l-663536 has been researched along with Edema* in 6 studies
6 other study(ies) available for l-663536 and Edema
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Lignan derivatives from Krameria lappacea roots inhibit acute inflammation in vivo and pro-inflammatory mediators in vitro.
The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID₅₀ 77 μg/cm²) as well compounds 1-11 (ID₅₀ 0.31-0.60 μmol/cm²) exhibited topical antiedematous properties comparable to those of indomethacin (ID₅₀ 0.29 μmol/cm²) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E₂ synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Austria; Benzofurans; Cyclooxygenase 1; Edema; Intramolecular Oxidoreductases; Krameriaceae; Lignans; Male; Mice; NF-kappa B; Plant Roots; Prostaglandin-E Synthases | 2011 |
Discovery of benzo[g]indol-3-carboxylates as potent inhibitors of microsomal prostaglandin E(2) synthase-1.
Selective inhibition of pro-inflammatory prostaglandin (PG)E(2) formation via microsomal PGE(2) synthase-1 (mPGES-1) might be superior over inhibition of all cyclooxygenase (COX)-derived products by non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs. We recently showed that benzo[g]indol-3-carboxylates potently suppress leukotriene biosynthesis by inhibiting 5-lipoxygenase. Here, we describe the discovery of benzo[g]indol-3-carboxylates as a novel class of potent mPGES-1 inhibitors (IC(50)0.1 microM). Ethyl 2-(3-chlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (compound 7a) inhibits human mPGES-1 in a cell-free assay (IC(50)=0.6 microM) as well as in intact A549 cells (IC(50)=2 microM), and suppressed PGE(2) pleural levels in rat carrageenan-induced pleurisy. Inhibition of cellular COX-1/2 activity was significantly less pronounced. Compound 7a significantly reduced inflammatory reactions in the carrageenan-induced mouse paw edema and rat pleurisy. Together, based on the select and potent inhibition of mPGES-1 and 5-lipoxygenase, benzo[g]indol-3-carboxylates possess potential as novel anti-inflammatory drugs with a valuable pharmacological profile. Topics: Animals; Anti-Inflammatory Agents; Carboxylic Acids; Cell Line, Tumor; Edema; Enzyme Inhibitors; Humans; Indoles; Inhibitory Concentration 50; Intramolecular Oxidoreductases; Magnetic Resonance Spectroscopy; Male; Mice; Microsomes; Pleurisy; Prostaglandin-E Synthases; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization | 2009 |
Differential modulation of cell recruitment and acute edema in a model of Polybia paulista venom-induced inflammation.
Hymenoptera stings are quite common and can cause inflammatory reactions (in nonallergic individuals) or serious reactions (in allergic individuals). Hymenoptera venom contains histamine, vasoactive kinins, serotonin, phospholipase A, phospholipase B, hyaluronidase, antigen 5 and mastoparans. Some of these substances are responsible for local pain, as well as for activation of complement and endothelial cells. Polybia paulista is a wasp typically found in the state of São Paulo, Brazil. In the present study, we evaluated inflammatory reactions in the peritoneal cavities of rats injected with P. paulista venom (PPV). We evaluated leukocyte recruitment and edema formation at the site of inflammation. After i.p. inoculation with PPV, there was dose-dependent and time-dependent recruitment of neutrophils, eosinophils and mononuclear cells. At 4 to 48 h after stimulus, administration of MK 886, a leukotriene synthesis inhibitor, completely abolished granulocyte recruitment to the peritoneal cavity. Therefore, leukotrienes seem to be the primary mediators of PPV-induced neutrophil and eosinophil recruitment. Inoculation with PPV also induced protein extravasation into the peritoneal cavity. This phenomenon was not inhibited by treatment with MK 886 or indomethacin (a prostaglandin synthesis inhibitor), demonstrating that neither leukotrienes nor prostaglandins are involved in this inflammatory reaction. However, edema formation was significantly inhibited by treatment with pyrilamine, indicating that the histamine H1 receptor plays a critical role in PPV-induced formation of acute edema. Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cimetidine; Dose-Response Relationship, Drug; Edema; Eosinophils; Histamine H1 Antagonists; Histamine H2 Antagonists; Indoles; Indomethacin; Leukocytes; Male; Neutrophil Infiltration; Peritoneal Cavity; Pyrilamine; Rats; Rats, Wistar; Wasp Venoms | 2006 |
The peroxisome proliferator-activated receptor alpha activator, Wy14,643, is anti-inflammatory in vivo.
The peroxisome proliferator-activated receptor system is exciting much interest as a novel point of therapeutic intervention in inflammation. Here, the effect of a peroxisome proliferator-activated receptor alpha agonist, [4-chloro-6-(2,3-xylidine)-pyrimidinylthio]acetic acid (Wy14,643), was examined in arachidonic acid-induced murine ear inflammation. 3-[1-(4-Chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid (MK886, a 5-lipoxygenase inhibitor) and indomethacin (a cyclo-oxygenase inhibitor) were used as reference compounds. Wy14,643 dose dependently inhibited ear swelling and polymorphonuclear leukocyte influx, as did MK886, associated with reduced tissue leukotriene B4 but not prostaglandin E2 levels. Unlike MK886, Wy14,643 did not inhibit ex vivo leukotriene B4 production. However, Wy14,643, but not MK886, induced peroxisomal enzyme activity. Indomethacin was less effective, though tissue prostaglandin E2 but not leukotriene B4 levels were reduced. Again, unlike indomethacin, Wy14,643 did not reduce ex vivo prostaglandin E2 production. However, indomethacin did increase peroxisomal enzyme activity but to a lesser extent than Wy14,643. This study demonstrates that peroxisome proliferator-activated receptor alpha activation can inhibit arachidonic acid-induced inflammation in part by enhancing degradation of leukotriene B4. Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Ear, External; Edema; Female; Indoles; Indomethacin; Inflammation; Leukotriene B4; Lipoxygenase Inhibitors; Mice; Neutrophils; Palmitoyl Coenzyme A; Peroxisomes; PPAR alpha; Prostaglandin-Endoperoxide Synthases; Pyrimidines | 2005 |
Microsomal prostaglandin E synthase-1 is a major terminal synthase that is selectively up-regulated during cyclooxygenase-2-dependent prostaglandin E2 production in the rat adjuvant-induced arthritis model.
To better define the role of the various prostanoid synthases in the adjuvant-induced arthritis (AIA) model, we have determined the temporal expression of the inducible PGE synthase (mPGES-1), mPGES-2, the cytosolic PGES (cPGES/p23), and prostacyclin synthase, and compared with that of cyclooxygenase-1 (COX-1) and COX-2. The profile of induction of mPGES-1 (50- to 80-fold) in the primary paw was similar to that of COX-2 by both RNA and protein analysis. Quantitative PCR analysis indicated that induction of mPGES-1 at day 15 was within 2-fold that of COX-2. Increased PGES activity was measurable in membrane preparations of inflamed paws, and the activity was inhibitable by MK-886 to >or=90% with a potency similar to that of recombinant rat mPGES-1 (IC(50) = 2.4 microM). The RNA of the newly described mPGES-2 decreased by 2- to 3-fold in primary paws between days 1 and 15 postadjuvant. The cPGES/p23 and COX-1 were induced during AIA, but at much lower levels (2- to 6-fold) than mPGES-1, with the peak of cPGES/p23 expression occurring later than that of COX-2 and PGE(2) production. Prostacyclin (measured as 6-keto-PGF(1alpha)) was transiently elevated on day 1, and prostacyclin synthase was down-regulated at the RNA level after day 3, suggesting a diminished role of prostacyclin during the maintenance of chronic inflammation in the rat AIA. These results show that mPGES-1 is up-regulated throughout the development of AIA and suggest that it plays a major role in the elevated production of PGE(2) in this model. Topics: Adjuvants, Immunologic; Animals; Antigens, Bacterial; Arthritis, Experimental; Cyclooxygenase 2; Cytosol; Dinoprostone; Disease Models, Animal; Edema; Epoprostenol; Hindlimb; Indoles; Injections, Intradermal; Intracellular Membranes; Intramolecular Oxidoreductases; Isoenzymes; Microsomes; Mycobacterium; Prostaglandin Antagonists; Prostaglandin-E Synthases; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; RNA, Messenger; Up-Regulation | 2003 |
Phorbol ester-induced leukotriene biosynthesis and tumor promotion in mouse epidermis.
In mouse skin in vivo the irritant and hyperplasiogenic tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) strongly increased the epidermal content of the cysteinyl leukotrienes LTC4, LTD4 and LTE4, but not of leukotriene LTB4. This effect was completely suppressed by the selective leukotriene biosynthesis inhibitor MK-886. Intragastric administration of MK-886 prevented phorbol ester-induced ear edema, but not epidermal hyperproliferation and tumor promotion. These data indicate that leukotrienes are involved in the pro-inflammatory effects of the phorbol ester, whereas its hyperproliferative and tumor-promoting activities do not depend on 5-lipoxygenase-catalyzed leukotriene formation. This action differs from several non-selective inhibitors of lipoxygenases that were found to inhibit tumor promotion in initiated mouse skin. Topics: Animals; Ear, External; Edema; Epidermis; Female; Hyperplasia; Indoles; Inflammation; Leukotriene B4; Mice; Skin Neoplasms; SRS-A; Tetradecanoylphorbol Acetate | 1994 |