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，具有很高的患病率和死亡率。MDD 在病理生理学上很复杂，治疗选择有限。蓝莓富含多酚，具有神经保护潜力。本研究的目的是研究蓝莓提取物对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) 和大脑皮层乙酰胆碱酯酶 (AChE) 活性的影响脂多糖 (LPS) 诱导的抑郁样行为小鼠的和海马体。我们还分析了花青素和吲哚胺 2 3-双加氧酶 (IDO) 之间的相互作用。瑞士男 小鼠（60 日龄）在腹膜内 LPS (0.83 mg/kg) 注射前 7 天接受载体、氟西汀 (20 mg/kg) 或蓝莓提取物 (100 或 200 mg/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 (200 mg/kg) 都减少了强迫游泳测试中的不动时间，而不影响运动活动。^{氟西汀减弱了 Na +} /K ⁺的减少- 大脑皮层中的 ATP 酶，而蓝莓提取物在海马体中促进了同样的效果。此外，氟西汀和蓝莓提取物减弱了海马体中 MAO-A 活性的降低。蓝莓提取物 (200 mg/kg) 还可阻止 LPS 诱导的海马 AChE 活性增加以及 LPS 上调大脑皮层肿瘤坏死因子 α、白细胞介素 (IL)-1β 和 IL-10 的相对 mRNA 表达. 分子对接分析揭示了 malvidin 3-半乳糖苷 (− 7.8 kcal/mol) 和 malvidin 3-葡萄糖苷 (− 7.9 kcal/mol) 残基与 IDO 的结合位点。总之，这些结果表明，蓝莓提取物改善了抑郁样行为，并减弱了 LPS 攻击小鼠大脑中的神经化学和分子变化。