Molecules (Nov 2024)

Toxicological Analysis of the Arylnaphthalene Lignan Justicidin B Using a <i>Caenorhabditis elegans</i> Model

  • Barbara Sciandrone,
  • Roméo Arago Dougué Kentsop,
  • Roberta Pensotti,
  • Gianluca Ottolina,
  • Iride Mascheretti,
  • Monica Mattana,
  • Maria Elena Regonesi

DOI
https://doi.org/10.3390/molecules29235516
Journal volume & issue
Vol. 29, no. 23
p. 5516

Abstract

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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 Caenorhabditis elegans to evaluate the safety of justicidin B produced by in vitro-grown adventitious roots of Linum lewisii. 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 C. elegans model as an appropriate tool to assess compounds’ toxicity before moving to more complex organisms.

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