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Anti-inflammatory effects of methyl ursolate obtained from a chemically derived crude extract of apple peels: potential use in rheumatoid arthritis

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Abstract

Ursolic acid (UA), a pentacyclic triterpene acid found in apple peels (Malus domestica, Borkh, Rosaceae), has a large spectrum of pharmacological effects. However, the vegetal matrix usually produces highly viscous and poorly soluble extracts that hamper the isolation of this compound. To overcome this problem, the crude EtOH–AcOEt extract of commercial apple peels was exhaustively treated with diazomethane, after which methyl ursolate (MU) was purified by column chromatography and characterized spectrometrically. The anti-inflammatory effects of UA and MU (50 mg/kg) were analyzed by zymosan-induced paw edema, pleurisy and in an experimental arthritis 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 the thoracic cavity; tibio-femoral edema by 40 and 48 %, respectively; and leukocyte influx into the synovial cavity after 6 h by 52 and 73 %, respectively. Additionally, both UA and MU decreased the levels of mediators related to synovial inflammation, such as KC/CXCL-1 levels by 95 and 90 %, TNF-α levels by 76 and 71 %, and IL-1β levels by 57 and 53 %, respectively. Both the compounds were equally effective when assayed in different inflammatory models, including experimental arthritis. Hence, MU may be considered to be a useful anti-inflammatory derivative to overcome the inherent poor solubility of UA for formulating pharmaceutical products.

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Acknowledgments

We are grateful for the financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico, MCTI (CNPq/Proc. 475751/2009-0;CNPq/Proc. 304588/2010-5).

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Authors and Affiliations

  1. Department of Natural Products, Medicines and Drugs Technology Institute (Farmanguinhos), Oswaldo Cruz Foundation, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ, 21041-250, Brazil

    Tatiana A. Pádua, Bianca S. S. C. de Abreu, Thadeu E. M. M. Costa, Marcos J. Nakamura, Maria das Graças Henriques, Antonio C. Siani & Elaine C. Rosas

  2. Chemistry Institute, Federal University of Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, RJ, Brazil

    Lígia M. M. Valente

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  1. Tatiana A. Pádua
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  2. Bianca S. S. C. de Abreu
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  3. Thadeu E. M. M. Costa
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Correspondence to Antonio C. Siani.

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Pádua, T.A., de Abreu, B.S.S.C., Costa, T.E.M.M. et al. Anti-inflammatory effects of methyl ursolate obtained from a chemically derived crude extract of apple peels: potential use in rheumatoid arthritis. Arch. Pharm. Res. 37, 1487–1495 (2014). https://doi.org/10.1007/s12272-014-0345-1

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  • DOI: https://doi.org/10.1007/s12272-014-0345-1

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