Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Eur J Pharmacol. 2017 Nov 15;815:501-511. doi: 10.1016/j.ejphar.2017.10.019. Epub 2017 Oct 12.
Conflicting data exist on the effect of ginsenosides on transactivation of human glucocorticoid receptor α (herein referred to as glucocorticoid receptor), and relatively little is known regarding the effect of these chemicals on transrepression of this receptor. We investigated the effect of 20(S)-protopanaxadiol (PPD), PPD-type ginsenosides (Rb1, Rb2, Rc, Rd, Rh2, and Compound K), 20(S)-protopanaxatriol (PPT), and PPT-type ginsenosides (Re, Rf, Rg1, and Rh1) on glucocorticoid receptor binding, transactivation, and transrepression. Each ginsenoside was less efficacious than dexamethasone (positive control) in binding to the ligand-binding domain of glucocorticoid receptor. Among the ginsenosides investigated, Rh2 had the smallest IC value (15 ± 1µM), whereas it was 0.02 ± 0.01µM for dexamethasone. In contrast to dexamethasone, none of the ginsenosides influenced glucocorticoid receptor transactivation or transrepression in LS180 human colorectal adenocarcinoma cells, as assessed in a dual-luciferase reporter gene assay. Rh2 did not affect the endogenous mRNA level of tyrosine aminotransferase (marker for glucocorticoid receptor transactivation) or corticosteroid-binding globulin (marker for glucocorticoid receptor transrepression) in HepG2 human hepatocellular carcinoma cells. This chemical also did not alter the response by a glucocorticoid receptor agonist (dexamethasone or Compound A) in the dual-luciferase reporter gene assay or target gene expression assay. In conclusion, ginsenosides were less efficacious and less potent than dexamethasone in binding to the ligand-binding domain of glucocorticoid receptor. The number of glycosylated groups was associated with a decrease in receptor binding potency. PPD-type and PPT-type ginsenosides are not modulators of glucocorticoid receptor transactivation or transrepression in LS180 and HepG2 cells.
关于人参皂苷对人糖皮质激素受体 α 的转录激活作用存在相互矛盾的数据（以下简称糖皮质激素受体），而关于这些化学物质对该受体转录抑制作用的了解相对较少。我们研究了 20(S)-原人参二醇（PPD）、PPD 型人参皂苷（Rb1、Rb2、Rc、Rd、Rh2 和 Compound K）、20(S)-原人参三醇（PPT）和 PPT 型人参皂苷（Re、Rf、Rg1 和 Rh1）对糖皮质激素受体结合、转录激活和转录抑制的影响。与地塞米松（阳性对照）相比，每种人参皂苷与糖皮质激素受体的配体结合域结合的效力都较低。在所研究的人参皂苷中，Rh2 的 IC 值最小（15±1µM），而地塞米松为 0.02±0.01µM。与地塞米松相反，在 LS180 人结直肠腺癌细胞中，没有一种人参皂苷会影响糖皮质激素受体的转录激活或转录抑制，这是通过双荧光素酶报告基因检测评估的。Rh2 不会影响 HepG2 人肝癌细胞中酪氨酸转氨酶（糖皮质激素受体转录激活的标志物）或皮质甾醇结合球蛋白（糖皮质激素受体转录抑制的标志物）的内源性 mRNA 水平。这种化学物质也不会改变糖皮质激素受体激动剂（地塞米松或 Compound A）在双荧光素酶报告基因检测或靶基因表达检测中的反应。总之，人参皂苷与人糖皮质激素受体的配体结合域的结合效力和强度均低于地塞米松。糖基化基团的数量与受体结合效力的降低有关。在 LS180 和 HepG2 细胞中，PPD 型和 PPT 型人参皂苷不是糖皮质激素受体转录激活或转录抑制的调节剂。
