Flavonoids Extracted From Daucus Carota Seeds as Selective Estrogen Receptor Modulators for Fertility Control

Abstract

The seeds of Daucus carota were proved to have a negative impact on reproductive hormone levels as well as on the estrous cycles in albino mice affecting the fertility status. The principal constituents of the Daucus carota extract were identified by HPLC and MS techniques. A few polyphenols viz. catechin, epicatechin, eriobictyol, peonidin, cyanidin, and pelargonidin were found to be present in the methanolic extract of Daucus carota. The present work involved a molecular computational study through integrated molecular docking, Molecular Dynamics (MD) simulations and molecular mechanics-generalized born surface area (MM-GBSA) calculations of these polyphenol compounds with estrogen receptor alpha. The Molecular Docking, MD simulation and binding free energy calculation studies carried out to reveal the molecular interaction of the polyphenols with human Estrogen Receptor (ER) which may interfere in the estrogen signaling in humans.

The interaction of these compounds with the estrogen receptor was studied by molecular docking simulation using the Schrodinger 2018 suit (Schrodinger, LLC, New York, NY, 2018). On the basis of binding energies, binding affinities and interacting residues it can be inferred that the flavonoids isolated from the extract can strongly bind to the active site of estrogen receptors and inhibit their normal functioning.

The results obtained from these computational approaches revealed that these polyphenols can selectively bind to ERα and can affect estrogen signaling in humans. The polyphenols have shown excellent docking scores with a high binding affinity towards the ERα receptor. The observation, which was further supported by the molecular dynamics simulation results, indicated that the selected flavonoids may act as potent Estrogen receptor modulators influencing female reproductive pathway. This study justifies the ethnomedicinal use of Daucus carota seeds to control fertility.

Keywords: antifertility, Daucus carota, docking, molecular dynamics