Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan.
J Agric Food Chem. 2010 Feb 10;58(3):1993-2000. doi: 10.1021/jf902221j.
Andrographolide (Ap) is a bioactive compound in Andrographis paniculata that is a Chinese herb. The pi class of glutathione S-transferase (GSTP) is one kind of phase II detoxification enzyme. Here we show that induction of GSTP protein and mRNA expression in rat primary hepatocytes by Ap was inhibited by forskolin and a variety of cAMP analogues. The inhibitory effect of the cAMP analogues was partially blocked by pretreatment with H89. In the presence of Ap, forskolin, or both, the expression of phospho-cAMP response element-binding protein (CREB) was increased. Ap alone had no effect on inducible cAMP early repressor (ICER) mRNA expression; however, Ap played a potentiating role in forskolin-induced ICER mRNA expression. An EMSA and immunoprecipitation assay showed that ICER binding to cAMP-response element (CRE) was increased in cells cotreated with Ap and forskolin for 3 and 8 h. Taken together, these results suggest that ICER is likely to be involved in the suppression of Ap-induced GSTP expression caused by the increase of cAMP in rat primary hepatocytes.
穿心莲内酯（Ap）是穿心莲中的一种生物活性化合物，是一种中国草药。π 类谷胱甘肽 S-转移酶（GSTP）是一种 II 相解毒酶。在这里，我们表明 Ap 诱导大鼠原代肝细胞中 GSTP 蛋白和 mRNA 表达被forskolin 和各种 cAMP 类似物抑制。cAMP 类似物的抑制作用可部分被 H89 预处理阻断。在 Ap、forskolin 或两者存在的情况下，磷酸化 cAMP 反应元件结合蛋白（CREB）的表达增加。Ap 单独对诱导型 cAMP 早期阻遏物（ICER）mRNA 表达没有影响；然而，Ap 在 forskolin 诱导的 ICER mRNA 表达中起增效作用。EMSA 和免疫沉淀测定表明，在 Ap 和 forskolin 共同处理 3 和 8 小时后，细胞中 ICER 与 cAMP 反应元件（CRE）的结合增加。综上所述，这些结果表明，ICER 可能参与了 cAMP 增加引起的 Ap 诱导的 GSTP 表达抑制，在大鼠原代肝细胞中。
