Wanda Germain Jean Magloire Ketcha, Starcke Susanne, Zierau Oliver, Njamen Dieudonné, Richter Tobias, Vollmer Günter
Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
Planta Med. 2007 Jun;73(6):512-8. doi: 10.1055/s-2007-967186. Epub 2007 May 7.
Griffonianone C (Griff C) is an isoflavone produced by Millettia griffoniana (Bail) and exhibits estrogenic properties in in vitro reporter gene assays. In order to validate its estrogenic potency in vivo, we administered subcutaneously Griff C (2, 10, or 20 mg/kg/d BW), 17beta-estradiol (10 microg/kg/d BW) as positive control, and a vehicle control to ovariectomized Wistar rats. After three consecutive days of treatment animals were sacrificed 24 hours after receiving the last dose. The uteri and livers were excised, weighed and stored for mRNA expression analysis by real-time PCR. The uterine wet weight was not significantly increased by Griff C, although there was a trend towards an increase. In contrast, 17beta-estradiol increased uterine wet weight 4.5-fold in comparison to the vehicle control. However, as revealed by real-time PCR Griff C affected the expression of estrogen-responsive genes in uterus and liver of ovariectomized rats. E2 induced a 550-fold stimulation of uterine C3 mRNA expression. Griff C at the dose 20 mg/kg/d BW caused a 50-fold up-regulation of complement C3 mRNA compared to the control. A significant increase in calcium binding protein 9-kilodalton mRNA expression was observed in the uterus of ovariectomized rats treated with E (2) (41-fold versus control) or 20 mg/kg/d BW of Griff C (25-fold versus control). In contrast, the expression of clusterin and progesterone receptor in the uterus was strongly decreased by both E2 and Griff C at the highest dose. We also found a repression of clusterin mRNA in the liver while carbonic anhydrase 2 and major acute phase protein were slightly up-regulated. In conclusion, Griff C showed a clear estrogenic action on uterine and hepatic tissues of ovariectomized rats, although its effect was less than the effect of estradiol. This suggests that some of the biological effects attributed to Millettia griffoniana are probably related to estrogen-mediated function.
格氏豆酮C（Griff C）是厚果崖豆藤（Millettia griffoniana (Bail)）产生的一种异黄酮，在体外报告基因试验中表现出雌激素特性。为了验证其在体内的雌激素效力，我们对去卵巢的Wistar大鼠皮下注射Griff C（2、10或20 mg/kg/天体重）、作为阳性对照的17β-雌二醇（10 μg/kg/天体重）以及溶剂对照。连续治疗三天后，在接受最后一剂24小时后处死动物。切除子宫和肝脏，称重并储存用于通过实时PCR进行mRNA表达分析。Griff C未显著增加子宫湿重，尽管有增加的趋势。相比之下，与溶剂对照相比，17β-雌二醇使子宫湿重增加了4.5倍。然而，实时PCR显示Griff C影响去卵巢大鼠子宫和肝脏中雌激素反应基因的表达。E2诱导子宫C3 mRNA表达增加550倍。与对照组相比，20 mg/kg/天体重剂量的Griff C使补体C3 mRNA上调50倍。在用E2（与对照组相比增加41倍）或20 mg/kg/天体重的Griff C（与对照组相比增加25倍）处理的去卵巢大鼠子宫中，观察到钙结合蛋白9千道尔顿mRNA表达显著增加。相比之下，E2和最高剂量的Griff C均使子宫中聚集素和孕激素受体的表达强烈降低。我们还发现肝脏中聚集素mRNA受到抑制，而碳酸酐酶2和主要急性期蛋白略有上调。总之，Griff C对去卵巢大鼠的子宫和肝脏组织显示出明显的雌激素作用，尽管其作用小于雌二醇。这表明厚果崖豆藤的一些生物学效应可能与雌激素介导的功能有关。
