Objectives: Nature offers potential solutions for different health issues through plantderived compounds, extensively utilized in modern medicine. Ellagic acid, a phenolic compound found in fruits like raspberries (Rubus idaeus, Rosaceae), nuts like Walnut (Juglans regia, Juglandaceae), vegetables like sprouted adzuki bean (Vigna angularis, Fabaceae), and plant parts like bark of oak (Quercus species, Fagaceae), holds significant therapeutic potential. This study aimed to assess the antifertility effects of Ellagic acid using network pharmacology and in vivo evaluation focusing on its anti-implantation, anti-ovulatory, and anti-estrogenic effects on female Wistar rats. This study investigates the hypothesis that ellagic acid modulates reproductive pathways to exert antifertility effects. Methods: Ellagic acid targets were predicted using the BindingDB database, followed by pathway enrichment analysis through the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Shiny Gene Ontology (ShinyGO) web-based tool. Combined data underwent network analysis and visualization in Cytoscape, identifying 37 potential protein targets enriched in reproductive pathways. In vivo experiments were conducted on Wistar female rats using three antifertility screening assays: anti-implantation, anti-ovulation, and anti-estrogenic activity. Results and Discussion: Ellagic acid (40 mg/kg) resulted in an 11.65% increase in pre-implantation loss and a 16.44% increase in post-implantation loss, leading to a total antifertility effect of 26.3%. Antiovulation studies revealed reduced follicular development, increased atretic follicles, and degenerative changes in granulosa cells. In the anti-estrogenic activity study, the ellagic acid-only group showed decreased uterine weight (101.2 mg). In comparison, the group treated with both ellagic acid and estradiol exhibited a significantly increased uterine weight (152.4 mg) compared to the control group (116.2 mg). Histological analysis of ovarian and uterine tissues corroborated these findings. Conclusion: The study highlights the potential of ellagic acid as a multi-target antifertility agent, demonstrating significant effects on implantation, ovulation, and estrogenic activity. These findings support its potential as a natural contraceptive. However, further research is required to optimize its application and assess its long-term safety.
Golmei et al. (Mon,) studied this question.