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西红花苷通过 mTOR 信号通路介导的抗抑郁作用及机制研究。

Study on Antidepressant Effect and Mechanism of Crocin Mediated by the mTOR Signaling Pathway.

机构信息

College of Chemical and Biological Engineering, Yichun University, Yichun, 336000, China.

出版信息

Neurochem Res. 2022 Oct;47(10):3126-3136. doi: 10.1007/s11064-022-03668-z. Epub 2022 Jul 8.

DOI:10.1007/s11064-022-03668-z
PMID:35804209
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9282155/
Abstract

Crocin is a monomer of Chinese traditional herbs extracted from saffron, relieving depression-like behavior. However, its underlying mechanism of action remains unclear. Herein, we explored whether crocin's antidepressant effect depended on the mammalian target of the rapamycin (mTOR) signaling pathway. The model of PC12 cells injury was established by corticosterone, the changes in cell survival rate were tested by the CCK-8 method, and the changes in cellular morphology were observed under a fluorescence microscope. The depression model was established by chronic unpredictable mild stress (CUMS), and its antidepressant effect was estimated by open field test (OFT), forced swimming test (FST), and tail suspension test (TST). Western blot was used to monitor the protein expression. The results showed that crocin could effectively improve cell survival rate and cellular synaptic growth, alleviate the depressive behavior of CUMS mice, and promote the expression of BDNF, P-mTOR, P-ERK, and PSD95. However, when rapamycin was pretreated, the antidepressant effects of crocin were inhibited. In summary, crocin plays a significant antidepressant effect. After pretreatment with rapamycin, the anti-depression effect of crocin was significantly inhibited. It is suggested that the mechanism of the anti-depression effect of crocin may be related to the mTOR signaling pathway.

摘要

西红花苷是从藏红花中提取的一种中药单体,具有抗抑郁作用。然而,其作用机制尚不清楚。本研究旨在探讨西红花苷的抗抑郁作用是否依赖于哺乳动物雷帕霉素靶蛋白(mTOR)信号通路。采用皮质酮建立 PC12 细胞损伤模型,通过 CCK-8 法检测细胞存活率的变化,荧光显微镜观察细胞形态的变化。采用慢性不可预知性温和应激(CUMS)建立抑郁模型,通过旷场实验(OFT)、强迫游泳实验(FST)和悬尾实验(TST)评估其抗抑郁作用。Western blot 法检测蛋白表达。结果表明,西红花苷能有效提高细胞存活率和细胞突触生长,缓解 CUMS 小鼠的抑郁行为,促进 BDNF、P-mTOR、P-ERK 和 PSD95 的表达。然而,预先给予雷帕霉素后,西红花苷的抗抑郁作用被抑制。综上所述,西红花苷具有显著的抗抑郁作用。预先给予雷帕霉素后,西红花苷的抗抑郁作用明显受到抑制。提示西红花苷的抗抑郁作用机制可能与 mTOR 信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5cc/9282155/9300889e00ef/11064_2022_3668_Fig3a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5cc/9282155/cc948ae2304f/11064_2022_3668_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5cc/9282155/72c71e807841/11064_2022_3668_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5cc/9282155/9300889e00ef/11064_2022_3668_Fig3a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5cc/9282155/cc948ae2304f/11064_2022_3668_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5cc/9282155/72c71e807841/11064_2022_3668_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5cc/9282155/9300889e00ef/11064_2022_3668_Fig3a_HTML.jpg

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J Proteome Res. 2022 Mar 4;21(3):788-797. doi: 10.1021/acs.jproteome.1c00516. Epub 2021 Oct 26.
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Merazin Hydrate Produces Rapid Antidepressant Effects Depending on Activating mTOR Signaling by Upregulating Downstream Synaptic Proteins in the Hippocampus.美拉扎林水合物通过上调海马体下游突触蛋白激活 mTOR 信号,产生快速抗抑郁作用。
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PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?
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