Reproductive toxicity of the hydroethanolic extract of the flowers of Acmella oleracea and spilanthol in zebrafish: In vivo and in silico evaluation

Abstract

Hydroethanolic preparations of Acmella oleracea is used in the north of Brazil as a female aphrodisiac. Thus, the objective of this study was to evaluate the action of the hydroethanolic extract of Acmella oleracea (EHFAo) flowers (21.873 and 44.457 mg/kg) and spilanthol (3 mg/kg) administered orally on reproductive performance and effects on the embryonic development of zebrafish F1 generation. It was observed that in the groups in which males and females received EHFAo and spilanthol, the spawning was interrupted, whereas in the groups in which only the females were treated, spawning occurred during the 21 days. Thus, in the histopathological evaluation of the gonads, it was possible to observe that the percentage of mature cells in the spermatozoa and females was significantly reduced. Only the embryo groups in which parental generation was treated with EHFAo showed lethal and teratogenic effects. On the other hand, the parental groups treated with the spilanthol presented only the lethality. Spilanthol and some metabolites showed good oral availability and important toxicological properties. Thus, it is suggested that the treatment of parental generation of zebrafish with EHFAo and spilanthol caused severe changes in the gonads and on fertility. However, on the embryo, the most striking effects in the development were recorded in the groups in which the parental generation was treated with the EHFAo, while the spilanthol influenced the lethality of the embryos.

Chemistry and Pharmacology of Alkylamides from Natural Origin

“…A. pyrethrum is used as an aphrodisiac in Indian ayurvedic medicine for the treatment of male sexual dysfunction, including infertility (Sharma et al 2013 ). A. oleracea is used in the north of Brazil as a female aphrodisiac (de Souza et al 2020 ). Phyllanthus fraternus is used for the treatment of malaria, jaundice, and various liver diseases by traditional healers and tribes in the northern region of India (Ghatapanadi et al 2011 ; Sarkhel 2015 ).…”

“…Plants containing alkylamides have been used traditionally for fertility and related purposes. These include L. meyenii used to enhance fertility and sexual behavior and as a remedy for menopausal symptoms (Valerio and Gonzales 2005 ), A. pyrethrum used as aphrodisiac in Indian ayurvedic medicine (Sharma et al 2013 ), and A. oleracea used as a female aphrodisiac in Brazil (de Souza et al 2020 ).…”

“…Its toxicity was also assessed in zebrafish. Orally administered spilanthol (3 mg/kg) was evaluated for its effects on reproductive performance and embryonic development of zebrafish F1 generation (de Souza et al 2020 ). Spilanthol interrupted spawning in the treated group and histopathological evaluation of the gonads revealed a reduction in the percentage of mature cells in the spermatozoa and in females.…”

“…Spilanthol interrupted spawning in the treated group and histopathological evaluation of the gonads revealed a reduction in the percentage of mature cells in the spermatozoa and in females. Also, spilanthol caused embryo lethality in parental groups treated with it as well as caused severe changes in the gonads and on fertility (de Souza et al 2020 ). More studies evaluating the toxicity of the so many available alkylamides with good pharmacological effects are required.…”

Libidibia ferrea (jucá), a Traditional Anti-Inflammatory: A Study of Acute Toxicity in Adult and Embryos Zebrafish (Danio rerio)

“…Souza et al [40] also used the absence of beating and egg coagulation as a parameter to account for the lethal effect on embryos, and evidenced cardiac edema, yolk sac edema, yolk edema, tail deformation, and scoliosis as teratogenic alterations in their study. Bittencourt et al [41] related future cardiovascular problems with teratogenic changes in the heart of embryos, which was similar in this study when increasing the dose of EHEFLf.…”