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可能涉及 L-精氨酸-一氧化氮通路在 Auraptene 对小鼠的抗抑郁活性中的作用。

Possible involvement of L-arginine-nitric oxide pathway in the antidepressant activity of Auraptene in mice.

机构信息

Medical plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

Behav Brain Funct. 2022 Feb 14;18(1):4. doi: 10.1186/s12993-022-00189-1.

DOI:10.1186/s12993-022-00189-1
PMID:35164803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8842875/
Abstract

BACKGROUND

Depression is one of the most common mental illnesses worldwide. Nitric oxide (NO) is involved in the pathophysiology of depression. Auraptene (a coumarin derivative) has been shown to possess pharmacological effects on neurological diseases.

PURPOSE

The present study aimed to investigate the possible role of the NO pathway in Auraptene antidepressant effects in male mice.

METHODS

Behavioral tests were used to assess depression-like behaviors. The mice received Auraptene at 10, 30, and 100 mg/kg, the combination of the sub-effective (ineffective) dose of Auraptene (10 mg/kg) and L-NAME, and the combination of the effective dose of Auraptene (30 mg/kg) and L-arginine. Finally, OFT, TST, FST, brain, serum MDA level, antioxidant capacity, hippocampus, and serum NO level were measured.

RESULTS

The data analysis showed that Auraptene (30 mg/kg) improved depression-like behaviors. Auraptene (30 mg/kg) also significantly reduced serum NO levels (P < 0.05) and significantly increased serum MDA (10 mg/kg, P < 0.05). Auraptene at 30 mg/kg also increased serum antioxidant capacity (P < 0.01). Co-administration of L-NAME and the sub-effective dose of Auraptene enhanced the effects of Auraptene. However, co-administration of the effective dose of Auraptene and L-arginine reduced the impacts of Auraptene.

CONCLUSIONS

The results showed that Auraptene causes antidepressant effects in a dose-dependent manner and acts as a prooxidant at 100 mg/kg, and exacerbates oxidative stress. The antidepressant effects of this active molecule are exerted by reducing the NO level in the hippocampus and serum, increasing the antioxidant capacity, and reducing the MDA level in the serum.

摘要

背景

抑郁症是全球最常见的精神疾病之一。一氧化氮(NO)参与抑郁症的病理生理学。花椒内酯(香豆素衍生物)已被证明对神经疾病具有药理作用。

目的

本研究旨在探讨 NO 通路在花椒内酯抗抑郁作用中的可能作用。

方法

采用行为学测试评估抑郁样行为。小鼠接受花椒内酯 10、30 和 100mg/kg、花椒内酯亚有效(无效)剂量(10mg/kg)与 L-NAME 的组合、花椒内酯有效剂量(30mg/kg)与 L-精氨酸的组合。最后,测量 OFT、TST、FST、大脑、血清 MDA 水平、抗氧化能力、海马体和血清 NO 水平。

结果

数据分析表明,花椒内酯(30mg/kg)改善了抑郁样行为。花椒内酯(30mg/kg)还显著降低了血清 NO 水平(P<0.05),并显著增加了血清 MDA(10mg/kg,P<0.05)。花椒内酯 30mg/kg 还增加了血清抗氧化能力(P<0.01)。L-NAME 和花椒内酯亚有效剂量的联合给药增强了花椒内酯的作用。然而,花椒内酯有效剂量和 L-精氨酸的联合给药降低了花椒内酯的影响。

结论

结果表明,花椒内酯以剂量依赖的方式引起抗抑郁作用,在 100mg/kg 时表现为促氧化剂,并加重氧化应激。该活性分子的抗抑郁作用是通过降低海马体和血清中的 NO 水平、增加抗氧化能力和降低血清 MDA 水平来实现的。

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