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钩吻素甲对人 SH-SY5Y 神经细胞基因表达的超敏性。

Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens.

机构信息

Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, Verona 37134, Italy.

出版信息

BMC Complement Altern Med. 2014 Mar 19;14:104. doi: 10.1186/1472-6882-14-104.

DOI:10.1186/1472-6882-14-104
PMID:24642002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3999908/
Abstract

BACKGROUND

Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract.

METHODS

Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions.

RESULTS

Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10(-9) M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range.

CONCLUSIONS

The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation.

摘要

背景

钩吻(Gelsemium sempervirens L.,Gelsemium s.)是一种传统药用植物,在超低剂量下被用作抗焦虑药,最近的动物模型也证实了这种活性。然而,其作用于神经系统的机制在很大程度上尚不清楚。本研究调查了用钩吻提取物递增稀释液处理的人神经细胞系的基因表达。

方法

从粗提取物开始,根据法国顺势疗法药典,制备了钩吻的六种 100×(百分度,c)稀释液(2c、3c、4c、5c、9c 和 30c)。人 SH-SY5Y 神经母细胞瘤细胞用测试稀释液暴露 24 小时,并用微阵列比较细胞与对照药物溶液处理的转录组。

结果

暴露于钩吻 2c 稀释液(所用的最高剂量,相当于 6.5×10(-9)M 的钩吻碱浓度)显著改变了 56 个基因的表达,其中 49 个基因下调,7 个基因过表达。下调的基因中有几个属于 G 蛋白偶联受体信号通路、钙稳态、炎症反应和神经肽受体。Fisher 精确检验应用于钩吻 2c 下调的 49 个基因组,表明即使差异大小分布在较小范围内,作用方向在高顺势稀释剂治疗中仍显著保持。

结论

该研究表明,钩吻是一种传统药物和顺势疗法中使用的药用植物,调节一系列与神经元功能相关的基因。即使在非常低的剂量/高稀释度(高达 30c)下,也检测到了小但具有统计学意义的反应,这表明人类神经细胞基因组对这种调节极其敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba73/3999908/0c916af7ddab/1472-6882-14-104-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba73/3999908/529bb51bdee5/1472-6882-14-104-1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba73/3999908/0c916af7ddab/1472-6882-14-104-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba73/3999908/529bb51bdee5/1472-6882-14-104-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba73/3999908/b594581fccfb/1472-6882-14-104-2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba73/3999908/0c916af7ddab/1472-6882-14-104-7.jpg

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