Kowalczyk, Joanna; Budzyńska, Barbara; Kurach, Łukasz; Pellegata, Daniele; El Sayed, Nesrine S; Gertsch, Jürg; Skalicka-Woźniak, Krystyna (2022). Neuropsychopharmacological profiling of scoparone in mice. Scientific reports, 12(1), p. 822. Springer Nature 10.1038/s41598-021-04741-3
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Scoparone (6,7-dimethoxycoumarin) is a simple coumarin from botanical drugs of Artemisia species used in Traditional Chinese Medicine and Génépi liquor. However, its bioavailability to the brain and potential central effects remain unexplored. We profiled the neuropharmacological effects of scoparone upon acute and subchronic intraperitoneal administration (2.5-25 mg/kg) in Swiss mice and determined its brain concentrations and its effects on the endocannabinoid system (ECS) and related lipids using LC-ESI-MS/MS. Scoparone showed no effect in the forced swimming test (FST) but, administered acutely, led to a bell-shaped anxiogenic-like behavior in the elevated plus-maze test and bell-shaped procognitive effects in the passive avoidance test when given subchronically and acutely. Scoparone rapidly but moderately accumulated in the brain (Cmax < 15 min) with an apparent first-order elimination (95% eliminated at 1 h). Acute scoparone administration (5 mg/kg) significantly increased brain arachidonic acid, prostaglandins, and N-acylethanolamines (NAEs) in the FST. Conversely, subchronic scoparone treatment (2.5 mg/kg) decreased NAEs and increased 2-arachidonoylglycerol. Scoparone differentially impacted ECS lipid remodeling in the brain independent of serine hydrolase modulation. Overall, the unexpectedly potent central effects of scoparone observed in mice could have toxicopharmacological implications for humans.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Pellegata, Daniele, Gertsch, Jürg |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Barbara Franziska Järmann-Bangerter |
Date Deposited: |
09 Mar 2022 11:21 |
Last Modified: |
05 Dec 2022 16:12 |
Publisher DOI: |
10.1038/s41598-021-04741-3 |
PubMed ID: |
35039558 |
BORIS DOI: |
10.48350/166389 |
URI: |
https://boris.unibe.ch/id/eprint/166389 |
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