Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.
Evid Based Complement Alternat Med. 2012;2012:650514. doi: 10.1155/2012/650514. Epub 2011 Jul 14.
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.
我们研究了三种甘草次酸衍生物（甘草酸（化合物 1）、甘草酸二钾（化合物 2）和甘草次酸（化合物 3））对哺乳动物聚合酶活性的抑制作用。在这些衍生物中，化合物 3 对属于 B、A、Y 和 X 家族的哺乳动物聚合酶α、β、κ 和 λ 的抑制作用最强，而化合物 1 和 2 则表现出中等抑制作用。在测试的这些衍生物中，化合物 3 对脂多糖（LPS）诱导的小鼠巨噬细胞 RAW264.7 和腹腔巨噬细胞产生肿瘤坏死因子-α（TNF-α）的抑制作用最强。此外，化合物 3 被发现可抑制工程化人胚肾（HEK）293 细胞中的核因子-κB（NF-κB）。另外，化合物 3 引起的 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的小鼠耳急性炎症减少程度大于化合物 1 和 2。总之，本研究发现，化合物 3 是化合物 1 和 2 的苷元，是一种基于哺乳动物聚合酶抑制的有前途的抗炎候选物。
