Ginsenoside-Rb1 from Panax ginseng C.A. Meyer Activates Estrogen Receptor-α and -β, Independent of Ligand Binding

We studied the estrogenic activity of a component of Panax ginseng, ginsenoside-Rb1. The activity of ginsenoside-Rb1 was characterized in a transient transfection system, using estrogen receptor isoforms and estrogen-responsive luciferase plasmids, in COS monkey kidney cells. Ginsenoside-Rb1 activated both alpha and beta estrogen receptors in a dose-dependent manner with maximal activity observed at 100 microm, the highest concentration examined. Activation was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that the effects were mediated through the estrogen receptor. Treatment with 17beta-estradiol or ginsenoside-Rb1 increased expression of the progesterone receptor, pS2, and estrogen receptor in MCF-7 cells and of AP-1-driven luciferase genes in COS cells. Although these data suggest that it is functionally very similar to 17beta-estradiol, ginsenoside-Rb1 failed to displace specific binding of [(3)H]17beta-estradiol from estrogen receptors in MCF-7 whole-cell ligand binding assays. Our results indicate that the estrogen-like activity of ginsenoside-Rb1 is independent of direct estrogen receptor association.

[1]  B. H. Ren,et al.  Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide , 2001, British journal of pharmacology.

[2]  J. Woo,et al.  Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause , 2003, Menopause.

[3]  S. Apers,et al.  Phytoestrogens: Recent Developments , 2003, Planta medica.

[4]  Xiu Chen,et al.  CARDIOVASCULAR PROTECTION BY GINSENOSIDES AND THEIR NITRIC OXIDE RELEASING ACTION , 1996, Clinical and experimental pharmacology & physiology.

[5]  P. Ramarao,et al.  Ginsenoside Rf potentiates U-50,488H-induced analgesia and inhibits tolerance to its analgesia in mice. , 2003, Life sciences.

[6]  Phytoestrogens and breast cancer prevention: what is the evidence? , 2003, American journal of obstetrics and gynecology.

[7]  A. Ulloa-Aguirre,et al.  The phosphatidylinositol 3-kinase inhibitor LY294002 binds the estrogen receptor and inhibits 17β-estradiol-induced transcriptional activity of an estrogen sensitive reporter gene , 2003, Molecular and Cellular Endocrinology.

[8]  M. A. Bowman,et al.  A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. , 2001, Archives of internal medicine.

[9]  P. Ramwell,et al.  The vascular protective effects of estrogen , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  A. Cassidy.  Potential risks and benefits of phytoestrogen-rich diets. , 2003, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[11]  R. Duda,et al.  American ginseng and breast cancer therapeutic agents synergistically inhibit MCF‐7 breast cancer cell growth , 1999, Journal of surgical oncology.

[12]  T. Lau,et al.  An in-vitro study of ginsenoside Rb1-induced teratogenicity using a whole rat embryo culture model. , 2003, Human reproduction.

[13]  D. Guo,et al.  Estrogen-like activity of ginsenoside Rg1 derived from Panax notoginseng. , 2002, The Journal of clinical endocrinology and metabolism.

[14]  C. Yuan,et al.  Ginseng pharmacology: multiple constituents and multiple actions. , 1999, Biochemical pharmacology.

[15]  Y. Lee,et al.  Estrogen-induced transcription of the progesterone receptor gene does not parallel estrogen receptor occupancy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Marquardt,et al.  Estrogenic effects of nonylphenol on pS2, ER and MUC1 gene expression in human breast cancer cells-MCF-7. , 1997, Chemico-biological interactions.

[17]  E. Ernst,et al.  How useful are unconventional cancer treatments? , 1999, European journal of cancer.

[18]  A. Fugh-Berman,et al.  Complementary and Alternative Medicine for Menopausal Symptoms: A Review of Randomized, Controlled Trials , 2002, Annals of Internal Medicine.

[19]  R. J. Chang,et al.  Estrogen bioactivity in fo-ti and other herbs used for their estrogen-like effects as determined by a recombinant cell bioassay. , 2003, The Journal of clinical endocrinology and metabolism.

[20]  Young Joo Lee,et al.  Ginsenoside-Rb1 acts as a weak phytoestrogen in MCF-7 human breast cancer cells , 2003, Archives of pharmacal research.

[21]  J. Jameson,et al.  Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H H Fong,et al.  Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. , 2001, Journal of agricultural and food chemistry.

[23]  Youngjoo Lee,et al.  A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[24]  P. Mellon,et al.  Estrogenic activity of herbs commonly used as remedies for menopausal symptoms , 2002, Menopause.

[25]  Hyun-Jeong Cho,et al.  Possible role of ginsenoside Rb1 on regulation of rat liver triglycerides. , 2002, Biological & pharmaceutical bulletin.

[26]  C. Yuan,et al.  Ginsenoside variability in American ginseng samples. , 2002, The American journal of clinical nutrition.

[27]  C. Beyer,et al.  Estrogen regulates tyrosine hydroxylase expression in the neonate mouse midbrain. , 2003, Journal of neurobiology.

[28]  M. Schumacher,et al.  Rapid effects of triiodothyronine on immediate‐early gene expression in Schwann cells , 2001, Glia.

[29]  S. Nah,et al.  Functional expression of a novel ginsenoside Rf binding protein from rat brain mRNA in Xenopus laevis oocytes. , 2002, Molecular Pharmacology.

[30]  J. Corton,et al.  Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β. , 1998, Endocrinology.

[31]  Xiao-ling Fang,et al.  Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. , 2003, Journal of ethnopharmacology.

[32]  C. Nicol,et al.  Peroxisome proliferator‐activated receptor α is involved in the regulation of lipid metabolism by ginseng , 2003, British journal of pharmacology.

[33]  L. Fang,et al.  Effects of ginsenosides on bovine adrenal tyrosine hydroxylase. , 1999, Journal of ethnopharmacology.

[34]  C. Léger,et al.  Wine phenolic antioxidants inhibit AP-1 transcriptional activity. , 2001, Journal of agricultural and food chemistry.