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Anim Cells Syst (Seoul). 2018 Mar 13;22(2):109-117. doi: 10.1080/19768354.2018.1426699. eCollection 2018.

Oleuropein reduces anxiety-like responses by activating of serotonergic and neuropeptide Y (NPY)-ergic systems in a rat model of post-traumatic stress disorder.

Lee B1, Shim I1,2, Lee H1,3, Hahm DH1,2.

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Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
The Graduate School of Basic Science of Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.


Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. This psychopathological response to traumatic stressors induces anxiety in rats. Oleuropein (OLE), a major compound in olive leaves, reportedly possesses several pharmacological properties, including anti-cancer, anti-diabetic, and anti-atherosclerotic and neuropsychiatric activities. However, the anxiolytic-like effects of OLE and its mechanism of action in PTSD are unclear. The present study used several behavioral tests to examine the effects of OLE on symptoms of anxiety in rats after a single prolonged stress (SPS) exposure by inhibiting the hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats received OLE (10, 50 and 70 mg/kg, i.p., once daily) for 14 days after SPS exposure. Daily OLE (70 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index and grooming behavior in the EPM test, and increased the time spent and number of central zone crossings in the open field test. OLE also blocked the SPS-induced decrease in hippocampal serotonin and neuropeptide Y expression in hippocampus. These findings suggest that OLE has anxiolytic-like effects on behavioral and biochemical symptoms similar to those observed in patients with PTSD.


Oleuropein; anxiety; post-traumatic stress disorder; serotonin; single prolonged stress

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