stronger than that of naproxen. PMID:24569111

Yang, Yun; Wang, Xinhui; Zhu, Qihua; Gong, Guoqing; Luo, Danmeng; Jiang, Aidou; Yang, Liyan; Xu, Yungen

2014-04-01

21

New potent topical anti-inflammatory steroids with reduced side effects: derivatives of steroid-16-carboxy esters.  

PubMed

Therapeutic use of anti-inflammatory steroids is limited due to their potential suppressive effects on pituitary-adrenal function and the immune system. Based on the antedrug concept, a new class of potent locally active compounds with reduced risk of side effects has been synthesized from prednisolone by introducing a metabolically labile methoxycarbonyl substituent at C-16. Results of topical application of the lead compound, methyl 11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate (P16CM;1), showed that it was 14 times more potent than prednisolone and that it had a greatly reduced tendency to cause systemic side effects. In the present investigations, we have demonstrated that chemical modifications such as 17- and/or 21-esterifications and 17,21-acetonidation of 1 further enhance topical activity in the croton oil ear edema model in rats. Following multiple topical ID50 applications of 1 or its derivatives, no thymolysis was noted. In the carrageenan-soaked sponge model of acute inflammation, all derivatives were potent inhibitors of leukocyte migration, generation of PGE2, and release of elastase. Taken together, these results indicate that esterification or acetonidation of hydroxyl groups at the 17 and/or 21 position, in combination with a labile C-16 methoxycarbonyl group, increases topical activity without concomitantly increasing the risk of side effects. PMID:2398470

Heiman, A S; Taraporewala, I B; McLean, H M; Hong, D; Lee, H J

1990-07-01

22

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

23

Pro- or anti-inflammatory role of apolipoprotein A-1 in high-density lipoproteins?  

PubMed

Apolipoprotein A-1 (apoA-1) is the principal protein fraction of high-density lipoprotein (HDL), conferring to the latter many of its pleiotropic atheroprotective functions. After its effect on cholesterol efflux, the second most studied feature of apoA-1 is its anti-inflammatory property. In addition, it interferes with lipid peroxidation and innate immune receptors. These anti-inflammatory effects are due to various properties, in particular the ability to inhibit the transendothelial migration of immune cells by reducing integrin expression, to inhibit monocyte activation and cytokine production induced by T-cell contact, to inhibit lipid peroxidation and to interfere with innate immune receptors. Recent studies have demonstrated that during chronic systemic inflammation HDL could lose some of its atheroprotective functions and become dysfunctional or even proinflammatory. Recent evidence suggests that specific post-translational modifications of apoA-1 transform this genuine anti-inflammatory molecule into a proinflammatory one. The structural changes include chlorination, nitration and carbamylation of amino acids by myeloperoxidase, oxidation by reactive carbonyls, as well as glycation. Humoral autoimmunity to apoA-1 and HDL has been reported in populations at high cardiovascular risk and constitutes another emerging mechanism contributing to the loss of functions of apoA-1 and HDL. The fact that in recent trials cholesteryl ester transfer protein inhibitors (torcerapib and dalcetrapib) have unfortunately failed to prevent cardiovascular disease despite increasing cholesterol efflux in vitro and HDL levels in vivo, further highlights the clinical importance of understanding the mechanisms driving apoA-1 and HDL towards pro- or anti-inflammatory molecules. These findings should not affect current dyslipidaemia management guidelines. PMID:23740387

Vuilleumier, Nicolas; Dayer, Jean-Michel; von Eckardstein, Arnold; Roux-Lombard, Pascale

2013-01-01

24

The anti-inflammatory compound BAY 11-7082 is a potent inhibitor of Protein Tyrosine Phosphatases  

PubMed Central

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

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

2013-01-01

25

NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions.  

PubMed

1. NS-398 (N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide) is a new non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. 2. The anti-inflammatory potency of NS-398 in rat carrageenin-induced edema was as potent as that of indomethacin and 8 times more potent than diclofenac. In rat adjuvant arthritis, NS-398 showed a therapeutic effect comparable to that seen with loxoprofen but less than that seen with indomethacin and diclofenac. 3. The analgesic potency of NS-398 in rat adjuvant arthritic pain was much the same as that of indomethacin, and was about 3-5 times higher than that of diclofenac and loxoprofen. In the Randall-Selitto method in rats, NS-398 was 2-7 times as potent as loxoprofen, diclofenac and indomethacin. In acetic acid-induced writhing in mice, NS-398 was equipotent to indomethacin and diclofenac. 4. In LPS-induced fever in rats, NS-398 was 1.5-4.5 times as potent as loxoprofen and indomethacin, but less potent than diclofenac. 5. NS-398 produced little gastric ulceration in doses of up to 1000 mg/kg, while reference drugs produced distinct stomach lesions in doses of 10-30 mg/kg. 6. NS-398 inhibited prostaglandin (PG) endoperoxide synthase from sheep seminal vesicle microsomes less potent than that of ibuprofen. PMID:8482483

Futaki, N; Yoshikawa, K; Hamasaka, Y; Arai, I; Higuchi, S; Iizuka, H; Otomo, S

1993-01-01

26

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

27

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

PubMed Central

Background Ursolic acid (UA), a pentacyclic triterpenoid carboxylic acid, is the major component of many plants including apples, basil, cranberries, peppermint, rosemary, oregano and prunes and has been reported to possess antioxidant and anti-tumor properties. These properties of UA have been attributed to its ability to suppress NF-?B (nuclear factor kappa B) activation. Since NF-?B, in co-ordination with NF-AT (nuclear factor of activated T cells) and AP-1(activator protein-1), is known to regulate inflammatory genes, we hypothesized that UA might exhibit potent anti-inflammatory effects. Methodology/Principal Findings The anti-inflammatory effects of UA were assessed in activated T cells, B cells and macrophages. Effects of UA on ERK, JNK, NF-?B, AP-1 and NF-AT were studied to elucidate its mechanism of action. In vivo efficacy of UA was studied using mouse model of graft-versus-host disease. UA inhibited activation, proliferation and cytokine secretion in T cells, B cells and macrophages. UA inhibited mitogen-induced up-regulation of activation markers and co-stimulatory molecules in T and B cells. It inhibited mitogen-induced phosphorylation of ERK and JNK and suppressed the activation of immunoregulatory transcription factors NF-?B, NF-AT and AP-1 in lymphocytes. Treatment of cells with UA prior to allogenic transplantation significantly delayed induction of acute graft-versus-host disease in mice and also significantly reduced the serum levels of pro-inflammatory cytokines IL-6 and IFN-?. UA treatment inhibited T cell activation even when added post-mitogenic stimulation demonstrating its therapeutic utility as an anti-inflammatory agent. Conclusions/Significance The present study describes the detailed mechanism of anti-inflammatory activity of UA. Further, UA may find application in the treatment of inflammatory disorders.

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

2012-01-01

28

Nonsteroidal anti-inflammatory drug flufenamic acid is a potent activator of AMP-activated protein kinase.  

PubMed

Flufenamic acid (FFA) is a nonsteroidal anti-inflammatory drug (NSAID). It has anti-inflammatory and antipyretic properties. In addition, it modulates multiple channel activities. The mechanisms underlying the pharmacological actions of FFA are presently unclear. Given that AMP-activated protein kinase (AMPK) has both anti-inflammatory and channel-regulating functions, we examined whether FFA induces AMPK activation. 1) Exposure of several different types of cells to FFA resulted in an elevation of AMPK? phosphorylation at Thr172. This effect of FFA was reproduced by functionally and structurally similar mefenamic acid, tolfenamic acid, niflumic acid, and meclofenamic acid. 2) FFA-induced activation of AMPK was largely abolished by the treatment of cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (an intracellular Ca(2+) chelator) or depletion of extracellular Ca(2+), whereas it was mimicked by stimulation of cells with the Ca(2+) ionophore 5-(methylamino)-2-({(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl}methyl)-1,3-benzoxazole-4-carboxylic acid (A23187) or ionomycin. 3) FFA triggered a rise in intracellular Ca(2+), which was abolished by cyclosporine, a blocker of mitochondrial permeability transition pore. Cyclosporine also abolished FFA-induced activation of AMPK. 4) Inhibition of Ca(2+)/calmodulin-dependent kinase kinase ? (CaMKK?) with 7-oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid acetate (STO-609) or down-regulation of CaMKK? with short interfering RNA largely abrogated FFA-induced activation of AMPK. 5) FFA significantly suppressed nuclear factor-?B activity and inducible nitric-oxide synthase expression triggered by interleukin-1? and tumor necrosis factor ?. This suppression was also largely abrogated by STO-609. Taken together, we conclude that FFA induces AMPK activation through the Ca(2+)-CaMKK? pathway. Activation of AMPK is a presently unrecognized important mechanism underlying the pharmacological effects of FFA. PMID:21765041

Chi, Yuan; Li, Kai; Yan, Qiaojing; Koizumi, Schuichi; Shi, Liye; Takahashi, Shuhei; Zhu, Ying; Matsue, Hiroyuki; Takeda, Masayuki; Kitamura, Masanori; Yao, Jian

2011-10-01

29

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.

2012-01-01

30

Prevention effects of ND-07, a novel drug candidate with a potent antioxidative action and anti-inflammatory action, in animal models of severe acute pancreatitis.  

PubMed

Oxidative stress and inflammation both play major roles in the development of the acute pancreatitis. Currently, a pancreatic enzyme inhibitor with limited efficacy is only clinically available in a few countries, and antioxidants or non-steroidal anti-inflammatory drugs (NSAIDs) provide only partial tissue protection in acute pancreatitis animal models. Here, we introduce a new drug candidate for treating acute pancreatitis named ND-07 [chemical name: 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid] that exhibits both potent antioxidative and anti-inflammatory activities. In an electron spin resonance (ESR) study, ND-07 almost blocked hydroxyl radical generation as low as 0.05 ?M and significantly suppressed DNA oxidation and cell death in a lipopolysaccharide (LPS)-stimulated pancreatic cell line. In a cerulein plus LPS-induced acute pancreatitis model, ND-07 pretreatment showed significant tissue protective effects, with reductions of serum amylase and lipase levels and pancreatic wet weights. ND-07 not only diminished the plasma levels of malondialdehyde (MDA) and nitric oxide but also significantly decreased prostaglandin E? (PGE?) and expression of tumor necrotizing factor-alpha (TNF-?) in the pancreatic tissue. In a severe acute necrotizing pancreatitis model induced by a choline deficient, ethionine-supplemented (CDE) diet, ND-07 dramatically protected the mortality even without any death, providing attenuation of pancreas, lung, and liver damages as well as the reductions in serum levels of lactate dehydrogenase (LDH), amylase and lipase, MDA levels in the plasma and pancreatic tissues, plasma levels of TNF-?, and interleukin-1 (IL-1?). These findings suggest that current dual synergistic action mechanisms of ND-07 might provide a superior protection for acute pancreatitis than conventional drug treatments. PMID:22575522

Lee, Jin Hwan; An, Chun San; Yun, Bok Sun; Kang, Kum Suk; Lee, Young Ae; Won, Sun Mi; Gwag, Byoung Joo; Cho, Sung Ig; Hahm, Ki-Baik

2012-07-15

31

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

PubMed

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

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

2014-06-10

32

Red mold rice extract represses amyloid beta peptide-induced neurotoxicity via potent synergism of anti-inflammatory and antioxidative effect.  

PubMed

Amyloid beta-peptide (Abeta), a risk of Alzheimer's disease (AD), causes cell death by inflammation and oxidative stress. Red mold rice (RMR) fermented by Monascus species is regarded as cholesterol-lowering functional food in virtue of the metabolite monacolin K identified as lovastatin. In addition, RMR is also demonstrated to express antioxidation because of multiple antioxidants. Therefore, this study focuses on the synergism of RMR against Abeta neurotoxicity and compares the effect between lovastatin and RMR including monacolin K and other functional metabolites. In this study, RE 568, an ethanol extract of RMR produced by strain Monascus purpureus NTU 568, is used to protect PC12 cell against Abeta40 neurotoxicity. All tests contain the treatments with lovastatin or RE 568 including equal monacolin K levels in order to compare the effect and investigate whether other metabolites of RE 568 provide potent assistance against Abeta40 neurotoxicity. In the results, monacolin K represses Abeta40 neurotoxicity via repressing small G-protein-mediated inflammation, and other metabolites of RE 568 also exhibit potent antioxidative ability against Abeta-induced oxidative stress. Importantly, stronger effects on repressing the Abeta40-induced cell death, inflammation, and oxidative stress are performed by RE 568 than that by the equal levels of lovastatin, which results from a potent synergism made up of monacolin K, antioxidants, and anti-inflammatory agents. The present study is the first report to demonstrate the potent synergistic protection of RMR against Abeta40 neurotoxicity, which would cause RMR to be developed as potential and novel functional food for the prophylaxis of AD pathogenesis. PMID:18438657

Lee, Chun-Lin; Wang, Jyh-Jye; Pan, Tzu-Ming

2008-07-01

33

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

PubMed Central

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

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

2012-01-01

34

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

PubMed Central

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

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

2012-01-01

35

Potent anti-inflammatory agent escin does not affect the healing of tibia fracture and abdominal wound in an animal model  

PubMed Central

Escin, a potent anti-inflammatory and anti-edematous agent, has been widely used clinically in preventing inflammatory edema after trauma, such as fracture and surgery. The aim of this study was to investigate whether escin has an inhibitory effect on fracture healing, and whether escin has an inhibitory effect on wound healing after surgery. Male New Zealand white rabbits underwent tibial mid-diaphyseal osteotomy, and were administered escin once per day for 10 days. At weeks 2, 4 and 6, bone fracture healing and bone mineral density were measured. The histologic examination of callus, osteocalcin, alkaline phosphatase, calcium and phosphate in the serum were also assayed. In another experiment, the rats underwent midline laparotomy, and received escin once prior to or after the operation. Six days later, the abdominal incision wounds were excised for measuring hydroxyproline levels. The results showed that there were no significant differences in fracture healing between the model and rabbits administered escin, and escin did not affect the hydroxyproline levels in the abdominal incision wounds of the rats. These findings suggest that escin has no inhibitory effect on fracture and wound healing in animal models.

ZHANG, LEIMING; WANG, HONGSHENG; WANG, TIAN; JIANG, NA; YU, PENGFEI; LIU, FEIYAN; CHONG, YATING; FU, FENGHUA

2012-01-01

36

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.

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

2013-01-01

37

Novel phosphoinositide 3-kinase ?,? inhibitor: potent anti-inflammatory effects and joint protection in models of rheumatoid arthritis.  

PubMed

Phosphoinositide 3-kinases ? and ? (PI3K? and PI3K?) are expressed in rheumatoid arthritis (RA) synovium and regulate innate and adaptive immune responses. We determined the effect of a potent PI3K?,? inhibitor, IPI-145, in two preclinical models of RA. IPI-145 was administered orally in rat adjuvant-induced arthritis (AA) and intraperitoneally in mouse collagen-induced arthritis (CIA). Efficacy was assessed by paw swelling, clinical scores, histopathology and radiography, and microcomputed tomography scanning. Gene expression and Akt phosphorylation in joint tissues were determined by quantitative real-time polymerase chain reaction and Western blot analysis. Serum concentrations of anti-type II collagen (CII) IgG and IgE were measured by immunoassay. T-cell responses to CII were assayed using thymidine incorporation and immunoassay. IPI-145 significantly reduced arthritis severity in both RA models using dosing regimens initiated before onset of clinical disease. Treatment of established arthritis with IPI-145 in AA, but not CIA, significantly decreased arthritis progression. In AA, histology scores, radiographic joint damage, and matrix metalloproteinase (MMP)-13 expression were reduced in IPI-145-treated rats. In CIA, joint histology scores and expression of MMP-3 and MMP-13 mRNA were lower in the IPI-145 early treatment group than in the vehicle group. The ratio of anti-CII IgG2a to total IgG in CIA was modestly reduced. Interleukin-17 production in response to CII was decreased in the IPI-145-treated group, suggesting an inhibitory effect on T-helper cell 17 differentiation. These data show that PI3K?,? inhibition suppresses inflammatory arthritis, as well as bone and cartilage damage, through effects on innate and adaptive immunity and that IPI-145 is a potential therapy for RA. PMID:24244039

Boyle, David L; Kim, Hae-Rim; Topolewski, Katharyn; Bartok, Beatrix; Firestein, Gary S

2014-02-01

38

Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity.  

PubMed

A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized for selective COX-2 inhibition with potent anti-inflammatory activity. Among the compounds tested, 9g (2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole) was found to be the most potent inhibitor of COX-2 with IC50 of 0.31 ?M showing promising degree of anti-inflammatory activity in the carrageenan-induced rat paw edema model with ED50 of 74.3 mg/kg. The lead compound 9g further showed suppression of acetic acid-induced writhes comparable to that of aspirin and gastro-sparing profile superior to the aspirin. Molecular docking analysis displayed higher binding affinity of ligands towards COX-2 than COX-1. PMID:24780593

Bansal, Sumit; Bala, Manju; Suthar, Sharad Kumar; Choudhary, Shivani; Bhattacharya, Shoumyo; Bhardwaj, Varun; Singla, Sumit; Joseph, Alex

2014-06-10

39

Discovery of a potent nanoparticle P-selectin antagonist with anti-inflammatory effects in allergic airway disease  

PubMed Central

The severity of allergic asthma is dependent, in part, on the intensity of peribronchial inflammation. P-selectin is known to play a role in the development of allergen-induced peribronchial inflammation and airway hyperreactivity. Selective inhibitors of P-selectin-mediated leukocyte endothelial-cell interactions may therefore attenuate the inflammatory processes associated with allergic airway disease. Novel P-selectin inhibitors were created using a polyvalent polymer nanoparticle capable of displaying multiple synthetic, low molecular weight ligands. By assembling a particle that presents an array of groups, which as monomers interact with only low affinity, we created a construct that binds extremely efficiently to P-selectin. The ligands acted as mimetics of the key binding elements responsible for the high-avidity adhesion of P-selectin to the physiologic ligand, PSGL-1. The inhibitors were initially evaluated using an in vitro shear assay system in which interactions between circulating cells and P-selectin-coated capillary tubes were measured. The nanoparticles were shown to preferentially bind to selectins expressed on activated endothelial cells. We subsequently demonstrated that nanoparticles displaying P-selectin blocking arrays were functionally active in vivo, significantly reducing allergen-induced airway hyperreactivity and peribronchial eosinophilic inflammation in a murine model of asthma.

John, Alison E.; Lukacs, Nicholas W.; Berlin, Aaron A.; Palecanda, Aiyappa; Bargatze, Robert F.; Stoolman, Lloyd M.; Nagy, Jon O.

2010-01-01

40

Discovery of a potent nanoparticle P-selectin antagonist with anti-inflammatory effects in allergic airway disease.  

PubMed

The severity of allergic asthma is dependent, in part, on the intensity of peribronchial inflammation. P-selectin is known to play a role in the development of allergen-induced peribronchial inflammation and airway hyperreactivity. Selective inhibitors of P-selectin-mediated leukocyte endothelial-cell interactions may therefore attenuate the inflammatory processes associated with allergic airway disease. Novel P-selectin inhibitors were created using a polyvalent polymer nanoparticle capable of displaying multiple synthetic, low molecular weight ligands. By assembling a particle that presents an array of groups, which as monomers interact with only low affinity, we created a construct that binds extremely efficiently to P-selectin. The ligands acted as mimetics of the key binding elements responsible for the high-avidity adhesion of P-selectin to the physiologic ligand, PSGL-1. The inhibitors were initially evaluated using an in vitro shear assay system in which interactions between circulating cells and P-selectin-coated capillary tubes were measured. The nanoparticles were shown to preferentially bind to selectins expressed on activated endothelial cells. We subsequently demonstrated that nanoparticles displaying P-selectin blocking arrays were functionally active in vivo, significantly reducing allergen-induced airway hyperreactivity and peribronchial eosinophilic inflammation in a murine model of asthma. PMID:14563683

John, Alison E; Lukacs, Nicholas W; Berlin, Aaron A; Palecanda, Aiyappa; Bargatze, Robert F; Stoolman, Lloyd M; Nagy, Jon O

2003-12-01

41

NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues.  

PubMed

Chronic inflammation is a hallmark of pulmonary diseases, which leads to lung parenchyma destruction (emphysema) and obstructive bronchiolitis occurring in both chronic obstructive pulmonary disease and asthma. Inflammation is strongly correlated with low intracellular cAMP levels and increase in specific cAMP hydrolyzing activity. The aim of the present study was to investigate the role of the cyclic phosphodiesterase type 4 (PDE4) in human lung and to determine the effects of NCS 613, a new PDE4 inhibitor, on lung inflammation and bronchial hyperresponsiveness. High cAMP-PDE activities were found in the cytosoluble fractions from human lung parenchyma and distal bronchi. PDE4 (rolipram sensitive) represented 40% and 56% of total cAMP-PDE activities in the above-corresponding tissues. Moreover, PDE4A, PDE4B, PDE4C, and PDE4D isoforms were detected in all three subcellular fractions (cytosolic, microsomal, and nuclear) with differential distributions according to specific variants. Pharmacological treatments with NCS 613 significantly decreased PDE4 activity and reduced I?B? degradation in cultured parenchyma, both of which are usually correlated with a lower inflammation status. Moreover, NCS 613 pretreatment potentiated isoproterenol-induced relaxations in human distal bronchi, while reducing TNF-?-induced hyperresponsiveness in cultured bronchi, as assessed in the presence of methacholine, U-46619, or histamine. This reducing effect of NCS 613 on human bronchi hyperresponsiveness triggered by TNF-? was related to a lower expression level of PDE4B and PDE4C, as well as a downregulation of the phosphorylated forms of p38-MAPK, CPI-17, and MYPT-1, which are known to control tone. In conclusion, specific PDE4 inhibitors, such as NCS 613, may represent an alternative and isoform-specific approach toward reducing human lung inflammation and airway overreactivity. PMID:21784969

Yougbare, Issaka; Morin, Caroline; Senouvo, Farid Yannick; Sirois, Chantal; Albadine, Roula; Lugnier, Claire; Rousseau, Eric

2011-10-01

42

Endoscopic and histopathological evaluation of acute gastric injury in high-dose acetaminophen and nonsteroidal anti-inflammatory drug ingestion with suicidal intent  

Microsoft Academic Search

AIM: To evaluate endoscopic and histopathologic aspects of acute gastric injury due to ingestion of high-dose acetaminophen and nonsteroidal anti- inflammatory drugs (NSAIDs) with respect to some risk factors and patient characteristics. METHODS: The study group consists of 50 patients admitted to emergency department with high dose analgesic ingestion (group ?) with suicidal intent. Thirty patients with or without mild

Aliye Soylu; Can Dolapcioglu; Kemal Dolay; Aydin Ciltas; Nurgul Yasar; Mustafa Kalayci; Halil Alis; Nurten Sever

2008-01-01

43

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.

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

2014-01-01

44

Potent anti-inflammatory activity of pyrenocine A isolated from the marine-derived fungus Penicillium paxilli Ma(G)K.  

PubMed

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

45

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.

2014-01-01

46

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

47

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

48

Heart failure is associated with impaired anti-inflammatory and antioxidant properties of high-density lipoproteins.  

PubMed

Oxidative stress and inflammation are hallmarks of the heart failure (HF) disease state. In the present study, we investigated the inflammatory/anti-inflammatory characteristics of high-density lipoproteins (HDL) in patients with HF. Ninety-six consecutive patients with systolic HF were followed in an advanced HF center, and 21 healthy subjects were recruited. Plasma was tested for HDL inflammatory index (HII) using a monocyte chemotactic activity assay, with HII >1.0 indicating proinflammatory HDL. We found significantly increased inflammatory properties of HDL in patients with HF (median HII 1.56 vs 0.59 in controls; p <0.0001). Serum amyloid A level was markedly elevated and the activity of paraoxonase-1, an HDL antioxidant enzyme, was significantly reduced in patients versus controls. HDL and albumin from patients with HF contained markedly elevated levels of oxidized products of arachidonic and linoleic acids. HDL function improved when plasma was treated in vitro with 4F, an apolipoprotein A-I mimetic peptide (40% reduction in HII, p <0.0001). There was no correlation found between HII level and ejection fraction or New York Heart Association functional class. In conclusion, HDL function is significantly impaired and oxidation products of arachidonic and linoleic acids are markedly elevated in patients with HF compared with non-HF controls. PMID:24050409

Kim, Juyong Brian; Hama, Susan; Hough, Greg; Navab, Mohamad; Fogelman, Alan M; Maclellan, W Robb; Horwich, Tamara B; Fonarow, Gregg C

2013-12-01

49

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

PubMed

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

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

2010-01-01

50

Anti-inflammatory and analgesic activities of SKLJI, a highly purified and injectable herbal extract of Lonicera japonica.  

PubMed

The parenteral route has many merits over the oral route, including greater predictability, reproducibility of absorption, and rapid drug action, but injectable phytomedicines are uncommon due to protein precipitating tannin and hemolytic saponin components. In this study, in an effort to develop a safe injectable analgesic phytomedicine, we prepared a tannin and saponin-free Lonicera japonica extract, SKLJI, through fractionation and column purification, and evaluated its anti-inflammatory and analgesic activities in in vivo experimental models of inflammation and pain. The removal of tannin and saponin resulted in loganin and sweroside-enriched SKLJI and it showed reduced hemolysis and protein precipitation. In efficacy tests, SKLJI inhibited croton oil- and arachidonic acid-induced ear edema, acetic acid-induced writhing, and carrageenan-induced rat hind paw hyperalgesia. Inhibition of cylcooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and 5-lipoxyfenase (5-LO) activities by SKLJI appeared to be the mechanism underlying anti-inflammatory and analgesic efficacy. Loganin and sweroside also showed anti-inflammatory and analgesic activities, suggesting that they might be active principles in the efficacy of SKLJI. These results suggest that SKLJI is a viable candidate for a new anti-inflammatory and analgesic phytomedicine that can be administered by the parenteral route. PMID:20944425

Ryu, Keun Ho; Rhee, Hae In; Kim, Joo Hyon; Yoo, Hunseung; Lee, Bong Yong; Um, Key-An; Kim, Keunyoung; Noh, Ji-Yoon; Lim, Kyung-Min; Chung, Jin-Ho

2010-01-01

51

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

PubMed

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

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

2013-10-01

52

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.

2013-01-01

53

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

Microsoft Academic Search

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

Jagat R Kanwar; Rupinder K Kanwar

2009-01-01

54

Anti-Inflammatory Iridoids of Botanical Origin  

PubMed Central

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

Viljoen, A; Mncwangi, N; Vermaak, I

2012-01-01

55

Anti-inflammatory properties of ?- and ?-tocopherol  

PubMed Central

Natural vitamin E consists of four different tocopherol and four different tocotrienol homologues (?, ?, ?, ?) that all have antioxidant activity. However, recent data indicate that the different vitamin E homologues also have biological activity unrelated to their antioxidant activity. In this review, we discuss the anti-inflammatory properties of the two major forms of vitamin E, ?-tocopherol (?T) and ?-tocopherol (?T), and discuss the potential molecular mechanisms involved in these effects. While both tocopherols exhibit anti-inflammatory activity in vitro and in vivo, supplementation with mixed (?T-enriched) tocopherols seems to be more potent than supplementation with ?T alone. This may explain the mostly negative outcomes of the recent large-scale interventional chronic disease prevention trials with ?T and thus warrants further investigation.

Reiter, Elke; Jiang, Qing; Christen, Stephan

2007-01-01

56

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

57

Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal.  

PubMed

Chronic inflammation is a critical factor in the pathogenesis of many inflammatory disease states including cardiovascular disease, cancer, diabetes, degenerative joint diseases and neurodegenerative diseases. Chronic inflammatory states are poorly understood, however it is known that dietary habits can evoke or attenuate inflammatory responses. Popular methods to deal with inflammation and its associated symptoms involve the use of non steroidal anti-inflammatory drugs, however the use of these drugs are associated with severe side effects. Therefore, investigations concerned with natural methods of inflammatory control are warranted. A traditional Mediterranean diet has been shown to confer some protection against the pathology of chronic diseases through the attenuation of pro-inflammatory mediators and this has been partially attributed to the high intake of virgin olive oil accompanying this dietary regime. Virgin olive oil contains numerous phenolic compounds that exert potent anti-inflammatory actions. Of interest to this paper is the recently discovered phenolic compound oleocanthal. Oleocanthal is contained in virgin olive oil and possesses similar anti-inflammatory properties to ibuprofen. This pharmacological similarity has provoked interest in oleocanthal and the few studies conducted thus far have verified its anti-inflammatory and potential therapeutic actions. A review of the health benefits of the Mediterranean diet and anti-inflammatory properties of virgin olive oil is presented with the additional emphasis on the pharmacological and anti-inflammatory properties of the phenolic compound oleocanthal. PMID:21443487

Lucas, Lisa; Russell, Aaron; Keast, Russell

2011-01-01

58

Non-steroidal Anti-inflammatory Drugs  

PubMed Central

Gastrointestinal, renal, hepatic, and hematological adverse effects are all associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Some patients are particularly at risk for such problems. Preventive measures and recommendations for managing and monitoring high-risk patients are presented. Patients receiving long-term NSAID therapy should be carefully monitored.

Cardario, Barbara; McKinnon, Allan A.

1991-01-01

59

Penicillitone, a potent in vitro anti-inflammatory and cytotoxic rearranged sterol with an unusual tetracycle core produced by Penicillium purpurogenum.  

PubMed

A rearranged sterol with an unusual tetracycle core skeleton, penicillitone (1), and a new sterol, penicillisterol (2), were obtained from the culture of the fungus Penicillium purpurogenum SC0070. Their structures were characterized by spectroscopic analysis, DFT/TDDFT compuations, and X-ray diffraction. Compound 1 demonstrated potent inhibitory effects on tumor cell growth and key pro-inflammatory cytokine production in macrophages. A biogenetic pathway with oxidative cleavage and vinylogous aldol addition as key reactions is proposed for 1. PMID:24576256

Xue, Jinghua; Wu, Ping; Xu, Liangxiong; Wei, Xiaoyi

2014-03-01

60

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

61

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.

Alajmi, Mohamed F.; Alam, Perwez

2014-01-01

62

Anti-inflammatory iridoids of botanical origin.  

PubMed

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

Viljoen, A; Mncwangi, N; Vermaak, I

2012-01-01

63

Anti-inflammatory treatment.  

PubMed

Inflammatory mucosal disorders are treated conventionally with potent or superpotent topical corticosteroids. For more than 20 years, topical cyclosporine has been used in the management of oral mucous membrane affections. Recently other topically applied calcineurin inhibitors, namely tacrolimus and pimecrolimus, expanded the armamentarium for the treatment of inflammatory mucosal diseases. This chapter places its main emphasis on the efficacy and safety of topical calcineurin inhibitors in the management of different oral and genital conditions, including anogenital lichen sclerosus (LS), oral and genital lichen planus, plasma cell balanitis and vulvitis, mucous membrane pemphigoid and pemphigus vulgaris, all conditions having usually a protracted course, requiring long-lasting treatment. There is current evidence for the effectiveness of both pimecrolimus and tacrolimus in the topical treatment of inflammatory oral mucosal diseases and genital dermatoses, especially oral lichen planus and genital LS. PMID:21325840

Fistarol, Susanna K; Itin, Peter H

2011-01-01

64

Anti-inflammatory activity of selected plants from Saudi Arabia.  

PubMed

Thirteen selected Saudi Arabian plants, belonging to seven different families, were tested for possible anti-inflammatory activity using the carrageenin-induced paw edema model in rats. The methanolic extracts of Vernonia schimperi, Trichodesma trichodesmoides var. tomentosum, and Anabasis articulata exhibited the highest anti-inflammatory activity. The active extracts were further subjected to fractionation with chloroform, ethyl acetate, and n-butanol and tested together with their mother liquor for their anti-inflammatory activity in the same rat model. The most potent fractions were the n-butanol fractions of Anabasis articulata and Vernonia shimperi and the aqueous mother liquor of Trichodesma trichodesmoides. Nevertheless, the three potent methanolic extracts showed higher anti-inflammatory activities than their individual fractions. The antioxidant properties were assessed by their in vitro 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activities. It was concluded that the anti-inflammatory activity is dependent, at least in part, on the reduction of prostaglandin (PGE2) and tumour necrosis factor-alpha (TNF-alpha) levels and cyclooxygenase-2 (COX-2) activity. PMID:24772817

Abdallah, Hossam M; Abdel-Naim, Ashraf B; Ashour, Osama M; Shehata, Ibrahim A; Abdel-Sattar, Essam A

2014-01-01

65

Anti-inflammatory activity of a high-molecular-weight cranberry fraction on macrophages stimulated by lipopolysaccharides from periodontopathogens.  

PubMed

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 juice concentrate on the pro-inflammatory cytokine response of macrophages induced by lipopolysaccharides (LPS) from Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum subsp. nucleatum, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Escherichia coli. Interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and Regulated on Activation Normal T-cell Expressed and Secreted (RANTES) production by macrophages treated with the cranberry fraction prior to stimulation by LPS was evaluated by ELISA. Our results clearly indicate that the cranberry fraction was a potent inhibitor of the pro-inflammatory cytokine and chemokine responses induced by LPS. This suggests that cranberry constituents may offer perspectives for the development of a new therapeutic approach to the prevention and treatment of periodontitis. PMID:16498070

Bodet, C; Chandad, F; Grenier, D

2006-03-01

66

Anti-Inflammatory Diet  

MedlinePLUS

... syrup are quickly digested leading to a rapid rise in blood sugar and a subsequent inflammatory cascade stimulated by insulin. • Red Meat – Avoid these meats when possible or eat organic grass-fed meat to reduce ingesting high levels ...

67

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

PubMed Central

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

2013-01-01

68

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

69

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

PubMed

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

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

2010-11-01

70

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

PubMed

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

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

2010-04-23

71

Inhibition of bacterial adherence to a high-water-content polymer by a water-soluble, nonsteroidal, anti-inflammatory drug.  

PubMed

Deposition and aggregation of lachrymal proteins on the contact lens surface can promote bacterial adherence. Lysozyme is the major tear protein and is also mainly responsible for the formation of protein deposits on contact lenses. Nonsteroidal anti-inflammatory drugs (NSAID) prevent protein aggregation. The effect of a water-soluble NSAID drug on bacterial adherence to high-water-content/ionic disposable contact lenses was examined in a radiolabeling study. Dose-related inhibition of adherence of Staphylococcus aureus, S. epidermidis, and Pseudomonas aeruginosa on both pretreated lenses and after adding the drug to the medium was investigated. When the drug was added to the media, maximal inhibition of S. aureus adherence was observed in trypticase soy broth (59-98% at the lower and higher drug concentrations, respectively); inhibition progressively decreased in calf aqueous humor (48-75%), lysozyme (34-63%), and saline (12-20%) solutions. Inhibition of adherence varied with the three bacterial species; it was maximal with S. aureus, intermediate with S. epidermidis, and minimal with P. aeruginosa. When lenses were pretreated with the drug, consistent, and even higher, inhibitory effects were observed. The results suggest that water-soluble NSAIDs could be used in preventive treatments for conjunctivae and corneal infections in contact lens wearers, and may provide a clue as to which compounds might inhibit protein interaction and bacterial adhesion. PMID:9740000

Arciola, C R; Montanaro, L; Caramazza, R; Sassoli, V; Cavedagna, D

1998-10-01

72

Relationship between the inhibitory activity on 'RCS' and prostaglandins synthesis and the anti-inflammatory activity of ketoprofen and several other non-steroidal anti-inflammatory agents.  

PubMed

In this study ketoprofen has been shown to be the most potent of all anti-inflammatory drugs in inhibiting the synthesis of prostaglandins and the 'rabbit-aorta contracting substance' (RCS), using the guinea-pig lung preparation. Although there did not appear to be a close relationship between the activities of the various drugs in inhibiting prostaglandins synthesis and in their anti-inflammatory activity, the compounds were ranked in the same order in both test systems. PMID:1013579

Guyonnet, J C; Julou, L

1976-01-01

73

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

Microsoft Academic Search

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

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

2008-01-01

74

Anti-inflammatory Agents: Present and Future  

PubMed Central

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

Dinarello, Charles A.

2012-01-01

75

High-throughput methods for measuring heparanase activity and screening potential antimetastatic and anti-inflammatory agents  

Microsoft Academic Search

Heparanase plays an important role in the degradation of the extracellular matrix. It is implicated in inflammation, tumor angiogenesis and metastasis. We have developed two high-throughput methods for measuring heparanase activity and screening potential inhibitors. The first method involves coating fibroblast growth factor (FGF) on microtiter plates and capturing fluorescein isothiocyanate (FITC)-labeled heparin sulfate (HS), which is used as a

Kuo-Sen Huang; Janna Holmgren; Linda Reik; Debra Lucas-McGady; John Roberts; Chao-Min Liu; Wayne Levin

2004-01-01

76

[Anti-inflammatory constituents from Inula japonica].  

PubMed

Chemical constituents of Inula japonica were isolated and purified by repeated column chromatographies, over silica gel, and Toyopearl HW-40, and preparative HPLC. On the basis of spectral data analysis, including NMR and MS data, the structures of the isolates were elucidated and their anti-inflammatory activities were assayed. Fifteen compounds were isolated from the ethyl acetate extract of I. japonica, and their structures were elucidated as dihydrosyringenin (1), (3S, 5R, 6S, 7E)-5,6-epoxy-3-hydroxy-7-megastigmen-9-one (2), (6R, 7E) -9-hydroxy-4,7-megastigmadien-3-one (3), arnidiol (4), taraxasterol acetate (5), 8,9,10-trihydroxythymol (6), taxifolin (7), luteolin (8), napetin (9), eupatin (10), spinacetin (11), quercetin (12), p-hydroxycinnamic acid (13), caffeic acid (14), and caffeoyl acetate (15). Compounds 1, 2, 7, 13 and 15 were isolated from the genus Inula for the first time, and compounds 3, 4, 9-11 and 14 were isolated from this plant for the first time. The anti-inflammatory activity result showed that compounds 3, 6-12 and 14 exhibited inhibition effect against leukotriene C4 (LTC4) synthesis and degranulation definitely in c-Kit Ligand (KL) induced mast cells, and compound 8 and 12 also had the suppression effect against lipopolysacharide(LPS) induced nitric oxide (NO) activity in RAW264.7 macrophages. It is firstly reported that compounds 7 and 9-11 possessed potent inhibition activities against LTC4 generation and degranulation in mast cells. PMID:24754174

Zhu, Hong; Tang, Sheng-An; Qin, Nan; Duan, Hong-Quan; Jin, Mei-Hua

2014-01-01

77

Endoscopic and histopathological evaluation of acute gastric injury in high-dose acetaminophen and nonsteroidal anti-inflammatory drug ingestion with suicidal intent  

PubMed Central

AIM: To evaluate endoscopic and histopathologic aspects of acute gastric injury due to ingestion of high-dose acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) with respect to some risk factors and patient characteristics. METHODS: The study group consists of 50 patients admitted to emergency department with high dose analgesic ingestion (group?I) with suicidal intent. Thirty patients with or without mild complaints of dyspepsia (group II) were selected as the control group. The study group was stratified according to the use of type and number of analgesics. Endoscopic findings were evaluated according to the Lanza score (LS), expressing the severity of the gastroduodenal damage and biopsies according to a scoring system based on histopathologic findings of acute erosive gastritis. RESULTS: Gastroduodenal damage was signifi-cantly more severe in group?I?compared to group II (P < 0.01). The LS was similar in both groups?Ia and Ib. However LS was significantly higher in patients who had ingested multiple NSAIDs (group?Ic) compared to other patients (P < 0.01). The LS was correlated to age (P < 0.01) and total amount of drug ingested (P < 0.05) in group?I; but it was not correlated with Helicobacter pylori (H pylori) infection or duration of exposure (P > 0.05). The biopsy score (BS) was higher in group?I?than group II (P < 0.01), and higher in group?Ib than group?Ia (P < 0.05). CONCLUSION: The histopathologic damage was more severe among NSAID ingesting patients compared to those ingesting only acetaminophen and there is no significant difference in the endoscopic findings between the groups. There is no significant difference in the LS between the groups. This lack of significance is remarkable in terms of the gastric effects of high-dose acetaminophen.

Soylu, Aliye; Dolapcioglu, Can; Dolay, Kemal; Ciltas, Aydin; Yasar, Nurgul; Kalayci, Mustafa; Alis, Halil; Sever, Nurten

2008-01-01

78

Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated.  

PubMed

The ascomycin macrolactam pimecrolimus is a novel inflammatory cytokine release inhibitor that so far has not been administered systemically to humans. In this phase I/II randomized double-blind, placebo-controlled, multiple rising dose proof of concept study psoriasis patients were treated with oral pimecrolimus or placebo. Gene profiling identified a common genomic profile with a downregulation of genes associated with inflammation but no changes in gene expression linked to drug-related side-effects. A steady state of pimecrolimus was reached after 5-10 d, Cmax, and area under the curve (0-24) was 54.5 ng per ml and 589.9 ng h per ml, respectively, at steady state at the highest dose. There was clear clinical efficacy in patients receiving 20 mg pimecrolimus twice daily and 30 mg twice daily with a reduction of Psoriasis Area and Severity Index by 60% and 75%, respectively. Histopatho logically and immunopathologically there was a reversion of the psoriatic phenotype towards normal. There were no notable clinical, laboratory, kidney function, or immunologic side-effects. We conclude that pimecrolimus taken orally is highly effective in a concentration-dependent manner in patients with psoriasis and on a short-term basis it is well tolerated and this is confirmed by its pharmacogenomic profile. The latter also indicates that pimecrolimus should be equally effective in other inflammatory skin diseases. PMID:12406334

Rappersberger, Klemens; Komar, Michael; Ebelin, Marie-Eve; Scott, Graham; Burtin, Pascale; Greig, Gerard; Kehren, Jeanne; Chibout, Salah-Dine; Cordier, Andre; Holter, Wolfgang; Richter, Leo; Oberbauer, Rainer; Stuetz, Anton; Wolff, Klaus

2002-10-01

79

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

PubMed Central

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

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

2011-01-01

80

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

PubMed Central

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

Kanwar, Jagat R; Kanwar, Rupinder K

2009-01-01

81

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

PubMed

Inhibition of platelet function by aspirin results from irreversible inhibition of platelet cyclooxygenase (COX)-1. While sufficient inhibition is obtained at antiplatelet doses (75-325 mg/day) in most (?95%) treated patients, the antiplatelet effect of aspirin and subsequent cardiovascular risk reduction is much less in clinical settings and disease-dependent. Several reasons for this "high on treatment platelet reactivity" are known. This paper reviews the evidence for an interaction between aspirin and other COX inhibitors, namely non-steroidal anti-inflammatory drugs (NSAIDs). Numerous experimental studies demonstrated a pharmacodynamic interaction between aspirin and NSAIDs. This likely occurs within the hydrophobic substrate channel of platelet COX-1 and might be explained by molecular competition between inhibitor drugs and substrate (arachidonic acid) at overlapping binding sites. This interaction is found with some compounds, notably ibuprofen and dipyrone (metamizole), but not with others, such as diclofenac and acetaminophen (paracetamol). Hence, this interaction is not a class effect of NSAIDs and/or non-steroidal analgesics but rather due to specific structural requirements which still remain to be defined. In vivo studies on healthy subjects and patients tend to confirm this type of interaction as well as large differences between NSAIDs and non-steroidal analgesics, respectively. These interactions may be clinically relevant and may increase the cardiovascular risk in long-term treatment for primary and secondary cardiovascular prevention in patients with chronic inflammation, such as rheumatoid arthritis. These patients have an elevated risk for myocardial infarctions and may require chronic antiplatelet treatment by aspirin in addition to treatment of inflammatory pain. PMID:23238666

Hohlfeld, T; Saxena, A; Schrör, K

2013-05-01

82

Nonsteroidal Anti-Inflammatory Drugs  

Microsoft Academic Search

\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?Nonsteriodal anti-inflammatory drugs (NSAIDs) relieve inflammation and pain by inhibiting the production of prostaglandins.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?Prostaglandin (PG) biosynthesis occurs via a three-enzyme cascade. Current NSAIDs inhibit the enzyme cyclooxygenase (COX),\\u000a accounting for their efficacy and toxicity.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?Pharmacologic properties of the different NSAIDs, including specificity for COX-1 or -2 and drug half-life, influence the\\u000a toxicity profile.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?The most

Leslie J. Crofford

83

Pre-concentration of non-steroidal anti-inflammatory drugs in water using dispersive liquid-liquid and single-drop microextraction with high-performance liquid chromatography.  

PubMed

In the present work the combination of two liquid-phase microextraction techniques involving dispersive liquid-liquid microextraction and single-drop microextraction as a new pre-concentration technique is developed for the separation and determination of acidic non-steroidal anti-inflammatory pharmaceutical compounds, namely, naproxen, diclofenac, and ibuprofen, in water samples using high-performance liquid chromatography ultra violet-detection. The extraction conditions were optimized and, under the optimal conditions, the method showed good linearity range of 0.1-1000 ?g L(-1) (R > 0.9990), acceptable reproducibilities (relative standard deviation% = 4.5-8.8%), low limits of detection (0.03-0.2 ?g L(-1) ), and satisfactory relative recoveries. The developed method was applied for the determination of anti-inflammatory drugs in river and waste water samples. PMID:22997034

Sarafraz-yazdi, Ali; Assadi, Hakimeh; Es'haghi, Zarrin; Danesh, Noor Mohammad

2012-09-01

84

Synthesis and assignment of absolute configuration of (-)-oleocanthal: a potent, naturally occurring non-steroidal anti-inflammatory and anti-oxidant agent derived from extra virgin olive oils.  

PubMed

[structure: see text] Effective total syntheses and the assignment of absolute configurations of both the (+)- and (-)-enantiomers of oleocanthal 1 (a.k.a. deacetoxy ligstroside aglycon), the latter derived from extra virgin olive oils and known to be responsible for the back of the throat irritant properties of olive oils, have been achieved. The absolute and relative stereochemistry of the naturally occurring enantiomer (-)-1 proved to be 3S,4E. Both syntheses begin with d-(-)-ribose, proceed in 12 steps, and are achieved with an overall yield of 7%. Both enantiomers proved to be non-steroidal anti-inflammatory and anti-oxidant agents. PMID:16235961

Smith, Amos B; Han, Qiang; Breslin, Paul A S; Beauchamp, Gary K

2005-10-27

85

[Estimating the anti-inflammatory activity of drugs by changes in the agranulocyte/granulocyte index].  

PubMed

It is suggested to assess the anti-inflammatory activity using the ratio of the sums of agranulocytes and granulocytes. On the model of carrageenan-induced inflammation in the rat limbs, the anti-inflammatory activity of NSAIDs and their combinations with antihypoxants was characterized in terms of limb size, leukogram, and the proposed index of anti-inflammatory activity. A high anti-inflammatory activity was observed for a combination of hypoxen with diclofenac and acetylsalicylic acid and a combination of metaprot with diclofenac. PMID:24555230

Platonov, I A; Novikov, V E; Iliukhin, S A

2013-01-01

86

Synthesis and biological evaluation of new heteroaryl carboxylic acid derivatives as anti-inflammatory-analgesic agents.  

PubMed

A series of nicotinic acid derivatives structurally related to niflumic acid and certain pyridazine-containing compounds have been synthesized and characterized by analytical and spectral data. All compounds were screened for their potential analgesic and anti-inflammatory activities. The compounds which displayed analgesic and anti-inflammatory activities were tested for ulcerogenicity and screened for in vivo inhibition of certain inflammatory cytokines such as tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Compounds 1c, 2a, 2b, and 5a have shown potent analgesic and anti-inflammatory activities. PMID:23370197

Abouzid, Khaled Abouzid Mohamed; Khalil, Nadia Abdalla; Ahmed, Eman Mohamed; Zaitone, Sawsan Abo-Bakr

2013-01-01

87

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

PubMed Central

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

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

2013-01-01

88

Anti-Inflammatory Effects of ?-Melanocyte-Stimulating Hormone in Celiac Intestinal Mucosa  

Microsoft Academic Search

Objectives: The peptide ?-melanocyte-stimulating hormone (?-MSH) possesses potent anti-inflammatory activities and has been previously implicated in the endogenous control of inflammatory reactions. The aim of the present research was to determine whether ?-MSH and its receptors participate in a localized anti-inflammatory response in the duodenal mucosa of celiac patients. Methods: Three series of experiments were performed, using duodenal biopsy pairs

Gualtiero Colombo; Roberto Buffa; Maria Teresa Bardella; Letizia Garofalo; Andrea Carlin; James M. Lipton; Anna Catania

2002-01-01

89

Nonsteroidal anti-inflammatory drugs: add an anti-ulcer drug for patients at high risk only. Always limit the dose and duration of treatment with NSAIDs.  

PubMed

In addition to their cardiac, renal, hepatic, cutaneous and neuropsychological adverse effects, nonsteroidal anti-inflammatory drugs (NSAIDs) can have severe effects on the entire gastrointestinal tract, including bleeding, perforation and occlusion. Which anti-ulcer drugs reduce the risk of the severe gastrointestinal adverse effects of NSAIDs, and which patients should receive them? To answer these questions, we conducted a review of the literature, using the standard Prescrire methodology. The main risk factors for severe gastrointestinal adverse effects during NSAID therapy are: a high dose regimen; age over 65 years; a history of gastric or duodenal ulcer or gastrointestinal bleeding; heavy use of both alcohol and tobacco; and concomitant treatment with a corticosteroid, antiplatelet drug, anticoagulant, or selective serotonin reuptake inhibitor (SSRI) antidepressant. Gastrointestinal symptoms and ulceration (on endoscopy) are poor predictors of severe gastrointestinal reactions. A meta-analysis examined randomised placebo-controlled trials of misoprostol in more than 11 000 patients. The results were mainly based on a large trial including about 9000 rheumatoid arthritis patients with an average age of 68 years. Misoprostol (400 microg to 800 microg/day, in 4 doses) prevented about 4 severe gastroduodenal events when 1000 patients over 60 years of age were treated for 6 months. Diarrhoea and other mild gastrointestinal disorders were frequent. There are no randomised trials comparing proton pump inhibitors (PPIs) and histamine H2 receptor antagonists versus misoprostol or versus placebo therapy for the prevention of severe adverse effects associated with NSAIDs. PPIs and H2 antagonists both reduce the incidence of gastric or duodenal ulceration detected by routine endoscopy. A randomised trial compared an H2 antagonist (famotidine) versus a PPI (pantoprazole) in 128 patients with an average age of 69 years who had a very high risk of serious gastrointestinal adverse effects while taking low-dose aspirin. After 48 weeks of treatment, pantoprazole was more effective than famotidine for the prevention of overt gastrointestinal bleeding. The symptomatic effects of PPIs and H2 antagonists may create a false sense of security, leading some patients to increase their NSAID use and resulting in a paradoxical increase in severe gastrointestinal effects. In practice, anti-ulcer drugs are not sufficiently effective to warrant their use by NSAID-treated adults who are not at high risk of severe gastrointestinal events. Misoprostol has proven efficacy in patients with risk factors for NSAID-induced severe gastroduodenal adverse effects, especially patients over 65 years of age, but it also has frequent adverse effects and necessitates 4 daily doses. Omeprazole is an alternative when the adverse effects or dosing frequency of misoprostol are unacceptable, provided patients are warned not to increase their NSAID consumption. PMID:21954519

2011-09-01

90

Problems in selection of topical anti-inflammatory corticosteroids  

PubMed Central

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

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

1973-01-01

91

High temperature-high efficiency liquid chromatography using sub-2 ?m coupled columns for the analysis of selected non-steroidal anti-inflammatory drugs and veterinary antibiotics in environmental samples.  

PubMed

A high efficiency HPLC method was developed by coupling three sub-2 ?m columns in series and operating them at high temperature for the separation of selected non-steroidal anti-inflammatory drugs and veterinary antibiotics in environmental samples. The separation was performed at 80°C to reduce the solvent viscosity, thus reducing the column backpressure. The chromatographic performance of high temperature-extended column length HPLC method was used to determine the most widely used non-steroidal anti-inflammatory drugs and veterinary antibiotics such as sulphonamides in wastewater samples. The method could simultaneously determine 24 pharmaceuticals in short analysis time with high efficiency. The method involved pre-concentration and clean-up by solid phase extraction (SPE) using Oasis HLB extraction cartridges. It was validated based on linearity, precision, detection and quantification limits, selectivity and accuracy. Good recoveries were obtained for all analytes ranging from 72.7% to 98.2% with standard deviations not higher than 6%, except for acetaminophen and acetyl salicylic acid, for which low recovery was obtained. The detection limits of the studied pharmaceuticals ranged from 2 to 16 ?g L(-1), while limits of quantification were in the range from 7 to 54 ?g L(-1) with UV detection. PMID:21819871

Shaaban, Heba; Górecki, Tadeusz

2011-09-19

92

Synthesis, biological evaluation and molecular docking of quinazoline-4(1H)-one derivatives as anti-inflammatory and analgesic agents.  

PubMed

Two series of 2-phenyl-4(3H) quinazolinone derivatives have been synthesized. Most of the tested quinazolinone derivatives showed considerable potent anti-inflammatory and analgesic activity of superior GIT safety profile in experimental rats in comparing to indomethacin as reference drug. Compounds VIa, VIb were the most potent anti-inflammatory in experimental rats in comparing to indomethacin as reference drug. Docking study into COX-2 has been made for derivatives of anti-inflammatory activity. PMID:21928711

Mohamed, Mosaad S; Kamel, Mohsen M; Kassem, Emad M M; Abotaleb, Nageh; Khedr, M; Ahmed, Marwa F

2011-01-01

93

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

94

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

PubMed

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. PMID:21741984

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

2011-09-01

95

Prescription Nonsteroidal Anti-Inflammatory Medicines  

MedlinePLUS

... Nonsteroidal anti-inflammatory drugs (also called NSAIDs) stop cyclooxygenase enzymes (also called COX enzymes) in your body ... What are some common prescription NSAIDs? There are 2 classes of prescription NSAIDs. Traditional NSAIDs include the ...

96

?-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs  

PubMed Central

??Melanocyte?stimulating hormone (??MSH) is a tridecapeptide derived from the proopiomelanocortin by post?translational processing. In addition to its effects on melanocytes, ??MSH has potent anti?inflammatory effects when administered systemically or locally. The anti?inflammatory effects of ??MSH are mediated by direct effects on cells of the immune system as well as indirectly by affecting the function of resident non?immune cells. ??MSH affects several pathways implicated in regulation of inflammatory responses such as NF??B activation, expression of adhesion molecules and chemokine receptors, production of pro?inflammatory cytokines and other mediators. Thus ??MSH may modulate inflammatory cell proliferation, activity and migration. The anti?inflammatory effects of ??MSH have been confirmed by means of animal models of inflammation such as irritant and allergic contact dermatitis, cutaneous vasculitis, asthma, inflammatory bowel disease, rheumatoid arthritis, ocular and brain inflammation. Most of the anti?inflammatory activities of ??MSH can be attributed to its C?terminal tripeptide KPV. K(D)PT, a derivative of KPV corresponding to the amino acid 193–195 of IL?1?, is currently emerging as another tripeptide with potent anti?inflammatory effects. The anti?inflammatory potential together with the favourable physiochemical properties most likely will allow these agents to be developed for the treatment of inflammatory skin, eye and bowel diseases, allergic asthma and arthritis.

Luger, Thomas A; Brzoska, Thomas

2007-01-01

97

Anti-inflammatory sesquiterpenes from Curcuma zedoaria  

Microsoft Academic Search

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

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

2006-01-01

98

Pyrazolone derivatives: synthesis, anti-inflammatory, analgesic, quantitative structure-activity relationship and in vitro studies.  

PubMed

Some 1-(4-chlorophenyl or benzenesulfonamide)-2,3- and/or 4-substituted-1H-pyrazol-5(4H)-one derivatives were synthesized and screened for their anti-inflammatory and analgesic activities, in addition to their ulcerogenic liability. They were found to be active as anti-inflammatory and analgesic agents. Compound 6b was found to be the most active as anti-inflammatory agent and compound 9b was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, cyclooxygenase-1/-2 (COX-1)/COX-2 isozyme selectivity was also done and the tested compounds showed equal inhibition to both isoforms. Moreover, 2D-quantitative structure-activity relationship (QSAR) studies revealed well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds. PMID:23902866

Ragab, Fatma Abdel-Fattah; Abdel-Gawad, Nagwa Mohamed; Georgey, Hanan Hanna; Said, Mona Fikry

2013-01-01

99

Anti-inflammatory constituents of the red alga Gracilaria verrucosa and their synthetic analogues.  

PubMed

A chemical study on the anti-inflammatory components of the red alga Gracilaria verrucosa led to the isolation of new 11-deoxyprostaglandins ( 1- 4), a ceramide ( 5), and a C 16 keto fatty acid ( 6), along with known oxygenated fatty acids ( 7- 14). Their structures were elucidated on the basis of NMR and MS data. The absolute configurations of compounds 1- 5 were determined by Mosher's method. The anti-inflammatory activity of the isolated compounds ( 1- 14) was evaluated by determining their inhibitory effects on the production of pro-inflammatory mediators (NO, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Compounds 9 and 10 exhibited the most potent activity. In the evaluation of these two compounds and derivatized analogues ( 15- 40), the anti-inflammatory activity was enhanced in some synthetic analogues. These enone fatty acids were investigated as potential anti-inflammatory leads for the first time. PMID:18220352

Dang, Hung The; Lee, Hye Ja; Yoo, Eun Sook; Shinde, Pramod B; Lee, Yoon Mi; Hong, Jongki; Kim, Dong Kyoo; Jung, Jee H

2008-02-01

100

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

101

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

PubMed

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

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

2013-04-01

102

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

103

The Role of Intestinal Microflora in Anti-Inflammatory Effect of Baicalin in Mice  

PubMed Central

Baicalin, a main constituent of the rhizome of Scutellaria baicalensis, is metabolized to baicalein and oroxylin A in the intestine before its absorption. To understand the role of intestinal microflora in the pharmacological activities of baicalin, we investigated its anti-inflammatory effect in mice treated with and without antibiotics. Orally administered baicalin showed the anti-inflammatory effect in mice than intraperitoneally treated one, apart from intraperitoneally administered its metabolites, baicalein and oroxylin A, which potently inhibited LPS-induced inflammation. Of these metabolites, oroxylin A showed more potent anti-inflammatory effect. However, treatment with the mixture of cefadroxil, oxytetracycline and erythromycin (COE) significantly attenuated the anti-inflammatory effect of orally administered baicalin in mice. Treatment with COE also reduced intestinal bacterial fecal ?-glucuronidase activity. The metabolic activity of human stools is significantly different between individuals, but neither between ages nor between male and female. Baicalin was metabolized to baicalein and oroxylin A, with metabolic activities of 1.427 ± 0.818 and 1.025 ± 0.603 pmol/min/mg wet weight, respectively. Baicalin and its metabolites also inhibited the expression of pro-inflammatory cytokines, TNF-? and IL-1?, and the activation of NF-?B in LPS-stimulated peritoneal macrophages. Of them, oroxylin A showed the most potent inhibition. Based on these findings, baicalin may be metabolized to baicalein and oroxylin A by intestinal microflora, which enhance its anti-inflammatory effect by inhibiting NF-?B activation.

Jung, Myung-Ah; Jang, Se-Eun; Hong, Sung-Woon; Hana, Myung Joo; Kim, Dong-Hyun

2012-01-01

104

High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation  

PubMed Central

Background The fatty acid mixture of human milk is ideal for the newborn but little is known about its composition in the first few weeks of lactation. Of special interest are the levels of long-chain PUFAs (LCPUFAs), since these are essential for the newborn’s development. Additionally, the LCPUFAs arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are precursors for lipid mediators which regulate inflammation. Methods We determined the composition of 94 human milk samples from 30 mothers over the first month of lactation for fatty acids using GC-MS and quantified lipid mediators using HPLC-MS/MS. Results Over the four weeks period, DHA levels decreased, while levels of ?C18:3 and ?C18:3 steadily increased. Intriguingly, we found high concentrations of lipid mediators and their hydroxy fatty acid precursors in human milk, including pro-inflammatory leukotriene B4 (LTB4) and anti-inflammatory and pro-resolving lipoxin A4 (LXA4), resolvin D1 (RvD1) and resolvin E1 (RvE1). Lipid mediator levels were stable with the exception of two direct precursors. Conclusions Elevated levels of DHA right after birth might represent higher requirements of the newborn and the high content of anti-inflammatory and pro-resolving lipid mediators and their precursors may indicate their role in neonatal immunity and may be one of the reasons for the advantage of human milk over infant formula.

2013-01-01

105

Anti-inflammatory effect of Marchantin M contributes to sensitization of prostate cancer cells to docetaxel.  

PubMed

As pro-inflammatory cytokines and chemokines contribute to the malignancy of many types of human cancer, we examined the anti-inflammatory effect of bisbibenzyls, a diverse bioactive group of naturally occurring compounds. Marchantin M (Mar M) was identified through a screening process of these compounds as a potent anti-inflammatory agent based on its capacity to inhibit LPS-induced IL6, IL1? and CCL2 expression in HUVECs and PBMCs without affecting cell proliferation. Since Mar M has been found to exhibit anticancer activity, we observed that Mar M treatment also resulted in decreases in the expressions of IL6, IL1? and TNF? in metastatic prostate cancer (PCa) cells. This effect was further confirmed in other cancer cell lines that express high level of pro-inflammatory cytokines. Furthermore, inactivation of NF-?B, a critical transcription factor controlling many pro-inflammatory cytokine expressions, was observed in Mar M-treated PCa cells as evidenced by decreased phosphor-p65 and subsequently phosphor-STAT3. Mar M also suppressed phosphorylation of IKB?, an inhibitor of NF-?B in the cytosol. However, reduced phosphor-p65 by Mar M was slightly increased when knockdown of IKB?, suggesting that Mar M may target upstream molecules of IKB?/NF-?B signaling. Finally, treatment with Mar M resulted in more enhanced-sensitivity of PCa cells to docetaxel-induced apoptosis than that of the IL6 blocking. Our study demonstrates the potential of the anti-inflammatory agent Mar M as an adjuvant to improve the efficacy of traditional anticancer agents such as docetaxel. PMID:24680871

Niu, Leilei; Deng, Jingti; Zhu, Fanghua; Zhou, Nan; Tian, Keli; Yuan, Huiqing; Lou, Hongxiang

2014-06-28

106

Evaluation of Anti-nociceptive and Anti-inflammatory Activities of Novel Chalcone Derivatives  

PubMed Central

Chalcone (1,3-diarylprop-2-en-1-one) derivatives have been introduced as selective cyclooxygenase-2 inhibitors. In the present study, anti-nociceptive and anti-inflammatory effects of eight novel compounds were evaluated in male mice and Wistar rats by using the writhing and formalin-induced paw edema tests respectively. The activities of the compounds were compared with celecoxib as a reference drug. Then, novel compounds were divided into two regioisomeric groups based on the position of the methylsulfonyl substitution. Compounds with substituents such as: 1) H, 2) Me, 3) F and 4) Cl at para position of the phenyl ring of (E)-3-(4-Methanesulfonylphenyl)-1-phenylprop-2 en-1-one were selected in the first group. The regioisomer compounds with 5) H, 6) Me, 7) F and 8) OMe substitutions at C-4 of phenyl ring of (E)-1-(4-Methanesulfonylphenyl)-3-phenylprop-2-en-1-one were chosen as second group. All compounds showed dose-dependent anti-nociceptive activity in writhing test. Interestingly, the potency of anti-nociceptive effect of compounds 1, 2, 5 and 6 were significantly higher than celecoxib. The regioisomeric compounds 1 and 5 with high anti-nociceptive effects, showed a significant dose-dependent anti inflammatory activity in the paw edema test as well. The results showed that compounds with no substituent or small size substituents at para position of the phenyl ring are the most potent compound in writhing test. Our results revealed that the introduction of a bulky group such as methoxy or chlorine at the vicinal aromatic chain of the derivatives decreases the anti-inflammatory/ anti-nociceptive effects. The comparison of estimated ED50 of each pair of the regioisomeric compounds indicates that the relative position of SO2Me to carbonyl moiety did not affect the potency.

Razmi, Ali; Zarghi, Afshin; Arfaee, Sara; Naderi, Nima; Faizi, Mehrdad

2013-01-01

107

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

Microsoft Academic Search

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

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

2002-01-01

108

Gastrointestinal delivery of anti-inflammatory nanoparticles.  

PubMed

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

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

2012-01-01

109

Anti-inflammatory studies on Polygonum glabrum.  

PubMed

Anti-inflammatory studies were conducted on a hot water decoction and on an ethanol extract of the stems of Polygonum glabrum. Effective anti-inflammatory activity was demonstrated against acute carrageenan-induced paw oedema, exudate and granuloma formation in the granuloma pouch test, acute and delayed reactions in formaldehyde arthritis, and acute primary and delayed secondary reactions in adjuvant-induced polyarthritis in albino rats. The acute toxicity in albino mice and 1-month studies on subacute toxicity in rats suggested a good margin of safety. The extract was more effective parenterally than by oral administration. PMID:3669687

Singh, B; Pandey, V B; Joshi, V K; Gambhir, S S

1987-05-01

110

Determination of residual nonsteroidal anti-inflammatory drugs in aqueous sample using magnetic nanoparticles modified with cetyltrimethylammonium bromide by high performance liquid chromatography.  

PubMed

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 (R (2) > 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

111

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.

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

2014-01-01

112

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

113

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

114

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.

2011-01-01

115

The role of anti-inflammatory drugs in colorectal cancer.  

PubMed

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

Wang, Dingzhi; DuBois, Raymond N

2013-01-01

116

Gastroscopic evaluation of anti-inflammatory agents*  

PubMed Central

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

Caruso, I; Porro, G Bianchi

1980-01-01

117

Anti-inflammatory properties of ?- and ?-tocopherol  

Microsoft Academic Search

Natural vitamin E consists of four different tocopherol and four different tocotrienol homologues (?,?, ?, ?) that all have antioxidant activity. However, recent data indicate that the different vitamin E homologues also have biological activity unrelated to their antioxidant activity. In this review, we discuss the anti-inflammatory properties of the two major forms of vitamin E, ?-tocopherol (?T) and ?-tocopherol

Elke Reiter; Qing Jiang; Stephan Christen

2007-01-01

118

Dual acting anti-inflammatory drugs: a reappraisal.  

PubMed

Rheumatic diseases are the most prevalent causes of disability in western countries, and non-steroidal anti-inflammatory drugs (NSAIDs) are still the most commonly used remedies. However, NSAIDs cause several serious adverse effects, the most important being from gastric injury to gastric ulceration and renal damage. Attempts to develop non-steroidal anti-inflammatory remedies devoid of these shortcomings-especially gastrointestinal toxicity-have followed several strategies. Non-steroidal anti-inflammatory drugs have, therefore, been associated with gastroprotective agents that counteract the damaging effects of prostaglandin synthesis suppression; however, a combination therapy introduces other problems of pharmacokinetics, toxicity, and patient's compliance. More recently, incorporation of a nitric oxide (NO)-generating moiety into the molecule of several NSAIDs was shown to greatly attenuate their ulcerogenic activity; however, several findings suggest a possible involvement of NO in the pathogenesis of arthritis and subsequent tissue destruction. A most promising approach seemed to be the preparation of novel NSAIDs, targeted at the inducible isoform of prostaglandin synthase (COX-2); they appear to be devoid of gastrointestinal toxicity, in that they spare mucosal prostaglandin synthesis. However, a number of recent studies have raised serious questions about the two central tenets that support this approach, namely that the prostaglandins that mediate inflammation and pain are produced solely via COX-2 and that the prostaglandins that are important in gastrointestinal and renal function are produced solely via COX-1. So, a growing body of evidence shows that COX-2 (not only COX-1) also plays a physiological role in several body functions and that, conversely, COX-1 (not only COX-2) may also be induced at sites of inflammation. More recent and puzzling data shows that COX-2 is induced during the resolution of an inflammatory response, and at this point it produces anti-inflammatory (PGD2 and PGF2alpha), but not proinflammatory (PGE2) prostaglandins; inhibition of COX-2 at this point thus results in persistence of the inflammation. Moreover, COX-2 selective NSAIDs have lost the cardiovascular protective effects of non-selective NSAIDs, effects which are mediated through COX-1 inhibition (in addition, COX-2 has a role in sustaining vascular prostacyclin production). The generation of other very important products of the arachidonic acid cascade (besides cyclooxygenase-produced metabolites) is inhibited neither by non-selective nor by COX-2 selective NSAIDs. The products generated by the 5-lipoxygenase pathway (leukotrienes) are particularly important in inflammation; indeed, leukotrienes increase microvascular permeability and are potent chemotactic agents. Moreover, inhibition of 5-lipoxygenase indirectly reduces the expression of TNF-alpha (a cytokine that plays a key role in inflammation). These data and considerations explain the efforts to obtain drugs able to inhibit both 5-lipoxygenase and cyclooxygenases, the so-called dual acting anti-inflammatory drugs. Such compounds retain the activity of classical NSAIDs, while avoiding their main drawbacks, in that curtailed production of gastroprotective prostaglandins is associated with a concurrent curtailed production of the gastro-damaging and bronchoconstrictive leukotrienes. Moreover, thanks to their mechanism of action, dual acting anti-inflammatory drugs could not merely alleviate symptoms of rheumatic diseases, but might also satisfy, at least in part, the criteria of a more definitive treatment. Indeed, leukotrienes are pro-inflammatory, increase microvascular permeability, are potent chemotactic agents and attract eosinophils, neutrophils and monocytes into the synovium. PMID:11735348

Bertolini, A; Ottani, A; Sandrini, M

2001-12-01

119

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

Microsoft Academic Search

Purpose: Glaucoma is the second leading cause of blindness. The ultimate cause of vision loss in glaucoma is thought to be retinal ganglion cell (RGC) death. Neuroprotection of RGC is therefore an important goal of glaucoma therapy. Several lines of evidence suggest that pigment epithelium derived factor (PEDF) is a potent anti-angiogenic, neuroprotective, and anti-inflammatory factor for neurons. In this

Xiaohong Zhou; Feng Li; Li Kong; James Chodosh; Wei Cao

2009-01-01

120

Anti-Inflammatory and Antinociceptive Activities of Bufalin in Rodents  

PubMed Central

The aims of this study were to evaluate the anti-inflammatory and analgesic effects of bufalin, a major component of “Chan-su.” We used a carrageenan-induced paw edema model to assess the anti-inflammatory activity of this compound, and Western blot analysis detected NF-?B signaling during this effect. The antinociceptive activities were evaluated by acetic acid-induced writhing, formalin, and hot-plate tests; open-field test investigated effects on the central nervous system. Our data showed that bufalin (0.3 and 0.6?mg/kg, i.p.) potently decreased carrageenan-induced paw edema. Bufalin down regulated the expression levels of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1? (IL-1?), interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?) during these treatments. Further studies demonstrated that bufalin significantly inhibited the activation of NF-?B signaling. Bufalin also reduced acetic acid-induced writhing and the licking time in the formalin test and increased hot-plate reaction latencies. Naloxone pretreatment (2?mg/kg, i.p.) in the early phases of the formalin test and hot-plate test significantly attenuated the bufalin-induced antinociception effects, which suggests the involvement of the opioid system. A reduction in locomotion was not observed in the open-field test after bufalin administration. Taken together, bufalin treatment resulted in in vivo anti-inflammatory and analgesic effects, and bufalin may be a novel, potential drug for the treatment of inflammatory diseases.

Huang, Yang; Yin, Junqiang; Lin, Wenqian

2014-01-01

121

Assessment of anti-inflammatory and hepatoprotective potency of Polyalthia longifolia var. pendula leaf in Wistar albino rats  

Microsoft Academic Search

The objective of the present study was to screen various solvent extracts of Polyalthia longifolia var. pendula (Annonaceae) leaf for anti-inflammatory activity and to evaluate the anti-inflammatory and hepatoprotective\\u000a potency of the potent solvent extract. Successive extraction was performed with six different solvents, viz. petroleum ether,\\u000a hexane, toluene, chloroform, acetone and methanol. Toluene, chloroform, acetone and methanol were used in

A. Tanna; R. Nair; S. Chanda

2009-01-01

122

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

123

Anti-inflammatory and pharmacokinetics evaluation of PEGylated ibuprofen tablet formulation.  

PubMed

To develop a novel PEGylated ibuprofen tablet formulations and evaluate its anti-inflammatory activity and pharmacokinetics profile in an animal model. Six batches of PEGylated ibuprofen tablets were prepared by direct compression using Avicel® and lactose as the binder diluents. In vivo anti-inflammatory activity of the tablets was carried out as well as the pharmacokinetics profiles. The PEGylated ibuprofen tablet reduced carrageenan-induced inflammation in experimental animals and sustained its anti-inflammatory action for over 10 h. The pharmacokinetics profile of the optimized formulations were greater than that of the marketed sample and the pure drug sample. In conclusion, PEGylation of ibuprofen conferred a high level of anti-inflammatory activity and slowed plasma clearance level, indicating sustained release. Thus, further exploration of this novel formulation to be used as an alternative carrier for this drug is required. PMID:24191762

Mumuni, Momoh A; Kenechukwu, Franklin Chimaobi; Chime, Salome Amarachi; Ogbonna, John Dike; Mora, A T

2014-06-01

124

Anti-inflammatory plant natural products for cancer therapy.  

PubMed

Much of the current research in cancer therapeutics is aimed at developing drugs or vaccines to target key molecules for combating tumor cell growth, metastasis, proliferation, or changes in the associated stromal microenvironment. Studies on a wide spectrum of plant secondary metabolites extractable as natural products from fruits, vegetables, teas, spices, and traditional medicinal herbs show that these plant natural products can act as potent anti-inflammatory, antioxidant or anticancer agents. The recent advances in genomics and metabolomics have enabled biologists to better investigate the potential use of immunomodulatory natural products for treatment or control of various cancerous diseases. The cancer preventive or protective activities of the various immunomodulatory natural products lie in their effects on cellular defenses including detoxifying and antioxidant enzyme systems, and the induction of anti-inflammatory and antitumor or antimetastasis responses, often by targeting specific key transcription factors like nuclear factor kappa B (NF-kappaB), activator protein (AP-1), signal transducers and activators of transcription (STAT) and others. This review presents recent findings and hypotheses on the molecular mechanisms through which various inflammatory activities are linked to tumorigenic processes and the specific immunomodulatory natural products that may suppress inflammation and the associated tumor progression and metastasis both IN VITRO and IN VIVO. In addition to tumor cells PER SE, the various associated roles of myeloid-derived suppressor cells, stromal fibroblasts, myofibroblasts, and inflammatory immune cells, and the possible effects of phytomedicines on these cells in the tumor microenvironment will be discussed. PMID:20432202

Aravindaram, Kandan; Yang, Ning-Sun

2010-08-01

125

[Anti-inflammatory effect of topically applied pranoprofen-gel].  

PubMed

The anti-inflammatory activity and mode of action of topically applied pranoprofen-gel were investigated in comparison with indomethacin-gel in experimental animals. Applied topically, 0.3 approximately 3% pranoprofen-gel inhibited carrageenin-induced paw edema, fracture-induced paw edema, carrageenin-induced increase in vascular permeability and adjuvant arthritis in rats and ultraviolet ray-induced erythema in guinea pigs dose-dependently, with a potency slightly greater than that of indomethacin-gel. In addition, pranoprofen-gel inhibited dose-dependently the formation of granuloma caused by a cotton pellet implantation, without affecting the weight of the thymus or adrenals and without inducing gastrointestinal lesions. Moreover, applied topically to carrageenin-treated rats, pranoprofen-gel inhibited dose-dependently, and more potently than indomethacin-gel, the production of a prostaglandin E2 (PGE2)-like substance in both the exudate of the carrageenin air pouch and the inflamed synovial membrane. Both drugs inhibited the potentiation of bradykinin-induced vascular permeability in rabbit skin by arachidonic acid, but not by PGE2. Pranoprofen was only one third as potent as indomethacin in inhibiting the production of PGE2 from the phagocytosing of killed bacteria by rat peritoneal leucocytes in vitro. These results show that pranoprofen-gel, applied topically, permeates well from the skin to the deep inflammatory site, relieving potently and long lastingly the inflammation by inhibiting PG production. As a topical anti-inflammatory agent, pranoprofen-gel is at least as effective as indomethacin-gel, so it may have good clinical use. PMID:3874127

Terasawa, M; Imayoshi, T; Iwahisa, Y; Maruyama, Y

1985-04-01

126

Design, synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity.  

PubMed

A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-?-D-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%). In contrast to diclofenac, the anti-inflammatory activity of these compounds was not only free from any side effects on the gastric mucosa but also showed significant anti-ulcerogenic activity in rat pyloric ligation and ethanol-induced gastric ulcer models similar to that of omeprazole. Together, these findings suggest that 12d and 15d are potent anti-inflammatory agents with concurrent anti-ulcerogenic activity and support its clinical promise as a component of therapeutic strategies for inflammation, for which the gastric side effects are always a major limitation. PMID:23453216

El-Nezhawy, Ahmed O H; Biuomy, Ayman R; Hassan, Fatma S; Ismaiel, Ayman K; Omar, Hany A

2013-04-01

127

Anti-inflammatory principles from Cordyceps sinensis.  

PubMed

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

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

2011-09-23

128

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.

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

2014-01-01

129

ANTI INFLAMMATORY ACTIVITY OF MORINGA OLIEFERA. LAM  

PubMed Central

The aqueous and ethanolic (90%) extract of the leaves of M.Oliera Lam (Fam: Moringaceae) were studied for their anti inflammatory action in ale albino rats. Two extracts exhibited maximum action within two hours of challenge. The aqueous extract sowed significant (P<0.01) odema suppression similar to that of Ibuprofen at the first hour of carrageenan injection. The results confirms the folkers claim of the plant.

Rao, K.N. Venkataswera; Gopalakrishnan, V.; Loganathan, V.; Nathan, S. Shanmuganathan

1999-01-01

130

Anti inflammatory activity of moringa oliefera. Lam.  

PubMed

The aqueous and ethanolic (90%) extract of the leaves of M.Oliera Lam (Fam: Moringaceae) were studied for their anti inflammatory action in ale albino rats. Two extracts exhibited maximum action within two hours of challenge. The aqueous extract sowed significant (P<0.01) odema suppression similar to that of Ibuprofen at the first hour of carrageenan injection. The results confirms the folkers claim of the plant. PMID:22556890

Rao, K N; Gopalakrishnan, V; Loganathan, V; Nathan, S S

1999-01-01

131

Non-steroidal anti-inflammatory drugs  

Microsoft Academic Search

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

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

132

Rotenoids from Boerhaavia diffusa as potential anti-inflammatory agents.  

PubMed

Five new (2, 3, 5, 7, and 9) and four known rotenoids (1, 4, 6, and 8) were isolated from a methanol extract of Boerhaavia diffusa roots. The structures of the new rotenoids were elucidated by spectroscopic data interpretation. The 70% ethanol extract, a rotenoid-rich fraction, and all isolated rotenoids were evaluated for their COX-1 and COX-2 inhibitory activities. Among the rotenoids tested, compound 7 showed the most potent COX-1 and COX-2 inhibition, with IC?? values of 21.7 ± 0.5 and 25.5 ± 0.6 ?M, respectively. Boeravinone B (6) exhibited significant anti-inflammatory activity (56.6% at 50 mg/kg) when evaluated in an in vivo carrageenan-induced rat paw model. PMID:23914900

Bairwa, Khemraj; Singh, Ishwari N; Roy, Somendu K; Grover, Jagdeep; Srivastava, Amit; Jachak, Sanjay M

2013-08-23

133

Evaluation of in vivo anti-inflammatory and analgesic activities of novel derivatives of Ugi-4CR.  

PubMed

In the present research, anti-inflammatory and analgesic activities of the synthesized agents derived from Ugi four-component reaction (Ugi-4CR) have been described. The synthesis was initiated by the imine formation under microwave irradiation. Ugi-4CR adducts has been achieved by the condensation of imine with aromatic aldehyde, 4- aminoantipyrine and ethylisocyanoacetate. The reaction was carried out at room temperature in presence of Fluorite as a catalyst. The novel Ugi derivatives were characterized on the basis of IR, 1H NMR, 13C NMR, Mass and Elemental analysis. All the synthesized agents were screened for their potential anti-inflammatory and analgesic activities using healthy wistar albino rats. Anti-inflammatory and analgesic activities were evaluated by Mercury displacement and Hot plate method using Diclofenac and Morphine Sulfate as standard reference drugs respectively. The screening data shows that synthesized compounds are potent agents to act as analgesic and anti-inflammatory drugs. PMID:23815582

Mohanram, Ipsita; Meshram, Jyotsna

2013-08-01

134

Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance of ursolic acid.  

PubMed

Salvia officinalis L. leaves, obtained from four plant populations of different origin, were investigated for their topical anti-inflammatory properties. The n-hexane and the chloroform extracts dose-dependently inhibited the Croton oil-induced ear oedema in mice, the chloroform extracts being the most active. By contrast, the methanol extracts showed a very low effect and the essential oil was inactive. Chemical and pharmacological investigation of the most potent chloroform extract, issued from an autochthonous sage population grown in the submediterranean climatic region of Slovenia, revealed ursolic acid as the main component involved in its anti-inflammatory activity. The anti-inflammatory effect of ursolic acid (ID50 = 0.14 microMoles/cm2) was two fold more potent than that of indomethacin (ID50 = 0.26 microMoles/cm2), which was used as a reference non-steroidal anti-inflammatory drug (NSAID). The content of ursolic acid in sage and sage-based remedies for the topical treatment of inflammatory diseases is proposed as a parameter for quality control purposes. PMID:11297842

Baricevic, D; Sosa, S; Della Loggia, R; Tubaro, A; Simonovska, B; Krasna, A; Zupancic, A

2001-05-01

135

Anti-inflammatory activity of extracts from leaves of Phyllanthus emblica.  

PubMed

Leaves and fruits of Phyllanthus emblica L. have been used for the anti-inflammatory and antipyretic treatment of rural populations in its growing areas in subtropical and tropical parts of China, India, Indonesia, and the Malay Peninsula. In the present study, leaves of Ph. emblica were extracted with ten different solvents (n-hexane, diethyl ether, methanol, tetrahydrofuran, acetic acid, dichloromethane, 1,4-dioxane, toluene, chloroform, and water). The inhibitory activity of the extracts against human polymorphonuclear leukocyte (PMN) and platelet functions was studied. Methanol, tetrahydrofuran, and 1,4-dioxane extracts (50 micrograms/ml) inhibited leukotriene B4-induced migration of human PMNs by 90% and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced degranulation by 25-35%. The inhibitory activity on receptor-mediated migration and degranulation of human PMNs was associated with a high proportion of polar compounds in the extracts as assessed by normal phase thin layer chromatography. Diethyl ether extract (50 micrograms/ml) inhibited calcium ionophore A23187-induced leukotriene B4 release from human PMNs by 40%, thromboxane B2 production in platelets during blood clotting by 40% and adrenaline-induced platelet aggregation by 36%. Ellagic acid, gallic acid and rutin, all compounds isolated earlier from Ph. emblica, could not explain these inhibitory activities on PMNs or platelets by Ph. emblica extracts. These results show that the leaves of Ph. emblica have inhibitory activity on PMNs and platelets, which confirm the anti-inflammatory and antipyretic properties of this plant as suggested by its use in traditional medicine. The data suggest that the plant leaves contain as yet unidentified polar compound(s) with potent inhibitory activity on PMNs and chemically different apolar molecule(s) which inhibit both prostanoid and leukotriene synthesis. PMID:9434603

Ihantola-Vormisto, A; Summanen, J; Kankaanranta, H; Vuorela, H; Asmawi, Z M; Moilanen, E

1997-12-01

136

The anti-inflammatory effect of A3 adenosine receptor agonists: a novel targeted therapy for rheumatoid arthritis.  

PubMed

Targeting the A(3) adenosine receptor (A(3)AR) to combat inflammation is a new concept based on two findings. First, A(3)AR is highly expressed in inflammatory cells, whereas low expression is found in normal tissues. This receptor was also found to be overexpressed in peripheral blood mononuclear cells, reflecting receptor status in the remote inflammatory process. Second, A(3)AR activation with a specific agonist induces de-regulation of the NF-kappaB signaling pathway in inflammatory cells, as well as initiation of immunomodulatory effects. The A(3)AR agonist CF-101 (known generically as IB-MECA) induces anti-inflammatory effects in experimental animal models of collagen- and adjuvant-induced arthritis. Combined therapy with CF-101 and methotrexate in adjuvant-induced arthritis rats yielded an additive anti-inflammatory effect. Methotrexate induced upregulation of A(3)AR, rendering the inflammatory cells more susceptible to CF-101. In Phase I and in Phase IIa human studies, CF-101 was safe, well tolerated and showed strong evidence of an anti-inflammatory effect in rheumatoid arthritis patients. In peripheral blood mononuclear cells withdrawn from the patients at base line, a statistically significant correlation between A(3)AR expression level and response to the drug was noted. It is suggested that A(3)AR may serve as a biologic marker to predict patient response to the drug. Taken together, this information suggests that A(3)AR agonists may be a new family of orally bioavailable drugs to be developed as potent inhibitors of autoimmune-inflammatory diseases. PMID:17922624

Bar-Yehuda, Sara; Silverman, Michael H; Kerns, William D; Ochaion, Avivit; Cohen, Shira; Fishman, Pnina

2007-10-01

137

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

PubMed Central

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

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

2011-01-01

138

A COMPARATIVE EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF THE BARK OF FICUS BENGALENSIS IN PLANTS OF DIFFERENT AGE  

PubMed Central

The medicinal plants have been selected for thorough studies from indigenous folk medicines, Ayurvedic, Unani and Siddha systems of medicines. The aim of this study deals with the comparative evaluation of anti-inflammatory activity of the bark of Ficus bengalensis in plants of different age. The anti-inflammatory activity was evaluated by rat paw edema model induced by carrageenan for acute inflammation and cotton pellet granuloma model for chronic inflammation. Indomethacin was used as a standard drug. The various extracts were studied for their anti-inflammatory activity in carrageenan-induced hind paw edema in rats and the paw volume was measured plethysmometrically from 0 to 3h after injection. We have determined the anti-inflammatory activity of various extracts of the bark of Ficus bengalensis with oral administration doses of 300 and 600 mg/kg/day of body weight to healthy animals. Positive results for flavonoids, sterols, and triterpene, tannins and saponins compounds were investigated by phytochemical analysis. The ethanolic extract of younger plant showed a greater anti-inflammatory effect compared with the standard drug indomethacin. Present studies besides confirming anti-inflammatory activity of the ethanolic extract of younger more potent than mature plant help to identify from the comparative study of the bark of Ficus bengalensis.

Patil, Vikas V.; Patil, Vijay R.

2010-01-01

139

Lyprinol—is it a Useful Anti-inflammatory Agent?  

Microsoft Academic Search

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

Sheila A. Doggrell

140

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

PubMed

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

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

2013-11-01

141

Anti-inflammatory and anti-nociceptive effects of the methanol extract of Fomes fomentarius.  

PubMed

In an attempt to find bioactive natural products with an anti-inflammatory activity, we evaluated the effects of the methanol extract of Fomes fomentarius (MEFF) on in vivo anti-inflammatory and anti-nociceptive activities. MEFF (50, 100 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed MEFF analgesic activity, as determined by an acetic acid-induced writhing test and a hot plate test in mice. To investigate the mechanism of the anti-inflammatory action of MEFF, we examined the effect of MEFF on lipopolysaccharide (LPS)-induced responses in murine macrophages cell line RAW 264.7. MEFF potently inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages. Consistent with these observations, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) levels were reduced by MEFF in a dose-dependent manner. Furthermore, MEFF suppressed nuclear factor-kappaB (NF-kappaB) activation in LPS-stimulated RAW 264.7 macrophages. These findings suggest that the anti-inflammatory and anti-nociceptive properties of the methanol extract of MEFF may result from the inhibition of iNOS and COX-2 expression through the down-regulation of NF-kappaB binding activity. PMID:15467201

Park, Young-Mi; Kim, In-Tae; Park, Hee-Juhn; Choi, Jong-Won; Park, Kun-Young; Lee, Jae-Dong; Nam, Byung-Hyouk; Kim, Deog-Gon; Lee, Jin-Yong; Lee, Kyung-Tae

2004-10-01

142

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

143

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

PubMed

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

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

1995-12-01

144

Brine Shrimp Cytotoxicity, Anti-inflammatory and Analgesic Properties of Woodfordia fruticosa Kurz Flowers.  

PubMed

The present study was designed to assess the cytotoxicity, anti-inflammatory and analgesic properties of methanol extract of Woodfordia fruticosa flowers. Cytotoxic activity of methanol extract of Woodfordia fruticosa flowers was tested using Artemia salina (Brine shrimp) bioassay. Two doses (400 and 600 mg/Kg) were evaluated for the anti-inflammatory activity against the carrageenan, histamine, dextran, serotonin and formaldehyde-induced rat paw edema, cotton pellet-induced granuloma and formaldehyde-induced analgesia in rats. In cytotoxicity study, extract caused 73% mortality of Brine shrimp larvae after 24 h at a concentration of 1000 ?g/mL. The results of the anti-inflammatory study showed that the extract produced significant (p < 0.05) decrease in paw volume in different models of paw edema. The extract also inhibited the formation of granuloma in cotton pellet-induced granuloma and reduced the frequency of formaldehyde-induced paw licking. These results showed that the methanol extract of Woodfordia fruticosa flowers have weak cytotoxic and potent anti-inflammatory compounds and justifies the traditional uses for the treatment of inflammatory conditions. PMID:24250512

Baravalia, Yogesh; Vaghasiya, Yogeshkumar; Chanda, Sumitra

2012-01-01

145

Brine Shrimp Cytotoxicity, Anti-inflammatory and Analgesic Properties of Woodfordia fruticosa Kurz Flowers  

PubMed Central

The present study was designed to assess the cytotoxicity, anti-inflammatory and analgesic properties of methanol extract of Woodfordia fruticosa flowers. Cytotoxic activity of methanol extract of Woodfordia fruticosa flowers was tested using Artemia salina (Brine shrimp) bioassay. Two doses (400 and 600 mg/Kg) were evaluated for the anti-inflammatory activity against the carrageenan, histamine, dextran, serotonin and formaldehyde-induced rat paw edema, cotton pellet-induced granuloma and formaldehyde-induced analgesia in rats. In cytotoxicity study, extract caused 73% mortality of Brine shrimp larvae after 24 h at a concentration of 1000 ?g/mL. The results of the anti-inflammatory study showed that the extract produced significant (p < 0.05) decrease in paw volume in different models of paw edema. The extract also inhibited the formation of granuloma in cotton pellet-induced granuloma and reduced the frequency of formaldehyde-induced paw licking. These results showed that the methanol extract of Woodfordia fruticosa flowers have weak cytotoxic and potent anti-inflammatory compounds and justifies the traditional uses for the treatment of inflammatory conditions.

Baravalia, Yogesh; Vaghasiya, Yogeshkumar; Chanda, Sumitra

2012-01-01

146

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

Microsoft Academic Search

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

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

2009-01-01

147

Structure-based design, synthesis and preliminary anti-inflammatory activity of bolinaquinone analogues  

Microsoft Academic Search

As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophage-like RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E2 (PGE2). This

Carmen Petronzi; Rosanna Filosa; Antonella Peduto; Maria Chiara Monti; Luigi Margarucci; Antonio Massa; Simona Francesca Ercolino; Valentina Bizzarro; Luca Parente; Raffaele Riccio; Paolo de Caprariis

2011-01-01

148

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

149

Anti-inflammatory and anti-angiogenic activities of Gastrodia elata Blume  

Microsoft Academic Search

Gastrodia elata Blume rhizome has been traditionally used as a folk medicine for centuries in Oriental countries. Its ethanol extract (GEE) and subsequent fractions were used to evaluate anti-angiogenic, anti-inflammatory and related activities of Gastrodia elata. GEE potently inhibited angiogenesis in the chick chorioallantoic membrane assay, and its n-butanol fraction (BuOH) exerted the higher inhibitory effect. In a dose-dependent manner,

Eun-Kyoung Ahn; Hye-Jin Jeon; Eun-Ju Lim; Hyun-Joo Jung; Eun-Hee Park

2007-01-01

150

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

Microsoft Academic Search

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

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

2001-01-01

151

Anti-inflammatory vs. inflammatory treatments for actinic keratoses.  

PubMed

The treatment of actinic keratoses (AKs) provides an important opportunity to prevent the development of squamous cell carcinoma. The recent discovery that cyclo-oxygenase-2 (COX-2) is a potential pharmacological target for skin tumours has prompted interest in using topical nonsteroidal anti-inflammatory drugs (NSAIDs) as a treatment for AKs. Topical 3% diclofenac in 2.5% hyaluronic acid gel (Solaraze) is currently the only NSAID licensed for the treatment of AKs. In randomised, double-blind studies, this therapy was effective in clearing AKs, with the efficacy increasing in proportion to the duration of treatment. Topical 3% diclofenac in 2.5% hyaluronic acid gel was well tolerated, with the vast majority of adverse events rated as mild or moderate. Older treatments, such as fluorouracil, which promotes an inflammatory response, are also effective in treating AKs, but are not acceptable to many patients because of severe irritation. Imiquimod is an alternative inflammatory treatment, which, although highly effective, is expensive and produces severe erythema, erosion and flaking in a large proportion of patients. Topical anti-inflammatory agents, such as 3% diclofenac in 2.5% hyaluronic acid gel, can facilitate the early treatment of AKs without the level of severe side-effects observed with some of the other therapies. PMID:17163919

Ortonne, Jean-Paul

2003-07-01

152

Flavone deglycosylation increases their anti-inflammatory activity and absorption  

PubMed Central

Scope Flavones have reported anti-inflammatory activities, but the ability of flavone-rich foods to reduce inflammation is unclear. Here, we report the effect of flavone glycosylation in the regulation of inflammatory mediators in vitro and the absorption of dietary flavones in vivo. Methods and results The anti-inflammatory activities of celery extracts, some rich in flavone aglycones and others rich in flavone glycosides, were tested on the inflammatory mediators tumor necrosis factor ? (TNF-?) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) in lipopolysaccharide-stimulated macrophages. Pure flavone aglycones and aglycone-rich extracts effectively reduced TNF-? production and inhibited the transcriptional activity of NF-?B, while glycoside-rich extracts showed no significant effects. Deglycosylation of flavones increased cellular uptake and cytoplasmic localization as shown by high-performance liquid chromatography (HPLC) and microscopy using the flavonoid fluorescent dye diphenyl-boric acid 2-aminoethyl ester (DPBA). Celery diets with different glycoside or aglycone contents were formulated and absorption was evaluated in mice fed with 5 or 10% celery diets. Relative absorption in vivo was significantly higher in mice fed with aglycone-rich diets as determined by HPLC-MS/MS (where MS/MS is tandem mass spectrometry). Conclusion These results demonstrate that deglycosylation increases absorption of dietary flavones in vivo and modulates inflammation by reducing TNF-? and NF-?B, suggesting the potential use of functional foods rich in flavones for the treatment and prevention of inflammatory diseases.

Hostetler, Gregory; Riedl, Ken; Cardenas, Horacio; Diosa-Toro, Mayra; Arango, Daniel; Schwartz, Steven; Doseff, Andrea I.

2014-01-01

153

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

154

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.

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

155

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.

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

2013-01-01

156

Pharmacogenetics of nonsteroidal anti-inflammatory drugs.  

PubMed

With the beginning of the Human Genome Project, an emerging field of science was brought to the forefront of the pharmaceutical community. Pharmacogenetics facilitates optimization of the current patient-centered care model and pharmacotherapy as a whole. Utilizing these ever-expanding branches of science to nonsteroidal anti-inflammatory drugs (NSAIDs) can provide novel opportunities to affect patient care. With a wide range of NSAID choices available as treatment options for relieving pain and/or reducing inflammation or fever, a more systematic way of selecting the ideal agent for the patients based upon their genetic information could spare them from a potentially permanent health-care condition. Furthermore, if a patient possesses or lacks certain alleles, serious adverse events can be anticipated and avoided. The tailoring of drug therapy can be achieved using the published data and cutting-edge genetic testing to attain a higher standard of care for patients. PMID:23044603

Wyatt, J E; Pettit, W L; Harirforoosh, S

2012-12-01

157

Corneal reepithelialization and anti-inflammatory agents.  

PubMed Central

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

Srinivasan, B D

1982-01-01

158

Antibacterial, anti-inflammatory and probiotic potential of Enterococcus hirae isolated from the rumen of Bos primigenius.  

PubMed

In the present study bacterial strains were isolated from the rumen fluids of Bos primigenius and investigated their in vitro probiotic properties with potent antibacterial activity and anti-inflammatory effects. 9 g positive bacterial isolates were obtained and three isolates could able to tolerate gastric conditions, high bile salt concentrations and exhibited significant bactericidal effect against the enteric pathogens Vibrio cholera, Enterococcus faecalis, Enterobacter aerogens, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi. Moreover it showed above 70 % cell surface hydrophobicity, significant low-invasion ability and potential adherence capacity in Caco-2 cells when compared with the control. The proinflammatory cytokines (TNF-?) was greatly reduced in rumen bacteria treatment and ARBS-1 modulate the immune response by activating the IL-4 secretion in parallel to TNF-? suppression. The 16s rRNA gene sequence of the active isolates were identified as Enterococcus hirae (ARBS-1), Pediococcus acidilactici (ARBS-4) and Bacillus licheniformis (ARBS-7). This study revealed the probiotic bactericidal properties of E. hirae obtained from the rumen of B. primigenius with potential antibacterial and anti-inflammatory effects. Future studies with the strains may yield some novel probiotic product for livestock's. PMID:24609495

Arokiyaraj, Selvaraj; Hairul Islam, Villianur Ibrahim; Bharanidharan, R; Raveendar, Sebastian; Lee, Jinwook; Kim, Do Hyung; Oh, Young Kyoon; Kim, Eun-Kyung; Kim, Kyoung Hoon

2014-07-01

159

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.

2014-01-01

160

Anti-inflammatory Effect of Palmitoylethanolamide on Human Adipocytes  

Microsoft Academic Search

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

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

2009-01-01

161

9a-azalides with anti-inflammatory activity  

US Patent & Trademark Office Database

Macrolides with anti-inflammatory activity are described. Particularly described are 9a-azalides and their anti-inflammatory activity without cladinose in position 3, the pharmaceutically acceptable salts thereof and the pharmaceutical composition that contain them as active principle.

2008-09-02

162

Artificial matrices with high-sulfated glycosaminoglycans and collagen are anti-inflammatory and pro-osteogenic for human mesenchymal stromal cells.  

PubMed

Bone healing has been described to be most efficient if the early inflammatory phase is resolved timely. When the inflammation elevates or is permanently established, bone healing becomes impaired and, moreover, bone destruction often takes place. Systemic disorders such as diabetes and bone diseases like arthritis and osteoporosis are associated with sustained inflammation and delayed bone healing. One goal of biomaterial research is the development of materials/surface modifications which support the healing process by inhibiting the inflammatory bone erosion and suppressing pro-inflammatory mediators and by that promoting the bone repair process. In the present study, the influence of artificial extracellular matrices (aECM) on the interleukin (IL)-1?-induced pro-inflammatory response of human mesenchymal stromal cells (hMSC) was studied. hMSC cultured on aECM composed of collagen I and high-sulfated glycosaminoglycan (GAG) derivatives did not secrete IL-6, IL-8, monocyte chemoattractant protein-1, and prostaglandin E2 in response to IL-1?. The activation and nuclear translocation of nuclear factor ?Bp65 induced by IL-1?, tumor necrosis factor-? or lipopolysaccharide was abrogated. Furthermore, these aECM promoted the osteogenic differentiation of hMSC as determined by an increased activity of tissue non-specific alkaline phosphatase (TNAP); however, the aECM had no effect on the IL-1?-induced TNAP activity. These data suggest that aECM with high-sulfated GAG derivatives suppress the formation of pro-inflammatory mediators and simultaneously promote the osteogenic differentiation of hMSC. Therefore, these aECM might offer an interesting approach as material/surface modification supporting the bone healing process. J. Cell. Biochem. 115: 1561-1571, 2014. © 2014 Wiley Periodicals, Inc. PMID:24706396

Hempel, Ute; Matthäus, Claudia; Preissler, Carolin; Möller, Stephanie; Hintze, Vera; Dieter, Peter

2014-09-01

163

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

PubMed Central

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

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

2012-01-01

164

Evaluation of antinociceptive and anti-inflammatory activity of hydromethanol extract of Cocos nucifera L.  

PubMed

Cocos nucifera L. (family: arecaceae) is generally straight unbranched plant, traditionally cultivated for its fruit (coconut) in home gardens. In the present study, anti-inflammatory and antinociceptive (analgesic) activity of hydromethanol extract of Cocos nucifera L. (HECN) was evaluated in animal models. HECN showed significant (p < 0.05) and dosedependent anti-inflammatory activity in carrageenan induced paw oedema models of inflammation and the result was comparable with the standard drug diclofenac. In addition, the extract also showed highly significant (p < 0.01) antinociceptive activity. HECN treated group showed increase in the reaction time in hot plate method and decrease the writhing induced by acetic acid in mice when compared with control group animal. The anti-inflammatory and antinociceptive activity observed in the present study could be attributed largely to the presence of its antioxidant phytoconstituents such as flavonoid, saponin and polyphenols. PMID:22527352

Naskar, Sagar; Mazumder, U K; Pramanik, G; Saha, P; Haldar, P K; Gupta, M

2013-02-01

165

Anti-inflammatory effects of methoxyphenolic compounds on human airway cells  

PubMed Central

Background The respiratory epithelium plays a central role in the inflammatory response in asthma and other diseases. Methoxyphenolic compounds are purported to be effective anti-inflammatory agents, but their effects on the airway epithelium have not been well characterized. Methods Human airway cells were stimulated with TNF-? in the presence or absence of 4-substituted methoxyphenols and resveratrol. The expression of various cytokines was measured by qPCR, ELISAs, and protein arrays. Reactive oxygen species (ROS) production was measured with a reactive fluorescent probe (3',6'-diacetate-2',7'-dichlorofluorescein). Activation of NF-?B was measured by nuclear translocation and phosphorylation. Ribonuclear protein association with mRNA was assessed with a biotin-RNA affinity isolation assay. Results Multiple inflammatory mediators were inhibited by methoxyphenols, including: CCL2, CCL5, IL-6, IL-8, ICAM-1, MIF, CXCL1, CXCL10, and Serpin E1. IC50 values were obtained for each compound that showed significant anti-inflammatory activity: diapocynin (20.3 ?M), resveratrol (42.7 ?M), 2-methoxyhydroquinone (64.3 ?M), apocynin (146.6 ?M), and 4-amino-2-methoxyphenol (410 ?M). The anti-inflammatory activity did not correlate with inhibition of reactive oxygen species production or NF-?B activation. However, methoxyphenols inhibited binding of the RNA-binding protein HuR to mRNA, indicating that they may act post-transcriptionally. Conclusions Methoxyphenols demonstrate anti-inflammatory activity in human airway cells. More potent compounds that act via similar mechanisms may have therapeutic potential as novel anti-inflammatory agents.

2012-01-01

166

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

PubMed

A simple high-performance liquid chromatography (HPLC) method with both ultraviolet (UV) and electrospray ionisation mass spectrometry (ESI-MS) detection has been developed for the determination of seven pharmaceuticals in counterfeit homeopathic preparations. Naproxen, Ketoprofen, Ibuprofen, Diclofenac, Piroxicam, Nimesulide and Paracetamol were separated by reversed phase chromatography with acetonitrile-water (0.1% acetic acid) mobile phase, and detected by UV at 245 nm and by ESI-MS in negative ionisation mode with the exception of Paracetamol which was detected in positive ionisation mode. Benzoic acid was used as internal standard (IS). This method was successfully applied to the analysis of homeopathic preparations like mother tinctures, solutions, tablets, granules, creams, and suppositories. Linearity was studied with UV detection in the 50-400 microg mL(-1) range and with ESI-MS in the 0.1-50 microg mL(-1) range. Good correlation coefficients were found in both UV and ESI-MS. Detection limits ranged from 0.18 to 41.5 ng in UV and from 0.035 to 1.00 ng in ESI-MS. PMID:17127029

Panusa, Alessia; Multari, Giuseppina; Incarnato, Giampaolo; Gagliardi, Luigi

2007-03-12

167

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

168

Application of statistical experimental design to the optimisation of microextraction by packed sorbent for the analysis of nonsteroidal anti-inflammatory drugs in human urine by ultra-high pressure liquid chromatography.  

PubMed

A new approach based on microextraction by packed sorbent (MEPS) and a reversed-phase ultra-high pressure liquid chromatography (UHPLC) method was developed and validated for the determination and quantification of nonsteroidal anti-inflammatory drugs (NSAIDs) (acetylsalicylic acid, ketoprofen, diclofenac, naproxen and ibuprofen) in human urine. The important factors that could influence the extraction were previously screened using the Plackett-Burman design approach. The optimal MEPS extraction conditions were obtained using C18 phase as a sorbent, small sample volume (20?L) and a short time period (approximately 5min) for the entire sample preparation step. The analytes were separated on a core-shell column (Poroshell 120 EC-C18; 100mm×3.0mm; 2.7?m) using a binary mobile phase composed of aqueous 0.1% trifluoroacetic acid and acetonitrile in the gradient elution mode (4.5min of analysis time). The analytical method was fully validated based on linearity, limits of detection (LOD), limits of quantification (LOQ), inter- and intra-day precision and accuracy, and extraction yield. Under optimised conditions, excellent linearity (R(2)>0.9991), limits of detection (1.07-16.2ngmL(-1)) and precision (0.503-9.15% RSD) were observed for the target drugs. The average absolute recoveries of the analysed compounds extracted from the urine samples were 89.4-107%. The proposed method was also applied to the analysis of NSAIDs in human urine. The new approach offers an attractive alternative for the analysis of selected drugs from urine samples, providing several advantages including fewer sample preparation steps, faster sample throughput and ease of performance compared to traditional methodologies. PMID:23876769

Magiera, Sylwia; Gülmez, ?efika; Michalik, Aleksandra; Baranowska, Irena

2013-08-23

169

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

Microsoft Academic Search

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

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

2009-01-01

170

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

PubMed Central

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

WANG, HONGSHENG; ZHANG, LEIMING; JIANG, NA; WANG, ZHENHUA; CHONG, YATING; FU, FENGHUA

2013-01-01

171

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

PubMed

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

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

2011-01-01

172

Anti-inflammatory activity of some novel alpha-amino naphthalene derivatives.  

PubMed

alpha-Acetylamino naphthalene (1) was reacted with different aromatic aldehydes and with primary or secondary amines to give alpha-aminonaphthylsubstitutedaryl chalkones (2-5) and alpha-(substituted aminoethyl)-amidonaphthalenes (14-25), respectively. These substituted chalkones were treated with hydrazinehydrate and hydroxylamine hydrochloride to give 1-acetyl-5-substitutedaryl-3-(alpha-aminonaphthyl)-2-pyrazolines (6-9) and alpha-(2-substitutedaryl-isoxazolin-4-yl)-aminonaphthalenes (10-13), respectively. Their chemical structures were confirmed by IR and 1H-NMR spectral data and elemental analysis. Studies of the anti-inflammatory and ulcerogenic activities and acute toxicity of these newly synthesized compounds were performed in vivo and compared with the standard drug, phenylbutazone (CAS 50-33-9). Some of these compounds showed potent anti-inflammatory activity and less ulcerogenic effects than phenylbutazone. PMID:12608014

Sharma, Shalabh; Srivastava, Virendra Kishore; Kumar, Ashok

2003-01-01

173

Omega-3 PUFA derived anti-inflammatory lipid mediator resolvin E1.  

PubMed

Inflammation is a defensive response to injury and infection, but excessive or inappropriate inflammation contributes to a range of acute and chronic human diseases. Clinical assessment of dietary supplementation of omega-3 polyunsaturated fatty acids (PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) indicate their beneficial impact on human diseases in which inflammation is suspected as a key component of the pathogenesis. Although the mechanism of EPA and DHA action is still not fully defined in molecular terms, recent studies have revealed that, during the course of acute inflammation, omega-3 PUFA-derived mediators including resolvins and protectins with potent anti-inflammatory and pro-resolving properties are produced. In this review, we provide an overview of the formation and actions of EPA-derived anti-inflammatory lipid mediator resolvin E1. PMID:19737659

Seki, Hiroyuki; Tani, Yukako; Arita, Makoto

2009-09-01

174

Use of topical nonsteroidal anti-inflammatory drugs in excimer laser photorefractive keratectomy.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce potent analgesic, antipyretic, and anti-inflammatory effects. We studied postoperative pain in 97 consecutive patients having photorefractive keratectomy (PRK) by an excimer laser with different topical NSAID protocols. Treatment with topical homatropine hydrobromide, either diclofenac sodium (Voltaren Ophthalmic) or ketorolac tromethamine (Acular), and a soft contact lens was most effective in achieving post-PRK analgesia. We also studied post-PRK myopic regression in 68 consecutive patients and found that flurbiprofen sodium (Ocufen), when added to topical steroid protocols, significantly reduced myopic regression for one year postoperatively more than steroids alone or steroids and diclofenac sodium. Diclofenac, used with topical steroids, had less of an additive effect on myopic regression than did flurbiprofen. Topical NSAIDs are useful adjuncts to PRK therapy, both to eliminate postoperative pain and to control post-PRK myopic regression. PMID:8006790

Arshinoff, S; D'Addario, D; Sadler, C; Bilotta, R; Johnson, T M

1994-03-01

175

Anti-inflammatory treatment in schizophrenia.  

PubMed

Antipsychotics, which act predominantly as dopamine D2 receptor antagonists, have several shortcomings. The exact pathophysiological mechanism leading to dopaminergic dysfunction in schizophrenia is still unclear, but inflammation has been postulated to be a key player in the pathophysiology of the disorder. A dysfunction in activation of the type 1 immune response seems to be associated with an imbalance in tryptophan/kynurenine metabolism; the degrading enzymes involved in this metabolism are regulated by cytokines. Kynurenic acid (KYNA), an N-methyl-d-aspartate antagonist, was found to be increased in critical regions of the central nervous system (CNS) in schizophrenia, resulting in reduced glutamatergic neurotransmission. The differential activation of microglial cells and astrocytes as functional carriers of the immune system in the CNS may also contribute to this imbalance. The immunological effects of many existing antipsychotics, however, rebalance in part the immune imbalance and overproduction of KYNA. The immunological imbalance results in an inflammatory state combined with increased prostaglandin E(2) production and increased cyclo-oxygenase-2 (COX-2) expression. Growing evidence from clinical studies with COX-2 inhibitors points to favorable effects of anti-inflammatory therapy in schizophrenia, in particular in an early stage of the disorder. Further options for immunomodulating therapies in schizophrenia will be discussed. PMID:23178230

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

2013-04-01

176

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

Microsoft Academic Search

Triterpenoids are pentacyclic secondary metabolites present in many terrestrial plants. Natural triterpenoids have been reported\\u000a to exhibit anti-inflammatory and anti-carcinogenic activities. Here, we show that modifications of ring A of boswellic acid\\u000a (2 cyano, 3 enone) resulted in a highly active growth inhibitory, anti-inflammatory, pro-differentiative and anti-tumour triterpenoid\\u000a compound called cyano enone of methyl boswellates (CEMB). This compound showed cytotoxic

Palaniyandi Ravanan; Sanjay K Singh; G S R Subba Rao; Paturu Kondaiah

177

Non-steroidal Anti-inflammatory Drugs and Hypertension.  

PubMed

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to alleviate pain of the patients who suffer from inflammatory conditions like rheumatoid arthritis, osteoarthritis, and other painful conditions like gout. This class of drugs works by blocking cyclooxgenases which in turn block the prostaglandin production in the body. Most often, NSAIDs and antihypertensive drugs are used at the same time, and their use increases with increasing age. Moreover, hypertension and arthritis are common in the elderly patients requiring pharmacological managements. An ample amount of studies put forth evidence that NSAIDs reduce the efficiency of antihypertensive drugs plus aggravate pre-existing hypertension or make the individuals prone to develop high blood pressure through renal dysfunction. This review will help doctors to consider the effects and risk factors of concomitant prescription of NSAIDs and hypertensive drugs. PMID:24242190

Zheng, Liuying; Du, Xinping

2014-06-01

178

Anti-inflammatory and anticancer drugs from nature.  

PubMed

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

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

2014-01-01

179

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.

2012-01-01

180

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.

2013-01-01

181

Anti-inflammatory triterpenoids from mysterious mushroom Ganoderma lucidum and their potential possibility in modern medicine.  

PubMed

Ganoderma lucidum, a mushroom long used in the East for a broad range of disorders, contains numerous pharmacologically active compounds. Very important of them are highly oxygenated anti-inflammatory triterpenes, which are the aim of this mini-review. PMID:10812678

Patocka, J

1999-01-01

182

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.

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

2012-01-01

183

Anti-Inflammatory and Antipruritic Effects of Luteolin from Perilla (P. frutescens L.) Leaves.  

PubMed

Perilla (Perilla frutescens L.) leaves have shown therapeutic efficacy in the treatment of inflammatory disorders, allergies, bronchial asthma, and systemic damage due to free radicals. In the present study we analyzed the active constituents in perilla leaves using high-performance liquid chromatography (HPLC) and isolated luteolin, a polyphenolic flavonoid. We investigated the anti-inflammatory and antipruritic properties of luteolin. Luteolin inhibited the secretion of inflammatory cytokines such as interleukin-1? (IL-1 ?) and tumor necrosis factor-? (TNF-?) from human mast cells (HMC-1) stimulated with phorbol myristate acetate plus calcium ionophore A23187 in a dose-dependent manner. Luteolin also significantly reduced the histamine release from rat peritoneal mast cells stimulated by compound 48/80, a potent histamine liberator. Furthermore, the administration of luteolin markedly inhibited the scratching behavior and vascular permeability induced by pruritogens, such as compound 48/80 or serotonin, in ICR mice. These results suggested that luteolin has potential as a therapeutic agent against inflammation and itch-related skin diseases. PMID:24871572

Jeon, In Hwa; Kim, Hyeon Soo; Kang, Hyun Ju; Lee, Hyun-Seo; Jeong, Seung Il; Kim, Sang Jun; Jang, Seon Il

2014-01-01

184

Anti-inflammatory activity of arctigenin from Forsythiae Fructus  

Microsoft Academic Search

Oleaceae Forsythiae Fructus has been used for anti-inflammatory, diuretics, antidote, and antibacterials in traditional herbal medicine. Our previous screening of medicinal plants showed that methanol (MeOH) extract of Forsythiae Fructus had significant anti-inflammatory activity, but the active ingredients remain unclear. For isolation of active ingredient of MeOH extract of Forsythiae Fructus, it was partitioned with n-hexane and ethylacetate (EtOAc), and

Hyo Sook Kang; Ji Yun Lee; Chang Jong Kim

2008-01-01

185

New anti-inflammatory formulation containing Synurus deltoides extract  

Microsoft Academic Search

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong\\u000a analgesic activityin vivo. In this study, new anti-inflammatory formulation containingS. deltoides extract as a major ingredient was prepared andin vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part ofS. deltoides extract, 0.9 part ofAngelica gigas

Yong Hwan Choi; Kun Ho Son; Hyeun Wook Chang; KiHwan Bae; Sam Sik Kang; Hyun Pyo Kim

2005-01-01

186

Feijoa sellowiana Berg fruit juice: anti-inflammatory effect and activity on superoxide anion generation.  

PubMed

Feijoa sellowiana Berg var. coolidge fruit juice was studied in vivo for the anti-inflammatory activity by carrageenin-induced paw edema test and in vitro for the effects on superoxide anion release from neutrophils in human whole blood. The fruit juice was analyzed by the high-performance liquid chromatography method, and quercetin, ellagic acid, catechin, rutin, eriodictyol, gallic acid, pyrocatechol, syringic acid, and eriocitrin were identified. The results showed a significant anti-inflammatory activity of F. sellowiana fruit juice, sustained also by an effective antioxidant activity observed in preliminary studies on 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. In particular, the anti-inflammatory activity edema inhibition is significant since the first hour (44.11%) and persists until the fifth hour (44.12%) of the treatment. The effect on superoxide anion release was studied in human whole blood, in the presence of activators affecting neutrophils by different mechanisms. The juice showed an inhibiting response on neutrophils basal activity in all experimental conditions. In stimulated neutrophils, the higher inhibition of superoxide anion generation was observed at concentration of 10(-4) and 10(-2) mg/mL in whole blood stimulate with phorbol-myristate-13-acetate (PMA; 20% and 40%) and with N-formyl-methionyl-leucyl-phenylalanine (FMLP; 15% and 48%). The significant reduction of edema and the inhibition of O2(-) production, occurring mainly through interaction with protein-kinase C pathway, confirm the anti-inflammatory effect of F. sellowiana fruit juice. PMID:24433073

Monforte, Maria T; Fimiani, Vincenzo; Lanuzza, Francesco; Naccari, Clara; Restuccia, Salvatore; Galati, Enza M

2014-04-01

187

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

PubMed

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

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

2013-11-20

188

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

PubMed

In addition to antibacterial activity, some macrolide antibiotics, such as azithromycin and clarithromycin, also exhibit anti-inflammatory properties in vitro and in vivo, although the targets and mechanism(s) of action remain unknown. The aim of the present study was to identify protein targets of azithromycin and clarithromycin which could potentially explain their anti-inflammatory effects. Using chemical proteomics approach, based on compound-immobilized affinity chromatography, valosin containing protein (VCP) was identified as a potential target of the macrolides. Validation studies confirmed the interaction of macrolides and VCP and gave some structural characteristics of this interaction. Cell based assays however, including the use of gene silencing and the study of VCP specific cellular functions in J774.A1 (murine macrophage) and IB3-1 (human cystic fibrotic epithelial) cell lines, failed to confirm an association between the binding of the macrolides to VCP and anti-inflammatory effects. These findings suggest the absence of an abundant high affinity protein target and the potential involvement of other biological molecules in the anti-inflammatory activity of macrolides. PMID:22209877

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

2012-02-29

189

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

PubMed Central

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

van der Velden, V H

1998-01-01

190

Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity.  

PubMed

Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses; however few studies have sought to identify the active phytochemical(s) in oat that mediate this anti-inflammatory activity. Avenanthramides are phenolic compounds present in oats at approximately 300 parts per million (ppm) and have been reported to exhibit anti-oxidant activity in various cell-types. In the current study we investigated whether these compounds exert anti-inflammatory activity in the skin. We found that avenanthramides at concentrations as low as 1 parts per billion inhibited the degradation of inhibitor of nuclear factor kappa B-alpha (IkappaB-alpha) in keratinocytes which correlated with decreased phosphorylation of p65 subunit of nuclear factor kappa B (NF-kappaB). Furthermore, cells treated with avenanthramides showed a significant inhibition of tumor necrosis factor-alpha (TNF-alpha) induced NF-kappaB luciferase activity and subsequent reduction of interleukin-8 (IL-8) release. Additionally, topical application of 1-3 ppm avenanthramides mitigated inflammation in murine models of contact hypersensitivity and neurogenic inflammation and reduced pruritogen-induced scratching in a murine itch model. Taken together these results demonstrate that avenanthramides are potent anti-inflammatory agents that appear to mediate the anti-irritant effects of oats. PMID:18461339

Sur, Runa; Nigam, Anu; Grote, Devon; Liebel, Frank; Southall, Michael D

2008-11-01

191

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

PubMed Central

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.

Mulla, WA; Kuchekar, SB; Thorat, VS; Chopade, AR; Kuchekar, BS

2010-01-01

192

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

193

Anti-inflammatory action of Pluchea sagittalis: involvement of an antioxidant mechanism.  

PubMed

Pluchea sagittalis, (Lam.) Cabr., a popular medicinal herb grown in South America, was studied for anti-inflammatory and antioxidant activities. The anti-edema action of P. sagittalis aqueous extract was assayed in different models of inflammation: 1) the mouse ear edema test induced by arachidonic acid and croton oil; 2) the rat hind-paw edema test produced by several inflammatory inductors: carrageenan, dextran, zymosan, platelet-activating factor (PAF) and arachidonic acid; 3) a subacute model based on the rat carrageenan air-pouch granuloma test. Blood leukocyte free radical production was measured by flow cytometry with 2',7'-dichlorofluorescin diacetate (DCFH-DA) in vivo, in rats with induced air-pouch granuloma, and in a model in vitro. stimulating leukocytes with hydrogen peroxide. The aqueous extract of P. sagittalis showed a marked anti-inflammatory effect in both ear edema tests, dextran and carrageenan hind-paw edemas and carrageenan air-pouch model. It also had a potent antioxidant activity in blood leukocytes, both in vivo and in vitro. Our results correlate the reduction of free radical production with the anti-inflammatory effect of this plant. PMID:8950305

Pérez-García, F; Marín, E; Cańigueral, S; Adzet, T

1996-01-01

194

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.

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

2011-01-01

195

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

Microsoft Academic Search

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

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

2012-01-01

196

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

PubMed Central

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

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

2010-01-01

197

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

Microsoft Academic Search

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

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

2009-01-01

198

Anti-inflammatory activity of parthenolide-depleted Feverfew (Tanacetum parthenium).  

PubMed

Extracts of Tanacetum parthenium (L.) Sch. Bip., a plant known under the common name "Feverfew", contains the sesquiterpene lactone parthenolide, a potent skin sensitizer. To eliminate the risk of skin sensitization from Feverfew, we developed a parthenolide-depleted extract of Feverfew (PD-Feverfew) and determined its effectiveness as an anti-inflammatory agent. We confirmed that PD-Feverfew was sufficiently depleted of parthenolide since PD-Feverfew did not inhibit TNF-alpha induced-NF-kappaB activity unlike parthenolide containing whole Feverfew. PD-Feverfew directly inhibited the activity of pro-inflammatory enzymes 5-lipoxygenase, phosphodiesterase-3 and phosphodiesterase-4. PD-Feverfew inhibited the release of pro-inflammatory mediators nitric oxide, PGE(2) and TNF-alpha from macrophages and TNF-alpha, IL-2, IFN-gamma and IL-4 from human peripheral blood mononuclear cells. Additionally, PD-Feverfew inhibited TPA-induced release of PGE(2) from human skin equivalents. In vivo, PD-Feverfew inhibited oxazolone-induced dermatitis, and was more potent than whole Feverfew in reducing TPA-induced dermatitis. Finally the efficacy of PD-Feverfew was confirmed clinically by a reduction in erythema in a methyl nicotinate-induced vasodilation model. In conclusion, our results indicate that PD-Feverfew extracts have potent anti-inflammatory activity suggesting that this botanical would be efficacious in relieving inflammation without inducing immune sensitization. PMID:19112586

Sur, R; Martin, K; Liebel, F; Lyte, P; Shapiro, S; Southall, M

2009-02-01

199

Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects.  

PubMed

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 (NaIO(4))-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

200

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.

Cianciolo, George J.; Pizzo, Salvatore V.

2012-01-01

201

Acetone has anti-inflammatory effects on experimental contact reactions.  

PubMed

The effects of a topically applied corticosteroid and its acetone vehicle on experimental allergic, toxic and irritant reactions are presented. The corticosteroid budesonide in acetone or acetone alone was applied to reactions immediately after and at different time intervals within the 1st h after provocation. Classical naked eye observation was performed and the dermal cellular infiltrate was differentiated and counted using a previously well-characterized method. "Treatment", whether with the steroid in acetone or acetone alone, had anti-inflammatory effects. For all reaction types, erythema and oedema diminished and a significant decrease in mononuclear cells was seen, when application occurred within the first 5 min after provocation. The effects were most marked for the toxic reaction to croton oil, the steroid and the vehicle being anti-inflammatory to the same extent. Application up to 60 min after provocation had anti-inflammatory effects for this reaction type. The mechanisms of acetone's anti-inflammatory effects are at present unclear. One possible explanation is that intercellular lipid organisation and, by extension, cellular membrane lipid organisation, are altered, influencing membrane receptor function. Possible anti-inflammatory effects of acetone should be considered in experimental and perhaps even clinical situations. Further investigation of the therapeutic possibilities of the finding seems warranted. PMID:10416704

Sjögren, F; Groth, O; Anderson, C

1999-07-01

202

Lyprinol--Is It a Useful Anti-Inflammatory Agent?  

PubMed Central

The New Zealand green lipped mussel preparation Lyprinol is available without a prescription from a supermarket, pharmacy or Web. The Food and Drug Administration have recently warned Lyprinol USA about their extravagant anti-inflammatory claims for Lyprinol appearing on the web. These claims are put to thorough review. Lyprinol does have anti-inflammatory mechanisms, and has anti-inflammatory effects in some animal models of inflammation. Lyprinol may have benefits in dogs with arthritis. There are design problems with the clinical trials of Lyprinol in humans as an anti-inflammatory agent in osteoarthritis and rheumatoid arthritis, making it difficult to give a definite answer to how effective Lyprinol is in these conditions, but any benefit is small. Lyprinol also has a small benefit in atopic allergy. As anti-inflammatory agents, there is little to choose between Lyprinol and fish oil. No adverse effects have been reported with Lyprinol. Thus, although it is difficult to conclude whether Lyprinol does much good, it can be concluded that Lyprinol probably does no major harm.

Doggrell, Sheila A.

2011-01-01

203

Modeling Natural Anti-Inflammatory Compounds by Molecular Topology  

PubMed Central

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

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

2011-01-01

204

Lyprinol-is it a useful anti-inflammatory agent?  

PubMed

The New Zealand green lipped mussel preparation Lyprinol is available without a prescription from a supermarket, pharmacy or Web. The Food and Drug Administration have recently warned Lyprinol USA about their extravagant anti-inflammatory claims for Lyprinol appearing on the web. These claims are put to thorough review. Lyprinol does have anti-inflammatory mechanisms, and has anti-inflammatory effects in some animal models of inflammation. Lyprinol may have benefits in dogs with arthritis. There are design problems with the clinical trials of Lyprinol in humans as an anti-inflammatory agent in osteoarthritis and rheumatoid arthritis, making it difficult to give a definite answer to how effective Lyprinol is in these conditions, but any benefit is small. Lyprinol also has a small benefit in atopic allergy. As anti-inflammatory agents, there is little to choose between Lyprinol and fish oil. No adverse effects have been reported with Lyprinol. Thus, although it is difficult to conclude whether Lyprinol does much good, it can be concluded that Lyprinol probably does no major harm. PMID:19383840

Doggrell, Sheila A

2011-01-01

205

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

PubMed

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

2011-10-18

206

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

PubMed Central

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

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

2012-01-01

207

IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.  

PubMed

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

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

2012-01-01

208

Evaluation of anti-inflammatory activity of Solanum xanthocarpum Schrad and Wendl (Ka??ak?ri) extract in laboratory animals  

PubMed Central

Context: Solanum xanthocarpum Schrad and Wendl (Ka??ak?ri) is a diffuse herb with prickly stem, traditionally used for the treatment of inflammation and one in the group of da?am?la (group of ten herbs) herbs commonly used drug in Ayurveda. Aims: In continuation of search for potent natural anti-inflammatory agents, the present research work was planned to evaluate the anti-inflammatory activity of ethanol extract of S. xanthocarpum whole plant. Settings and Design: The ethanol extract was evaluated at dose 10, 30 and 100 mg/kg p.o. in rats. Materials and Methods: Using pharmacological screening models carrageenan induced rat paw edema, histamine induced rat paw edema and cotton pellet granuloma in rats. Statistical Analysis Used: Data obtained was analyzed statistically using analysis of variance followed by post-hoc Dunnett test, P < 0.05 is considered as statistically significant. Results: Acute treatment didn’t show anti-inflammatory activity against carrageenan and histamine induced paw edema. However, administration of 100 mg/kg p.o for 7 day reduced the granuloma formation in cotton pellet granuloma model. Conclusions: Present results support the traditional use of plant for anti-inflammatory activity. In brief, the results provide scientific pharmacological basis for the therapeutic use of S. xanthocarpum.

More, Shraddha K.; Lande, Anirudha A.; Jagdale, Priti G.; Adkar, Prafulla P.; Ambavade, Shirishkumar D.

2013-01-01

209

Anti-inflammatory effects of 81 chinese herb extracts and their correlation with the characteristics of traditional chinese medicine.  

PubMed

Inducible nitrogen oxide synthase (iNOS) is the primary contributor of the overproduction of nitric oxide and its inhibitors have been actively sought as effective anti-inflammatory agents. In this study, we prepared 70% ethanol extracts from 81 Chinese herbs. These extracts were subsequently evaluated for their effect on nitrogen oxide (NO) production and cell growth in LPS/IFN?-costimulated and unstimulated murine macrophage RAW264.7 cells by Griess reaction and MTT assay. Extracts of Daphne genkwa Sieb.et Zucc, Caesalpinia sappan L., Iles pubescens Hook.et Arn, Forsythia suspensa (Thunb.) Vahl, Zingiber officinale Rosc, Inula japonica Thunb., and Ligusticum chuanxiong Hort markedly inhibited NO production (inhibition > 90% at 100??g/mL). Among active extracts (inhibition > 50% at 100??g/mL), Rubia cordifolia L., Glycyrrhiza glabra L., Iles pubescens Hook.et Arn, Nigella glandulifera Freyn et Sint, Pueraria lobata (Willd.) Ohwi, and Scutellaria barbata D. Don displayed no cytotoxicity to unstimulated RAW246.7 cells while increasing the growth of LPS/IFN?-costimulated cells. By analyzing the correlation between their activities and their Traditional Chinese Medicine (TCM) characteristics, herbs with pungent flavor displayed potent anti-inflammatory capability. Our study provides a series of potential anti-inflammatory herbs and suggests that herbs with pungent flavor are candidates of effective anti-inflammatory agents. PMID:24696703

Chen, Chang-Liang; Zhang, Dan-Dan

2014-01-01

210

Anti-Inflammatory Effects of 81 Chinese Herb Extracts and Their Correlation with the Characteristics of Traditional Chinese Medicine  

PubMed Central

Inducible nitrogen oxide synthase (iNOS) is the primary contributor of the overproduction of nitric oxide and its inhibitors have been actively sought as effective anti-inflammatory agents. In this study, we prepared 70% ethanol extracts from 81 Chinese herbs. These extracts were subsequently evaluated for their effect on nitrogen oxide (NO) production and cell growth in LPS/IFN?-costimulated and unstimulated murine macrophage RAW264.7 cells by Griess reaction and MTT assay. Extracts of Daphne genkwa Sieb.et Zucc, Caesalpinia sappan L., Iles pubescens Hook.et Arn, Forsythia suspensa (Thunb.) Vahl, Zingiber officinale Rosc, Inula japonica Thunb., and Ligusticum chuanxiong Hort markedly inhibited NO production (inhibition > 90% at 100??g/mL). Among active extracts (inhibition > 50% at 100??g/mL), Rubia cordifolia L., Glycyrrhiza glabra L., Iles pubescens Hook.et Arn, Nigella glandulifera Freyn et Sint, Pueraria lobata (Willd.) Ohwi, and Scutellaria barbata D. Don displayed no cytotoxicity to unstimulated RAW246.7 cells while increasing the growth of LPS/IFN?-costimulated cells. By analyzing the correlation between their activities and their Traditional Chinese Medicine (TCM) characteristics, herbs with pungent flavor displayed potent anti-inflammatory capability. Our study provides a series of potential anti-inflammatory herbs and suggests that herbs with pungent flavor are candidates of effective anti-inflammatory agents.

Chen, Chang-Liang; Zhang, Dan-Dan

2014-01-01

211

Interaction of the Anti-Inflammatory Annexin A1 Protein and Tacrolimus Immunosuppressant in the Renal Function of Rats  

Microsoft Academic Search

Background: Tacrolimus (FK) is currently widely used in transplant immunosuppression and the treatment of autoimmune diseases. However, FK induces nephrotoxicity which is characterized by functional and structural renal injury. The ubiquitous protein annexin A1 (ANXA1) has potent anti-inflammatory effects and protects against ischemia\\/reperfusion injury. We investigated the effects of exogenous ANXA1 treatment in an experimental model of acute FK nephrotoxicity.

Leandro P. Araujo; Renata R. Truzzi; Gloria E. Mendes; Marcus A. M. Luz; Emmanuel A. Burdmann; Sonia M. Oliani

2010-01-01

212

Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype  

Microsoft Academic Search

BACKGROUND: Luteolin, a plant derived flavonoid, exerts a variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen and nitrogen species. Luteolin also shows potent anti-inflammatory activities by inhibiting nuclear factor kappa B (NFkB) signaling in immune cells. To better understand the immuno-modulatory effects of this important flavonoid, we performed a genome-wide expression analysis in pro-inflammatory

Konstantin Dirscherl; Marcus Karlstetter; Stefanie Ebert; Dominik Kraus; Julia Hlawatsch; Yana Walczak; Christoph Moehle; Rudolf Fuchshofer; Thomas Langmann

2010-01-01

213

Evaluation of anti-inflammatory and antioxidant activities of Peltigera rufescens lichen species in acute and chronic inflammation models  

Microsoft Academic Search

The anti-inflammatory effects of the methanol extract of the lichen species Peltigera rufescens (Weis.) Humb (MEPR) (Peltigeraceae) on acute (carrageenan-induced) and chronic (cotton pellet granule) phases of inflammation\\u000a were investigated. The MEPR was capable of reducing carrageenan-induced inflammation and showed a potent antiproliferative\\u000a effect (63.5%) in the chronic inflammation model. Inflammation is related to neutrophil infiltration and the production of

Sevil Tanas; Fehmi Odabasoglu; Zekai Halici; Ahmet Cakir; Hayati Aygun; Ali Aslan; Halis Suleyman

2010-01-01

214

Isolation and characterization of novel protein with anti-fungal and anti-inflammatory properties from Aloe vera leaf gel  

Microsoft Academic Search

The Aloe protein of 14kDa from the Aloe vera leaf gel was isolated by an ion exchange chromatography using DEAE-cellulose and CM-cellulose column. The purified Aloe protein exhibited a potent anti-fungal activity against Candida paraprilosis, Candida krusei and Candida albicans. In addition, the purified Aloe protein also showed an anti-inflammatory property against pure lipoxygenase and cyclooxygenase-2 with 84% and 73%

Swagata Das; Biswajit Mishra; Kamaldeep Gill; Abhay Kumar Singh; Mou Sinha; Sujata Sharma; Immaculata Xess; Krishna Dalal; Tej Pal Singh; Sharmistha Dey

2011-01-01

215

N-amino acid linoleoyl conjugates: anti-inflammatory activities  

PubMed Central

Several N-linked amino acid-linoleic acid conjugates were studied for their potential as anti inflammatory agents. The parent molecule, N-linoleoylglycine was tested in an in vivo model, the mouse peritonitis assay where it showed activity in reducing leukocyte migration at doses as low as 0.3 mg/kg when administered by mouth in safflower oil. Harvested peritoneal cells produced elevated levels of the inflammation- resolving eicosanoid 15-deoxy-?13,14-PGJ2. These results are similar to those obtained in earlier studies with N-arachidonoylglycine. An in vitro model using mouse macrophage RAW cells was used to evaluate a small group of structural analogs for their ability to stimulate 15-deoxy-?13,14-PGJ2 production. The D-alanine derivative was the most active while the D-phenylalanine showed almost no response. A high degree of stereo specificity was observed comparing the D and L alanine isomers; the latter being the less active. It was concluded that linoleic acid conjugates could provide suitable templates in a drug discovery program leading to novel agents for promoting the resolution of chronic inflammation.

Burstein, Sumner; McQuain, Catherine; Salmonsen, Rebecca; Seicol, Benjamin

2012-01-01

216

Anti-inflammatory activity of some Saudi Arabian medicinal plants.  

PubMed

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

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

1986-01-01

217

Anti-inflammatory new coumarin from the Ammi majus L  

PubMed Central

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

2012-01-01

218

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

219

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.

2014-01-01

220

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

221

Anti-inflammatory and anti-ulcerogenic properties of Stachytarpheta cayennensis (L.C. Rich) Vahl  

Microsoft Academic Search

In the present work, the anti-inflammatory and gastroprotective properties of ethanolic extracts of Stachytarpheta cayennesis (L.C. Rich) Vahl (Verbenaceae) were assessed. Chromatographic analysis of the crude ethanolic extract, SC01, revealed high concentrations of the iridoid ipolamiide, whereas the SC02, the second ethanolic extract, presented the arylpropanoid verbacoside as a major constituent. The oral administration of SC01 (100mg\\/kg) into Swiss mice

C. Penido; K. A. Costa; D. O. Futuro; S. R. Paiva; M. A. C. Kaplan; M. R. Figueiredo; M. G. M. O. Henriques

2006-01-01

222

Novel anti-inflammatory ?-3 PUFAs from the New Zealand green-lipped mussel, Perna canaliculus  

Microsoft Academic Search

The present study has identified in the marine mollusc, Perna canaliculus, an homologous series of novel omega 3 polyunsaturated fatty acids (?-3 PUFA) with significant anti-inflammatory (AI) activity. The free fatty acid (FFA) class was isolated from a supercritical-CO2 lipid extract of the tartaric acid-stabilised freeze-dried mussel powder by normal phase chromatography, followed by reversed-phase high performance liquid chromatography (RP–HPLC).

A. P. Treschow; L. D. Hodges; P. F. A. Wright; P. M. Wynne; N. Kalafatis; T. A. Macrides

2007-01-01

223

Non-steroidal anti-inflammatory drugs and peptic ulcer perforation  

Microsoft Academic Search

A retrospective study is reported in which the ingestion of non-steroidal anti-inflammatory drugs (NSAID) in 269 patients with perforated peptic ulceration and 269 age\\/sex matched controls admitted between 1973-1982 was compared. A highly significant statistical difference was found (p less than 0.001) in those aged over 65. There was no statistical difference, however, in those aged under 65. Furthermore we

D S Collier; J A Pain

1985-01-01

224

Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals  

Microsoft Academic Search

The antioxidant and anti-inflammatory activities of two transition metal complexes of bioflavonoid rutin, Fe(rut)Cl3 and Cu(rut)Cl2, were studied. It was found that Cu(rut)Cl2 was a highly efficient in vitro and ex vivo free radical scavenger that sharply decreased (by 2–30 times compared to the parent rutin): oxygen radical production by xanthine oxidase, rat liver microsomes, and rat peritoneal macrophages; the

Igor B Afanas’eva; Elena A Ostrakhovitch; Elena V Mikhal’chik; Galina A Ibragimova; Ludmila G Korkina

2001-01-01

225

The production of anti-inflammatory cytokines in whole blood by physico-chemical induction  

Microsoft Academic Search

Objective and design: Cytokines such as interleukin-1 (IL-1) play an important role in degenerative musculo-skeletal diseases, including osteoarthritis, and a multitude of inflammatory disorders. Agents that inhibit the action of such cytokines have a high therapeutic potential in such diseases. Here we describe a new method for enhancing the production of the interleukin-l receptor antagonist (IL-1Ra) and other anti-inflammatory cytokines

H. Meijer; J. Reinecke; C. Becker; G. Tholen; P. Wehling

2003-01-01

226

LCMS ANALYSIS OF SELECTED SULFUR-CONTAINING NONSTEROID ANTI-INFLAMMATORY AGENTS: APPLICATIONS TO PHARMACEUTICAL PRODUCTS  

Microsoft Academic Search

A rapid, specific, sensitive, and reproducible high performance liquid chromatography-mass spectrometric assay has been developed for the quantitation of five sulfur-containing non-steroid anti-inflammatory drugs (NSAIDs), namely, celecoxib (Cel), piroxicam (Per), rofecoxib (Rof), sulindac (Sul), and tenoxicam (Ten), in available tablets and capsules. The examined compounds were extracted from the dosage forms with methanol and chromatographed on a Shim-Pack column using

Mohammed E. Abdel-Hamid

2000-01-01

227

Phytochemical screening and anti-inflammatory actions of Alangium salviifolium root extract.  

PubMed

Alangium salviifolium root was screened for phytochemical and anti-inflammatory properties. The percentage inhibition of carrageenan induced paw oedema was studied in rats. Alangium salvifolium gave maximum extractive values with Ethanol and the Loss on Drying value, total ash value and acid-insoluble ash and water soluble ash values were within limits. The extract gave positive tests for phytosterols, triterpenes, flavonoids, carbohydrates and alkaloids. The extract was free from glycosides, saponins, tannins, proteins and amino acids. In acute toxicity studies, Alangium salviifolium root extract was found to be safe up to 3000?mg?kg?ą, p.o. in the albino rats. The Alangium salviifolium root gave significant per cent inhibition of the maximal paw oedema and very highly significant per cent inhibition of total paw oedema during 6?h. This study revealed that Alangium salviifolium root has good anti-inflammatory actions when compared with Diclofenac sodium. PMID:22008064

Ahad, Hindustan Abdul; Padmaja, B Suma; Sravanthi, M; Ramyasree, P; Kavitha, K

2012-01-01

228

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

229

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

PubMed Central

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

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

2010-01-01

230

Nonsteroidal anti-inflammatory drugs in early pregnancy  

Microsoft Academic Search

A study was performed of congenital malformations in infants whose mothers used nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy. Data were obtained from an ongoing prospective recording of drug use during the first trimester. During the period July 1, 1995 through December 31, 1998, 2557 infants were born to women who reported the use of NSAIDs in early pregnancy. The

Anders Ericson; Bengt A. J. Källén

2001-01-01

231

Anti-inflammatory activity of Indian black tea (Sikkim variety)  

Microsoft Academic Search

In this study, the anti-inflammatory (in reference to the cardinal signs of inflammation) and other related pharmacological activities of the hot water extract of black tea (Camellia sinensis, Sikkim variety) were evaluated along with certain standard drugs. The extract showed significant inhibitory activity against carrageenin, histamine, serotonin and prostaglandin-induced pedal inflammation. The extract inhibited exudative inflammation. The tea extract also

A. K. Nag Chaudhuri; Sanmoy Karmakar; Dilip Roy; Siddhartah Pal; Mintu Pal; Tuhinadri Sen

2005-01-01

232

Microglia Activation and Anti-inflammatory Regulation in Alzheimer's Disease  

PubMed Central

Inflammatory regulators, including endogenous anti-inflammatory systems, can down-regulate inflammation thus providing negative feedback. Chronic inflammation can result from imbalance between levels of inflammatory mediators and regulators during immune responses. As a consequence, there are heightened inflammatory responses and irreversible tissue damage associated with many age-related chronic diseases. Alzheimer's disease (AD) brain is marked by prominent inflammatory features, in which microglial activation is the driving force for the elaboration of an inflammatory cascade. How the regulation of inflammation loses its effectiveness during AD pathogenesis remains largely unclear. In this article, we will first review current knowledge of microglial activation and its association with AD pathology. We then discuss four examples of anti-inflammatory systems that could play a role in regulating microglial activation: CD200/CD200 receptor, vitamin D receptor, peroxisome proliferator-activated receptors, and soluble receptor for advanced glycation end products. Through this, we hope to illustrate the diverse aspects of inflammatory regulatory systems in brain and neurodegenerative diseases such as AD. We also propose the importance of neuronal defense systems, because they are part of the integral inflammatory and anti-inflammatory systems. Augmenting the anti-inflammatory defenses of neurons can be included in the strategy for restoration of balanced immune responses during aging and neurodegenerative diseases.

Kuo, Yu-Min; Beach, Thomas; Walker, Douglas G.

2010-01-01

233

Anti-inflammatory activity of some traditional medicinal plants.  

PubMed

The ethanol extract of roots, fruits and roots of solanum indicum and saccharum munja respectively and water soluble resin of commiphora myrrha were studied for antiinflammatory activity against carrageenin induced oedema in rats, the significant antiinflammatory activity were found in former two plants will slight anti inflammatory activity was observed in latter plant. PMID:22556885

Singh, R K; Joshi, V K; Gambhir, S S

1998-10-01

234

ANTI-INFLAMMATORY ACTIVITY OF SOME TRADITIONAL MEDICINAL PLANTS  

PubMed Central

The ethanol extract of roots, fruits and roots of solanum indicum and saccharum munja respectively and water soluble resin of commiphora myrrha were studied for antiinflammatory activity against carrageenin induced oedema in rats, the significant antiinflammatory activity were found in former two plants will slight anti inflammatory activity was observed in latter plant.

Singh, R.K.; Joshi, V.K.; Gambhir, S.S.

1998-01-01

235

Hepatocellular damage from non-steroidal anti-inflammatory drugs  

Microsoft Academic Search

Summary Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the management of rheumatological disorders, and as analgesics and antipyretics. Hepatotoxicity is an uncommon, but potentially lethal complication, which usually occurs within 12 weeks of starting therapy. It can occur with all NSAIDs, but appears to be more common with diclofenac and particularly sulindac. Female patients aged >50 years, with autoimmune

N. O'connor; P. I. DARGAN; A. L. JONES

2003-01-01

236

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

237

Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children  

Microsoft Academic Search

: Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction

Mona Iancovici Kidon; Liew Woei Kang; Chiang Wen Chin; Lim Siok Hoon; Van Bever Hugo

2007-01-01

238

Anti-inflammatory mechanism of inflamed-tissue factor  

Microsoft Academic Search

The early postulation that irritation of tissue could release a substance which acted as anti-inflammatory agent at a remote site of the body, led further to show that administration of inflammatory exudate results in suppression of experimental inflammations (Rindani [22], Robinson and Robson [23], Billingham, Robinson and Robson [2], Bonta and De Vos [6]). Little is known however as to

I. L. Bonta; J. Noordhoek

1973-01-01

239

Anti-inflammatory Activity of Some Essential Oils  

Microsoft Academic Search

There are many diseases that are associated with inflammation, such as infections by bacteria, virus and protozoa, autoimmune diseases such as arthritis and diabetes, Alzheimer's disease, and cancer. There are many medications available to prevent or minimize the progression of the inflammation; they include non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, but they have some secondary effects. Traditional medicine has been

Salud Pérez G; Miguel Zavala S; Lucina Arias G; Miguel Ramos L

2011-01-01

240

Determination of corticosteroids, anabolic steroids, and basic nonsteroidal anti-inflammatory drugs in milk and animal tissues.  

PubMed

A quantitative LC/MS/MS method was developed for the determination of 14 steroidal compounds and three basic nonsteroidal anti-inflammatory drugs (detected as metabolites) in bovine milk and animal muscle tissue. The proposed method is sufficiently sensitive and highly selective for residue applications. The described approach offers the possibility to detect, quantify, and confirm anti-inflammatory drugs belonging to two widely diverging chemical categories. The employed single-stage SPE step (mixed mode cation exchange) retains both steroids and basic metabolites of nonsteroidal anti-inflammatory drugs. The method is capable of handling widely diverging relevant concentration ranges (0.1 microg/kg for dexamethasone and 100 microg/kg for metamizol metabolites) for the individual compounds with a single extraction, cleanup, and LC/MS/MS procedure. It provides good analyte precision and accuracy data. PMID:24672888

Kaufmann, Anton; Butcher, Patrick; Maden, Kathryn; Walker, Stephan; Widmer, Mirjam

2014-01-01

241

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

242

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.

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

2013-01-01

243

Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs.  

PubMed Central

Many non-steroidal anti-inflammatory drugs (NSAIDs) (including sulphasalazine, sulindac, indomethacin, naproxen, salicylic acid, ibuprofen, piroxicam and mefenamic acid) were found to be competitive inhibitors (with respect to folate) of avian liver phosphoribosylaminoimidazolecarboxamide formyltransferase (AICAR transformylase, EC 2.1.2.3) and bovine liver dihydrofolate reductase (EC 1.5.1.3). In contrast, aspirin and the antipyretic-analgesic drugs acetaminophen and antipyrine were weak inhibitors of these enzymes. Structure-activity correlation suggests that an aromatic ring with a side chain containing a carboxylic acid is a requirement for competitive inhibition of the transformylase. The above-listed NSAIDs also inhibited the folate-coenzyme-mediated biosynthesis of serine from glycine and formate (i.e., the C1 index) by human blood mononuclear cells (BMCs) in experiments where the drug was added to a culture of BMCs. Acetaminophen had a weak inhibitory effect on the C1 index. Consistent with the results obtained in vitro is the observation that the C1 index of BMCs from rheumatoid-arthritis patients treated with drugs which possess little antifolate activity (e.g. acetaminophen) is higher than the C1 index of BMCs from rheumatoid-arthritis patients treated with NSAIDs possessing more potent antifolate activity (e.g. sulindac, sulphasalazine, naproxen and ibuprofen). The mean activity of the transformylase in BMCs taken from healthy humans was 1.98 nmol of product/h per 10(6) cells and the activity was positively correlated with BMC folate levels. These results are consistent with the hypothesis that (1) the antifolate activity of NSAIDs, and hence cytostatic consequences, are important factors in producing anti-inflammatory activity and (2) aspirin exerts its anti-inflammatory effects after its conversion into salicylic acid, which possesses greater antifolate activity than its parent compound.

Baggott, J E; Morgan, S L; Ha, T; Vaughn, W H; Hine, R J

1992-01-01

244

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.

Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

2014-01-01

245

Anti-oxidant, anti-inflammatory and immunomodulating properties of an enzymatic protein hydrolysate from yellow field pea seeds  

Microsoft Academic Search

Purpose  Enzymatic protein hydrolysates of yellow pea seed have been shown to possess high anti-oxidant and anti-bacterial activities.\\u000a The aim of this work was to confirm the anti-oxidant, anti-inflammatory and immunomodulating activities of an enzymatic protein\\u000a hydrolysate of yellow field pea seeds.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The anti-oxidant and anti-inflammatory properties of peptides from yellow field pea proteins (Pisum sativum L.) were investigated in LPS\\/IFN-?-activated

Fatou Ndiaye; Tri Vuong; Jairo Duarte; Rotimi E. Aluko; Chantal Matar

246

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

PubMed

The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOS(EtOH)). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOS(EtOH) was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOS(EtOH) exhibited antioxidative activity using the DPPH assay (IC(50), 0.743 mg/mL). The DPPH radical scavenging activity of MOS(EtOH) was five times higher that that of vitamin C. MOS(EtOH) was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOS(EtOH) (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl(4)-treated group. Histological evaluation showed that MOS(EtOH) reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOS(EtOH) were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOS(EtOH) has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOS(EtOH) for relieving pain and inflammation in folk medicine. PMID:23364614

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

2013-01-01

247

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

PubMed Central

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

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

2013-01-01

248

Cell-based screening assay for anti-inflammatory activity of bioactive compounds.  

PubMed

Excess dietary intake may induce metabolic inflammation which is associated with insulin resistance and cardiovascular disease. Recent evidence indicates that dietary bioactive compounds may diminish metabolic inflammation. To identify anti-inflammatory bioactives, we developed a screening assay using the human H293-NF-?B-RE-luc2P reporter cell line. Under optimised conditions we determined the anti-inflammatory activity of vegetables and purified bioactives, by monitoring their potency to inhibit TNF-?-induced NF-?B activity, as assessed by sensitive chemiluminescence detection in a 96-well assay format. Minced broccoli seedlings reduced NF-?B activity by 16%, while sulphoraphane, the dominant bioactive in broccoli seedlings, inhibited NF-?B activity with an IC50 of 5.11?mol/l. Short-chain fatty acids also reduced NF-?B activity in the order butyrate>propionate?acetate with IC50 of 51, 223, and 1300?mol/l, respectively. The H293-NF-?B-RE-luc2P reporter cell line is a sensitive tool for rapid high-throughput screening for bioactives with anti-inflammatory activity. PMID:25053041

Meijer, Kees; Vonk, Roel J; Priebe, Marion G; Roelofsen, Han

2015-01-01

249

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

250

Binary graft modification of polypropylene for anti-inflammatory drug-device combo products.  

PubMed

Temperature- and pH-responsive copolymers were ?-ray grafted onto polypropylene (PP) to provide its surface with capability to load and to control the release of nonsteroidal anti-inflammatory drugs (NSAIDs) with the aim of being useful as component of drug-eluting medical devices. Poly(N,N'-dimethylaminoethylmethacrylate) (PDMAEMA) or poly(4-vinylpyridine) (P4VP) were grafted onto PP films via a direct method, and then poly(N-isopropylacrylamide) (PNIPAAm) was grafted applying a preirradiation method. The binary graft copolymers showed hemocompatibility and certain capability to adsorb albumin. (PP-g-DMAEMA)-g-NIPAAm exhibited higher affinity for ibuprofen and, particularly, diclofenac than (PP-g-4VP)-g-NIPAAm. Sustained release was observed under physiological conditions. Cytotoxicity and anti-inflammatory activity of NSAID-eluting (PP-g-DMAEMA)-g-NIPAAm films were evaluated on RAW 264.7 macrophage cells. First, dose dependence of anti-inflammatory activity and cytotoxicity of ibuprofen and diclofenac on RAW 264.7 cells were investigated to elucidate the ranges of drug concentration that the graft copolymers should provide. Optimal concentrations of diclofenac and ibuprofen at which they reduce inflammation while maintaining cell viability were determined to be 200 ?g/mL and above 400 ?g/mL in culture medium. Sequential grafting of DMAEMA and NIPAAm made PP surface to exhibit remarkably high affinity to diclofenac, being able to load and to regulate drug release fulfilling in vitro requirements to avoid inflammatory response. PMID:24615379

Melendez-Ortiz, Hector Ivan; Díaz-Rodríguez, Patricia; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Bucio, Emilio

2014-04-01

251

Anti-inflammatory properties of culinary herbs and spices that ameliorate the effects of metabolic syndrome.  

PubMed

Obesity and metabolic syndrome are increasing global health problems. In addition to the malnutrition of a sedentary lifestyle, high calorie intake leads to obesity with many negative health consequences. Macrophages infiltrate adipose tissue and induce chronic inflammation by secreting pro-inflammatory cytokines, including COX-2 and iNOS, among other mediators of inflammation. Free fatty acids mediate adipose tissue signalling through toll-like receptor 4 and the expression of these pro-inflammatory mediators via NF-?B or JNK. PPAR ? activators can inhibit the activation of NF-?B, down-regulating the expression of pro-inflammatory cytokines. Here we provide an overview of how different culinary herbs and spices exert anti-inflammatory activities and the extent to which they activate PPAR ? and PPAR ?, inhibit the activation of NF-?B, and enhance expression of anti-inflammatory cytokines. Spices can play essential roles as anti-inflammatory agents in our diet, acting as pan PPAR activators and improving insulin sensitivity, counteracting dyslipidaemia and weight gain. The effects of chronic inflammation caused by obesity are counteracted and, consequently, the progression of diseases associated with chronic inflammation slowed. PMID:22226987

Jungbauer, Alois; Medjakovic, Svjetlana

2012-03-01

252

Synthesis and biological evaluation of curcumin-like diarylpentanoid analogues for anti-inflammatory, antioxidant and anti-tyrosinase activities.  

PubMed

A series of 46 curcumin related diarylpentanoid analogues were synthesized and evaluated for their anti-inflammatory, antioxidant and anti-tyrosinase activities. Among these compounds 2, 13 and 33 exhibited potent NO inhibitory effect on IFN-gamma/LPS-activated RAW 264.7 cells as compared to L-NAME and curcumin. However, these series of diarylpentanoid analogues were not significantly inhibiting NO scavenging, total radical scavenging and tyrosinase enzyme activities. The results revealed that the biological activity of these diarylpentanoid analogues is most likely due to their action mainly upon inflammatory mediator, inducible nitric oxide synthase (iNOS). The present results showed that compounds 2, 13 and 33 might serve as a useful starting point for the design of improved anti-inflammatory agents. PMID:19359068

Lee, Ka-Heng; Ab Aziz, Farida Haryani; Syahida, Ahmad; Abas, Faridah; Shaari, Khozirah; Israf, Daud Ahmad; Lajis, Nordin Haji

2009-08-01

253

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

PubMed

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

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

2012-01-01

254

Imaging the Efficacy of Anti-Inflammatory Liposomes in a Rabbit Model of Atherosclerosis by Non-Invasive Imaging  

PubMed Central

Nanomedicine can provide a potent alternative to current therapeutic strategies for atherosclerosis. For example, the encapsulation of anti-inflammatory drugs into liposomes improves their pharmacokinetics and biodistribution, thereby enhancing bioavailability to atherosclerotic plaques and improving therapeutic efficacy. The evaluation of this type of experimental therapeutics can greatly benefit from in vivo evaluation to assess biological changes, which can be performed by non-invasive imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Here, we will illustrate the methods for inducing atherosclerosis in a rabbit model, the production of anti-inflammatory liposomes and monitoring of therapeutic efficacy of experimental therapeutics with the above-mentioned imaging techniques.

Lobatto, Mark E.; Calcagno, Claudia; Metselaar, Josbert M.; Storm, Gert; Stroes, Erik S. G.; Fayad, Zahi A.; Mulder, Willem J. M.

2013-01-01

255

Isolation and characterization of novel protein with anti-fungal and anti-inflammatory properties from Aloe vera leaf gel.  

PubMed

The Aloe protein of 14 kDa from the Aloe vera leaf gel was isolated by an ion exchange chromatography using DEAE-cellulose and CM-cellulose column. The purified Aloe protein exhibited a potent anti-fungal activity against Candida paraprilosis, Candida krusei and Candida albicans. In addition, the purified Aloe protein also showed an anti-inflammatory property against pure lipoxygenase and cyclooxygenase-2 with 84% and 73% inhibition, respectively, and was verified by binding with these proteins by real time method by the phenomenon of surface plasmon resonance. This Aloe protein is a novel protein possessing antifungal and anti-inflammatory properties and thus sets a platform to be used as a medicinal plant product. PMID:20888359

Das, Swagata; Mishra, Biswajit; Gill, Kamaldeep; Ashraf, Md Saquib; Singh, Abhay Kumar; Sinha, Mou; Sharma, Sujata; Xess, Immaculata; Dalal, Krishna; Singh, Tej Pal; Dey, Sharmistha

2011-01-01

256

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

Microsoft Academic Search

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

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

1990-01-01

257

Anti-inflammatory, gastroprotective, and cytotoxic effects of Sideritis scardica extracts.  

PubMed

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and N-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 µg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity. PMID:22274814

Tadi?, Vanja M; Jeremic, Ivica; Dobric, Silva; Isakovic, Aleksandra; Markovic, Ivanka; Trajkovic, Vladimir; Bojovic, Dragica; Arsic, Ivana

2012-03-01

258

Differential inhibition of human prostaglandin endoperoxide synthase-1 and -2 by nonsteroidal anti-inflammatory drugs.  

PubMed

We have evaluated the selectivity in vitro of various conventional nonsteroidal anti-inflammatory drugs (NSAIDs) and new anti-inflammatory compounds (NS-398, L-745,337 and SC58125) in inhibiting the cyclooxygenase activity of platelet prostaglandin endoperoxide synthase (PGHS)-1 and monocyte PGHS-2 in a human whole blood assay. The effects of the compounds towards the cyclooxygenase activity of monocyte PGHS-2 induced in response to lipopolysaccharide (LPS) was evaluated by measuring the levels of PGE2 produced in plasma. The effects of the same inhibitors on platelet PGHS-1 activity were assessed by allowing 1-ml whole blood samples to clot at 37 degrees C for 1 h in the presence of the compounds and measuring immunoreactive TXB2 levels in serum. Under these experimental conditions, most compounds resulted equipotent towards the two isozymes. Differently, meloxicam, nimesulide and diclofenac were approximately 10- to 20-fold more potent in inhibiting the cyclooxygenase activity of monocyte PGHS-2 than platelet PGHS-1. L-745,337, NS-398 and SC58125 achieved selective inhibition of monocyte PGHS-2 (IC50, PGHS-1/IC50, PGHS-2: < 100) and may provide adequate tools to test the contribution of this novel pathway of arachidonate metabolism to human inflammatory disease and to verify the hypothesis that the common side-effects of NSAIDs are due primarily to their ability to affect the activity of PGHS-1. PMID:9444611

Patrignani, P; Panara, M R; Sciulli, M G; Santini, G; Renda, G; Patrono, C

1997-12-01

259

Topical anti-inflammatory activity of extracts and compounds from Hypericum perforatum L.  

PubMed

Three preparations of Hypericum perforatum L. (a hydroalcoholic extract, a lipophilic extract and an ethylacetic fraction) and the pure compounds hypericin, adhyperforin, amentoflavone, hyperoside, isoquercitrin, hyperforin dicyclohexylammonium (DHCA) salt and dicyclohexylamine were evaluated for their topical anti-inflammatory activity. H. perforatum preparations provoked a dose-dependent reduction of Croton-oil-induced ear oedema in mice, showing the following rank order of activity: lipophilic extract > ethylacetic fraction > hydroalcoholic extract (ID50 (dose that inhibited oedema by 50%) 220, 267 and >1000 microg cm(-2), respectively). Amentoflavone (ID50 0.16 micromol cm(-2)), hypericin (ID50 0.25 micromol cm(-2)), hyperforin DHCA salt (ID50 0.25 micromol cm(-2)) and adhyperofrin (ID50 0.30 micromol cm(-2)) had anti-inflammatory activity that was more potent or comparable to that of indometacin (ID50 0.26 micromol cm(-2)), whereas isoquercitrin and hyperoside were less active (ID50 about 1 micromol cm(-2)). As dicyclohexylamine alone was inactive, the effect of hyperforin DHCA salt can be attributed completely to the phloroglucinol moiety. The pharmacological activity and phytochemical profile of the tested extracts and fraction suggest that different constituents are involved in the topical antiphlogistic property of H. perforatum in-vivo. PMID:17524236

Sosa, Silvio; Pace, Roberto; Bornancin, Anna; Morazzoni, Paolo; Riva, Antonella; Tubaro, Aurelia; Della Loggia, Roberto

2007-05-01

260

[Anti-inflammatory activity of the dry distillation tar of delipidated soybean (Glyteer) (2)].  

PubMed

The anti-inflammatory effects of Glyteer (GL) were investigated by its local administration using the CMC-pouch method in rats, and the effects were compared with those of betamethasone 17-valerate (BV, 1 mg), phenylbutazone (PB, 10 mg), flufenamic acid (FA, 10 mg), bufexamac (BM, 10 and 20 mg), bendazac (BZ, 10 and 20 mg), icthammol (IT, 10 mg) and pine tar (PT, 10 mg). At three hours after CMC-treatment, GL (10 mg) significantly inhibited not only the protein exudation, but also the leucocyte migration. The inhibitory activity of GL on the leucocyte migration had the same potency as that of FA, but was stronger than those of PB, BV, BM, BZ, IT and PT. Furthermore, in relation to the leucocyte migration, GL markedly inhibited not only the neutrophil, but also the macrophage migration. At three hours after CMC-treatment, the inhibitory activity of GL on the neutrophil migration had the same potency as those of PB and FA, but was stronger than those of BV, BM, BZ, IT and PT. On the other hand, GL, BM, BZ, FA, IT and PT had an inhibitory activity on the macrophage migration, and the activity was more potent in GL, FA and IT. From these results, it is suggested that the inhibition of GL on increased vascular permeability and leucocyte migration is one of the mechanisms of its anti-inflammatory action. PMID:3371789

Takeuchi, K; Ito, K; Namikawa, S

1988-01-01

261

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

PubMed

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

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

1979-04-20

262

Anti-inflammatory and chondroprotective activity of (+)-?-pinene: structural and enantiomeric selectivity.  

PubMed

Previous studies have suggested that ?-pinene, a common volatile plant metabolite, may have anti-inflammatory effects in human chondrocytes, thus exhibiting potential antiosteoarthritic activity. The objective of this study was to further characterize the potential antiosteoarthritic activity of selected pinene derivatives by evaluating their ability to modulate inflammation and extracellular matrix remodeling in human chondrocytes and to correlate the biological and chemical properties by determining whether the effects are isomer- and/or enantiomer-selective. To further elucidate chemicopharmacological interactions, the activities of other naturally occurring monoterpenes with the pinane nucleus were also investigated. At noncytotoxic concentrations, (+)-?-pinene (1) elicited the most potent inhibition of the IL-1?-induced inflammatory and catabolic pathways, namely, NF-?B and JNK activation and the expression of the inflammatory (iNOS) and catabolic (MMP-1 and -13) genes. (-)-?-Pinene (2) was less active than the (+)-enantiomer (1), and ?-pinene (3) was inactive. E-Pinane (4) and oxygenated pinane-derived compounds, pinocarveol (5), myrtenal (6), (E)-myrtanol (7), myrtenol (8), and (Z)-verbenol (9), were less effective or even completely inactive and more cytotoxic than the pinenes tested (1-3). The data obtained show isomer- and enantiomer-selective anti-inflammatory and anticatabolic effects of ?-pinene in human chondrocytes, (+)-?-pinene (1) being the most promising for further studies to determine its potential value as an antiosteoarthritic drug. PMID:24455984

Rufino, Ana T; Ribeiro, Madalena; Judas, Fernando; Salgueiro, Lígia; Lopes, Maria C; Cavaleiro, Carlos; Mendes, Alexandrina F

2014-02-28

263

Secondary metabolites of ponderosa lemon (Citrus pyriformis) and their antioxidant, anti-inflammatory, and cytotoxic activities.  

PubMed

Column chromatography of the dichloromethane fraction from an aqueous methanolic extract of fruit peel of Citrus pyriformis Hassk. (Rutaceae) resulted in the isolation of seven compounds including one coumarin (citropten), two limonoids (limonin and deacetylnomilin), and four sterols (stigmasterol, ergosterol, sitosteryl-3-beta-D-glucoside, and sitosteryl-6'-O-acyl-3-beta-D-glucoside). From the ethyl acetate fraction naringin, hesperidin, and neohesperidin were isolated. The dichloromethane extract of the defatted seeds contained three additional compounds, nomilin, ichangin, and cholesterol. The isolated compounds were identified by MS (EI, CI, and ESI), 1H, 13C, and 2D-NMR spectral data. The limonoids were determined qualitatively by LC-ESI/MS resulting in the identification of 11 limonoid aglycones. The total methanolic extract of the peel and the petroleum ether, dichloromethane, and ethyl acetate fractions were screened for their antioxidant and anti-inflammatory activities. The ethyl acetate fraction exhibited a significant scavenging activity for DPPH free radicals (IC50 = 132.3 microg/mL). The petroleum ether fraction inhibited 5-lipoxygenase with IC50 = 30.6 microg/mL indicating potential anti-inflammatory properties. Limonin has a potent cytotoxic effect against COS7 cells [IC50 = (35.0 +/- 6.1) microM] compared with acteoside as a positive control [IC50 = (144.5 +/- 10.96) microM]. PMID:21950163

Hamdan, Dalia; El-Readi, Mahmoud Zaki; Tahrani, Ahmad; Herrmann, Florian; Kaufmann, Dorothea; Farrag, Nawal; El-Shazly, Assem; Wink, Michael

2011-01-01

264

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

265

Anti-inflammatory and antipyretic effects of boldine.  

PubMed

Boldine, an antioxidant alkaloid isolated from Peumus boldus, exhibits a dose-dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED50 of 34 mg/kg. Boldine also reduces bacterial pyrogen-induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg/kg p.o. In vitro studies carried out in rat aortal rings revealed that boldine is an effective inhibitor of prostaglandin biosynthesis, promoting 53% inhibition at 75 microM. The latter in vitro effect may be mechanistically linked to the anti-inflammatory and antipyretic effects of boldine exerted in vivo. PMID:7879695

Backhouse, N; Delporte, C; Givernau, M; Cassels, B K; Valenzuela, A; Speisky, H

1994-10-01

266

Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases  

PubMed Central

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

Ishiguro, Hitoshi; Kawahara, Takashi

2014-01-01

267

Antibiotic and anti-inflammatory therapies for cystic fibrosis.  

PubMed

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

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

2013-10-01

268

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

PubMed Central

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

2013-01-01

269

Anti-Inflammatory Therapy in Chronic Disease: Challenges and Opportunities  

PubMed Central

A number of widespread and devastating chronic diseases, including atherosclerosis, type 2 diabetes, and Alzheimer’s disease, have a pathophysiologically important inflammatory component. In these diseases, the precise identity of the inflammatory stimulus is often unknown and, if known, is difficult to remove. Thus, there is interest in therapeutically targeting the inflammatory response. Although there has been success with anti-inflammatory therapy in chronic diseases triggered by primary inflammation dysregulation or autoimmunity, there are considerable limitations. In particular, the inflammatory response is critical for survival. As a result, redundancy, compensatory pathways, and necessity narrow the risk:benefit ratio of anti-inflammatory drugs. However, new advances in understanding inflammatory signaling and its links to resolution pathways, together with new drug development, offer promise in this area of translational biomedical research.

Tabas, Ira; Glass, Christopher K.

2013-01-01

270

Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach  

PubMed Central

The design of new drugs with better physiochemical properties, adequate absorption, distribution, metabolism, and excretion, effective pharmacologic potency and lacking toxicity remains is a challenge. Inflammation is the initial trigger of several different diseases, such as Alzheimer's disease, asthma, atherosclerosis, colitis, rheumatoid arthritis, depression, cancer; and disorders such as obesity and sexual dysfunction. Although inflammation is not the direct cause of these disorders, inflammatory processes often increase related pain and suffering. New anti-inflammatory drugs developed using molecular hybridization techniques to obtain multiple-ligand drugs can act at one or multiple targets, allowing for synergic action and minimizing toxicity. This work is a review of new anti-inflammatory drugs developed using the molecular modification approach.

Bosquesi, Priscila Longhin; Melo, Thais Regina Ferreira; Vizioli, Ednir Oliveira; dos Santos, Jean Leandro; Chung, Man Chin

2011-01-01

271

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

272

Anti-inflammatory properties of micropatterned titanium coatings  

Microsoft Academic Search

Prolonged inflammation and reactive oxygen species (ROS) generated around an implanted biosensor are the primary causes of the foreign body response, including encapsulation of biosensor membranes. We have previously demonstrated that TiO2 surfaces reduce ROS. Here we in- vestigated the potential of using the anti-inflammatory properties of TiO2 in the design of biosensor membranes with improved long-term in vivo transport

Herman Sahlin; Ramiro Contreras; Daniel F. Gaskill; Lars M. Bjursten; John A. Frangos

2006-01-01

273

Hepatoprotective and anti-inflammatory activities of Plantago major L  

PubMed Central

Objective: The aim of this study was to investigate anti-inflammatory and hepatoprotective activities of Plantago major L. (PM). Materials and Methods: Anti-inflammatory activity: Control and reference groups were administered isotonic saline solution (ISS) and indomethacin, respectively. Plantago major groups were injected PM in doses of 5 mg/kg (PM-I), 10 mg/kg (PM-II), 20 mg/kg (PM-III) and 25 mg/kg (PM-IV). Before and three hours after the injections, the volume of right hind-paw of rats was measured using a plethysmometer. Hepatoprotective Activity: The hepatotoxicity was induced by carbon tetrachloride (CCl4) administration. Control, CCl4 and reference groups received isotonic saline solution, CCl4 and silibinin, respectively. Plantago major groups received CCl4 (0.8 ml/kg) and PM in doses of 10, 20 and 25 mg/kg, respectively for seven days. Blood samples and liver were collected on the 8th day after the animals were killed. Results: Plantago major had an anti-inflammatory effect matching to that of control group at doses of 20 and 25 mg/kg. It was found that reduction in the inflammation was 90.01% with indomethacin, 3.10% with PM-I, 41.56% with PM-II, 45.87% with PM-III and 49.76% with PM-IV. Median effective dose (ED50) value of PM was found to be 7.507 mg/kg. Plantago major (25 mg/kg) significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels when compared to the CCl4 group. The histopathological findings showed a significant difference between the PM (25 mg/kg) and CCl4 groups. Conclusion: The results showed that PM had a considerable anti-inflammatory and hepatoprotective activities.

Turel, Idris; Ozbek, Hanefi; Erten, Remzi; Oner, Ahmet Cihat; Cengiz, Nureddin; Yilmaz, Orhan

2009-01-01

274

Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update  

PubMed Central

After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal anti-inflammatory drugs are the second cause of hypersensitivity to drugs. Acute manifestations affect the respiratory tract (aspirin exacerbated respiratory disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis). Correct diagnosis and treatment in order to prevent unnecessary morbidity and the potential risk of death from these severe reactions, and to provide proper medical advice on future drug use frequently requires the participation of allergology specialists familiar with these clinical conditions.

Sanchez-Borges, Mario; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo; Gonzalez-Aveledo, Luis

2010-01-01

275

Anti-inflammatory and antipyretic effects of boldine  

Microsoft Academic Search

Boldine, and antioxidant alkaloid isolated fromPeumus boldus, exhibits a dose-dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED50 of 34 mg\\/kg. Boldine also reduces bacterial pyrogen-induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg\\/kg p.o.In vitro studies carried out in rat aortal rings revealed

N. Backhouse; C. Delporte; M. Givernau; B. K. Cassels; A. Valenzuela; H. Speisky

1994-01-01

276

Anti-inflammatory and antinociceptive activity of Thymus pubescens extract  

Microsoft Academic Search

Thymus pubescens is an aromatic and medicinal plant, which has been widely distributed in Iran. The anti-inflammatory and analgesic effects of the T. pubescens aerial parts methanol extract were studied at doses of 50–400 mg\\/kg i.p. using carrageenan-induced edema, formalin, hot plate and writhing tests. The extract produced a significant decrease in the degree of swelling, 3 h after carrageenan injection and

Mitra Mahmoudi; Katayoun Morteza-Semnani; Elham Mojra

2008-01-01

277

Granulomatous Interstitial Nephritis after Nonsteroidal Anti-Inflammatory Drugs  

Microsoft Academic Search

Electrolyte and renal hemodynamic imbalance, acute interstitial nephritis with nephrotic-range proteinuria, papillary necrosis, tubular necrosis, and vasculitis are complications after intake of nonsteroidal anti-inflammatory drugs (NSAID). We report on 2 cases of biopsy-proven granulomatous interstitial nephritis with rapidly progressing renal insufficiency. Patient 1 was on ketoprofen for 7 months and indomethacin for 10 weeks before admission to hospital. The medication

Anke Schwarz; Peter H. Krause; Frieder Keller; Gerd Offermann; Michael J. Mihatsch

1988-01-01

278

A Review of Non-Steroidal Anti-Inflammatory Drugs  

PubMed Central

An increasing number of non-steroidal anti-inflammatory drugs (NSAIDs) is available for clinical use each year. This article reviews significant differences between NSAIDs currently available in Canada, and helps the clinician to evaluate new NSAIDs. While their mechanism of action and efficacy are similar, side effects and cost vary considerably from one agent to another. Because all NSAIDs can produce adverse effects, patients, especially if they are elderly, should be selected carefully for treatment with a particular agent.

Rosenbloom, David; Craven, Marilyn A.

1983-01-01

279

Anti-inflammatory properties of diclofenac transition metalloelement complexes  

Microsoft Academic Search

As part of our research into understanding drug-metalloelement interactions, we have prepared complexes of Cu(II), Co(II), Ni(II), Mn(II), Fe(II), Fe(III), and Pd(II) with Diclofenac, in order to investigate their anti-inflammatory activity. Their inhibitory effects on rat or mouse paw edema induced by Carrageenan, Con-A, Nystatin, and Baker's yeast were compared with those of Diclofenac. Furthermore, the action of Diclofenac's metalloelement

Maria Konstandinidou; Angeliki Kourounakis; Minas Yiangou; Lygeri Hadjipetrou; Dimitra Kovala-Demertzi; Sotiris Hadjikakou; Mavroudis Demertzis

1998-01-01

280

Nonsteroidal anti-inflammatory drug-induced hepatoxicity.  

PubMed

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

Unzueta, Alberto; Vargas, Hugo E

2013-11-01

281

IL6 and APPs: anti-inflammatory and immunosuppressive mediators  

Microsoft Academic Search

Acute inflammation is accompanied by changes in the concentrations of acute phase proteins (APPs), While much is known about the cytokines involved in the initiation of inflammation, less is known about the mediators involved in its resolution. Recent data suggest that interleukin 6 (IL-6) and IL-6-regulated APPs are anti-inflammatory and immuno-suppressive, and may negatively regulate the acute phase response.

Herbert Tilg; Charles A. Dinarello; James W. Mier

1997-01-01

282

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

PubMed Central

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

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

2014-01-01

283

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%), octocrylčne and isoamyl p-methoxycinnamate (82%), PEG-25 PABA and homosalate (80%), octyl triazone and phenylbenzimidazole sulfonic acid (78%), octyl dimethyl PABA (75%), bis-ethylhexyloxyphenol methoxyphenyl triazine and diethylamino hydroxybenzoyl hexylbenzoate (70%). These filters were tested at various concentrations, including their maximum authorized dose. We detected a dose-response relationship. Conclusions/Significance The anti-inflammatory effect of a sunscreen ingredient may affect the in vivo SPF value.

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

2012-01-01

284

Calcium fructoborate--potential anti-inflammatory agent.  

PubMed

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

Scorei, Romulus Ion; Rotaru, Petre

2011-12-01

285

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.

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

2011-01-01

286

Anti-inflammatory activity and composition of Senecio salignus Kunth.  

PubMed

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

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

2013-01-01

287

Anti-inflammatory effects of Allium schoenoprasum L. leaves.  

PubMed

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

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

2014-04-01

288

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

289

Structure-based design, synthesis and preliminary anti-inflammatory activity of bolinaquinone analogues.  

PubMed

As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophage-like RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E2 (PGE2). This optimization process led to the identification of three strictly correlated compounds with comparable and higher inhibitory potency than BLQ on PGE2 production. To evaluate the affinity of BLQ and its analogues for hsPLA2, surface plasmon resonance (SPR) experiments were performed. PMID:21163556

Petronzi, Carmen; Filosa, Rosanna; Peduto, Antonella; Monti, Maria Chiara; Margarucci, Luigi; Massa, Antonio; Ercolino, Simona Francesca; Bizzarro, Valentina; Parente, Luca; Riccio, Raffaele; de Caprariis, Paolo

2011-02-01

290

Synergism between paracetamol and nonsteroidal anti-inflammatory drugs in experimental acute pain.  

PubMed

The antinociception induced by the intraperitoneal coadministration of combinations of paracetamol with the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, ketoprofen, meloxicam, metamizol, naproxen, nimesulide, parecoxib and piroxicam was studied by isobolographic analysis in the acetic acid abdominal constriction test of mice (writhing test). The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curves of fixed ratio combinations of paracetamol with each NSAID. By isobolographic analysis, this ED50 was compared to the theoretical additive ED50 calculated from the ED(50) of paracetamol and of each NSAID alone obtained from ED50 dose-response curves. As shown by isobolographic analysis, all the combinations were synergistic, the experimental ED50s being significantly smaller than the theoretically calculated ED50s. The results of this study demonstrate potent interactions between paracetamol and NSAIDs and validate the clinical use of combinations of these drugs in the treatment of pain conditions. PMID:16480830

Miranda, Hugo F; Puig, Margarita M; Prieto, Juan Carlos; Pinardi, Gianni

2006-03-01

291

Flavonoid glycosides from Microtea debilis and their cytotoxic and anti-inflammatory effects.  

PubMed

Two new 5-O-glucosylflavones, 5-O-?-D-glucopyranosyl cirsimaritin (1) and 5, 4'-O-?-D-diglucopyranosyl cirsimaritin (2), four known flavonoids, cirsimarin (3), cirsimaritin (4), salvigenin (5), 4', 5-dihydroxy-7-methoxyflavone (6), and a norisoprenoid, vomifoliol (7), have been isolated from the aerial parts of Microtea debilis. All isolates were tested for cytotoxicity in human cancer cell lines (Hep G2, COLO 205, and HL-60) and anti-inflammatory activities in LPS-treated RAW264.7 macrophages. Compound 6 was found to be a potent inhibitor to nitrite production in macrophages. Compounds 2, 4, 6, and 7 showed moderate anti-proliferative activity against COLO-205 cells with IC(50) values of 7.1, 13.1, 6.1, and 6.8 ?M, respectively. PMID:20804824

Bai, Naisheng; He, Kan; Roller, Marc; Lai, Ching-Shu; Shao, Xi; Pan, Min-Hsiung; Bily, Antoine; Ho, Chi-Tang

2011-03-01

292

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.

2012-01-01

293

Pten deletion in RIP-Cre neurons protects against type 2 diabetes by activating the anti-inflammatory reflex.  

PubMed

Inflammation has a critical role in the development of insulin resistance. Recent evidence points to a contribution by the central nervous system in the modulation of peripheral inflammation through the anti-inflammatory reflex. However, the importance of this phenomenon remains elusive in type 2 diabetes pathogenesis. Here we show that rat insulin-2 promoter (Rip)-mediated deletion of Pten, a gene encoding a negative regulator of PI3K signaling, led to activation of the cholinergic anti-inflammatory pathway that is mediated by M2 activated macrophages in peripheral tissues. As such, Rip-cre(+) Pten(flox/flox) mice showed lower systemic inflammation and greater insulin sensitivity under basal conditions compared to littermate controls, which were abolished when the mice were treated with an acetylcholine receptor antagonist or when macrophages were depleted. After feeding with a high-fat diet, the Pten-deleted mice remained markedly insulin sensitive, which correlated with massive subcutaneous fat expansion. They also exhibited more adipogenesis with M2 macrophage infiltration, both of which were abolished after disruption of the anti-inflammatory efferent pathway by left vagotomy. In summary, we show that Pten expression in Rip(+) neurons has a critical role in diabetes pathogenesis through mediating the anti-inflammatory reflex. PMID:24747746

Wang, Linyuan; Opland, Darren; Tsai, Sue; Luk, Cynthia T; Schroer, Stephanie A; Allison, Margaret B; Elia, Andrew J; Furlonger, Caren; Suzuki, Akira; Paige, Christopher J; Mak, Tak W; Winer, Daniel A; Myers, Martin G; Woo, Minna

2014-05-01

294

Radical scavenging and anti-inflammatory activity of extracts from Opuntia humifusa Raf.  

PubMed

Opuntia humifusa Raf. (O. humifusa Raf.) is a member of the Cactaceae family. To determine the antioxidative and anti-inflammatory effects of this herb, various solvent fractions (methanol, hexane, chloroform, ethyl acetate, butanol, and water) prepared from the leaves of cacti were tested using DPPH (2,2-diphenyl-l-picrylhydrazyl radical) and xanthine oxidase assays, and nitric oxide (NO)-producing macrophage cells. We found that O. humifusa Raf. displayed potent antioxidative and anti-inflammatory activity. Thus, all solvent fractions, except for the water layer, showed potent scavenging effects. The scavenging effect of the ethyl acetate fraction was higher than that of the other fractions, with IC50 values of 3.6 and 48.2 microg mL(-1). According to activity-guided fractionation, one of the active radical scavenging principles in the ethyl acetate fraction was found to be quercetin. In contrast, only two fractions (chloroform and ethyl acetate) significantly suppressed nitric oxide production from the lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, chloroform and ethyl acetate fractions significantly blocked the expression of inducible nitric oxide synthetase (iNOS) and interleukin-6 (IL-6) from the RAW264.7 cells stimulated by LPS. Moreover, ethyl acetate fractions significantly blocked the expression of IL-1beta from the RAW264.7 cells stimulated by LPS. Therefore, the results suggested that O. humifusa Raf. may modulate radical-induced toxicity via both direct scavenging activity and the inhibition of reactive species generation, and the modulation of the expression of inflammatory cytokines. Finally, O. humifusa Raf. may be useful as a functional food or drug against reactive species-mediated disease. PMID:16393471

Cho, Jae Youl; Park, Seung-Chun; Kim, Tae-Wan; Kim, Kil-Soo; Song, Jae-Chan; Kim, Sang-Keun; Lee, Hui-Min; Sung, Hye-Jin; Park, Hwa-Jin; Song, Yong-Beom; Yoo, Eun-Sook; Lee, Choong-Hwan; Rhee, Man-Hee

2006-01-01

295

Green synthesis and anti-inflammatory studies of a series of 1,1-bis(heteroaryl)alkane derivatives.  

PubMed

Molecular iodine has been used as an efficient catalyst for a double Friedel-Crafts reaction of various heteroarenes, i.e. 2-methylfuran, 2-ethylfuran, 2-methylthiophene, pyrrole, N-methylpyrrole and indole, using aldehydes as alkylating agents under "open-flask" conditions with toluene or water as the reaction media. In the presence of 10 mol% iodine in toluene at room temperature, both aliphatic and aromatic aldehydes reacted smoothly to give the corresponding bis(heteroaryl)alkanes in good to excellent yields. Interestingly, with water as the solvent, the bis(heteroaryl)alkane adducts were obtained in moderate to good yields. The use of mild reaction conditions, low catalyst loadings, and eco-friendly reagents in a single step synthesis are the advantages of the present procedure. In an effort to discover novel non-steroidal anti-inflammatory agents, the synthesized bis(heteroaryl)alkanes were evaluated for the anti-inflammatory activity in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage model. These compounds (50 ?M) significantly inhibited NO production and did not exhibit significant cytotoxic effects on macrophage cells. Among them, bis[(5-methyl)2-furyl](4-nitrophenyl) methane exhibited the most potent inhibition of NO with IC50 value of 42.4 ± 1.9, which is similar to that of the positive control, aminoguanidine (43.3 ± 2.5 ?M). Thus, the bis[(5-methyl)2-furyl](4-nitrophenyl) methane could be considered a lead compound for the development of novel anti-inflammatory agents. PMID:24996142

Jaratjaroonphong, Jaray; Tuengpanya, Surisa; Saeeng, Rungnapha; Udompong, Sarinporn; Srisook, Klaokwan

2014-08-18

296

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

PubMed

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

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

2012-06-01

297

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

298

Impact of Anti-Inflammatory Agents on the Gene Expression Profile of Stimulated Human Neutrophils: Unraveling Endogenous Resolution Pathways  

PubMed Central

Adenosine, prostaglandin E2, or increased intracellular cyclic AMP concentration each elicit potent anti-inflammatory events in human neutrophils by inhibiting functions such as phagocytosis, superoxide production, adhesion and cytokine release. However, the endogenous molecular pathways mediating these actions are poorly understood. In the present study, we examined their impact on the gene expression profile of stimulated neutrophils. Purified blood neutrophils from healthy donors were stimulated with a cocktail of inflammatory agonists in the presence of at least one of the following anti-inflammatory agents: adenosine A2A receptor agonist CGS 21680, prostaglandin E2, cyclic-AMP-elevating compounds forskolin and RO 20-1724. Total RNA was analyzed using gene chips and real-time PCR. Genes encoding transcription factors, enzymes and regulatory proteins, as well as secreted cytokines/chemokines showed differential expression. We identified 15 genes for which the anti-inflammatory agents altered mRNA levels. The agents affected the expression profile in remarkably similar fashion, suggesting a central mechanism limiting cell activation. We have identified a set of genes that may be part of important resolution pathways that interfere with cell activation. Identification of these pathways will improve understanding of the capacity of tissues to terminate inflammatory responses and contribute to the development of therapeutic strategies based on endogenous resolution.

St-Onge, Mireille; Dumas, Aline; Michaud, Annick; Laflamme, Cynthia; Dussault, Andree-Anne; Pouliot, Marc

2009-01-01

299

Copper(II) complexes of a nonsteroidal anti-inflammatory drug niflumic acid. Synthesis, crystal structure of tetrakis-?-(2-[3-(trifluoromethyl)phenyl]aminonicotinato)bis(dimethylsulfoxide)dicopper(II) complex at 190 K. Anti-inflammatory properties  

Microsoft Academic Search

The synthesis and characterization of three complexes with a potent nonsteroidal anti-inflammatory drug niflumic acid {2-[3-(trifluoromethyl)phenyl]aminonicotinic acid} with formula [Cu(niflumato)2L] (L=H2O, DMSO=dimethylsulfoxide, DMF=N,N-dimethylformamide) were investigated. The crystal and molecular structure of the {Cu(niflumato)2(DMSO)}2 was reported. Crystallographic data are as follows: monoclinic system, space group P21\\/n, Z=2, a=11.1318(8), b=17.513(2), c=15.336(1) Ĺ, ?=103.316(8)°, V=2909.4(4) Ĺ3. The structure was refined to R=0.030 and

F. T Greenaway; E Riviere; J. J Girerd; X Labouze; G Morgant; B Viossat; J. C Daran; M Roch Arveiller; Nguyen-Huy Dung

1999-01-01

300

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

PubMed Central

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

Kariyawasam, Harsha H

2011-01-01

301

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 Ottanŕ; 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

302

Sucrose permeability as a marker for nonsteroidal anti-inflammatory gastroduodenal injury: how sweet is it?  

PubMed

The authors report that sucrose is a novel permeability marker in the evalution of proximal gastrointestinal (GI) injury. In patients undergoing endoscopy and in volunteers who were chronically taking nonsteroidal anti-inflammatory drugs (NSAIDs), the sucrose permeability test accurately identified patients with severe gastritis and gastric ulcer. The sucrose permeability test did not detect other types of proximal GI injury as reliably. Given the propensity of NSAIDs to cause upper GI injury, the authors suggest that this test can be used to identify people who might be at high risk from the sequelae of NSAID ingestion. This interesting marker deserves further evaluation in targeted prospective studies. PMID:7885621

DeMeo, M

1995-01-01

303

Hepatoprotective and anti-inflammatory activities of Ballota glandulosissima.  

PubMed

Water extract of Ballota glandulosissima Hub.-Mor & Patzak (Lamiaceae) (BG) was investigated for anti-inflammatory activity using the carrageenan-induced rat paw oedema test and for hepatoprotective effect on carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. Biochemical parameters of hepatic damage such as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin concentrations were determined. CCl(4) (0.8 mL/kg i.p. for 7 days) treatment increased the serum AST, ALT, ALP and bilirubin levels significantly as compared to controls. Treatment of animals with BG (100 mg/kg, i.p.) +CCl(4) (0.8 mL/kg i.p.) for 7 days significantly ameliorated the levels of AST, ALT and ALP elevated by the CCl(4) treatment alone. The results of biochemical tests were also confirmed by histopathological examination. BG together with CCl(4) treatment decreased the balloning degeneration but did not produced apoptosis of hepatocytes, centrilobular and bridging necrosis observed in the CCl(4) treatment alone. BG, at 100 mg/kg per os, showed a significant reduction (34.22%) in rat paw oedema induced by carrageenan. The reference anti-inflammatory drugs etodolac (50 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly reduced the oedeme by 43.42 and 95.70%, respectively. The present study reveals that the water extract of Ballota glandulosissima possesses promising protective activity against CCl(4) induced hepatic damage and anti-inflammatory activity in rats. PMID:15507327

Ozbek, Hanefi; Cito?lu, Gülçin Saltan; Dülger, Haluk; U?ra?, Serdar; Sever, Betül

2004-12-01

304

Influenza ("Bird Flu"), inflammation and anti-inflammatory/analgesic drugs.  

PubMed

The spectre of an influenza pandemic is being widely mooted. Most of the strategies explored to date for controlling or treating the condition have centred on controlling the spread of the infection, the use of vaccines or anti-viral agents. There has been relatively little discussion about treating the lung and systemic inflammatory reactions that occur during influenza infection. In this review a range of therapeutic agents are proposed to treat the inflammatory reactions, principally in the lung as well as the systemic cytokine-mediated immuno-inflammatory reactions that may be a major cause of the morbidity and mortality associated with influenza infections. Among these are pentoxifylline, the statins, the macrolide antibiotics (e.g. azithromycin, clarithromycin, erythromycin), resveratrol (a component of wine and fruits with inhibitory effects on influenza virus replication) and nutraceuticals (including those that contain flavonoids, the marine oils eicosapentanoic and docosanoic acids or the green-lipped mussel extract, Liprinol which may by virtue of the inhibitory effects on the production or actions of pro-inflammatory cytokines, be useful for their anti-inflammatory actions. The efficacy, mode of actions and side effects of non-steroidal anti-inflammatory drugs (NSAIDs) are considered. There are a number of issues relating to their use in treating the inflammatory reactions in the respiratory tract. Among these are the development of gastro-intestinal ulcers and bleeding and hepato-renal reactions in patients that may because of severe systemic inflammation be prone to the development of these adverse reactions. There are also theoretical issues concerning the impact of COX-1 mediating reduction in prostaglandin and increased cytokine production that might have some negative consequences for respiratory inflammation.In conclusion, further consideration should be given to exploring the actions of these anti-inflammatory agents to control the respiratory inflammatory in influenza infections which can have serious consequences for the outcome of the infection. PMID:16835706

Rainsford, K D

2006-03-01

305

Anti-inflammatory activity of Abutilon indicum extract.  

PubMed

Abutilon indicum Linn. had been broadly used for its reported biological activities in indigenous system of medicine. The ethanolic extract of the whole plant of A. indicum Linn. was evaluated for its anti-inflammatory activity at doses 250, 500 and 750?mg?kg?ą using the carrageenan-induced paw oedema in healthy Wistar albino rats. Results of in vivo activity led to the conclusion that the ethanolic extract of A. indicum showed predominantly significant activity in a dose-dependent manner, which is comparable to the reference standard ibuprofen. The results prove the traditional use of plant in the treatment of inflammation. PMID:21999427

Tripathi, Priyanka; Chauhan, N S; Patel, J R

2012-01-01

306

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

307

Synthesis of antioxidative and anti-inflammatory drugs glucoconjugates.  

PubMed

Glucoconjugates of (+/-)-ibuprofen, (+/-)-alpha-tocopherol (vitamin E), gentisic acid, gallic acid, 2,6-bis(tert-butyl)-4-thiophenol, and N-acetyl-L-cysteine were prepared with the objective of increasing the bioavailability of such antioxidant and anti-inflammatory drugs. The O-glucosides were synthesized using benzylated alpha-D-glucopyranosyl trichloracetimidate as glycosyl donor. For the synthesis of the S-glucosides, the glycosyl donor 1,2,3,4,6-penta-O-acetyl-beta-D-glucopyranose provided higher yields than the corresponding O-acetylated imidate. PMID:10741829

Uhrig, R K; Picard, M A; Beyreuther, K; Wiessler, M

2000-03-24

308

Triterpenoid saponins with anti-inflammatory activity from Codonopsis lanceolata.  

PubMed

Six triterpenoid saponins, including a new compound named codonolaside III, were isolated from the roots of Codonopsis lanceolata. The spectral and chemical data revealed the structure of codonolaside III to be 3- O-[ beta- D-xylopyranosyl -(1-->3)- beta- D-glucuronopyranosyl]-3 beta,16 alpha-dihydroxyolean-12-ene-28-oic acid 28- O-[ beta- D-xylopyranosyl-(1-->4)- alpha- L-rhamnpyranosyl-(1-->2)][ beta- D-glucopyranosyl -(1-->4)]- alpha- L-arabinopyranosyl ester. The xylene-induced mouse ear edema inhibitory effect assay disclosed codonolaside and codonolasides I - III as the major anti-inflammatory constituents in this crude drug. PMID:18666043

Xu, Li-Ping; Wang, Hao; Yuan, Zhong

2008-09-01

309

Nitro-fatty acids: novel anti-inflammatory lipid mediators  

PubMed Central

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

Rubbo, H.

2013-01-01

310

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.

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

2013-01-01

311

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

PubMed

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

Rubbo, H

2013-09-01

312

Nonsteroidal anti-inflammatory drug-induced hepatotoxicity.  

PubMed

Nonsteroidal anti-inflammatory drugs are among the most common drugs associated with drug-induced liver injury, with an estimated incidence of between 3 and 23 per 100,000 patient years. Nimesulide, sulindac, and diclofenac seem to be associated with the highest risk and the only risk factor consistently identified is the concomitant use of other hepatotoxic drugs. Diclofenac-induced liver injury is a paradigm for drug-related hepatotoxicity. Recent studies suggest that genetic factors favoring the formation and accumulation of the reactive acylglucuronide metabolite of diclofenac and an enhanced immune response to the metabolite-protein adducts are associated with increased susceptibility to hepatotoxicity. PMID:17723920

Aithal, Guruprasad P; Day, Christopher P

2007-08-01

313

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

PubMed Central

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

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

2009-01-01

314

A hexane fraction of American ginseng suppresses mouse colitis and associated colon cancer: anti-inflammatory and proapoptotic mechanisms.  

PubMed

Ulcerative colitis is a chronic inflammatory condition associated with a high colon cancer risk. We have previously reported that American ginseng extract significantly reduced the inflammatory parameters of chemically induced colitis. The aim of this study was to further delineate the components of American ginseng that suppress colitis and prevent colon cancer. Among five different fractions of American ginseng (butanol, hexane, ethylacetate, dichloromethane, and water), a hexane fraction has particularly potent antioxidant and proapoptotic properties. The effects of this fraction were shown in a mouse macrophage cell line (ANA-1 cells), in a human lymphoblastoid cell line (TK6), and in an ex vivo model (CD4(+)/CD25(-) primary effector T cells). A key in vivo finding was that compared with the whole American ginseng extract, the hexane fraction of American ginseng was more potent in treating colitis in a dextran sodium sulfate (DSS) mouse model, as well as suppressing azoxymethane/DSS-induced colon cancer. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) labeling of inflammatory cells within the colonic mesenteric lymph nodes was elevated in mice consuming DSS + the hexane fraction of American ginseng. Results are consistent with our in vitro data and with the hypothesis that the hexane fraction of American ginseng has anti-inflammatory properties and drives inflammatory cell apoptosis in vivo, providing a mechanism by which this fraction protects from colitis in this DSS mouse model. This study moves us closer to understanding the molecular components of American ginseng that suppress colitis and prevent colon cancer associated with colitis. PMID:22293630

Poudyal, Deepak; Le, Phuong Mai; Davis, Tia; Hofseth, Anne B; Chumanevich, Alena; Chumanevich, Alexander A; Wargovich, Michael J; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Windust, Anthony; Hofseth, Lorne J

2012-04-01

315

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

316

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.

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

317

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

318

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

PubMed Central

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

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

2013-01-01

319

The anti-inflammatory properties of cocoa flavanols.  

PubMed

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

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

2006-01-01

320

Anti-inflammatory effects of Z-ligustilide nanoemulsion.  

PubMed

The Z-ligustilide (LIG) was studied for its anti-inflammatory activities with prepared LIG nanoemulsions (LIGNE). Healthy male adult Wistar rats were used in the study. Endotoxin-induced uveitis (EIU) was induced by a footpad injection of 200 ?g lipopolysaccharide. EIU rats were administered orally with saline, LIG (20 mg/kg/day), and LIGNE (20 mg LIG /kg/day), respectively. Twenty-four hours later, rats were euthanized, and blood was collected from either right marginal ear vein to estimate inflammatory cells and inflammatory mediators. The drug dissolution profiles of LIGNE in both phosphate buffer pH 6.8 and 0.1 N HCl showed complete dissolution within 20 min. Pharmacokinetic studies suggested a significant increase (P?anti-inflammatory animal testing revealed that LIGNE led to an improvement in oral bioavailability. PMID:23007925

Ma, Zhaoji; Bai, Lunhao

2013-04-01

321

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

PubMed

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

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

2005-11-01

322

Anti-inflammatory triterpenoids from the stems of microtropis fokienensis.  

PubMed

Three new ursane- and four new oleanane- type triterpenoids 1-7 were isolated, along with six known compounds 8-13, from the methanolic extract of Microtropis fokienensis. All structures were elucidated by mass and NMR spectroscopic methods. The isolates 4-10 and known compounds 14-17 that were previously isolated from this material were evaluated for anti-inflammatory activity based on effects against superoxide anion generation and elastase release by neutrophils in response to fMLP/CB. 11?,30-Dihydroxy-2,3-seco-olean-12-en-2,3-dioic anhydride (7) was the first triterpene anhydride from the genus of Microtropis to have the ring A expanded to a seven-membered ring; it showed significant anti-inflammatory activity against superoxide anion generation and elastase release. Unexpectedly, 30-hydroxy-2,3-seco-lup-20(29)-ene-2,3-dioic acid (17) showed the best effect against superoxide anion generation and elastase release with IC50 values of 0.06 ± 0.01 and 1.03 ± 0.35 µg/mL, respectively. Compound 17 had a dioic acid function, and compound 7 had an anhydride function modification in ring A; both showed promising activity in the target assays. PMID:24736870

Chen, I-Hsiao; Du, Ying-Chi; Hwang, Tsong-Long; Chen, I-Fen; Lan, Yu-Hsuan; Yen, Hsin-Fu; Chang, Fang-Rong; Wu, Yang-Chang

2014-01-01

323

Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks.  

PubMed

Non steroidal anti-inflammatory drugs (NSAIDs) are still the most commonly used remedies for rheumatic diseases. But NSAIDs produce serious adverse effects, the most important being gastric injury up to gastric ulceration and renal damage. Several strategies have been adopted in order to avoid these shortcomings, especially gastrointestinal toxicity. So, non steroidal anti-inflammatory drugs have been associated with gastroprotective agents that counteract the damaging effects of prostaglandin synthesis suppression: however, a combination therapy introduces problems of pharmacokinetics, toxicity, and patient s compliance. Also incorporation of a nitric oxide (NO)-generating moiety into the molecule of several NSAIDs was shown to greatly attenuate their ulcerogenic activity: however, several findings suggest a possible involvement of NO in the pathogenesis of arthritis and subsequent tissue destruction. A most promising approach seemed to be the preparation of novel NSAIDs, specific for the inducible isoform of cyclooxygenase (COX-2): they appear to be devoid of gastrointestinal toxicity, in that they spare mucosal prostaglandin synthesis. However, a number of recent studies raised serious questions about the two central tenets that support this approach, namely that the prostaglandins that mediate inflammation and pain are produced solely via COX-2 and that the prostaglandins that are important in gastrointestinal and renal function are produced solely via COX-1. So, increasing evidence shows that COX-2 (not only COX-1) also plays a physiological role in several body functions and that, conversely, COX-1 (not only COX-2) may also be induced at sites of inflammation. Moreover, COX-2 selective NSAIDs have lost the cardiovascular protective effects of non-selective NSAIDs, effects which are mediated through COX-1 inhibition (in addition, COX-2 has a role in sustaining vascular prostacyclin production). The products generated by the 5-lipoxygenase pathway (leukotrienes) are particularly important in inflammation: indeed, leukotrienes increase microvascular permeability and are potent chemotactic agents; moreover, inhibition of 5-lipoxygenase indirectly reduces the expression of TNF-alpha (a cytokine that plays a key role in inflammation). This explains the efforts to obtain drugs able to inhibit both 5-lipoxygenase and cyclooxygenases: the so-called dual acting anti-inflammatory drugs. Such compounds retain the activity of classical NSAIDs, while avoiding their main drawbacks, in that curtailed production of gastroprotective prostaglandins is associated with a concurrent curtailed production of the gastro-damaging and bronchoconstrictive leukotrienes. Moreover, thanks to their mechanism of action, dual acting anti-inflammatory drugs could not merely alleviate symptoms of rheumatic diseases, but might also satisfy, at least in part, the criteria of curative drugs. Indeed, leukotrienes are pro-inflammatory, increase microvascular permeability, are potent chemotactic agents and attract eosinophils, neutrophils and monocytes into the synovium. Finally, recent data strongly suggest that dual inhibitors may have specific protective activity also in neurodegeneration. PMID:12733982

Bertolini, A; Ottani, A; Sandrini, M

2002-05-01

324

Modulation of Intestinal Inflammation by Yeasts and Cell Wall Extracts: Strain Dependence and Unexpected Anti-Inflammatory Role of Glucan Fractions  

PubMed Central

Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb) reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation. Mice received a single oral challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS) for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb, Sc1 to Sc4), as well as mannoprotein (MP) and ?-glucan crude fractions prepared from Sc2 and highly purified ?-glucans prepared from C. albicans were used in this curative model, starting 3 days after C. albicans challenge. Mice were assessed for the clinical, histological and inflammatory responses related to DSS administration. Strain Sc1-1 gave the same level of protection against C. albicans as Sb when assessed by mortality, clinical scores, colonization levels, reduction of TNF? and increase in IL-10 transcription. When Sc1-1 was compared with the other S. cerevisiae strains, the preparation process had a strong influence on biological activity. Interestingly, some S. cerevisiae strains dramatically increased mortality and clinical scores. Strain Sc4 and MP fraction favoured C. albicans colonization and inflammation, whereas ?-glucan fraction was protective against both. Surprisingly, purified ?-glucans from C. albicans had the same protective effect. Thus, some yeasts appear to be strong modulators of intestinal inflammation. These effects are dependent on the strain, species, preparation process and cell wall fraction. It was striking that ?-glucan fractions or pure ?-glucans from C. albicans displayed the most potent anti-inflammatory effect in the DSS model.

Jawhara, Samir; Habib, Khalid; Maggiotto, Francois; Pignede, Georges; Vandekerckove, Pascal; Maes, Emmanuel; Dubuquoy, Laurent; Fontaine, Thierry; Guerardel, Yann; Poulain, Daniel

2012-01-01

325

Degradable magnesium-based implant materials with anti-inflammatory activity.  

PubMed

The objective of this study was to prepare a new biodegradable Mg-based biomaterial, which provides good mechanical integrity in combination with anti-inflammatory function during the degradation process. The silver element was used, because it improved the mechanical properties as an effective grain refiner and it is also treated as a potential anti-inflammatory core. The new degradable Mg-Zn-Ag biomaterial was prepared by zone solidification technology and extrusion. The mechanical properties were mostly enhanced by fine grain strengthening. In addition, the alloys exhibited good cytocompatibility. The anti-inflammatory function of degradation products was identified by both interleukin-1? and nitric oxide modes. The anti-inflammatory impact was significantly associated with the concentration of silver ion. It was demonstrated that Mg-Zn-Ag system was a potential metallic stent with anti-inflammatory function, which can reduce the long-term dependence of anti-inflammatory drug after coronary stent implantation. PMID:23203562

Peng, Qiuming; Li, Kun; Han, Zengsheng; Wang, Erde; Xu, Zhigang; Liu, Riping; Tian, Yongjun

2013-07-01

326

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

PubMed Central

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

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

2013-01-01

327

Anti-inflammatory, analgesic and ulcerogenic properties of S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin.  

PubMed

The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-beta-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-beta-cyclodextrin were investigated in three animal models and compared with those of racemic ibuproxam, racemic ibuprofen and its optical enantiomer S-(+)-ibuprofen. The anti-inflammatory activities of racemic ibuprofen, S-(+)-ibuprofen and racemic ibuproxam in carrageenan-induced paw oedema in rats were almost equipotent and slightly greater than those of S-(+)-ibuproxam and S-(+)-ibuproxam-beta-cyclodextrin, and significantly greater than that of racemic ibuproxam-beta-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-beta-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-beta-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen and S-(+)ibuprofen. These results indicate that S-(+)-ibuproxam-beta-cyclodextrin could be a novel potent anti-inflammatory and analgesic agent with a therapeutic index more favourable than that of the classical non-steroid anti-inflammatory drugs ibuprofen and ibuproxam. PMID:8961164

Bole-Vunduk, B; Verhnjak, K; Zmitek, J

1996-11-01

328

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

Microsoft Academic Search

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

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

1982-01-01

329

Nepafenac, a Unique Nonsteroidal Prodrug with Potential Utility in the Treatment of Trauma-Induced Ocular Inflammation: I. Assessment of Anti-Inflammatory Efficacy  

Microsoft Academic Search

Nepafenac, the amide analog of 2-amino-3-benzoylbenzeneacetic acid (amfenac), was examined in preclinical models for its potential utility as a topical ocular anti-inflammatory agent. Diclofenac was selected as the reference compound. In contrast to diclofenac (IC50 = 0.12 µM), nepafenac exhibited only weak COX-1 inhibitory activity (IC50 = 64.3 µM). However, amfenac was a potent inhibitor of both COX-1 (IC50 =

Daniel A. Gamache; Gustav Graff; Milton T. Brady; Joan M. Spellman; John M. Yanni

2000-01-01

330

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

331

Anti-inflammatory and anti-ulcerogenic properties of Stachytarpheta cayennensis (L.C. Rich) Vahl.  

PubMed

In the present work, the anti-inflammatory and gastroprotective properties of ethanolic extracts of Stachytarpheta cayennesis (L.C. Rich) Vahl (Verbenaceae) were assessed. Chromatographic analysis of the crude ethanolic extract, SC01, revealed high concentrations of the iridoid ipolamiide, whereas the SC02, the second ethanolic extract, presented the arylpropanoid verbacoside as a major constituent. The oral administration of SC01 (100 mg/kg) into Swiss mice failed to inhibit paw oedema and pleural exudation induced by carrageenan and zymosan, whereas SC02 (100 mg/kg, p.o.) inhibited oedema and protein extravasation in all instances. Both extracts inhibited total leukocyte accumulation into the pleural cavity 4 and 24h after the intrathoracic (i.t.) injection of carrageenan, due to the inhibition of neutrophil and mononuclear cell influx, whereas only SC02 was able to inhibit leukocyte mobilization induced by zymosan (100 microg/cavity, i.t.). SC02 inhibited LPS (250 ng/cavity)-induced total leukocyte, neutrophil and eosinophil accumulation in the pleural cavity, whereas SC01 selectively inhibited neutrophil influx. In addition, our data indicates that the extract SC02 presents an important anti-ulcerogenic activity, since it inhibited diclofenac-induced (100 mg/kg, p.o.) gastric ulcera. Overall, these data provide evidence for the anti-inflammatory and gastroprotective properties of Stachytarpheta cayennensis, supporting its use in folk medicine for such purposes. PMID:16219439

Penido, C; Costa, K A; Futuro, D O; Paiva, S R; Kaplan, M A C; Figueiredo, M R; Henriques, M G M O

2006-03-01

332

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.

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

333

Enhanced anti-influenza agents conjugated with anti-inflammatory activity.  

PubMed

Influenza therapy with a single targeted compound is often limited in efficacy due to the rapidly developed drug resistance. Moreover, the uncontrolled virus-induced cytokines could cause the high mortality of human infected by H5N1 avian influenza virus. In this study, we explored the novel dual-targeted bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents. In particular, the caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1) and ZA-7-CA-amide (7) showed simultaneous inhibition of influenza virus neuraminidase and suppression of pro-inflammatory cytokines. These ZA conjugates provided remarkable protection of cells and mice against influenza infections. Intranasal administration of low dosage (<1.2 ?mol/kg/day) of ZA conjugates exhibited much greater effect than the combination therapy with ZA and the anti-inflammatory agents in protection of the lethally infected mice by H1N1 or H5N1 influenza viruses. PMID:22963087

Liu, Kung-Cheng; Fang, Jim-Min; Jan, Jia-Tsrong; Cheng, Ting-Jen R; Wang, Shi-Yun; Yang, Shi-Ting; Cheng, Yih-Shyun E; Wong, Chi-Huey

2012-10-11

334

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

PubMed

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

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

2013-01-01

335

[How to manage the interruption of a treatment with anti-inflammatory corticosteroids?].  

PubMed

A prolonged treatment with anti-inflammatory corticosteroids induces an inhibition of ACTH secretion from pituitary corticotroph cells. An abrupt interruption of such a treatment potentially leads to the risk of an acute adrenal failure, in particular in stressing situations. The inertia in reactivation of the secretion of the stimulating hypothalamic factors (CRH and AVP) and consecutively of ACTH can be responsible for an inability to adapt the secretion of glucocorticoids in response to stress. A short-time treatment (<3 weeks) with anti-inflammatory corticoids does not expose to this risk. On the contrary, a more prolonged treatment, especially with high daily doses, needs to perform an evaluation of the level of corticotroph secretion. This evaluation should be done before to consider that either stopping the treatment is out of risk or if the initiation of a substitutive treatment with hydrocortisone is required. The measurement of morning plasma cortisol level already provides a significant information. As to whether that is needed, a dynamic evaluation can be performed. Among the available tests, the Synacthen(®)test, easy to perform and using at best 1?g of ?1-24 ACTH, appears the most finely informative to answer this question and to choose the most adapted follow-up. PMID:24613064

Kuhn, Jean-Marc; Prévost, Gaëtan

2014-04-01

336

The anti-inflammatory activities of Staphylococcus aureus.  

PubMed

Staphylococcus aureus is a versatile and harmful pathogen in both hospital- and community-associated infections that range from superficial to systemic infections. S. aureus engages a multitude of mechanisms to subvert the innate immune response of the host, including inhibition of complement activation and neutralization of anti-microbial peptides. In addition, inflammatory cell and phagocyte recruitment is an integral part of the innate defense to staphylococcal infection and comprises a well-coordinated multi-step cascade of adhesive events. Recent and rapidly growing experimental evidence indicates the existence of a machinery of anti-adhesive and anti-chemotactic moieties of S. aureus that allow the bacterium to interfere with specific adhesive steps of the homing mechanism of leukocytes. Understanding the functions of these S. aureus-derived anti-inflammatory agents could also provide the platform for designing new therapies in several inflammatory and autoimmune diseases. PMID:17681885

Chavakis, Triantafyllos; Preissner, Klaus T; Herrmann, Mathias

2007-09-01

337

Non Steroidal Anti-Inflammatory Drugs and Inflammatory Bowel Disease  

PubMed Central

Inflammatory Bowel Diseases (IBD) are an immune mediated chronic or relapsing disorders of the gastrointestinal (GI) tract. IBD is characterized by a chronic intestinal inflammatory process with various components contributing to the pathogenesis of the disease including environmental factors such as smoking or use of Non Steroidal Anti-Inflammatory Drugs (NSAIDS). NSAIDS are among the most commonly used medications for the treatment of various inflammatory conditions. The main factor limiting NSAIDS use is the concern for the development of gastrointestinal toxicity including mucosal injury. A possible association between the use of NSAIDS and the onset or relapse of IBD has been repeatedly suggested. This article will review the current concepts and evidence of the relationship between IBD and NSAIDS.

Klein, Amir; Eliakim, Rami

2010-01-01

338

Anti-inflammatory cyclopeptides from exocarps of sugar-apples.  

PubMed

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

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

2014-06-01

339

Anti-inflammatory therapy for obstructive sleep apnea in children  

PubMed Central

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

Friedman, Bat-Chen; Goldman, Ran D.

2011-01-01

340

Anti-inflammatory effects of hydroxycinnamic acid derivatives  

SciTech Connect

NF-{kappa}B family of transcription factors are involved in numerous cellular processes, including differentiation, proliferation, and inflammation. It was reported that hydroxycinnamic acid derivatives (HADs) are inhibitors of NF-{kappa}B activation. Rice bran oil contains a lot of phytosteryl ferulates, one of HADs. We have investigated effects of phytosteryl ferulates on NF-{kappa}B activation in macrophage. Cycloartenyl ferulate (CAF), one of phytosteryl ferulates, significantly reduced lipopolysaccharide (LPS)-induced NO production and mRNA expression of inducible NO synthase and cyclooxygenese-2 but upregulated SOD activity. Electrophoresis mobility shift assay revealed that CAF inhibited DNA-binding of NF-{kappa}B. CAF and phytosteryl ferulates probably have potentially anti-inflammatory properties.

Nagasaka, Reiko [Department of Food Science and Technology, Tokyo University of Marine Science and Technology, 5-7 Konan 4, Minato, Tokyo 108-8477 (Japan); Chotimarkorn, Chatchawan [Department of Food Science and Technology, Tokyo University of Marine Science and Technology, 5-7 Konan 4, Minato, Tokyo 108-8477 (Japan); Shafiqul, Islam Md. [Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657 (Japan); Hori, Masatoshi [Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657 (Japan); Ozaki, Hiroshi [Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657 (Japan); Ushio, Hideki [Department of Food Science and Technology, Tokyo University of Marine Science and Technology, 5-7 Konan 4, Minato, Tokyo 108-8477 (Japan)]. E-mail: hushio@kaiyodai.ac.jp

2007-06-29

341

Immunomodulatory/anti-inflammatory effects of Baccharis dracunculifolia leaves.  

PubMed

A possible immunomodulatory/anti-inflammatory effect of Baccharis dracunculifolia (Bd) and its major compound--caffeic acid (Ca)--on cytokines production (IL-1?, IL-6 and IL-10) by murine macrophages was investigated. Cells were incubated with Bd and Ca, and the inhibitory concentrations were tested before or after macrophages challenge with LPS. Bd and Ca stimulated IL-1? and inhibited IL-6 and IL-10 production. In LPS-challenge protocols, Bd prevented LPS action either before or after LPS challenge, whereas Ca prevented LPS effects only after LPS addition. Bd modulatory action on cytokines production may be at least in part mediated by Ca, since it has been shown to inhibit the transcription factor NF-?B. Further studies are still needed to evaluate Bd efficacy in inflammatory diseases, in order to explore its antiinflammatory activity in vivo. PMID:23163304

Bachiega, T F; de Sousa, J P B; Bastos, J K; Sforcin, J M

2013-01-01

342

Risk of stroke associated with nonsteroidal anti-inflammatory drugs  

PubMed Central

Nonsteroidal anti-inflammatory drugs (NSAIDs), both cyclooxygenase (COX)-2-selective and nonselective agents, have been associated with the increased risk of adverse cardiovascular events. The majority of studies have focused on myocardial infarction as the primary cardiovascular outcome. However, the association between NSAIDs and the risk of stroke events is not as clear, although an understanding of this association is important since stroke continues to be a significant cause of morbidity and mortality. Various factors may contribute to an association between NSAIDs and stroke, including hypertension and thrombosis. Additionally, the risk may vary with different NSAID types. In this review, we discuss the relevant literature assessing the possible association between NSAID use and stroke events, along with the potential mechanisms and the possible directions for future study.

Park, Ki; Bavry, Anthony A

2014-01-01

343

Anti-inflammatory and radical scavenge effects of Arctium lappa.  

PubMed

The effects of Arctium lappa L. (root) on anti-inflammatory and free radical scavenger activity were investigated. Subcutaneous administration of A. lappa crude extract significantly decreased carrageenan-induced rat paw edema. When simultaneously treated with CCl4, it produced pronounced activities against CCl4-induced acute liver damage. The free radical scavenging activity of its crude extract was also examined by means of an electron spin resonance (ESR) spectrometer. The IC50 of A. lappa extract on superoxide and hydroxyl radical scavenger activity was 2.06 mg/ml and 11.8 mg/ml, respectively. These findings suggest that Arctium lappa possess free radical scavenging activity. The inhibitory effects on carrageenan-induced paw edema and CCl4-induced hepatotoxicity could be due to the scavenging effect of A. lappa. PMID:8874669

Lin, C C; Lu, J M; Yang, J J; Chuang, S C; Ujiie, T

1996-01-01

344

Topical delivery of nonsteroidal anti-inflammatory drugs for osteoarthritis.  

PubMed

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

Herndon, Christopher M

2012-01-01

345

Nonsteroidal Anti-Inflammatory Drugs and the Kidney  

PubMed Central

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result.

Horl, Walter H.

2010-01-01

346

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.

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

2010-01-01

347

Anti-inflammatory and Antinociceptive Activities of Azadirachtin in Mice.  

PubMed

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-? in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p.?o.) administration of azadirachtin (120?mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-? induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120?mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120?mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120?mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10?mg/kg, i.?p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain. PMID:24871207

Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

348

The anti-inflammatory mechanisms of Hsp70  

PubMed Central

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

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

2012-01-01

349

Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease.  

PubMed Central

The prostaglandins produce elevation of intraocular pressure and breakdown of the blood-aqueous barrier. They act via the secondary messenger system, cyclic AMP. Although the pathogenesis of many forms of ocular inflammation, both external and internal, is unclear, it is evident that some forms of ocular inflammation are prostaglandin-mediated, at least in part. Others may be totally mediated by prostaglandin synthesis. At present the corticosteroids are the mainstay of therapy of these conditions. However, the corticosteroids are poor inhibitors of prostaglandin synthesis and have many deleterious side effects such as induction of ocular hypertension, cataract, and infection. The search for new agents that will obviate these side effects and be more specific for the disease process is crucial. The discovery that the mode of action of many nonsteroidal anti-inflammatory agents is via inhibition of prostaglandin synthesis places a premium on elucidating which of these agents is most effective and least toxic in the eye and by which route of administration. The arachidonic acid screening model is ideal for initially choosing which agent has the greatest potential clinically. Arachidonic acid, a PGE2 precursor, when given topically also elevates intraocular pressure and aqueous humor protein, and these effects are blocked by the nonsteroidal anti-inflammatory drugs. This occurs if the arachidonic acid is injected into the vitreous humor, too, providing evidence that this in vivo model involves intraocular mechanisms. Utilizing the arachidonic acid system, a comparative study of nonsteroidal inhibitors of prostaglandin synthesis shows that the most effective of 14 agents were flurbiprofen solution and suspensions of polysorbate-dispersed indoxole, meclofenamic acid, indomethacin, and clonixin. Animal uveitis is not an ideal model for the human condition. Nevertheless, proving the superior efficacy of a screened drug in this system will identify those drugs to be tested in the human disease states. Only after the very few best drugs of this nature are identified should the ultimate steps of human testing be initiated.

Podos, S M

1976-01-01

350

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

Abstract 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

351

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

352

Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity  

Microsoft Academic Search

The present study was conducted to evaluate in vitro and in vivo the antioxidant and anti-inflammatory properties of a cantaloupe melon (Cucumis melo LC., Cucurbitaceae) extract (CME) selected for its high superoxide dismutase activity. Peritoneal macrophages were pre-activated in vitro with 300IU of interferon-? (IFN-?) and were then challenged in culture with IgGl\\/anti-IgG1 immune complexes (IgG1IC) in presence of various

Ioannis Vouldoukis; Dominique Lacan; Caroline Kamate; Philippe Coste; Alphonse Calenda; Dominique Mazier; Marc Conti; Bernard Dugas

2004-01-01

353

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

PubMed Central

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

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

2011-01-01

354

PRELIMINARY PHYTOCHEMICAL AND ANTI-INFLAMMATORY ACTIVITY OF BARK OF COMMIPHORA BERRYI (ARN) ENGLOR  

PubMed Central

Various extracts (Petroleum ether, Benzene, Chloroform and Methanol) of Commiphora Berryi (Arn) Englor were subjected to preliminary phytochemical evaluation and it was shown that same extracts were evaluated for its anti-inflammatory activity against carrageenin induced rat paw oedema. Diclofenac sodium (30mg/kg), a non-steroidal anti-inflammatory agent was used as a standard drug for comparison.

Mainvannan, R.; Jawahar, N.; Ganesh, E. Sai; Manivannan, C. Jothi; Judie, S.

2004-01-01

355

Preliminary phytochemical and anti-inflammatory activity of bark of commiphora berryi (arn) englor.  

PubMed

Various extracts (Petroleum ether, Benzene, Chloroform and Methanol) of Commiphora Berryi (Arn) Englor were subjected to preliminary phytochemical evaluation and it was shown that same extracts were evaluated for its anti-inflammatory activity against carrageenin induced rat paw oedema. Diclofenac sodium (30mg/kg), a non-steroidal anti-inflammatory agent was used as a standard drug for comparison. PMID:22557152

Mainvannan, R; Jawahar, N; Ganesh, E Sai; Manivannan, C Jothi; Judie, S

2004-07-01

356

The anti-inflammatory effect of a pomegranate husk extract on inflamed adipocytes and macrophages cultivated independently, but not on the inflammatory vicious cycle between adipocytes and macrophages.  

PubMed

Obese adipose tissues contain a higher proportion of inflamed macrophages than the normal adipose tissue. Adipocytes and macrophages are known to secrete pro-inflammatory markers that establish the systemic inflammation leading to metabolic complications. CCL-2 secreted by hypertrophied adipocytes attracts and activates macrophages in the adipose tissue. These cells, in turn, secrete TNF? and other pro-inflammatory molecules. The pomegranate husk extract and its phenolic constituents, punicalagin and ellagic acid, have exhibited an anti-inflammatory effect. In this study, we used an in vitro coculture system of 3T3-L1 murine adipocytes and RAW 264.7 macrophages to investigate the potential anti-inflammatory effects of these compounds on the vicious cycle between both cell types. The pomegranate husk extract presented an anti-inflammatory effect on the inflamed cells cultivated independently, as suggested by a decrease of (i) CCL-2 secretion by both cell types, (ii) adipocyte IL-6 expression and secretion, and (iii) macrophage TNF? secretion. Nevertheless and surprisingly, no anti-inflammatory effect was observed in coculture. Punicalagin, at the same concentration as that found in the pomegranate extract, had a more potent effect than the extract and in coculture; it reduced significantly the IL-6 secretion. Ellagic acid decreased TNF? and CCL-2 macrophage secretion, CCL-2 adipocyte secretion and, in coculture, it reduced IL-6 secretion and expression by adipocytes. These results indicate that the pomegranate husk extract has an anti-inflammatory action on adipocytes and macrophages but seems to be not able to reduce the inflammatory vicious cycle between both cells. Ellagitannin and punicalagin showed a better effect on inflammation suggesting that PHE will be a good candidate for more investigations. PMID:24336779

Winand, Julie; Schneider, Yves-Jacques

2014-02-01

357

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

358

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.

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

2013-01-01

359

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.

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

360

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

361

Broad neutralization coverage of HIV by multiple highly potent antibodies  

Microsoft Academic Search

Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost

Laura M. Walker; Michael Huber; Katie J. Doores; Emilia Falkowska; Robert Pejchal; Jean-Philippe Julien; Sheng-Kai Wang; Alejandra Ramos; Po-Ying Chan-Hui; Matthew Moyle; Jennifer L. Mitcham; Phillip W. Hammond; Ole A. Olsen; Pham Phung; Steven Fling; Chi-Huey Wong; Sanjay Phogat; Terri Wrin; Melissa D. Simek; Wayne C. Koff; Ian A. Wilson; Dennis R. Burton; Pascal Poignard

2011-01-01

362

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.

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

2014-01-01

363

Anti-inflammatory properties of anthraquinones and their relationship with the regulation of P-glycoprotein function and expression.  

PubMed

There is a growing interest in natural products that potentially have anti-inflammatory properties and inhibit P-glycoprotein (P-gp) function. In this report, we assessed the effects of anthraquinone derivatives from rhubarb on LPS-induced RAW 264.7 macrophages to determine their anti-inflammatory potential. The derivatives were also tested in Caco-2 cell lines to evaluate the inhibition of the drug efflux function of P-gp. The transport abilities were examined and the cellular accumulation of rhodamine-123 (R-123) was also measured. Electorphoretic mobility shift assay (EMSA) was performed to check the activator protein-1 (AP-1) DNA binding affinity. Five anthraquinones were tested to determine their inhibitory activities on NO production and the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the level of prostaglandin E(2) (PGE(2)) was determined in LPS-induced RAW264.7 macrophages. Emodin was found to be the most potent inhibitor, and it also reduced paw swelling in the mouse model of carrageenan-induced paw edema. In Caco-2 cells, emodin elevated the accumulation of R-123 and decreased the efflux ratio of R-123, which indicates the inhibition of P-gp function. The inhibition of COX-2 protein by emodin paralleled the decrease in P-gp expression. In addition, mitogen-activated protein kinase (MAPK) expression was decreased through the prevention of AP-1 DNA binding, which leads to downregulation in the expression of P-gp. Our data indicate that the decrease of P-gp expression is caused by the decreased expression of COX-2 through the MAPK/AP-1 pathway. Based on our results, we suggest that anti-inflammatory drugs with COX-2 inhibitory activity might be used to modulate P-gp function and expression. PMID:23174748

Choi, Ran Joo; Ngoc, Tran Minh; Bae, Kihwan; Cho, Hyun-Jong; Kim, Dae-Duk; Chun, Jaemoo; Khan, Salman; Kim, Yeong Shik

2013-01-23

364

In vivo and in vitro anti-inflammatory and anti-nociceptive effects of the methanol extract of Inonotus obliquus.  

PubMed

The mushroom Inonotus obliquus (Fr.) Pilát (Hymenochaetaceae), has been traditionally used for the treatment of gastrointestinal cancer, cardiovascular disease and diabetes in Russia, Poland and most of Baltic countries. This study was designed to investigate the anti-inflammatory and anti-nociceptive effects of the methanol extract from Inonotus obliquus (MEIO) in vivo and in vitro. MEIO (100 or 200 mg/(kgday), p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activity, as determined by an acetic acid-induced abdominal constriction test and a hot plate test in mice. To reveal the mechanism of the anti-inflammatory effect of MEIO, we examined its effect on lipopolysaccharide (LPS)-induced responses in a murine macrophage cell line RAW 264.7. MEIO was found to significantly inhibit the productions of nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages. Consistent with these observations, MEIO potently inhibited the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, MEIO inhibited the LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB), and this was associated with the prevention of inhibitor kappaB degradation and a reduction in nuclear p65 protein levels. Taken together, our data indicate that the anti-inflammatory and anti-nociceptive properties of MEIO may be due to the inhibition of iNOS and COX-2 expression via the down-regulation of NF-kappaB binding activity. PMID:15905055

Park, Young-Mi; Won, Jong-Heon; Kim, Yang-Hee; Choi, Jong-Won; Park, Hee-Juhn; Lee, Kyung-Tae

2005-10-01

365

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

366

Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.  

PubMed

Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-?B and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. PMID:22067901

Shoeb, Mohammad; Ramana, Kota V

2012-01-01

367

Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis.  

PubMed

Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-gamma and dexamethasone, whilst the pro-inflammatory cytokine TNF-alpha had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins. PMID:12780697

Friese, M A; Manuelian, T; Junnikkala, S; Hellwage, J; Meri, S; Peter, H H; Gordon, D L; Eibel, H; Zipfel, P F

2003-06-01

368

Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis  

PubMed Central

Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-? and dexamethasone, whilst the pro-inflammatory cytokine TNF-? had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins.

FRIESE, M A; MANUELIAN, T; JUNNIKKALA, S; HELLWAGE, J; MERI, S; PETER, H H; GORDON, D L; EIBEL, H; ZIPFEL, P F

2003-01-01

369

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

PubMed Central

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

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

2011-01-01

370

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

PubMed Central

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

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

2011-01-01

371

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

PubMed

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; Zhang, Shu-Ling; Jin, Feng; Pang, Ran; Dong, Ji-Hua

2010-03-01

372

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

PubMed

Seeds of Kupeelu (Strychnos nux-vomica Linn.), a known poisonous drug, is used extensively in various Ayurvedic formulations with great therapeutic significance. Ayurveda recommends the administration of Kupeelu only after passing through specific purificatory procedures in different media like cow's urine (Go mutra), cow's milk (Go dugdha), cow's ghee (Go ghrita), Kanji (thin gruel) etc. Strychnos nux vomica seeds are extensively advocated for nervous debility, paralysis, and weakness of limbs, sexual weakness, dyspepsia, and dysentery and in rheumatism where it can be assumed that besides other properties, Kupeelu may have some sort of anti-inflammatory activity too. In the present study, the powder of raw and processed Kupeelu seeds (processed / purified with Kanji i.e sour gruel) as test drugs were assessed for anti-inflammatory activity by employing Carrageenan and Formaldehyde induced hind paw oedema in Wistar strain albino rats at a dose of 22.5 mg/kg body weight orally. This study reveals that both raw and purified Kupeelu showed presence of highly significant anti-inflammatory activity against formaldehyde induced hind paw oedema, but did not have similar activity against Carrageenan induced hind paw oedema. PMID:23284209

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

2011-10-01

373

Staging Anti-Inflammatory Therapy in Alzheimer's Disease  

PubMed Central

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD) is controversial because conclusions from numerous epidemiological studies reporting delayed onset of AD in NSAID users have not been corroborated in clinical trials. The purpose of this personal view is to revise the case for NSAIDs in AD therapeutics in light of: (i) the last report from the only primary prevention trial in AD, ADAPT, which, although incomplete, points to significant protection in long-term naproxen users, and (ii) the recently proposed dynamic model of AD evolution. The model contends that there is a clinical silent phase in AD that can last up to 20?years, the duration depending on life style habits, genetic factors, or cognitive reserve. The failure of many purported disease-modifying drugs in AD clinical trials is forcing the view that treatments will only be efficacious if administered pre-clinically. Here we will argue that NSAIDs failed in clinical trials because they are disease-modifying drugs, and they should be administered in early stages of the disease. A complete prevention trial in cognitively normal individuals is thus called for. Further, the shift of anti-inflammatory treatment to early stages uncovers a knowledge void about the targets of NSAIDs in asymptomatic individuals. AD researchers have mostly relied on post-mortem analysis of A? plaque-laden brains from demented patients or animal models, thus drawing conclusions about AD pathogenesis based on late symptoms. We will discuss evidence in support that defective, not excessive, inflammation underlies AD pathogenesis, that NSAIDs are multifunctional drugs acting on inflammatory and non-inflammatory targets, and that astrocytes and microglia may play differing roles in disease progression, with an emphasis of ApoE?4 as a key, undervalued target of NSAIDs. According to a meta-analysis of epidemiological data, NSAIDs afford an average protection of 58%. If this figure is true, and translated into patient numbers, NSAID treatment may revive as a worth pursuing strategy to significantly reduce the socio-economical burden imposed by AD.

Lichtenstein, Mathieu P.; Carriba, Paulina; Masgrau, Roser; Pujol, Aurora; Galea, Elena

2010-01-01

374

Anti-inflammatory properties of desipramine and fluoxetine  

PubMed Central

Background Antidepressants are heavily prescribed drugs and have been shown to affect inflammatory signals. We examined whether these have anti-inflammatory properties in animal models of septic shock and allergic asthma. We also analysed whether antidepressants act directly on peripheral cell types that participate in the inflammatory response in these diseases. Methods The antidepressants desipramine and fluoxetine were compared in vivo to the glucocorticoid prednisolone, an anti-inflammatory drug of reference. In a murine model of lipopolysaccharides (LPS)-induced septic shock, animals received the drugs either before or after injection of LPS. Circulating levels of tumour necrosis factor (TNF)-? and mortality rate were measured. In ovalbumin-sensitized rats, the effect of drug treatment on lung inflammation was assessed by counting leukocytes in bronchoalveolar lavages. Bronchial hyperreactivity was measured using barometric plethysmography. In vitro production of TNF-? and Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES) from activated monocytes and lung epithelial cells, respectively, was analysed by immunoassays. Reporter gene assays were used to measure the effect of antidepressants on the activity of nuclear factor-?B and activator protein-1 which are involved in the control of TNF-? and RANTES expression. Results In the septic shock model, all three drugs given preventively markedly decreased circulating levels of TNF-? and mortality (50% mortality in fluoxetine treated group, 30% in desipramine and prednisolone treated groups versus 90% in controls). In the curative trial, antidepressants had no statistically significant effect, while prednisolone still decreased mortality (60% mortality versus 95% in controls). In ovalbumin-sensitized rats, the three drugs decreased lung inflammation, albeit to different degrees. Prednisolone and fluoxetine reduced the number of macrophages, lymphocytes, neutrophils and eosinophils, while desipramine diminished only the number of macrophages and lymphocytes. However, antidepressants as opposed to prednisolone did not attenuate bronchial hyperreactivity. In vitro, desipramine and fluoxetine dose-dependently inhibited the release of TNF-? from LPS-treated monocytes. In lung epithelial cells, these compounds decreased TNF-?-induced RANTES expression as well as the activity of nuclear factor-?B and activator protein-1. Conclusion Desipramine and fluoxetine reduce the inflammatory reaction in two animal models of human diseases. These antidepressants act directly on relevant peripheral cell types to decrease expression of inflammatory mediators probably by affecting their gene transcription. Clinical implications of these observations are discussed.

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

2007-01-01

375

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

PubMed

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

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

2006-08-01

376

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

PubMed

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

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

2013-06-01

377

Carbopol 974P in the prescription of dental anti-inflammatory hydrogels.  

PubMed

The aim of this study was to assess applicative properties of the produced acc. to own prescription dental anti-inflammatory hydrogel with Carbopol 974P. Ketoprofen pharmaceutical availability was tested from hydrogel with Carbopol 974P and to compare - from hydrogels of similar prescription produced on the base of xanthan gum carboxymethylcellulose sodium salt. Very high pharmaceutical availability of ketoprofen was obtained from hydrogel with Carbopol 974P which is related to specific linear crosslinking of polyacrylic acid. The tests of physicochemical properties of hydrogel with Carbopol 974P demonstrated that it has high pH not creating the risk of demineralisation after its application in oral cavity. Introduction of zinc chloride into the prescription of hydrogel with Carbopol 974P improves rheological parameters of the preparation i.e. decreases structural viscosity, the value of yield stress and increases extensibility but decreases ketoprofen pharmaceutical availability by about 15%. PMID:18661704

Ko?odziejska, Justyna

2008-01-01

378

Synthesis, biological evaluation and molecular docking of novel series of spiro [(2H,3H) quinazoline-2,1'- cyclohexan]-4(1H)- one derivatives as anti-inflammatory and analgesic agents.  

PubMed

Three series of Spiro [(2H,3H) quinazoline-2,1'-cyclohexan]-4(1H)-one derivatives have been synthesized. Some of the novel quinazolinone derivatives IIe, VIIIc, XIc, XIIb, XIIc, XVIb showed considerable potent anti-inflammatory and analgesic activity of superior G.I.T. safety profile in experimental rats in comparing to indomethacin and tramadol as reference drugs. Docking study into COX-2 has been made for derivatives of highest anti-inflammatory activity. The compound XVIb showed the nearest RMSD value to that of indomethacin. PMID:20137837

Amin, K M; Kamel, M M; Anwar, M M; Khedr, M; Syam, Y M

2010-06-01

379

Design, Synthesis, and StructureActivity Relationship, Molecular Modeling, and NMR Studies of a Series of a Phenyl Alkyl Ketones as Highly Potent and Selective Phosphodiesterase4 Inhibitors  

Microsoft Academic Search

Phosphodiesterase 4 catalyzes the hydrolysis of cyclic AMP and is a target for the development of anti-inflammatory agents. We have designed and synthesized a series of phenyl alkyl ketones as PDE4 inhibitors. Among them, 13 compounds were identified as having submicromolar ICââ values. The most potent compounds have IC50 values of in the mid- to low-nanomolar range. Compound 5v also

Shilong Zheng; Gurpreet Kaur; Huanchen Wang; Minyong Li; Megan Macnaughtan; Xiaochuan Yang; Suazette Reid; James Prestegard; Binghe Wang

2008-01-01

380

Synthesis of 3-((2,4-dichlorophenoxy)methyl)-1,2,4-triazolo(thiadiazoles and thiadiazines) as anti-inflammatory and molluscicidal agents.  

PubMed

A series of fused and non fused 1,2,4-triazoles with (2,4-dichlorophenoxy) moiety are prepared utilizing 3-((2,4-dichlorophenoxy)methyl)-4-amino-4H-1,2,4-triazole-5-thiol (3). The latter on reaction with carboxylic acids, ethylchloroformate, ethylcyanoacetate and sodium nitrite gives five membered fused triazole derivatives 4a-d, 5, 6, 7 and 10, respectively. The six membered heterocycles 11, 12 and 14 are prepared by cyclization of compound 3 with phenacyl bromide, chloroacetic acid and alpha-bromoketone respectively. Most of the newly synthesized compounds were screened for their anti-inflammatory and molluscicidal activities. The compounds 4b, 4d, 11 and 14 showed potent anti-inflammatory activities in dose dependent manner while compounds 3, 4b, 8 and 10 exhibited promising molluscicidal activities. PMID:20153090

El Shehry, M F; Abu-Hashem, A A; El-Telbani, E M

2010-05-01

381

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

PubMed

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

382

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.

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

2014-01-01

383

Evaluation of the anti-inflammatory and liver-protective effects of anoectochilus formosanus, ganoderma lucidum and gynostemma pentaphyllum in rats.  

PubMed

The pharmacological effects of Anoectochilus formosanus, Ganoderma lucidum and Gynostemma pentaphyllum were studied against carrageenan-induced paw edema and CC1(4)-induced hepatotoxicity in rats. The water extracts of G. pentaphyllum and G. lucidum were found to possess significant anti-inflammatory activity against carrageenan induced edema. The administration of Gynostemma pentaphyllum displayed an activity even more potent than indomethacin. In contrast, Anoectochilus formosanus showed a delayed onset of anti-inflammatory activity starting from 4 hrs post carrageenan administration. However, A. formosanus significantly decreased the acute increase in serum GOT and GPT level caused by CC1(4). Histological changes such as necrosis, fatty change, ballooning degeneration, inflammatory infiltration of lymphocytes and Kupffer cells around the central vein were simultaneously improved by the treatment of A. formosanus. PMID:8328423

Lin, J M; Lin, C C; Chiu, H F; Yang, J J; Lee, S G

1993-01-01

384

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.

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

2012-01-01

385

Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells.  

PubMed

Epidemiological studies suggest that the treatments of anti-inflammatory agents and anti-oxidants slow the progress of neurological diseases. Lignans are anti-oxidants and phytoestrogens found in a variety of plants. In this study, we investigated the neuroprotective effect of macelignan on glutamate-induced neurotoxicity and reactive oxygen species (ROS) in murine hippocampal HT22 cell line. Macelignan significantly attenuated the ROS production and neurotoxicity induced by glutamate in HT22 cell. Also, the properties of macelignan as an anti-inflammatory agent were investigated in microglials activation by lipopolysaccharide (LPS). It potently suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase, that consequently resulted in the reduction of nitric oxide in LPS-treated microglial cells. It also significantly suppressed the production of pro-inflammatory cytokine tumor necrosis factor-alpha and interleukin-6. These results suggest that macelignan possesses therapeutic potentials against neurodegenerative diseases with oxidative stress and neuroinflammation. PMID:15883012

Jin, Da-Qing; Lim, Chol Seung; Hwang, Jae Kwan; Ha, Ilho; Han, Jung-Soo

2005-06-17

386

Synthesis of 2-mercapto-3-substituted-5,6-dimethylthieno[2,3- d] pyrimidin-4(3 H)-ones as new analgesic, anti-inflammatory agents  

Microsoft Academic Search

A new series of 2-mercapto-3-substituted-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones were synthesised by reacting 3-amino-2-mercapto-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one with different aldehydes and ketones. The starting material 3-amino-2-mercapto-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one was synthesised from 2-amino-3-carbethoxy-4,5-dimethyl thiophene by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, among these compound AS1 showed more potent analgesic and anti-inflammatory activities and

V. Alagarsamy; S. Vijayakumar; V. Raja Solomon

2007-01-01

387

Modification of palm oil for anti-inflammatory nutraceutical properties.  

PubMed

Palm oil is one of the most important edible oils in the world. Its composition (rich in palmitate and oleate) make it suitable for general food uses but its utility could be increased if its fatty acid quality could be varied. In this study, we have modified a palm olein fraction by transesterification with the n-3 polyunsaturated fatty acids, alpha-linolenate or eicosapentaenoic acid (EPA). Evaluation of the potential nutritional efficacy of the oils was made using chondrocyte culture systems which can be used to mimic many of the degenerative and inflammatory pathways involved in arthritis. On stimulation of such cultures with interleukin-1alpha, they showed increased expression of cyclooxygenase-2, the inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), IL-1alpha and IL-1beta and the proteinase ADAMTS-4. This increased expression was not affected by challenge of the cultures with palm olein alone but showed concentration-dependent reduction by the modified oil in a manner similar to EPA. These results show clearly that it is possible to modify palm oil conveniently to produce a nutraceutical with effective anti-inflammatory properties. PMID:19449050

Zainal, Zaida; Longman, Andrea J; Hurst, Samantha; Duggan, Katrina; Hughes, Clare E; Caterson, Bruce; Harwood, John L

2009-07-01

388

Non-steroidal anti-inflammatory drugs in Indian rivers.  

PubMed

Pharmaceutical concentration data for Indian surface waters are currently scarce. Sewage often enters Indian rivers without prior treatment, and so previously reported environmental concentrations from regions with routinely implemented sewage treatment cannot simply be used to predict concentrations in Indian surface water. Improved knowledge of pharmaceutical concentrations in Indian waters would enable determination of potential risks posed to aquatic wildlife and human health in this region. The concentrations of five common non-steroidal anti-inflammatory drugs (NSAIDs; diclofenac, ketoprofen, naproxen, ibuprofen, and acetylsalicylic acid) were determined in surface waters from 27 locations of the Kaveri, Vellar, and Tamiraparani Rivers in southern India. The samples were extracted by solid-phase extraction and analyzed by GC-MS. The measured concentrations of four of the five drugs in this reconnaissance were relatively similar to those reported elsewhere (ND-200 ng/l); however, acetylsalicylic acid, the most readily degradable of the investigated drugs, was found at all sites and at considerably higher concentrations (up to 660 ng/l) than reported in European surface waters. This is the first report on the occurrence of NSAIDs in Indian rivers. The finding of elevated concentrations of acetylsalicylic acid is most likely a result of direct discharges of untreated sewage. Therefore, readily degradable pharmaceuticals may present larger concern in regions without consistent sewage treatment. Based on measured environmental concentrations, the risks of direct toxicity to aquatic wildlife and of humans consuming the water are discussed. PMID:23832803

Shanmugam, Govindaraj; Sampath, Srimurali; Selvaraj, Krishna Kumar; Larsson, D G Joakim; Ramaswamy, Babu Rajendran

2014-01-01

389

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

390

HIV-1 Vpr and anti-inflammatory activity.  

PubMed

New and effective approaches for inflammatory diseases based on novel mechanisms of action are needed. One potential source of anti-inflammatory drugs exists among viruses. Viruses have evolved to infect, replicate within, and kill human cells through diverse mechanisms. They accomplish this fact by finding ways to out with the host's complex immune machinery. It is possible that the viral proteins and pathways involved in the downregulation of host immune function during infection can be exploited as a therapeutic in diseases that result in the overactivity of the immune system. Indeed, the human immunodeficiency virus type 1 (HIV-1) protein, Vpr, affects cells in a number of ways that may prove useful for exploitation for the treatment of inflammatory diseases. Vpr has effects on T-cell proliferation, cytokine production, chemokine production, and Nuclear Factor kappa B (NF-kappaB)-mediated transcription. Importantly, it has been observed that Vpr downregulates NF-kappaB and the production of pro-inflammatory cytokines such as TNF-alpha, and IL-12. These activities are worthy of further examination for control of hyperinflammatory and hyperproliferative conditions. PMID:15142381

Muthumani, Karuppiah; Desai, Brijal M; Hwang, Daniel S; Choo, Andrew Y; Laddy, Dominick J; Thieu, Khanh P; Rao, Rushil G; Weiner, David B

2004-04-01

391

Nucleic acid-binding polymers as anti-inflammatory agents  

PubMed Central

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

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

2011-01-01

392

Anti-inflammatory and immunomodulatory activities of rifamycin SV.  

PubMed

There have been several reports showing convincing evidence for non-bactericidal activities of the rifamycin antibiotics. In particular, the parent compound rifamycin SV has been employed in a limited number of cases to treat rheumatoid arthritis. Moreover, rifamycin SV and its derivative rifaximin have been found to be effective in experimental animal models of gut inflammation. The efficacy of rifamycin SV and rifaximin in these settings has been attributed partially to indirect non-bactericidal activities. To better clarify the mechanisms by which these two antibiotics exert their non-bactericidal effects, their activities were compared in in vitro cellular models of immunomodulation and inflammation. Both antibiotics were found to inhibit cytokine and chemokine synthesis from lipopolysaccharide-activated THP-1 monocytes and macrophages. It was also demonstrated, for the first time, that rifamycin SV exerts anti-inflammatory activities in HT-29 colonic epithelial cells. Moreover, rifamycin SV is also very effective in downregulating secretion of inflammatory cytokines from human CD4 T-cells. In general, both antibiotics show similar activities on all four cell types tested. However, rifamycin SV is less cytotoxic than rifaximin when tested in these cells. PMID:23756321

Rosette, Caridad; Buendia-Laysa, Fernando; Patkar, Seema; Moro, Luigi; Celasco, Giuseppe; Bozzella, Roberta; Ajani, Mauro; Gerloni, Mara

2013-08-01

393

Hepatocellular damage from non-steroidal anti-inflammatory drugs.  

PubMed

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the management of rheumatological disorders, and as analgesics and antipyretics. Hepatotoxicity is an uncommon, but potentially lethal complication, which usually occurs within 12 weeks of starting therapy. It can occur with all NSAIDs, but appears to be more common with diclofenac and particularly sulindac. Female patients aged >50 years, with autoimmune disease, and those on other potentially hepatotoxic drugs, appear to be particularly susceptible. Liver function test abnormalities generally settle within 4-6 weeks of stopping the causative drug. However, some patients may develop acute liver failure and successful orthotopic liver transplantation may be undertaken in such patients. Recent in vitro animal studies have shown that the mechanism of diclofenac toxicity relates both to impairment of ATP synthesis by mitochondria, and to production of active metabolites, particularly n,5-dihydroxydiclofenac, which causes direct cytotoxicity. Mitochondrial permeability transition (MPT) has also been shown to be important in diclofenac-induced liver injury, resulting in generation of reactive oxygen species, mitochondrial swelling and oxidation of NADP and protein thiols. Physicians and hepatologists must be vigilant to the hepatotoxic potential of any NSAID, as increased awareness, surveillance and reporting of these events will lead to a better understanding of the risk factors and the pathophysiology of NSAID-related hepatotoxicity. PMID:14566034

O'Connor, N; Dargan, P I; Jones, A L

2003-11-01

394

Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children  

PubMed Central

Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX)-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

2007-01-01

395

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

396

Phytochemical analysis and anti-inflammatory potential of Hyphaene thebaica L. fruit.  

PubMed

Metabolite profiling and biological activity are reported from organic and aqueous extracts of the fruit from the desert palm Hyphaene thebaica. Phenolics and oxylipids profiles were determined using UPLC-PDA-TOF (ultra performance-photodiode array-time of flight) high-resolution mass spectrometry in order to obtain the molecular formula and exact mass Under optimized conditions, 17 compounds were simultaneously identified and quantified including 2 cinnamic acid derivatives, 5 flavonoids, 6 fatty acids, 2 sphingolipids, a lignan, and a stilbene. Sugars composition in the fruit was characterized and quantified by (1) H-NMR (nuclear magnetic resonance) with sucrose detected as the major component in fruit at a level of 219 mg/g. Fruit organic extracts anti-inflammatory potential was assessed in vitro by cyclooxygenase-1 enzyme inhibition. PMID:24025087