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(L.) 蒙奇甲醇提取物通过上调去甲肾上腺素能神经元中的ERK信号通路减轻焦虑样行为。

Attenuation of Anxiety-Like Behavior by (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons.

作者信息

Borgonetti Vittoria, Les Francisco, López Víctor, Galeotti Nicoletta

机构信息

Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.

Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, 50830 Zaragoza, Spain.

出版信息

Pharmaceuticals (Basel). 2020 Dec 17;13(12):472. doi: 10.3390/ph13120472.

DOI:10.3390/ph13120472
PMID:33348565
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7766703/
Abstract

The long-term use of anxiolytic and antidepressant drugs can cause a plethora of side effects and the use of complementary and alternative medicine, which is generally considered safer than conventional medicine, is consistently increasing. (L.) Moench methanolic extract (HSE) has shown MAO-A inhibitory properties in previous studies. With the aim of obtaining innovative and safer therapies for mood disorders, this study investigated the potential activity of HSE in the management of anxiety- and depression-related symptoms. HSE showed dose-dependent (30-100 mg/kg p.o.) anxiolytic-like activity in the light dark box and marble burying tests, without any antidepressant-like activity, as shown by the results of the tail suspension test. Additionally, HSE did not have any effect on the modulation of pain, which highlights its selectivity in the control of anxiety-related behavior. At active doses, HSE did not produce any sedative effect or result in impaired motor coordination and memory functions. Western blotting experiments showed the ability of HSE to counteract the reduction in the phosphorylation of ERK44/42, to restore brain-derived neurotrophic factor (BDNF) expression and to return cyclic AMP response element binding (CREB) levels to basal levels in noradrenergic hippocampal neurons of mice exposed to an anxiety-related environment, which indicates a protective role against anxiety behavior. These results suggest that oral administration of HSE might represent an interesting opportunity for the management of anxiety disorders.

摘要

长期使用抗焦虑和抗抑郁药物会引发大量副作用,而通常被认为比传统药物更安全的补充和替代医学的使用量则在持续增加。在之前的研究中,唇形科植物莫氏薄荷甲醇提取物(HSE)已显示出单胺氧化酶A(MAO-A)抑制特性。为了获得针对情绪障碍的创新且更安全的疗法,本研究调查了HSE在管理焦虑和抑郁相关症状方面的潜在活性。在明暗箱和大理石掩埋试验中,HSE呈现出剂量依赖性(口服30 - 100毫克/千克)的抗焦虑样活性,而悬尾试验结果表明其没有任何抗抑郁样活性。此外,HSE对疼痛调节没有任何影响,这突出了其在控制焦虑相关行为方面的选择性。在有效剂量下,HSE不会产生任何镇静作用,也不会导致运动协调和记忆功能受损。蛋白质免疫印迹实验表明,HSE能够抵消暴露于焦虑相关环境的小鼠去甲肾上腺素能海马神经元中细胞外信号调节激酶44/42(ERK44/42)磷酸化的降低,恢复脑源性神经营养因子(BDNF)的表达,并使环磷酸腺苷反应元件结合蛋白(CREB)水平恢复到基础水平,这表明其对焦虑行为具有保护作用。这些结果表明,口服HSE可能是管理焦虑症的一个有趣选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/605c/7766703/1bd76ff4c3e0/pharmaceuticals-13-00472-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/605c/7766703/4e2b2760554d/pharmaceuticals-13-00472-g002.jpg
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