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(+)-香芹酮,一种具有潜在神经退行性疾病防治活性的单萜类化合物:体外、体内和离体研究。

-(+)-Carvone, a Monoterpene with Potential Anti-Neurodegenerative Activity-In Vitro, In Vivo and Ex Vivo Studies.

机构信息

Department of Inorganic Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.

Independent Laboratory of Behavioral Studies, Medical University of Lublin, 4A Chodźki, 20-093 Lublin, Poland.

出版信息

Molecules. 2024 Sep 13;29(18):4365. doi: 10.3390/molecules29184365.

DOI:10.3390/molecules29184365
PMID:39339360
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11434264/
Abstract

Carvone, a natural monoterpene, has been identified in various plants, giving them a characteristic scent. Enantiomers (-(-) and -(+)) reveal specific biological activities that are successfully used in traditional medicine for their antifungal, antibacterial, antiparasitic, and anti-influenza properties. The presented paper is based on -(+)-carvone, characterized by a specific caraway scent, which revealed rich biological activities both in vitro and in vivo. Thus, the aim of the study was to evaluate the potential anti-neurodegenerative activity of -(+)-carvone, including in vitro experiments (butyrylcholinesterase inhibitory, neuro- and hepatotoxicity as well as neuro- and hepatoprotective activity), in vivo (memory acquisition, locomotor activity), and ex vivo (determination of -(+)-carvone's level in tissues collected from mice). Results revealed the multidirectional character of -(+)-carvone. It has been shown that -(+)-carvone is capable of butyrylcholinesterase inhibition (40% for 0.025 mg applied onto the plate), and neuroprotection and hepatoprotection at selective concentrations against reactive oxygen species generation and lipid peroxidation along with non-hepatotoxicity character. Additionally, multiple-dose administration of the monoterpene at a dose of 100 mg/kg had a positive influence on memory acquisition. Gas chromatography-mass spectrometry analysis of the plasma and the brain showed that -(+)-carvone can cross the blood-brain barrier and accumulate in the hippocampus (0.217 µg/mg of tissue), a crucial part of the brain associated with cognition and mental functions.

摘要

香芹酮,一种天然单萜,已在多种植物中被发现,赋予它们特有的气味。对映异构体((-(-)和-(+))) 揭示了特定的生物活性,这些活性已成功用于传统医学,具有抗真菌、抗菌、抗寄生虫和抗流感特性。本文基于 (-(+)-香芹酮,具有独特的葛缕子气味,具有丰富的体外和体内生物活性。因此,本研究旨在评估 -(+)-香芹酮的潜在神经退行性疾病活性,包括体外实验(丁酰胆碱酯酶抑制、神经毒性和肝毒性以及神经和肝保护活性)、体内实验(记忆获取、运动活性)和离体实验(测定从小鼠收集的组织中 -(+)-香芹酮的水平)。结果揭示了 -(+)-香芹酮的多向性。结果表明, -(+)-香芹酮能够抑制丁酰胆碱酯酶(在平板上应用 0.025 mg 时抑制 40%),并且在选择性浓度下具有神经保护和肝保护作用,可对抗活性氧生成和脂质过氧化,同时具有非肝毒性特征。此外,在 100 mg/kg 的剂量下多次给予单萜对记忆获取有积极影响。血浆和大脑的气相色谱-质谱分析表明, -(+)-香芹酮可以穿过血脑屏障并在海马体中积累(组织中 0.217 µg/mg),海马体是大脑中与认知和精神功能相关的关键部位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/93c4f4d6b97d/molecules-29-04365-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/932070b8df31/molecules-29-04365-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/30fe0dd3e594/molecules-29-04365-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/1eb8e19fd1b4/molecules-29-04365-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/0bb935049358/molecules-29-04365-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/ac223ba6fcd8/molecules-29-04365-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/ae92483143f4/molecules-29-04365-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/93c4f4d6b97d/molecules-29-04365-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/932070b8df31/molecules-29-04365-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/30fe0dd3e594/molecules-29-04365-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/1eb8e19fd1b4/molecules-29-04365-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/0bb935049358/molecules-29-04365-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/ac223ba6fcd8/molecules-29-04365-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/ae92483143f4/molecules-29-04365-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c229/11434264/93c4f4d6b97d/molecules-29-04365-g007.jpg

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