Antunes Michelle S, Jesse Cristiano R, Ruff Jossana Rodrigues, de Oliveira Espinosa Dieniffer, Gomes Nathalie Savedra, Altvater Elza Eliza Tenório, Donato Franciele, Giacomeli Renata, Boeira Silvana Peterini
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
Eur J Pharmacol. 2016 Oct 15;789:411-420. doi: 10.1016/j.ejphar.2016.07.042. Epub 2016 Jul 25.
Depression is a serious mental disorder that is becoming more common. To better treat patients suffering from this illness, elucidation of the underlying psychopathological and neurobiological mechanisms of depression is needed. Based on the evidence, we sought to investigate the effects of hesperidin in a model of depression induced by olfactory bulbectomy (OB). C57BL/6 mice were treated with hesperidin (50mg/kg) and imipramine (10mg/kg, positive control) after OB induction. The brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels and acetylcholinesterase activity were analyzed in the hippocampus of the mice. The behavioral parameters were also verified in the model of depression induced by OB. This study demonstrated that OB increased the pro-inflammatory cytokines levels and acetylcholinesterase activity in the hippocampus, exploratory activity in the open field test and immobility in the forced swimming test in mice. In addition, OB decreased the BDNF and NGF levels in the hippocampus, grooming time in the splash test and memory consolidation in the Morris water maze task. Treatment with hesperidin, similar to imipramine, was effective in preventing these behavioral and neurochemical alterations. We suggest that the main targets of hesperidin are pro-inflammatory cytokine modulation, helping to maintain brain plasticity and acetylcholinesterase activity regulation, which are closely linked with antidepressant-like action, as shown by behavior tests. This study demonstrated that there is a pharmacological effect of hesperidin in alterations induced by OB in mice, indicating that hesperidin could be useful as a treatment for depression.
抑郁症是一种日益常见的严重精神障碍。为了更好地治疗患有这种疾病的患者，需要阐明抑郁症潜在的心理病理和神经生物学机制。基于现有证据，我们试图研究橙皮苷在嗅球切除（OB）诱导的抑郁症模型中的作用。OB诱导后，对C57BL/6小鼠给予橙皮苷（50mg/kg）和丙咪嗪（10mg/kg，阳性对照）治疗。分析小鼠海马中脑源性神经营养因子（BDNF）、神经生长因子（NGF）、白细胞介素1β（IL-1β）和白细胞介素6（IL-6）水平以及乙酰胆碱酯酶活性。还在OB诱导的抑郁症模型中验证了行为参数。本研究表明，OB增加了小鼠海马中的促炎细胞因子水平和乙酰胆碱酯酶活性、旷场试验中的探索活动以及强迫游泳试验中的不动时间。此外，OB降低了海马中的BDNF和NGF水平、溅水试验中的梳理时间以及莫里斯水迷宫任务中的记忆巩固。与丙咪嗪类似，橙皮苷治疗可有效预防这些行为和神经化学改变。我们认为，橙皮苷的主要作用靶点是促炎细胞因子调节，有助于维持大脑可塑性和乙酰胆碱酯酶活性调节，行为测试表明这些与抗抑郁样作用密切相关。本研究表明，橙皮苷对OB诱导的小鼠改变具有药理作用，表明橙皮苷可作为抑郁症的一种治疗药物。
