Exploring the Toxicity and Therapeutic Potential of A. dahurica and A. pubescens in Zebrafish Larvae: Insights into Anxiety Treatment Mechanisms

This study assessed the toxicity and therapeutic potential of <i>Angelica dahurica</i> and <i>Angelica pubescens</i> using <i>Danio rerio</i> (zebrafish) larvae. Toxicity was evaluated through mortality, malformations, and gene expression changes related to stress and the HPA axis. <i>A. dahurica</i> demonstrated low toxicity (LD50 (50% lethal dose) >200 µg/mL), with no significant malformations at 15-30 µg/mL, although higher doses caused edemas and heart defects. <i>A. pubescens</i> exhibited higher toxicity, with 100% mortality at 200 µg/mL and severe malformations. Both species showed potential cardiotoxicity, slowing heart rates after prolonged exposure. Gene expression studies suggested <i>A. dahurica</i> had stress-protective effects, increasing <i>nr3c1</i> expression, while <i>A. pubescens</i> had dose-dependent effects, with lower concentrations having anxiolytic properties and higher concentrations increasing stress. Interestingly, diazepam showed unexpected gene expression changes, highlighting the influence of environmental and dosage factors. In conclusion, both species show therapeutic potential for anxiety, with <i>A. dahurica</i> showing promising effects at lower concentrations. However, <i>A. pubescens</i> requires careful dosage management due to its higher toxicity risks. Further studies are needed to optimize therapeutic applications and fully understand mechanisms of action.