Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative |
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Authors: | Fatin Jannus Marta Medina-ODonnell Veronika E Neubrand Milagros Marín Maria J Saez-Lara M Rosario Sepulveda Eva E Rufino-Palomares Antonio Martinez Jose A Lupiaez Andres Parra Francisco Rivas Fernando J Reyes-Zurita |
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Affiliation: | 1.Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva, 18071 Granada, Spain; (F.J.); (M.M.); (M.J.S.-L.); (E.E.R.-P.); (J.A.L.);2.Department of Organic Chemistry, Faculty of Sciences, University of Granada, Av. Fuentenueva, 18071 Granada, Spain; (A.M.); (A.P.);3.Department of Cell Biology, Faculty of Sciences, University of Granada, Av. Fuentenueva, 18071 Granada, Spain; (V.E.N.); (M.R.S.) |
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Abstract: | Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1β, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes. |
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Keywords: | oleanolic acid triterpenes derivatives diamine-(PEG)ylated oleanolic acid OADP anti-inflammatory mechanism RAW 264 7 cell line TPA-induced acute ear edema |
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