In vitro and in silico perspectives on estrogenicity of tanshinones from Salvia miltiorrhiza. (1st January 2019)

• Record Type: Journal Article
• Authors: Zhang, Tiehua; Zhong, Shuning; Wang, Yongjun; Dong, Shuyue; Guan, Tianzhu; Hou, Ligang; Xing, XiaoJia; Zhang, Jie; Li, Tiezhu
• Is Part Of: Food chemistry. Volume 270(2019)
• Page Start: 281
• Page End: 286
• Publication Date: 2019-01-01
• Subjects: Estrogenic activity -- Tanshinones -- Fluorescence polarization -- Luciferase reporter assay -- Molecular docking; Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; 664
• DOI: 10.1016/j.foodchem.2018.07.098
• Languages: English
• ISSNs: 0308-8146

Abstract

Highlights: The structure-activity relationship for estrogenic tanshinones was investigated. Tanshinones exhibited dose-dependent binding to human estrogen receptor α. Tanshinones acted as agonists in an estrogen response element reporter gene assay. Molecular modeling showed potential for predicting affinities of novel compounds. Abstract: This work aims to investigate the structure-activity relationship for binding and activation of human estrogen receptor α ligand binding domain (hERα-LBD) with tanshinones by a combination of in vitro and in silico approaches. The recombinant hERα-LBD was expressed in E. coli strain. The direct binding interactions of tanshinones with hERα-LBD and their ERα agonistic potency were investigated by fluorescence polarization (FP) and reporter gene assays, respectively. FP assay suggested that the tested tanshinones can bind to hERα-LBD as affinity ligands. Tanshinones acted as agonists of hERα 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 hERα-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 .