UMLS:C0003864 - FACTA Search

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Query: UMLS:C0003864 (arthritis)
69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the participation of lipid mediators in an experimental immune complex (IC) arthritis model in rats. The animals were subjected to intraarticular injection of anti-bovine sertLm albumin (BSA) IgG antibodies followed by i.v. injection of BSA. Histopathological analysis of the synovial membranes disclosed infiltration of polymorphonuclear (PMN) cells and vascular congestion. Slight increase in vascular permeability, measured by Evans blue dye extravasation into the joints, was detected after 3 h of arthritis. Cellular influx into the articular cavities was most evident at the sixth hour of arthritis with predominance of PMN. Pretreatment with either indomethacin, a cyclooxygenase inhibitor, or L-660,711, a peptido-leukotriene antagonist, did not inhibit cell infiltration, whereas pretreatment with either L-663,536, a 5-lipoxygenase inhibitor, or L-655,240, a thromboxane antagonist, significantly inhibited the phenomenon. Pretreatment with WEB 2170, a platelet activating factor (PAF) antagonist, also significantly inhibited cell influx. These results suggest that thromboxane, LTB(4) and PAF mediate cell infiltration in this IC arthritis model.
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PMID:Immune complex induced arthritis in rats: role of lipid mediators on cell infiltration. 1847 6

Yucca schidigera Roezl. (Agavaceae) has been traditionally used to treat a variety of diseases including arthritis and rheumatism. Phenolic constituents isolated from yucca bark, such as resveratrol, trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, and the yuccaols, have been shown to possess various activities in vitro, such as antioxidant, radical scavenging, iNOS expression inhibitory, and platelet aggregation inhibitory effects. In the present study, the influence of a phenolic-rich fraction from yucca bark and of its main phenolic constituents on key enzymes of arachidonate metabolism was investigated. The fraction and the pure phenolics were shown to inhibit COX-1, COX-2, and LTB 4 formation by 5-LOX in vitro to different extents. The degree of COX-1 inhibition was found to be strongly dependent on the substitution pattern of ring B of the stilbenic moiety. The same trend was observed for the COX-2 inhibitory potential, which was, however, in general much lower for the yuccaols as compared with resveratrol. Resveratrol was also the only compound possessing an LTB 4 formation inhibitory activity. The inhibitory activity on key enzymes of arachidonate metabolism observed in this study might contribute to the explanation of the anti-inflammatory and antiplatelet effects observed for Y. schidigera and its phenolic constituents.
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PMID:Influence of phenolic constituents from Yucca schidigera bark on arachidonate metabolism in vitro. 1877 71

Milk whey proteins contain major components of alpha-lactalbumin (alphaLA) and beta-lactoglobulin (betaLG), and a minor component of lactoferrin (LF). It has been reported that LF reduces nociception and inflammation in various animal models. However, the efficacy of alphaLA and betaLG has not been clarified. This study aimed to assess the efficacy of alphaLA and betaLG in various animal models such as acetic acid-induced writhing, carrageenan-induced paw inflammation, and adjuvant induced-arthritis. Orally administered alphaLA showed (i) inhibition of writhing induced by acetic acid in mice; (ii) suppression of nociception and inflammation in rat footpads caused by carrageenan in rat; and (iii) therapeutic effects on the development of adjuvant-induced pain and inflammation in rat. In contrast, betaLG had no effects in these animal models. To clarify the anti-nociceptive and anti-inflammatory mechanisms of alphaLA, we examined the levels of interleukin (IL)-6 and prostaglandin (PG)E(2) in carrageenan-injected paw exudates. The administration of alphaLA 1 h before carrageenan injection inhibited the increased formation of IL-6 and PGE(2) in paw exudates. Next, we demonstrated in vitro enzyme-inhibition assay; cyclooxygenase (COX), phospholipase A(2), and 5-lipoxygenase. alphaLA inhibited COX and phospholipase A(2) activities. alphaLA inhibited COX and phospholipase A(2) activities. Moreover, alphaLA showed selectivity on COX-2 as compared with COX-1. However, 5-lipoxygenase activity was not affected by alphaLA. These results suggest that alphaLA is a safe and useful natural drug for patients that require anti-inflammatory drugs, as alphaLA is contained in dairy food and is frequently ingested as daily food.
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PMID:Novel functions of bovine milk-derived alpha-lactalbumin: anti-nociceptive and anti-inflammatory activity caused by inhibiting cyclooxygenase-2 and phospholipase A2. 1925 79

Using ex vivo skin as a model, this work tested the hypothesis that the major pharmacologically active components of topically applied Harpagophytum procumbens (H. procumbens) can elicit anti-inflammatory responses in deeper tissues post-transcutaneous delivery. Using Franz-type diffusion cells, ethanol extract of powdered H. procumbens tuber was dosed onto freshly excised porcine skin. After 24 h the receptor phase was recovered, analysed for the major glycosides of DC, then used directly to dose further freshly excised skin membranes. After 6h the skin was recovered and probed for the expression of the three major enzymes involved in the inflammatory factors: cyclooxygenase (COX-2) and its product prostaglandin E2 (PGE-2), lipoxygenase (5-LOX), and inducible nitric oxide (iNOS), using immunocytochemistry and Western blotting analyses. It was found that the receptor phase at 24 h contained (0.8, 25, 1.8, 3 x 10(-3)) micromol mL(-1) of harpagoside, harpagide, verbascoside, 8-O-p-coumaroyl-harpagide, respectively. When applied to skin, this solution effectively inhibited the expression of COX-2 and its product PGE-2. However, it did not have a significant effect on either 5-LOX or iNOS compared to control samples (PBS only). These data support the hypothesis that the transcutaneous delivery of H. procumbens can treat inflammation in deeper tissues such as in arthritis. Moreover, a novel ex vivo model has been described for assessing the potential anti-inflammatory activity of permeants delivered to deeper subcutaneous regions.
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PMID:A novel ex vivo skin model for the assessment of the potential transcutaneous anti-inflammatory effect of topically applied Harpagophytum procumbens extract. 1938 33

Eicosanoids and other bioactive lipid mediators are indispensable regulators of biological processes, as demonstrated by the numerous inflammatory diseases resulting from their dysregulation, including cancer, hyperalgesia, atherosclerosis, and arthritis. Despite their importance, a robust strategy comparable with gene or protein array technology for comprehensively analyzing the eicosanoid metabolome has not been forthcoming. We have developed liquid chromatography-tandem mass spectrometry methodology that quantitatively and comprehensively analyzes the eicosanoid metabolome and utilized this approach to characterize eicosanoid production during experimental Lyme arthritis in mice infected with the bacterium Borrelia burgdorferi. Eicosanoids were extracted throughout infection from the joints of Lyme arthritis-resistant and -susceptible mice and subjected to lipidomic profiling. We identified temporal and quantitative differences between these mouse strains in the production of eicosanoids, which correlated with differences in arthritis development. The eicosanoid biosynthetic enzyme cyclooxygenase (COX)-2 has been implicated in the regulation of Lyme arthritis pathology, and subsequent lipidomic profiling of B. burgdorferi-infected COX-2(-/-) mice identified reductions not only in COX-2 products but, surprisingly, also significant off-target reductions in 5-lipoxygenase metabolites. Our results demonstrate the utility of a comprehensive lipidomic approach for identifying potential contributors to disease pathology and may facilitate the development of more precisely targeted treatment strategies.
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PMID:Lipidomic analysis of dynamic eicosanoid responses during the induction and resolution of Lyme arthritis. 1948 88

Rice bran, the outer bran and germ of the kernel and a by-product of rice milling, is rich in phytonutrients but has been underutilized because of lipid content instability. New methods for the processing of rice bran have yielded a stabilized form that is increasingly used in foods and dietary supplements. Recent studies have documented a role for stabilized rice bran (SRB) in treating diabetes and arthritis, although little is known of the bioactive compounds that impart these health benefits. Here we characterize the chemical composition of three extracts of SRB and identify the functional bioactives contributing to the inhibitory properties against three key pro-inflammatory enzymes (cyclooxygenase [COX] 1, COX2, and 5-lipoxygenase [5-LOX]) that control the inflammatory cascade involved in impaired joint health, pain, and arthritis. One extract (SRB-AI) demonstrated significant COX1 and COX2 inhibitory activities with 50% inhibitory concentration (IC(50)) values for COX1 and COX2 of 305 and 29 microg/mL, respectively, but no 5-LOX inhibition. The second extract (SRB-AII) inhibited COX1, COX2, and 5-LOX with IC(50) values of 310, 19, and 396 microg/mL, respectively. The third extract (SRB-AIII), a blend of SRB-AI and SRB-AIII, inhibited COX1, COX2, and 5-LOX with respective IC(50) values of 48, 11, and 197 microg/mL. Analysis of the extracts by direct analysis in real time time of flight-mass spectrometry revealed that SRB-AI, SRB-AII, and SRB-AIII contain over 620, 770, and 810 compounds, respectively. Of these, 17 were identified as key bioactives for COX and/or LOX inhibition. These SRB extracts have applications for functional foods and dietary supplements for control of inflammation and joint health.
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PMID:Pro-inflammatory enzymes, cyclooxygenase 1, cyclooxygenase 2, and 5-lipooxygenase, inhibited by stabilized rice bran extracts. 1962 11

In a previous study, we reported a new gamma-hydroxybutenolide derivative, 4-benzo[b]thiophen-2-yl-3-bromo-5-hydroxy-5H-furan-2-one (BTH), as inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) expression in lypopolysaccharide (LPS) stimulated RAW 264.7 and TPH-1 cells, without affecting cyclooxygenase-2 (COX-2). In this study, we evaluated the in vivo effect of BTH on some acute and chronic inflammatory animal models in relation to its inhibitory profile on mPGES-1 expression. In the zymosan-induced mouse air pouch model, BTH produced a dose-dependent inhibition of prostaglandin E(2) (PGE(2)) production and mPGES-1 protein expression in pouch exudates without any effect on COX-2 protein expression. This behavior was confirmed in the chronic model of collagen-induced arthritis, where administration of BTH (5 mg/kg) clearly reduced PGE(2) and mPGES-1 expression in joint tissues, whereas COX-2 was unaffected. These effects were accompanied by the suppression of clinical and histopathological manifestations of disease such as the loss of proteoglycan, and the destruction of surface cartilage. Other enzymes participating in the metabolism of arachidonic acid, such as prostaglandin I(2) synthase, tromboxane A(2) synthase or 5-lipoxygenase were unaffected by this compound. The acetic acid-induced hyperalgesia model in LPS-sensitized mice showed a dose-dependent analgesic effect of BTH, exerting an ED(50) value of 6.2 mg/kg. Our data suggest that inhibition of mPGES-1 protein expression in acute and chronic inflammatory models by BTH, could provide a potential therapeutic target and a pharmacological tool to discern the role of the inducible enzymes COX-2 and mPGES-1 in inflammatory pathologies.
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PMID:Anti-inflammatory and analgesic activity of a novel inhibitor of microsomal prostaglandin E synthase-1 expression. 1968 18

Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India, were evaluated for their protective effect in acute and chronic models of inflammation. Carrageenan induced rat paw edema and adjuvant induced arthritis were employed as the experimental models of acute and chronic inflammation respectively. Isolated polyphenolic and alkaloid fraction (AFR) from Ruta graveolens and evaluated its anti inflammatory activity in carrageenan induced acute model. AFR with a dose 10 mg/kg showed higher anti inflammatory effect than polyphenols and standard drug diclofenec. AFR significantly decreased the paw edema in arthritic rats. TBARS, COX-2, 5-LOX and MPO level were decreased and the levels of antioxidant enzymes and GSH level were increased on treatment with AFR. The increment in CRP level and ceruloplasmin level observed in arthritic animals were also found to be significantly restored in AFR treated rats. The results demonstrated the potential beneficiary effect of isolated polyphenolic and alkaloid fraction of Ruta graveolens L. on acute and chronic models of inflammation in rats.
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PMID:Protective effects of isolated polyphenolic and alkaloid fractions of Ruta graveolens L. on acute and chronic models of inflammation. 1977 30

Mast cells play an important role in both innate and acquired immunity as well as several pathological conditions including allergy, arthritis and neoplasia. They influence these processes by producing a variety of mediators including cytokines, chemokines and eicosanoids. Very little is currently known about the spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and leukotrienes), produced by canine mast cells. This is important since modulating mast cell derived eicosanoids may help in the treatment of autoimmune and inflammatory disorders. The purpose of this study was to investigate the spectrum of eicosanoids produced by normal canine mast cells and to evaluate the effects of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid production and release. Canine bone marrow derived cultured mast cells (cBMCMCs) expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4, and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs carprofen (Rimadyl) and deracoxib (Deramaxx) inhibited PGD2 and PGE2 production but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following treatment while tepoxilan (Zubrin), a pan COX/LOX inhibitor, markedly reduced the production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA) prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs with IL-4 and SCF sensitized these cells to degranulation in response to substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar to those produced by mast cells from other species. Tepoxilan appeared to be the most effective NSAID for blocking eicosanoid production and thus may be useful for modulating mast cell mediated responses in dogs.
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PMID:Characterization and modulation of canine mast cell derived eicosanoids. 2003 14

Lipid mediators derived from arachidonic acid through the cyclooxygenase and lipoxygenase pathways are known to be important mediators of inflammation. Studies in mouse models demonstrated an important role for the high-affinity leukotriene B(4) receptor BLT1 in arthritis, atherosclerosis, and asthma. BLT2, a low-affinity leukotriene B(4) receptor, was also shown to be a high-affinity receptor for cyclooxygenase-1 derived 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid. However, its biochemical activities and physiological roles remain unknown. In this study, we developed mice deficient in BLT2 by targeted disruption. The BLT2(-/-) mice developed normally, and analysis of immune cells showed that disruption of BLT2 did not alter BLT1 expression or function. Mast cells from the C57BL/6 mice but not from the BLT2(-/-) mice showed intracellular calcium mobilization in response to 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid. In an autoantibody-induced inflammatory arthritis model, the BLT2(-/-) mice showed reduced incidence and severity of disease, including protection from bone and cartilage loss. Reciprocal bone marrow transplant experiments identified that loss of BLT2 expression on a bone marrow-derived cell lineage offers protection against severe disease. Thus, BLT2, a unique receptor for 5-lipoxygenase- and cyclooxygenase-1-derived lipid mediators, represents a novel target for therapies directed at treating inflammation associated with arthritis.
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PMID:Nonredundant roles for leukotriene B4 receptors BLT1 and BLT2 in inflammatory arthritis. 2065 22

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