Acmella oleracea (L) R. K. Jansen Reproductive Toxicity in Zebrafish: An In Vivo and In Silico Assessment

The plant species Acmella oleracea L. is used in the north of Brazil for the treatment of a range of illnesses, such as tuberculosis, flu, cough, and rheumatism and as an anti-inflammatory agent; besides, hydroethanolic formulations with this species are popularly used as a female aphrodisiac agent. However, currently, there are no studies performed evaluating its effect on embryonic development. Hence, this research aimed to evaluate the effects of the hydroethanolic extract of A. oleracea (EHFAo) on the reproductive performance (parental) and embryonic development (F1 generation) of zebrafish, at concentrations of 50, 100, and 200 μg/L. Histopathology of parental gonads after 21 days of exposure to EHFAo reveals few alterations in the ovaries and testes, not impairing the reproduction; an increase of eggs deposition was observed in animals treated with EHFAo at the highest concentrations. Nevertheless, concerning the embryonic development of F1, teratogenic effects were observed including tail deformation, cardiac and yolk edema, scoliosis, and growth retardation; these alterations were more prominent in the groups born from progenitors exposed to the highest concentrations (100 and 200 μg/L.); but only the occurrence of yolk and cardiac edema had a statistically significant difference when compared to the control group. The chromatographic analysis shows that spilanthol (affinin) was the primary compound found in the EHFAo. Hence, in silico assessment was performed to evaluate the pharmacokinetic and toxicological properties of this molecule and 37 metabolites derived from it. Overall, our data show that the treatment caused no detrimental changes in progenitors regarding their gonads or fertility but caused some potentially teratogenic activity in embryos, which may be due to the action of spilanthol’s metabolites M3, M6, M7, M8, M16, M28, and M31.