Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Programa de Pós-Graduação em Bioquímica e Bioprospecção - Laboratório de Neuroquímica, Inflamação e Câncer, Universidade Federal de Pelotas, Prédio 29, Campus Capão do Leão, s/n, Caixa Postal 354, Pelotas, RS, CEP 9601090, Brazil.
Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Programa de Pós-Graduação em Bioquímica e Bioprospecção - Laboratório de Biomarcadores, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Neurochem Res. 2023 Mar;48(3):846-861. doi: 10.1007/s11064-022-03813-8. Epub 2022 Nov 10.
Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders with high rates of prevalence and mortality. MDD is pathophysiologically complex, and treatment options are limited. Blueberries are rich in polyphenols and have neuroprotective potential. The aim of this study was to investigate the effects of blueberry extract on neuroinflammatory and neuroplasticity parameters, as well as Na/K-ATPase, monoamine oxidase-A (MAO-A), and acetylcholinesterase (AChE) activities in the cerebral cortex and hippocampus of mice subject to lipopolysaccharide (LPS)-induced depressive-like behavior. We also analyzed the interaction between anthocyanins and indoleamine 2 3-dioxygenase (IDO). Male Swiss mice (60-day-old) received vehicle, fluoxetine (20 mg/kg), or blueberry extract (100 or 200 mg/kg) intragastrically for 7 days before intraperitoneal LPS (0.83 mg/kg) injection. Twenty-four hours after LPS administration, the mice were subjected to behavioral tests. Both fluoxetine and blueberry extract (200 mg/kg) decreased the immobility time in the forced swim test, without affecting locomotor activity. Fluoxetine attenuated the decrease of Na/K-ATPase in the cerebral cortex, while blueberry extract promoted this same effect in the hippocampus. Additionally, fluoxetine and blueberry extract attenuated the decrease in the activity of MAO-A in the hippocampus. Blueberry extract (200 mg/kg) also prevented LPS-induced increase in AChE activity in the hippocampus as well as LPS upregulation of relative mRNA expression of tumor necrosis factor alpha, interleukin (IL)-1β, and IL-10 in the cerebral cortex. Molecular docking analysis revealed binding sites for malvidin 3-galactoside (- 7.8 kcal/mol) and malvidin 3-glucoside (- 7.9 kcal/mol) residues with IDO. Taken together, these results indicate that blueberry extract improved depression-like behavior and attenuated the neurochemical and molecular changes in the brains of mice challenged with LPS.
重度抑郁症（MDD）是最常见的神经精神疾病之一，具有较高的患病率和死亡率。MDD 的病理生理学非常复杂，治疗选择有限。蓝莓富含多酚，具有神经保护潜力。本研究旨在探讨蓝莓提取物对脂多糖（LPS）诱导的抑郁样行为小鼠大脑皮质和海马神经炎症和神经可塑性参数以及 Na/K-ATP 酶、单胺氧化酶-A（MAO-A）和乙酰胆碱酯酶（AChE）活性的影响。我们还分析了花色苷和吲哚胺 2,3-双加氧酶（IDO）之间的相互作用。雄性瑞士小鼠（60 天大）接受载体、氟西汀（20mg/kg）或蓝莓提取物（100 或 200mg/kg）灌胃 7 天，然后腹腔内注射 LPS（0.83mg/kg）。LPS 给药后 24 小时，对小鼠进行行为测试。氟西汀和蓝莓提取物（200mg/kg）均减少了强迫游泳试验中的不动时间，而不影响运动活性。氟西汀减弱了皮质 Na/K-ATP 酶的减少，而蓝莓提取物促进了海马中的这种相同作用。此外，氟西汀和蓝莓提取物减弱了海马 MAO-A 活性的降低。蓝莓提取物（200mg/kg）还防止了 LPS 诱导的海马 AChE 活性增加以及 LPS 上调皮质中肿瘤坏死因子-α、白细胞介素（IL）-1β和 IL-10 的相对 mRNA 表达。分子对接分析显示，矢车菊素 3-半乳糖苷（-7.8kcal/mol）和矢车菊素 3-葡萄糖苷（-7.9kcal/mol）残基与 IDO 具有结合位点。综上所述，这些结果表明蓝莓提取物改善了抑郁样行为，并减轻了 LPS 挑战的小鼠大脑中的神经化学和分子变化。
