In vitro and in silico perspectives on estrogenicity of tanshinones from Salvia miltiorrhiza

摘要

This work aims to investigate the structure-activity relationship for binding and activation of human estrogen receptor alpha ligand binding domain (hER alpha-LBD) with tanshinones by a combination of in vitro and in silico approaches. The recombinant hER alpha-LBD was expressed in E. coli strain. The direct binding interactions of tanshinones with hER alpha-LBD and their ER alpha agonistic potency were investigated by fluorescence polarization (FP) and reporter gene assays, respectively. FP assay suggested that the tested tanshinones can bind to hER alpha-LBD as affinity ligands. Tanshinones acted as agonists of hER alpha as demonstrated by transactivation of estrogen response element (ERE) in transiently transfected MCF-7 cells and by molecular docking of these compounds into the hydrophobic binding pocket of hER alpha-LBD. Interestingly, comparison of the calculated binding energies versus Connolly solvent-excluded volume and experimental binding affinities showed a good correlation. This work may provide insight into chemical and pharmacological characterization of novel bioactive compounds from Salvia miltiorrhiza.