Herbal medicines remain integral to traditional and modern healthcare, with Ashwagandha (Withania somnifera) being one of the most widely utilised for its adaptogenic and neuroprotective properties. However, concerns regarding safety and herb–drug interactions necessitate systematic toxicological evaluation. Zebrafish (Danio rerio), owing to their genetic similarity to humans and high-throughput potential, have emerged as powerful models in preclinical toxicology. This review synthesises recent evidence from zebrafish-based assays, rodent studies, and clinical trials to evaluate Ashwagandha’s safety profile. Literature was critically analysed to highlight experimental approaches, including embryotoxicity, neurotoxicity, and cardiotoxicity assays, alongside molecular insights into oxidative stress, mitochondrial dysfunction, and cytochrome P450 interactions. Findings indicate that Ashwagandha demonstrates a broad safety margin, with zebrafish models revealing dose-dependent therapeutic and toxic effects. At optimal concentrations, extracts confer neuroprotection, immunomodulation, and stress resilience, consistent with mammalian and clinical outcomes. Conversely, excessive dosing may induce developmental and metabolic disturbances, underscoring the need for standardised protocols. Zebrafish data also align closely with rodent and human evidence, reinforcing translational validity. Zebrafish provide an efficient, predictive, and ethically sustainable platform for assessing Ashwagandha’s toxicological profile. Their integration into drug discovery and regulatory pipelines enhances the reliability of safety assessments, supporting the advancement of Ashwagandha as a standardised therapeutic.
Murali* et al. (Thu,) studied this question.