Estrogenic properties of isoflavones derived from Millettia griffoniana

• Published in: Phytomedicine (Stuttgart) 2006-02, Vol.13 (3), p.139-145
• Main Authors: Ketcha Wanda, G.J.M., Njamen, D., Yankep, E., Tagatsing Fotsing, M., Tanee Fomum, Z., Wober, J., Starcke, S., Zierau, O., Vollmer, G.
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - analysis; Alkaline Phosphatase - biosynthesis; beta-Galactosidase - analysis; beta-Galactosidase - biosynthesis; Biological Assay - methods; Cell Line; Dose-Response Relationship, Drug; Enzyme Induction - drug effects; Estradiol - analogs & derivatives; Estradiol - pharmacology; Health aspects; Hormone therapy; Humans; In vitro bioassays; Isoflavones; Isoflavones - chemistry; Isoflavones - pharmacology; Leguminosae; Luciferase; Luciferases - analysis; Luciferases - biosynthesis; Millettia - chemistry; Phytoestrogens - chemistry; Phytoestrogens - pharmacology; Plant Bark - chemistry; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Roots - chemistry; Receptors, Estrogen - drug effects; Recombinant Proteins - biosynthesis; Root bark; Saccharomyces cerevisiae; β-galactosidase
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2005.06.003

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 (ER α)-dependent assays. In a yeast-based ER α assay, all test substances and 17 β-estradiol as endogenous agonist, showed a significant induction of β-galactosidase activity. The test compounds at the concentration of 5×10 −6 M could achieve 59–121% of the β-galactosidase induction obtained with 10 −8 M 17 β-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 ER α. 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.