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Tatiana A. Pa´dua,Bianca S. S. C. de Abreu,Thadeu E. M. M. Costa,Marcos J. Nakamura,Lı´gia M. M,Antonio C. Siani,Elaine C. Rosas 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.11
Ursolic acid (UA), a pentacyclic triterpene acidfound in apple peels (Malus domestica, Borkh, Rosaceae),has a large spectrum of pharmacological effects. However,the vegetal matrix usually produces highly viscous andpoorly soluble extracts that hamper the isolation of thiscompound. To overcome this problem, the crude EtOH–AcOEt extract of commercial apple peels was exhaustivelytreated with diazomethane, after which methyl ursolate(MU) was purified by column chromatography and characterizedspectrometrically. The anti-inflammatory effectsof UA and MU (50 mg/kg) were analyzed by zymosaninducedpaw edema, pleurisy and in an experimentalarthritis model. After 4 h of treatment with UA and MU,paw edema was reduced by 46 and 44 %, respectively. Both UA and MU inhibited protein extravasation into thethoracic cavity; tibio-femoral edema by 40 and 48 %,respectively; and leukocyte influx into the synovial cavityafter 6 h by 52 and 73 %, respectively. Additionally, bothUA and MU decreased the levels of mediators related tosynovial inflammation, such as KC/CXCL-1 levels by 95and 90 %, TNF-a levels by 76 and 71 %, and IL-1b levelsby 57 and 53 %, respectively. Both the compounds wereequally effective when assayed in different inflammatorymodels, including experimental arthritis. Hence, MU maybe considered to be a useful anti-inflammatory derivative toovercome the inherent poor solubility of UA for formulatingpharmaceutical products.