Ambient Mass Spectrometry Imaging Reveals Spatiotemporal Brain Distribution and Neurotransmitter Modulation by 1,8-Cineole: An Epoxy Monoterpene in Mongolian Medicine Sugmel-3.

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites Pub Date : 2025-09-22 DOI:10.3390/metabo15090631

Jisiguleng Wu, Qier Mu, Junni Qi, Hasen Bao, Chula Sa

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引用次数: 0

Abstract

Background/Objectives: 1,8-Cineole, an epoxy monoterpene, is a key volatile component of Sugmel-3, a traditional Mongolian medicine used for treating insomnia. Although previous studies suggest that 1,8-Cineole can cross the blood-brain barrier (BBB), its precise spatiotemporal distribution in the brain and its in situ association with alterations in neurotransmitter (NT) levels remain unclear. This study utilized ambient mass spectrometry imaging (AFADESI-MSI) to investigate the dynamic brain distribution of 1,8-Cineole and its major metabolite, as well as their correlation with NT levels. Methods: Sprague Dawley rats (n = 3 per time point) received oral administration of 1,8-Cineole (65 mg/kg). Brain tissues were harvested 5 min, 30 min, 3 h, and 6 h post dose and analyzed using AFADESI-MSI. The spatial and temporal distributions of 1,8-Cineole, its metabolite 2-hydroxy-1,8-Cineole, key neurotransmitters (e.g., 5-HT, GABA, glutamine, melatonin), and related endogenous metabolites were mapped across 13 functionally distinct brain microregions. Results: AFADESI-MSI demonstrated rapid brain entry of 1,8-Cineole and its metabolite, with distinct spatiotemporal pharmacokinetics. The metabolite exhibited higher brain exposure, with 1,8-Cineole predominant in the cortex (CTX) and hippocampus (HP), while its metabolite showed pronounced accumulation in the pineal gland (PG), alongside CTX/HP. Region-dependent alterations in neurotransmitter levels (notably in PG, HP) correlated with drug concentrations, with observed increases in key molecules of the serotonergic and GABAergic pathways. Conclusions: Using AFADESI-MSI, this study provides the first spatiotemporal map of 1,8-Cineole and its metabolite in the brain. The correlation between their region-specific distribution and local neurotransmitter alterations suggests a direct mechanistic link to Sugmel-3's sedative-hypnotic efficacy, guiding future target identification.

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环境质谱成像揭示蒙药Sugmel-3中环氧单萜1,8-桉树脑的时空分布和神经递质调节。

背景/目的：1,8-桉树脑是一种环氧单萜，是治疗失眠的蒙药苏梅尔-3的主要挥发性成分。尽管先前的研究表明1,8-桉树脑素可以穿过血脑屏障（BBB），但其在大脑中的精确时空分布及其与神经递质（NT）水平改变的原位关联尚不清楚。本研究利用环境质谱成像（AFADESI-MSI）研究1,8-桉树脑及其主要代谢物的动态脑分布及其与NT水平的相关性。方法：大鼠（每个时间点n = 3只）口服1,8-桉树脑（65 mg/kg）。分别于给药后5分钟、30分钟、3小时和6小时采集脑组织，使用AFADESI-MSI进行分析。绘制了1,8-桉树脑及其代谢物2-羟基-1,8-桉树脑、关键神经递质（如5-HT、GABA、谷氨酰胺、褪黑激素）和相关内源性代谢物在13个功能不同的脑微区中的时空分布。结果：AFADESI-MSI显示1,8-桉树脑及其代谢物快速进入脑，具有明显的时空药代动力学。其代谢物表现出较高的脑暴露，1,8-桉树脑主要存在于皮层（CTX）和海马（HP）中，而其代谢物在松果体（PG）和CTX/HP中均有明显的积累。神经递质水平的区域依赖性改变（特别是PG和HP）与药物浓度相关，观察到血清素能和gaba能通路的关键分子增加。结论：利用AFADESI-MSI，本研究首次提供了1,8-桉树脑及其代谢物在大脑中的时空图谱。它们的区域特异性分布与局部神经递质改变之间的相关性表明，Sugmel-3的镇静催眠作用与其直接的机制联系，为未来的靶标识别提供指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

5.70

自引率

7.30%

发文量

1070

审稿时长

17.17 days

期刊介绍： Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.