Glycyrrhizic acid: novel potential protein targets

To date, a large body of data has been accumulated on the biological activity of a low-toxic natural glycoside, glycyrrhizic acid (GA), but the mechanism of its action at the molecular level has not been fully studied. Expanding knowledge about the spectrum of cellular protein targets of GA contributes to understanding new features of pharmacodynamics. The aim of the work was the experimental identification of a tissue-specific spectrum of protein molecules interacting with GA in a model system. Samples of an intact rat liver tissue lysate were incubated with GA covalently immobilized on EAH-Sepharose 4B, followed by elution of affinity-isolated protein molecules and their trypsinolysis. Using mass spectrometric analysis, 88 potential protein targets of GA were identified. According to the results of gel chromatographic separation of the rat liver lysate and semi-quantitative analysis of proteins, GA influenced Aldh6a1, Decr1, and Sod1 in fractions. Molecular docking in the Flare™ program used to model protein complexes with GA, resulted in selection of 5 proteins (Acox2, Acr1c9, Maoa, Mat1a, Nalcn), which formed complexes with GA with the most favorable ΔG and Rank score parameters. More than half (57%) of the affinity-isolated proteins are involved in the processes of basic cellular metabolism and biotransformation of endogenous and exogenous compounds. Data on the associations of potential protein targets of GA with diseases and different types of biological activity of GA have been systematized and compared.