Wanda G J M Ketcha, Njamen D, Yankep E, Fotsing M Tagatsing, Fomum Z Tanee, Wober J, Starcke S, Zierau O, Vollmer G
Molecular Cell Physiology und Endocrinology, Technical University Dresden, Germany.
Phytomedicine. 2006 Feb;13(3):139-45. doi: 10.1016/j.phymed.2005.06.003. Epub 2005 Sep 13.
In most developing countries, 70-80% of the population still resort to traditional medicine for their primary health care. This medicine utilises medicinal plants which are traditionally taken as concoction and infusion. The root and stem bark of Millettia griffoniana (Leguminosae), has been reported to contain isoflavonoids, alkaloids, and diterpenoids. The possible benefit of some bioactive isoflavones derived from M. griffoniana prompted us to screen them for estrogenic activity. Six isoflavones and coumarin derived from M. griffoniana (bail) namely, compound nos. 1-6 (Fig. 1) were tested for their potential estrogenic activities in three different estrogen receptor alpha (ERalpha)-dependent assays. In a yeast-based ERalpha assay, all test substances and 17beta-estradiol as endogenous agonist, showed a significant induction of beta-galactosidase activity. The test compounds at the concentration of 5 x 10(-6) M could achieve 59-121% of the beta-galactosidase induction obtained with 10(-8) M 17beta-estradiol (100%). In the reporter gene assay based on stably transfected MCF-7 cells (MVLN cells), the estrogen responsive induction of luciferase was also stimulated by the M. griffoniana isoflavones. In Ishikawa cells, all substances exhibited estrogenic activity revealed by the induction of alkaline phosphatase (AlkP) activity. The estrogenic activities of isoflavones from M. griffoniana could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ERalpha. Although all substances showed estrogenic effects, 4'-methoxy-7-O-[(E)-3-methyl-7-hydroxymethyl-2,6-octadienyl]isoflavone (7-O-DHF), Griffonianone C (GRIF-C), and 3',4'-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone (7-O-GISO) were found to be the most potent of tested substances. In summary, estrogenic activities of the isoflavones derived from M. griffoniana were described for the first time using reporter gene assays and the estrogen-inducible AlkP Ishikawa model.
在大多数发展中国家，70%-80%的人口仍依靠传统医学进行初级卫生保健。这种医学使用传统上作为煎剂和浸剂服用的药用植物。据报道，格氏崖豆藤（豆科）的根和茎皮含有异黄酮、生物碱和二萜类化合物。格氏崖豆藤衍生的一些生物活性异黄酮的潜在益处促使我们筛选它们的雌激素活性。对从格氏崖豆藤（bail）中提取的六种异黄酮和香豆素，即化合物编号1-6（图1），在三种不同的雌激素受体α（ERα）依赖性试验中测试了它们的潜在雌激素活性。在基于酵母的ERα试验中，所有测试物质以及作为内源性激动剂的17β-雌二醇，均显示出β-半乳糖苷酶活性的显著诱导。浓度为5×10⁻⁶ M的测试化合物可达到用10⁻⁸ M 17β-雌二醇（100%）获得的β-半乳糖苷酶诱导率的59%-121%。在基于稳定转染的MCF-7细胞（MVLN细胞）的报告基因试验中，格氏崖豆藤异黄酮也刺激了荧光素酶的雌激素反应性诱导。在石川细胞中，所有物质通过碱性磷酸酶（AlkP）活性的诱导表现出雌激素活性。格氏崖豆藤异黄酮的雌激素活性可被纯雌激素拮抗剂ICI 182,780完全抑制，这表明这些化合物通过ERα发挥其活性。尽管所有物质都显示出雌激素作用，但发现4'-甲氧基-7-O-[(E)-3-甲基-7-羟甲基-2,6-辛二烯基]异黄酮（7-O-DHF）、格氏崖豆藤酮C（GRIF-C）和3',4'-二羟基-7-O-[(E)-3,7-二甲基-2,6-辛二烯基]异黄酮（7-O-GISO）是测试物质中最有效的。总之，首次使用报告基因试验和雌激素诱导的AlkP石川模型描述了格氏崖豆藤衍生异黄酮的雌激素活性。
