Safety Evaluation of Subchronic Oral Administration of Oleuropein and its Semisynthetic Peracetylated Derivative

Olive leaf extracts are a natural source of phenolic compounds; this includes secoiridoid oleuropein (OLE), which has been widely investigated for its beneficial health effects. Previous in vitro studies have revealed antiproliferative and antioxidant activity in peracetylated oleuropein that is even stronger than oleuropein itself. The aim of the present study was to evaluate the effect of the subchronic administration of oleuropein, and for the first time, also evaluate its semisynthetic peracetylated derivative (peracetylated oleuropein, Ac-OLE). OLE and Ac-OLE were orally administered to male C57BL/6JOlaHsd mice at doses of 20 mg/kg/day for 15 weeks. In comparison to the control group, there were no treatment-related clinical signs of toxicity, nor were there any changes to note in body weight, food consumption, hematological and clinical chemistry parameters, or liver weight. Moreover, the histological examination of the liver, kidney, and lungs did not reveal any morphological alterations. These findings demonstrate that no adverse effects may be attributed to the subchronic oral administration of 20 mg/kg/day of Ac-OLE. However, additional experiments are necessary to clarify the action of the peracetylated compound in light of its therapeutic use.