Vemu Bhaskar, Nauman Mirielle C, Veenstra Jacob P, Johnson Jeremy J
University of Illinois at Chicago, College of Pharmacy, Department of Pharmacy Practice.
Int J Nutr. 2019;4(2):38-45. Epub 2019 Jun 16.
The mangosteen fruit is a popular Southeast Asian fruit consumed for centuries. There have been a variety of xanthones isolated from the fruit, bark, roots and leaves with each having unique chemical and physical properties. Previously, the most abundant xanthone α-mangostin has been shown to inhibit CDK4. Herein we describe the role of selected xanthones from the mangosteen inhibiting CDK4. The evidence we provide here is that key functional groups are required to inhibit the CDK4 protein to prevent the phosphorylation of downstream targets critical to inhibiting uncontrolled cell cycle progression. To define the properties of xanthones for inhibiting CDK4 we utilized a cell free biochemical assay to identify inhibitors of CDK4. The following xanthones were used for the analysis: α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinone C and garcinone D, 9-hydroxycalabaxanthone, and 3-isomangostin These results further substantiate the unique pharmacological properties of individual xanthones and how a mixture of xanthones may be responsible for a multi-targeted effect in cell based pharmacology systems.
山竹果是一种深受欢迎的东南亚水果，几个世纪以来一直被食用。人们已从这种水果的果实、树皮、根和叶中分离出多种呫吨酮，每种呫吨酮都具有独特的化学和物理性质。此前已表明，含量最高的呫吨酮α-倒捻子素能够抑制细胞周期蛋白依赖性激酶4（CDK4）。在此，我们描述了山竹果中选定的呫吨酮对CDK4的抑制作用。我们在此提供的证据是，抑制CDK4蛋白以防止对抑制不受控制的细胞周期进程至关重要的下游靶点磷酸化需要关键官能团。为了确定呫吨酮抑制CDK4的特性，我们利用无细胞生化测定法来鉴定CDK4的抑制剂。分析使用了以下呫吨酮：α-倒捻子素、β-倒捻子素、γ-倒捻子素、藤黄菌素、8-脱氧藤黄菌素、藤黄酮C和藤黄酮D、9-羟基卡拉巴呫吨酮以及3-异倒捻子素。这些结果进一步证实了各个呫吨酮独特的药理特性，以及呫吨酮混合物如何在基于细胞的药理系统中产生多靶点效应。
