A Molecular Docking Study of Phytoestrogenic Compounds from Hypericum perforatum L. and Anethum graveolens L. with Two Isoforms of Estrogen Receptor

Estrogens play a key role in the growth, development and maintenance of a wide range of tissues. Physiological responses to estrogen in specific tissues are mediated by at least two isoforms of the estrogen receptor alpha (ERα) and beta (ERβ). Currently, medicinal plants are widely used in the treatment and control of diseases due to their lower cost and fewer side effects than synthetic drugs, including Hypericum perforatum L. and Anethum graveolens L. Hypericum perforatum L. is effective in premenstrual syndrome, and Anethum graveolens L. as a regulator, effective in sex hormones and dysmenorrhea. The main purpose of the present study was to compare the molecular interaction of phytoestrogenic compounds of the studied plants with these two isoforms of estrogen receptor through molecular docking.

This molecular docking study was performed in 2021. The Molecular docking method was used to calculate the molecular interaction with the aim of additional investigation of the possible hormonal effects of phytoestrogenic compounds in the studied plants. Evaluation of theoretical binding site of flavonoid phytoestrogenic compounds fisetin, kaempferol, quercetin, myricetin, tetramethyl stilbene, trans-Anethole, limonene, resveratrol, and genistein as an agonist or antagonist was performed by ERα and ERβ. The amino acid residues involved in the interaction, the free binding energy and the binding constant were determined. The collected data were analyzed using different software and compared with the results of related articles. 

By examining the binding energy and different conformations of phytoestrogenic compounds into ERs, fisetin, kaempferol, quercetin, myricetin and resveratrol were selected as the best potential ligands. The results confirm that these compounds were quite sterically compatible with the location at the active site occupied by the 17β-estradiol endogenous agonist as full agonist and partial agonist genistein. The results of molecular docking provided evidence of the binding of phytoestrogenic compounds to ERα and ERβ with a bond-free energy of -5.26 to -8.47 kcal/mol and a binding constant of 131.62 µM to 614.61 nM and their interaction with key residues of active site including Glu353, Arg394 and His524 of ERα and Glu305, Arg346 and His475 of ERβ as partial agonist. 

The interaction of the best phytoestrogenic compounds with the key amino acids of active site ERs such as the partial agonist of genistein was desirable. Valuable results of molecular docking in identifying the most important phytoestrogenic compounds can be considered as a starting point for optimization in the rational design of drugs in the treatment of estrogen-sensitive diseases.