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Effects Of Extracts From Paederia Scandens On Acute Gouty Arthritis Induced By Monosodium Urate Crystals And Its Mechanisms

Posted on:2009-01-13Degree:MasterType:Thesis
Country:ChinaCandidate:Y MaFull Text:PDF
GTID:2144360242987029Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Acute gouty arthritis (GA) is thought to be an inflammatory response to microcrystals of monosodium urate monohydrate (MSU) that precipitate in joint tissues from supersaturated body fluids or are shed from preexisting articular deposits. Extracts from Paederia scandens (LOUR.) MERRILL (Rubiaceae) (EPS) are paederoside, asperuloside, paederosidic acid, deacety lasperuloside, scandoside, asperulosidic acid and so on. Our former studies indicated that EPS have protective effects against inflammation. Effects of EPS on GA model were investigated. The main results are as following:1 Effect of EPS on GA rat modelWe studied the effects of EPS on acute gouty arthritis induced by monosodium urate crystal in rats. Monosodium urate monohydrate (MSU) crystals were administered into rat ankle joints. Ankle joint volume of rats was measured by volume meter; the level of TNF-αand IL-1βwas determined by radioimmunoassay; mRNA expression of TNF-αand IL-1βof synovial tissue in GA rats was analyzed by RT-PCR, and expression of NF-κB by immunohistochemistry was detected.The results showed that EPS (4500, 2250 mg·kg-1, ig, qd×9d) could significantly inhibit joint swelling of rats, improve the gaits and the histopathologic changes, could inhibited the increase of TNF-αand IL-1βlevel; EPS possessed antigout arthritis effects; its mechanism may be related to inhibit the product of IL-1βand TNF-α; At the same time, 4500, 2250 mg·kg-1 of EPS inhibited mRNA expression of TNF-αand IL-1βof synovial tissue and decreased the biologically activity of NF-κB. The results suggested that EPS possesses antiinflammatory effects by modulating pro-inflammatory mediators'production from synovial tissue and inactivate NF-κB pathway transmembrane signal transduction which plays a crucial role in pathogenesis of this disease.2 Effect of EPS on GA rabbit modelWe studied the effects of EPS on acute gouty arthritis induced by monosodium urate in rabbits. Monosodium urate monohydrate (MSU) crystals were administered into rabbits'joints. Increases in joint size, and leukocyte infiltration to synovial fluids were analyzed. PGE2 activity was measured after increasing periods of time; expression of COX-2 by immunohistochemistry; COX-2 mRNA levels were monitored by RT-PCR.The results showed that EPS (2300, 1150 mg·kg-1, ig, qd×7d) could significantly inhibit joint swelling of rabbits, improve the histopathologic changes, could inhibited the expression of COX-2 and COX-2mRNA in synovium of GA rabbits; These results suggested that EPS could inhibit PGE2 activity, COX-2 expression and PGE2 activity and down-regulate COX-2mRNA expression in synovial tissue from GA rabbits, which might be one of molecular mechanisms of its anti-inflammatory effects in GA rabbits.3 ConclusionsIn summary, our results demonstrated that EPS had anti-inflammatory action on animal model. The mechanisms of its effect on GA might be associated with its action on down-regulatation of MSU crystals-induced TNF-αand IL-1βproduction by inhibiting their expressions at the gene level. Furthermore, these inhibitions might be correlated with the blockage of NF-κB activation in synovial tissue, In addition, EPS was also down-regulate COX-2 and COX-2mRNA expressions.
Keywords/Search Tags:Extracts from paederia scandens, Gouty arthritis, MSU, Animal model, mechanisms
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