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应激暴露小鼠的抑郁和焦虑亚急性症状:巴西胡椒叶凝集素(SteLL)的作用。

Subacute symptoms of depression and anxiety in stress-exposed mice: Role of Schinus terebinthifolia Raddi leaf lectin (SteLL).

作者信息

de Lima Bárbara Raíssa Ferreira, de Siqueira Patriota Leydianne Leite, de Oliveira Marinho Amanda, da Costa Jainaldo Alves, Ribeiro Beatriz Galdino, de Souza Santos Valéria Bianca, Napoleão Daniella Carla, Cavalcanti Jorge Vinícius Fernandes Lima, Vieira Leucio Duarte, Pereira Michelly Cristiny, de Melo Rego Moacyr Jesus Barreto, Pitta Maira Galdino da Rocha, Napoleão Thiago Henrique, Paiva Patrícia Maria Guedes, da Rosa Michelle Melgarejo

机构信息

Biochemistry Department, Center of Biosciences, Universidade Federal de Pernambuco, Recife, Brazil.

Department of Chemical Engineering, Center for Technology and Geosciences, Universidade Federal de Pernambuco, Recife, Brazil.

出版信息

J Ethnopharmacol. 2025 Feb 11;341:119343. doi: 10.1016/j.jep.2025.119343. Epub 2025 Jan 11.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Anxiety and depression are leading causes of disability worldwide, often exacerbated by chronic stress. Schinus terebinthifolia Raddi. has been used in traditional medicine for several purposes. Among these, the use of bark-and-leaf tea and leaf decoction to treat depression has been reported. Previous studies showed that the S. terebinthifolia leaf lectin (SteLL) can ameliorate anxiety and depression symptoms in mice.

AIM OF THE STUDY

To investigate SteLL as a compound from S. terebinthifolia leaf able to alleviate symptoms of depression and anxiety in an unpredictable chronic mild stress (UCMS) animal model.

METHODS

Mice were subjected to four-week UCMS and then treated with SteLL at 2 and 4 mg/kg (i.p.) or with fluoxetine at 10 mg/kg i.p. (positive control) for 21 days. Behavioral assessments were conducted using the open field test, elevated plus maze, tail suspension test, and sucrose preference test. Serum corticosterone and inflammatory markers (cytokines) levels were determined. The levels of cytokine, oxidative stress indicators and monoamines in brain homogenates were also measured to understand the biochemical changes induced by SteLL treatment.

RESULTS

SteLL treatment at both doses significantly (p < 0.05) alleviated the stress-induced behavior in mice, reducing the anxiety and depression signals in all tests. SteLL administration increased the brain levels of monoamines noradrenaline and serotonin in comparison with UCMS control mice that received only vehicle. SteLL reduced superoxide production, lipid peroxidation and improved reduced glutathione (GSH) levels in the brain. The lectin also increased serum and brain levels of anti-inflammatory cytokine IL-4, while reducing levels of pro-inflammatory cytokines. Serum corticosterone levels were not decreased by lectin treatment.

CONCLUSION

Our findings highlight SteLL as a neuromodulatory agent from S. terebinthifolia leaves effective in subacute and stress-induced anxiety and depression through modulation of monoaminergic, oxidative stress, and inflammatory pathways. The data shows the potential of this lectin as a therapeutic agent for stress-related neuropsychological disorders.

摘要

民族药理学相关性

焦虑和抑郁是全球范围内导致残疾的主要原因,常因慢性应激而加剧。裂叶漆树(Schinus terebinthifolia Raddi.)在传统医学中有多种用途。其中,树皮和树叶茶以及树叶煎剂用于治疗抑郁症的情况已有报道。先前的研究表明,裂叶漆树叶片凝集素(SteLL)可改善小鼠的焦虑和抑郁症状。

研究目的

研究裂叶漆树叶片中的化合物SteLL在不可预测的慢性轻度应激(UCMS)动物模型中减轻抑郁和焦虑症状的能力。

方法

将小鼠进行为期四周的UCMS处理,然后分别用2mg/kg和4mg/kg的SteLL(腹腔注射)或10mg/kg的氟西汀(腹腔注射,阳性对照)处理21天。使用旷场试验、高架十字迷宫试验、悬尾试验和蔗糖偏好试验进行行为评估。测定血清皮质酮和炎症标志物(细胞因子)水平。还测量了脑匀浆中细胞因子、氧化应激指标和单胺的水平,以了解SteLL处理引起的生化变化。

结果

两种剂量的SteLL处理均显著(p<0.05)减轻了小鼠的应激诱导行为,在所有试验中均降低了焦虑和抑郁信号。与仅接受赋形剂的UCMS对照小鼠相比,SteLL给药增加了脑中去甲肾上腺素和血清素单胺水平。SteLL减少了超氧化物的产生、脂质过氧化,并提高了脑中还原型谷胱甘肽(GSH)水平。该凝集素还增加了血清和脑中抗炎细胞因子IL-4的水平,同时降低了促炎细胞因子水平。凝集素处理未降低血清皮质酮水平。

结论

我们的研究结果表明,SteLL是裂叶漆树叶片中的一种神经调节剂,通过调节单胺能、氧化应激和炎症途径,对亚急性和应激诱导的焦虑和抑郁有效。数据显示了这种凝集素作为应激相关神经心理障碍治疗药物的潜力。

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