Ole-Oxy, a Semi-Synthetic Analog of Oleuropein, Ameliorates Acute Skin and Colon Inflammation in Mice
Nikolaos V. Angelis,
Efthymios Paronis,
Georgia Sarikaki,
Antonios Kyriakopoulos,
Anna Agapaki,
Pigi-Maria Niotopoulou,
Christina C. Knai,
Pavlos Alexakos,
Odyssefs Liagkas,
Konstantinos F. Mavreas,
Constantin N. Baxevanis,
Alexios-Leandros Skaltsounis,
Ourania E. Tsitsilonis,
Ioannis K. Kostakis
Affiliations
Nikolaos V. Angelis
Flow Cytometry Unit, Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15784 Athens, Greece
Efthymios Paronis
Flow Cytometry Unit, Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15784 Athens, Greece
Georgia Sarikaki
Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15774 Athens, Greece
Antonios Kyriakopoulos
Department of Plastic Surgery, Evaggelismos Hospital, 10676 Athens, Greece
Anna Agapaki
Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece
Pigi-Maria Niotopoulou
Flow Cytometry Unit, Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15784 Athens, Greece
Christina C. Knai
Flow Cytometry Unit, Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15784 Athens, Greece
Pavlos Alexakos
Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece
Odyssefs Liagkas
Flow Cytometry Unit, Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15784 Athens, Greece
Konstantinos F. Mavreas
PharmaGnose S.A., 57 km National Road Athinon-Lamia, 32011 Inofyta, Greece
Constantin N. Baxevanis
Flow Cytometry Unit, Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15784 Athens, Greece
Alexios-Leandros Skaltsounis
Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15774 Athens, Greece
Ourania E. Tsitsilonis
Flow Cytometry Unit, Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15784 Athens, Greece
Ioannis K. Kostakis
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, Ilisia, 15771 Athens, Greece
Inflammation is a key process in the pathophysiology of various diseases, with macrophages playing a central role in the inflammatory response. This study investigates the anti-inflammatory potential of a newly synthesized analog of oleuropein (OP), the major olive tree (Olea europaea) metabolite. This derivative of OP, named Ole-Oxy, was designed by introducing an oxygen atom between the aromatic ring and the aliphatic chain of OP, to enhance interaction with proteins and improve bioactivity. Ole-Oxy demonstrated notable anti-inflammatory effects in vitro, particularly in phorbol 12-myristate 13-acetate-differentiated THP-1 macrophages, where it markedly reduced interleukin-6, tumor necrosis factor-α, and reactive oxygen species (ROS) levels, surpassing the effects of OP. In vivo, Ole-Oxy was evaluated in mouse models of acute skin and colon inflammation, showing significant efficacy in C57BL/6J mice, likely due to their Th1-biased immune response. Our results suggest that Ole-Oxy modulates inflammation through ROS scavenging and differential macrophage activation, underscoring the need for further research to fully elucidate its mechanism of action and optimize its pharmacokinetic properties for future therapeutic applications.
