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

## TL;DR

This study evaluates the anxiolytic effects of 8-Methoxypeucedanin in zebrafish and its impact on genes related to neuronal activity.

## Contribution

The study reveals a U-shaped dose-response effect of 8-MP and its novel modulation of c-fos and bdnf gene expression in anxiety.

## Key findings

- 8-Methoxypeucedanin showed significant anxiolytic activity in zebrafish larvae with a U-shaped dose-response.
- 8-MP significantly downregulated the expression of c-fos and bdnf genes, suggesting a novel mechanism of action.
- The findings suggest 8-MP could be a natural alternative to synthetic anxiolytics without serious side effects.

## Abstract

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 Peucedanum luxurians Tamamsch. (Apiaceae). The primary objective of the presented study was to assess the anxiolytic activity of 8-MP using a zebrafish (Danio rerio) model of anxiety. Danio rerio 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 c-fos and bdnf, 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 c-fos and bdnf genes was significantly downregulated, providing novel insights into the mechanisms of action of the tested furanocoumarin.