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We investigated the inhibitory effect of three glycyrrhizin derivatives, such as Glycyrrhizin (compound  1 ), dipotassium glycyrrhizate (compound  2 ) and glycyrrhetinic acid (compound  3 ), on the activity of mammalian pols. Among these derivatives, compound  3  was the strongest inhibitor of mammalian pols   α  ,   β  ,   κ  , and   λ  , which belong to the B, A, Y, and X families of pols, respectively, whereas compounds  1  and  2  showed moderate inhibition. Among the these derivatives tested, compound  3  displayed 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, compound  3  was found to inhibit the action of nuclear factor-  κ  B (NF-  κ  B) in engineered human embryonic kidney (HEK) 293 cells. In addition, compound  3  caused greater reduction of 12- O -tetradecanoylphorbol-13-acetate-(TPA-) induced acute inflammation in mouse ear than compounds  1  and  2 . In conclusion, this study has identified compound  3 , which is the aglycone of compounds  1  and  2 , as a promising anti-inflammatory candidate based on mammalian pol inhibition.

Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities