Antidepressant-like effects of solidagenone on mice with bacterial lipopolysaccharide (LPS)-induced depression.,Behavioural Brain Research

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Antidepressant-like effects of solidagenone on mice with bacterial lipopolysaccharide (LPS)-induced depression.
Behavioural Brain Research ( IF 2.6 ) Pub Date : 2020-08-17 , DOI: 10.1016/j.bbr.2020.112863
Gelvani Locateli ₁ , Bianca de Oliveira Alves ₂ , Daniela Miorando ₂ , Jackeline Ernetti ₂ , Kelly Alievi ₂ , Gabriela Adriany Lisboa Zilli ₂ , Patrícia Zanotelli Serpa ₁ , Cristian Alex Dalla Vecchia ₁ , Luisa Mota da Silva ₃ , Liz Girardi Müller ₄ , Walter Antônio Roman Junior ₅

Affiliation

Background

Considering the pharmacological potential of solidagenone from Solidago chilensis, the present investigation was carried out to evaluate its antidepressant-like effect in mice with bacterial lipopolysaccharide (LPS)-induced depressive like behavior and its mode of action through the measurement of neuroinflammatory and oxidative markers.

Materials and methods

In the prophylactic test, the mice were pretreated with solidagenone (1, 10 or 100 mg/kg, p.o) and after one hour received LPS. In therapeutic test, the mice received LPS and after 5 h were treated with solidagenone (1, 10 or 100 mg/kg, p.o). In both experimental approaches, the animals were submitted to OFT and to the TST after 6 and 24 h of the LPS administration, respectively. One hour after the TST the animals were euthanized, the blood was collected, the cortex was removed and biochemical analyzes were performed for measurement of the inflammatory and oxidative stress markers.

Results

The LPS induced sickness- and depressive-like behaviors and increased the cortical activity of myeloperoxidase (MPO), as well as the IL-6 and TNF amount. Interestingly, the pretreatment with solidagenone at 100 mg/kg avoided the behavioral alterations in OFT. In the mice post treated with solidagenone, all tested doses of resulted in an antidepressant-like effect evidenced by the decrease in immobility time in the TST. This effect was accompanied by a decrease in the MPO activity and in the IL-6 and TNF levels in the cortex in parallel to the increase in catalase activity.

Conclusions

The solidagenone has a promissor antidepressant-like potential, which can result of its beneficial action in the neuroinflammation process and due its antioxidant capability at the central nervous system.

中文翻译：

Solidagenone对细菌脂多糖（LPS）诱导的抑郁症小鼠的抗抑郁样作用。

背景

考虑到来自一枝黄花的 Solidagenone 的药理潜力，本研究旨在通过测量神经炎症和氧化标志物来评估其在细菌脂多糖 (LPS) 诱导的抑郁样行为小鼠中的抗抑郁样作用及其作用模式。

材料和方法

在预防性试验中，小鼠用固酮（1、10 或 100 毫克/千克，口服）预处理，1 小时后接受 LPS。在治疗试验中，小鼠接受 LPS，5 小时后用 Solidagenone（1、10 或 100 毫克/千克，口服）治疗。在两种实验方法中，动物分别在 LPS 给药 6 和 24 小时后接受 OFT 和 TST。TST 后一小时，将动物安乐死，收集血液，去除皮质，并进行生化分析以测量炎症和氧化应激标志物。

结果

LPS 诱导疾病和抑郁样行为，并增加髓过氧化物酶 (MPO) 的皮质活性，以及 IL-6 和 TNF 的量。有趣的是，用 100 mg/kg 固酮预处理避免了 OFT 的行为改变。在用 Solidagenone 治疗后的小鼠中，所有测试剂量的 TST 中不动时间的减少都证明了抗抑郁药的作用。这种作用伴随着皮质中 MPO 活性和 IL-6 和 TNF 水平的降低，同时与过氧化氢酶活性的增加平行。