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Natural Science Foundation of China","award":["2025QN08017"],"award-info":[{"award-number":["2025QN08017"]}]},{"name":"National Natural Science Foundation of China","award":["zyylxk202403"],"award-info":[{"award-number":["zyylxk202403"]}]},{"name":"Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Bioanalysis of Mongolian medicines","award":["82560825"],"award-info":[{"award-number":["82560825"]}]},{"name":"Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Bioanalysis of Mongolian medicines","award":["YKD2022TD037"],"award-info":[{"award-number":["YKD2022TD037"]}]},{"name":"Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Bioanalysis of Mongolian medicines","award":["NJYT23135"],"award-info":[{"award-number":["NJYT23135"]}]},{"name":"Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Bioanalysis of Mongolian 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construction innovation team project","award":["2024MYYLXK006"],"award-info":[{"award-number":["2024MYYLXK006"]}]},{"name":"Inner Mongolia Medical University \u201cFirst-class Discipline\u201d construction innovation team project","award":["2025QN08017"],"award-info":[{"award-number":["2025QN08017"]}]},{"name":"Inner Mongolia Medical University \u201cFirst-class Discipline\u201d construction innovation team project","award":["zyylxk202403"],"award-info":[{"award-number":["zyylxk202403"]}]},{"name":"the Youth Science Fund Project of Inner Mongolia Natural Science Foundation","award":["82560825"],"award-info":[{"award-number":["82560825"]}]},{"name":"the Youth Science Fund Project of Inner Mongolia Natural Science Foundation","award":["YKD2022TD037"],"award-info":[{"award-number":["YKD2022TD037"]}]},{"name":"the Youth Science Fund Project of Inner Mongolia Natural Science Foundation","award":["NJYT23135"],"award-info":[{"award-number":["NJYT23135"]}]},{"name":"the Youth Science Fund Project of Inner Mongolia Natural Science Foundation","award":["2024MYYLXK006"],"award-info":[{"award-number":["2024MYYLXK006"]}]},{"name":"the Youth Science Fund Project of Inner Mongolia Natural Science Foundation","award":["2025QN08017"],"award-info":[{"award-number":["2025QN08017"]}]},{"name":"the Youth Science Fund Project of Inner Mongolia Natural Science Foundation","award":["zyylxk202403"],"award-info":[{"award-number":["zyylxk202403"]}]},{"name":"Inner Mongolia Medical University TCM \u201cFirst-class Discipline\u201d Construction Research Project","award":["82560825"],"award-info":[{"award-number":["82560825"]}]},{"name":"Inner Mongolia Medical University TCM \u201cFirst-class Discipline\u201d Construction Research Project","award":["YKD2022TD037"],"award-info":[{"award-number":["YKD2022TD037"]}]},{"name":"Inner Mongolia Medical University TCM \u201cFirst-class Discipline\u201d Construction Research Project","award":["NJYT23135"],"award-info":[{"award-number":["NJYT23135"]}]},{"name":"Inner Mongolia Medical University TCM \u201cFirst-class Discipline\u201d Construction Research Project","award":["2024MYYLXK006"],"award-info":[{"award-number":["2024MYYLXK006"]}]},{"name":"Inner Mongolia Medical University TCM \u201cFirst-class Discipline\u201d Construction Research Project","award":["2025QN08017"],"award-info":[{"award-number":["2025QN08017"]}]},{"name":"Inner Mongolia Medical University TCM \u201cFirst-class Discipline\u201d Construction Research Project","award":["zyylxk202403"],"award-info":[{"award-number":["zyylxk202403"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>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\u2013brain 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\u2032s sedative\u2013hypnotic efficacy, guiding future target identification.<\/jats:p>","DOI":"10.3390\/metabo15090631","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:08:03Z","timestamp":1758542883000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ambient Mass Spectrometry Imaging Reveals Spatiotemporal Brain Distribution and Neurotransmitter Modulation by 1,8-Cineole: An Epoxy Monoterpene in Mongolian Medicine Sugmel-3\u00a0"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0339-1365","authenticated-orcid":false,"given":"Jisiguleng","family":"Wu","sequence":"first","affiliation":[{"name":"College of Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qier","family":"Mu","sequence":"additional","affiliation":[{"name":"College of Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junni","family":"Qi","sequence":"additional","affiliation":[{"name":"College of Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasen","family":"Bao","sequence":"additional","affiliation":[{"name":"College of Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chula","family":"Sa","sequence":"additional","affiliation":[{"name":"College of Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","unstructured":"Yutog, Y. 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