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

Abstract

This study assessed the toxicity and therapeutic potential of Angelica dahurica and Angelica pubescens using Danio rerio (zebrafish) larvae. Toxicity was evaluated through mortality, malformations, and gene expression changes related to stress and the HPA axis. A. dahurica 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. A. pubescens 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 A. dahurica had stress-protective effects, increasing nr3c1 expression, while A. pubescens 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 A. dahurica showing promising effects at lower concentrations. However, A. pubescens requires careful dosage management due to its higher toxicity risks. Further studies are needed to optimize therapeutic applications and fully understand mechanisms of action.