Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities

Abstract

We investigated the inhibitory effect of three glycyrrhizin derivatives, such as Glycyrrhizin (compound1), dipotassium glycyrrhizate (compound2) and glycyrrhetinic acid (compound3), on the activity of mammalian pols. Among these derivatives, compound3was the strongest inhibitor of mammalian polsα,β,κ, andλ, which belong to the B, A, Y, and X families of pols, respectively, whereas compounds1and2showed moderate inhibition. Among the these derivatives tested, compound3displayed strongest suppression of the production of tumor necrosis factor-α(TNF-α) induced by lipopolysaccharide (LPS) in a cell-culture system using mouse macrophages RAW264.7 and peritoneal macrophages derived from mice. Moreover, compound3was found to inhibit the action of nuclear factor-κB (NF-κB) in engineered human embryonic kidney (HEK) 293 cells. In addition, compound3caused greater reduction of 12-O-tetradecanoylphorbol-13-acetate-(TPA-) induced acute inflammation in mouse ear than compounds1and2. In conclusion, this study has identified compound3, which is the aglycone of compounds1and2, as a promising anti-inflammatory candidate based on mammalian pol inhibition.