Independent Laboratory of Behavioral Studies, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
Molecules. 2022 Feb 10;27(4):1179. doi: 10.3390/molecules27041179.
Imperatorin, a naturally derived furanocoumarin, exerts promising neuropharmacological properties. Therefore, it might be applicable in the treatment of brain diseases such as depression. In the present project, we aimed to investigate the sex-dependent effects of imperatorin (1, 5, and 10 mg/kg) on behavior and neurochemistry associated with antidepressant effects. The depressive-like behaviors of male and female Swiss mice were investigated in a forced swim test (FST). Subsequently, High-Performance Liquid Chromatography (HPLC) was used to evaluate the level of serotonin, its metabolite, 5-HIAA, and noradrenaline, in mouse brains. The study revealed that only males responded to imperatorin (1 and 5 mg/kg) treatment and caused an antidepressant effect, such as with respect to depressive-like behaviors, lowering immobility time and increasing immobility latency. The HPLC analysis demonstrated that serotonin levels in the prefrontal cortex of females decreased with the middle dose of imperatorin (5 mg/kg), while in the male prefrontal cortex, the lower dose (1 mg/kg) boosted serotonin levels. There were no evident changes observed with respect to noradrenaline and serotonin metabolite levels in the male hippocampus. To conclude, we propose that imperatorin has antidepressant potential, seemingly only in males, influencing brain serotonin level, but the direct mechanism of action requires further investigation.
欧前胡素，一种天然衍生的呋喃香豆素，具有有前景的神经药理学特性。因此，它可能适用于治疗抑郁症等脑部疾病。在本项目中，我们旨在研究欧前胡素（1、5 和 10mg/kg）对与抗抑郁作用相关的行为和神经化学的性别依赖性影响。通过强迫游泳试验（FST）研究雄性和雌性瑞士小鼠的抑郁样行为。随后，采用高效液相色谱法（HPLC）评估小鼠大脑中 5-羟色胺、其代谢物 5-HIAA 和去甲肾上腺素的水平。研究表明，只有雄性对欧前胡素（1 和 5mg/kg）治疗有反应，并产生抗抑郁作用，例如降低抑郁样行为的不动时间和增加不动潜伏期。HPLC 分析表明，雌性前额叶皮层中的 5-羟色胺水平随着欧前胡素中剂量（5mg/kg）的增加而降低，而在雄性前额叶皮层中，低剂量（1mg/kg）则增加 5-羟色胺水平。在雄性海马体中，未见去甲肾上腺素和 5-羟色胺代谢物水平的明显变化。总之，我们提出欧前胡素具有抗抑郁潜力，似乎仅在雄性中发挥作用，影响大脑 5-羟色胺水平，但直接作用机制需要进一步研究。
