Estrogen receptor modulation of some polyphenols extracted from Daucus carota as a probable mechanism for antifertility effect: An in silico study

Abstract

The seeds of Daucus carota, traditionally used by women in many countries to prevent conception, were proved to have negative impact on reproductive hormone levels as well as on the estrous cycles in albino mice affecting the fertility status. This study is an attempt to investigate the possible role of polyphenols present in the seeds in hampering the reproductive processes. The Molecular Docking, Molecular Dynamics (MD) simulation and binding free energy calculation studies reveal that six polyphenols present in the seeds can bind with the active sites of human Estrogen Receptor (ER) and may interfere in the estrogen signaling in human. These polyphenols were found to bind to a conservative pocket of ER[Formula: see text], which is comprised of residues 343–388, 421–428 and 525–540. Docking studies indicated the presence of strong hydrogen bonding, pi–pi interactions and numerous hydrophobic interactions that stabilize the ER[Formula: see text]-polyphenol complexes. The docked complexes were further subjected to MM/GBSA analysis to calculate binding free energies. Molecular dynamic simulation studies carried out for a period of 20[Formula: see text]ns revealed low RMS deviation values suggesting high accuracy of the docking poses and stability of the complexes. Out of the six polyphenols, catechin and epicatechin have shown highest binding affinity towards the ER[Formula: see text] receptor. These findings will help in identifying ER modulators of plant origin targeting ER alpha and predicting their effects on the reproductive hormone homeostasis. Moreover, this study may form preliminary basis for further identification of potential herbal antifertility agents.