| Autor: |
Widelski J; Medicinal Plant Unit, Department of Pharmacognosy, Medical University of Lublin, 20-093 Lublin, Poland., Kasica N; Department of Animal Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland., Maciąg M; Independent Laboratory of Behavioral Studies, Medical University of Lublin, 20-093 Lublin, Poland., Luca SV; Biothermodynamics, TUM School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.; Department of Pharmacognosy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania., Budzyńska B; Independent Laboratory of Behavioral Studies, Medical University of Lublin, 20-093 Lublin, Poland., Fondai D; Department of Pharmacy, Faculty of Medicine, University of Prishtina, 10000 Prishtina, Kosovo., Podlasz P; Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland., Skalicka-Woźniak K; Department of Chemistry of Natural Products, Medical University of Lublin, 20-093 Lublin, Poland. |
| Abstrakt: |
Anxiety is one of the most common central nervous system disorders, affecting at least one-quarter of the worldwide population. The medications routinely used for the treatment of anxiety (mainly benzodiazepines) are a cause of addiction and are characterized by many undesirable side effects. Thus, there is an important and urgent need for screening and finding novel drug candidates that can be used in the prevention or treatment of anxiety. Simple coumarins usually do not show side effects, or these effects are much lower than in the case of synthetic drugs acting on the central nervous system (CNS). This study aimed to evaluate the anxiolytic activity of three simple coumarins from Peucedanum luxurians Tamamsch, namely officinalin, stenocarpin isobutyrate, and officinalin isobutyrate, in a 5 dpf larval zebrafish model. Moreover, the influence of the tested coumarins on the expression of genes involved in the neural activity ( c-fos , bdnf ) or dopaminergic ( th1 ), serotoninergic ( htr1Aa , htr1b , htr2b ), GABA-ergic ( gabarapa , gabarapb ), enkephalinergic ( penka , penkb ), and galaninergic ( galn ) neurotransmission was assessed by quantitative PCR. All tested coumarins showed significant anxiolytic activity, with officinalin as the most potent compound. The presence of a free hydroxyl group at position C-7 and the lack of methoxy moiety at position C-8 might be key structural features responsible for the observed effects. In addition, officinalin and its isobutyrate upregulated the expression of genes involved in neurotransmission and decreased the expression of genes connected with neural activity. Therefore, the coumarins from P. luxurians might be considered as promising drug candidates for the therapy of anxiety and related disorders. |
