Bertollo Amanda Gollo, Soares Silvio José Batista, Amaral Severina Silva, de Medeiros Jesiel, Nicolleti Ana Olivia Albino, Ibrahim Hélio Jungkenn, Kreuz Kelli Maria, Schuh Laysa Anacleto, da Silva Brunna Varela, Mingoti Maiqueli Eduarda Dama, Roman Junior Walter Antônio, Bohnen Lilian Caroline, da Silva Gilnei Bruno, Manica Daiane, Bagatini Margarete Dulce, Ignácio Zuleide Maria
Laboratory of Physiology Pharmacology and Psychopathology, Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, 89815-899, Brazil.
Program in Health Sciences, Community University of Chapecó Region, Unochapecó, Chapecó, SC, Brazil.
Mol Biol Rep. 2025 May 24;52(1):498. doi: 10.1007/s11033-025-10576-2.
Stress in childhood can harm brain development, leading to biological and systemic dysfunctions that, along with genetic factors, may contribute to major depressive disorder (MDD) in adulthood. MDD treatment is complex, with current drugs taking time to show effects and not working for many patients. As a result, medicinal plants, like Aloysia citriodora (A. citriodora), are being studied as treatments for resistant depression. The main objective of this proposal was to evaluate the treatment with the hydroalcoholic extract of the medicinal species A. citriodora Palau on depressive-like behaviors in rats subjected to chronic stress in childhood and on mechanisms involved in neuroprotection through the evaluation of neuroinflammation and oxidative stress.
The maternal deprivation (MD) protocol was used during the first ten days of life. At the beginning of adulthood, the animals were treated for fourteen days. At the end of the treatments, the animals underwent the forced swimming behavioral test and were then euthanized for analysis of oxidative stress and inflammation markers.
The stress caused by the MD protocol in rats culminated in a significant increase in depressive-like behaviors in adulthood, an increase in the expression of inflammatory substances IL-1 β and IL-6 in the animals' hippocampus, and an increase in the activity of oxidative stress parameters, such as myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS), in serum and hippocampus. The treatment with A. citriodora reduced depressive-like behaviors similar to the group treated with escitalopram. Regarding markers of inflammation in nervous tissue, it was observed that animals treated with A. citriodora had lower levels than those treated with escitalopram and the control group, and even more significantly when compared to the MD group treated with saline. The treatments reduced MPO activity in the serum of animals that underwent the MD protocol. TBARS was decreased in the serum and ultimately reversed in the hippocampus. Moreover, molecular docking studies have demonstrated that baicalein and quercetin-7-O-glucoside interact efficiently with IL-1β and IL-6.
PM stress increased depressive-like behavior and increased markers of oxidative stress and inflammation. Treatment with the Aloysia citriodora extracts significantly reduced depressive-like behavior and markers of oxidative stress and inflammation, suggesting an antidepressant, antioxidant, and anti-inflammatory effect.
童年期应激会损害大脑发育，导致生物和全身性功能障碍，这些与遗传因素一起，可能会导致成年期的重度抑郁症（MDD）。MDD的治疗很复杂，目前的药物需要时间才能显示出效果，而且对许多患者无效。因此，像柠檬马鞭草（Aloysia citriodora）这样的药用植物正在被研究用于治疗难治性抑郁症。本研究的主要目的是评估药用植物柠檬马鞭草（A. citriodora Palau）的水醇提取物对童年期遭受慢性应激大鼠的抑郁样行为的治疗作用，以及通过评估神经炎症和氧化应激来研究其神经保护机制。
在出生后的前十天采用母婴分离（MD）方案。成年初期，对动物进行为期十四天的治疗。治疗结束后，对动物进行强迫游泳行为测试，然后安乐死以分析氧化应激和炎症标志物。
MD方案给大鼠造成的应激最终导致成年期抑郁样行为显著增加，动物海马中炎性物质白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达增加，血清和海马中氧化应激参数如髓过氧化物酶（MPO）和硫代巴比妥酸反应性物质（TBARS）的活性增加。柠檬马鞭草治疗可减轻抑郁样行为，与艾司西酞普兰治疗组相似。关于神经组织中的炎症标志物，观察到柠檬马鞭草治疗的动物水平低于艾司西酞普兰治疗组和对照组，与生理盐水治疗的MD组相比甚至更低。这些治疗降低了接受MD方案动物血清中的MPO活性。血清中的TBARS降低，海马中的TBARS最终逆转。此外，分子对接研究表明，黄芩苷和槲皮素-7-O-葡萄糖苷与IL-1β和IL-6有效相互作用。
围产期应激增加了抑郁样行为以及氧化应激和炎症标志物。柠檬马鞭草提取物治疗显著降低了抑郁样行为以及氧化应激和炎症标志物，表明其具有抗抑郁、抗氧化和抗炎作用。
