Protective role of Algerian <i>Myrtus communis</i> L. against pesticide mixture-induced reproductive toxicity: a combined experimental and molecular dynamics insights targeting steroidogenesis pathway

This study aims to assess the impact of myrtle methanolic extract (Mex) in mitigating imidacloprid (Imi) and chlorothalonil (Chl)-induced prostate and testicular dysfunction in rats after 28 days of oral exposure.High-performance liquid chromatography coupled with ultraviolet-visible spectroscopy analysis (HPLC/UV-Vis) identified 12 compounds, with flavonols (40.23%), phenolic acids (33.19%), and flavanols (21.58%) as the main classes. Testosterone (T) and follicle-stimulating hormone (FSH) levels dropped sharply in the Imi + Chl group.Redox impairment was marked by mitochondrial swelling in groups that received Imi, Chl, or both individually or in combination. In contrast, Mex combined with the Imi + Chl mixture significantly restored these alterations to normal levels. Histopathological analysis of the prostate further confirmed these effects.Pesticides and bioactive compounds from Mex were docked into key enzymes involved in steroid biosynthesis, followed by MD simulations. Molecular mechanics/generalized born surface area (MMGBSA) binding energies indicated that rutin and epigallocatechin gallate (EGCG) from Mex-50 may compete with pesticides for the active sites of aromatase and steroid 5-alpha reductase type-II (SRD5A2), offering significant protection to the steroid biosynthesis pathway.