title: Inhibitory effects of glycyrrhetinic Acid on DNA polymerase and inflammatory activities.
abstract: 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-κB (NF-κB) 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.
authors.affiliation: Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ishida
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
authors.forename: Saori
authors.initials: S
authors.lastname: Yagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Irino
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Shigeto
authors.initials: S
authors.lastname: Mizuno
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida