2,3-cis-2R,3R-(-)-epiafzelechin-3-O-p-coumarate, a novel flavan-3-ol isolated from Fallopia convolvulus seed, is an estrogen receptor agonist in human cell lines

Jennifer C. Brennan, Michael S. Denison, Dirk M. Holstege, Prokopios Magiatis, Jerry L. Dallas, Elisa G. Gutierrez, Anatoly A. Soshilov, James R. Millam

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: The plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence.Methods: Analytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β.Results: Two compounds, emodin and the novel flavan-3-ol, (-)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400% of maximum estradiol [E2] induction) but not in the breast cell line.Conclusion: This study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist.

Original languageEnglish (US)
Article number133
JournalBMC Complementary and Alternative Medicine
Volume13
DOIs
StatePublished - Jun 14 2013

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Convolvulus
Emodin
Phytoestrogens
Estrogen Receptors
Seeds
Estrogens
Cell Line
Breast
Human Activities
Analytical Chemistry Techniques
Breast Neoplasms
Optical Rotation
Rhizome
Chinese Traditional Medicine
Circular Dichroism
flavan-3-ol
epiafzelechin
Fallopia
Biological Products
Reporter Genes

Keywords

  • (-)-epiafzelechin-3-O-p-coumarate (rhodoeosein)
  • Bioassay-directed fractionation
  • Emodin
  • Estrogen receptor
  • Fallopia convolvulus
  • HPLC/MS/NMR
  • Phytoestrogens
  • Relative estrogenic potency
  • Transfection

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

2,3-cis-2R,3R-(-)-epiafzelechin-3-O-p-coumarate, a novel flavan-3-ol isolated from Fallopia convolvulus seed, is an estrogen receptor agonist in human cell lines. / Brennan, Jennifer C.; Denison, Michael S.; Holstege, Dirk M.; Magiatis, Prokopios; Dallas, Jerry L.; Gutierrez, Elisa G.; Soshilov, Anatoly A.; Millam, James R.

In: BMC Complementary and Alternative Medicine, Vol. 13, 133, 14.06.2013.

Research output: Contribution to journalArticle

Brennan, Jennifer C. ; Denison, Michael S. ; Holstege, Dirk M. ; Magiatis, Prokopios ; Dallas, Jerry L. ; Gutierrez, Elisa G. ; Soshilov, Anatoly A. ; Millam, James R. / 2,3-cis-2R,3R-(-)-epiafzelechin-3-O-p-coumarate, a novel flavan-3-ol isolated from Fallopia convolvulus seed, is an estrogen receptor agonist in human cell lines. In: BMC Complementary and Alternative Medicine. 2013 ; Vol. 13.
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title = "2,3-cis-2R,3R-(-)-epiafzelechin-3-O-p-coumarate, a novel flavan-3-ol isolated from Fallopia convolvulus seed, is an estrogen receptor agonist in human cell lines",
abstract = "Background: The plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence.Methods: Analytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β.Results: Two compounds, emodin and the novel flavan-3-ol, (-)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400{\%} of maximum estradiol [E2] induction) but not in the breast cell line.Conclusion: This study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist.",
keywords = "(-)-epiafzelechin-3-O-p-coumarate (rhodoeosein), Bioassay-directed fractionation, Emodin, Estrogen receptor, Fallopia convolvulus, HPLC/MS/NMR, Phytoestrogens, Relative estrogenic potency, Transfection",
author = "Brennan, {Jennifer C.} and Denison, {Michael S.} and Holstege, {Dirk M.} and Prokopios Magiatis and Dallas, {Jerry L.} and Gutierrez, {Elisa G.} and Soshilov, {Anatoly A.} and Millam, {James R.}",
year = "2013",
month = "6",
day = "14",
doi = "10.1186/1472-6882-13-133",
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TY - JOUR

T1 - 2,3-cis-2R,3R-(-)-epiafzelechin-3-O-p-coumarate, a novel flavan-3-ol isolated from Fallopia convolvulus seed, is an estrogen receptor agonist in human cell lines

AU - Brennan, Jennifer C.

AU - Denison, Michael S.

AU - Holstege, Dirk M.

AU - Magiatis, Prokopios

AU - Dallas, Jerry L.

AU - Gutierrez, Elisa G.

AU - Soshilov, Anatoly A.

AU - Millam, James R.

PY - 2013/6/14

Y1 - 2013/6/14

N2 - Background: The plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence.Methods: Analytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β.Results: Two compounds, emodin and the novel flavan-3-ol, (-)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400% of maximum estradiol [E2] induction) but not in the breast cell line.Conclusion: This study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist.

AB - Background: The plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence.Methods: Analytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β.Results: Two compounds, emodin and the novel flavan-3-ol, (-)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400% of maximum estradiol [E2] induction) but not in the breast cell line.Conclusion: This study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist.

KW - (-)-epiafzelechin-3-O-p-coumarate (rhodoeosein)

KW - Bioassay-directed fractionation

KW - Emodin

KW - Estrogen receptor

KW - Fallopia convolvulus

KW - HPLC/MS/NMR

KW - Phytoestrogens

KW - Relative estrogenic potency

KW - Transfection

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U2 - 10.1186/1472-6882-13-133

DO - 10.1186/1472-6882-13-133

M3 - Article

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JO - BMC Complementary and Alternative Medicine

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SN - 1472-6882

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