Toxicological Analysis of the Arylnaphthalene Lignan Justicidin B Using a Caenorhabditis elegans Model

The screening of plant-derived compounds with anti-cancer properties is a promising strategy to meet the growing need for new, safe and effective anti-cancer drugs. Justicidin B is a plants secondary metabolite that displays anti-cancer properties in several tumor cells. Therefore, it represents a good candidate. We used the 3R-compliant organism <i>Caenorhabditis elegans</i> to evaluate the safety of justicidin B produced by <i>in vitro</i>-grown adventitious roots of <i>Linum lewisii</i>. We showed that a dose of 100 µg/mL justicidin B does not affect worm vitality in either short-term or chronic administration; in contrast, the 200 µg/mL dose induces a lifespan reduction, but only in short-term daily treatment. We attributed this effect to its accumulation in lipofuscin granules in the pharynx as observed through confocal analysis. HPLC analysis confirmed the higher accumulation justicidin B with a 200 µg/mL dose but also revealed the presence of metabolic derivatives that could be responsible for the toxicity. We also demonstrated that the 100 µg/mL dose does not affect worm fertility or development. Our results highlight the safety of justicidin B, supporting its employment in cancer therapy, and encourage the use of a <i>C. elegans</i> model as an appropriate tool to assess compounds' toxicity before moving to more complex organisms.