8-Methoxypeucedanin: Evaluation of Anxiolytic Effects and Modulation of Neuronal Activity Related Genes in a Zebrafish Anxiety Mode

For thousands of years, medicinal plants and their constituents have been used, mostly empirically/ethnopharmacologically, to cure patients with central nervous system (CNS) disorders. Anxiolytics derived from natural products (NPs) often share similar mechanisms of action to synthetic ones (e.g., benzodiazepines, BDZs). Although typically as effective as synthetic anxiolytics, NPs are considered to be devoid of the serious side effects linked to the use of BDZs. 8-Methoxypeucedanin (8-MP) is a rare furanocoumarin present in the fruits of <i>Peucedanum luxurians</i> Tamamsch. (Apiaceae). The primary objective of the presented study was to assess the anxiolytic activity of 8-MP using a zebrafish (<i>Danio rerio</i>) model of anxiety. <i>Danio rerio</i> larvae at 5 days post-fertilization (dpf) were used, with reversed thigmotaxis considered as an index of the anxiolytic activity. In addition to the behavioral study, qPCR analyses were performed to assess the role of 8-MP in modulating the expression of <i>c-fos</i> and <i>bdnf</i>, two key genes involved in neural activity. As evidenced by the behavioral study, 8-MP (1.5-15 µM) exhibited a significant influence on anxiety, with a U-shape dose-response effect. Moreover, the expression of <i>c-fos</i> and <i>bdnf</i> genes was significantly downregulated, providing novel insights into the mechanisms of action of the tested furanocoumarin.