Efficient In Vitro and In Vivo Anti‐Inflammatory Activity of a Diamine‐PEGylated Oleanolic Acid Derivative Jannus, Fatin Medina-O'Donnell, Marta Neubrand, Veronika Elisabeth Marín Alejo, Milagros Sáez Lara, María José Sepúlveda Justo, María Del Rosario Rufino Palomares, Eva Martínez Rodríguez, Antonio Lupiáñez Cara, José Antonio Parra Sánchez, Andrés Rivas, Francisco Reyes Zurita, Fernando Jesús Oleanolic acid Triterpenes derivatives Diamine‐(PEG)ylated oleanolic acid OADP Anti‐inflammatory mechanism RAW 264.7 cell line TPA‐induced acute ear edema 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 in‐ flammatory 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. 2021-09-30T06:43:09Z 2021-09-30T06:43:09Z 2021 info:eu-repo/semantics/article : Jannus, F.; Medina‐O’Donnell, M.; Neubrand, V.E.; Marín, M.; Saez‐Lara, M.J.; Sepulveda, M.R.; Rufino‐Palomares, E.E.; Martinez, A.; Lupiañez, J.A.; Parra, A.; Rivas, F; Reyes‐Zurita, F.J. Efficient In Vitro and In Vivo Anti‐Inflammatory Activity of a Diamine‐PEGylated Oleanolic Acid Derivative. Int. J. Mol. Sci. 2021, 22, 8158. https://doi.org/10.3390/ ijms22158158 http://hdl.handle.net/10481/70538 10.3390/ijms22158158 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI