Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities

Nittaya Boonmuen, Ping Gong, Zulfiqar Ali, Amar G. Chittiboyina, Ikhlas Khan, Daniel R. Doerge, William G Helferich, Kathryn E. Carlson, Teresa Anne Martin, Pawinee Piyachaturawat, John A. Katzenellenbogen, Benita S Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

Licorice root extracts are often consumed as botanical dietary supplements by menopausal women as a natural alternative to pharmaceutical hormone replacement therapy. In addition to their components liquiritigenin (Liq) and isoliquiritigenin (Iso-Liq), known to have estrogenic activity, licorice root extracts also contain a number of other flavonoids, isoflavonoids, and chalcones. We have investigated the estrogenic activity of 7 of these components, obtained from an extract of Glycyrrhiza glabra powder, namely Glabridin (L1), Calycosin (L2), Methoxychalcone (L3), Vestitol (L4), Glyasperin C (L5), Glycycoumarin (L6), and Glicoricone (L7), and compared them with Liq, Iso-Liq, and estradiol (E2). All components, including Liq and Iso-Liq, have low binding affinity for estrogen receptors (ERs). Their potency and efficacy in stimulating the expression of estrogen-regulated genes reveal that Liq and Iso-Liq and L2, L3, L4, and L6 are estrogen agonists. Interestingly, L3 and L4 have an efficacy nearly equivalent to E2 but with a potency ca. 10,000-fold less. The other components, L1, L5 and L7, acted as partial estrogen antagonists. All agonist activities were reversed by the antiestrogen, ICI 182,780, or by knockdown of ERα with siRNA, indicating that they are ER dependent. In HepG2 hepatoma cells stably expressing ERα, only Liq, Iso-Liq, and L3 stimulated estrogen-regulated gene expression, and in all cases gene stimulation did not occur in HepG2 cells lacking ERα. Collectively, these findings classify the components of licorice root extracts as low potency, mixed ER agonists and antagonists, having a character akin to that of selective estrogen receptor modulators or SERMs.

Original languageEnglish (US)
Pages (from-to)42-49
Number of pages8
JournalSteroids
Volume105
DOIs
StatePublished - Jan 1 2016

Fingerprint

Dietary supplements
Glycyrrhiza
Selective Estrogen Receptor Modulators
Dietary Supplements
Estrogen Receptors
Estrogens
Hep G2 Cells
Genes
Chalcones
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Replacement Therapy
Flavonoids
Gene expression
Powders
Small Interfering RNA
Hepatocellular Carcinoma
Estradiol
liquiritigenin
isoliquiritigenin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities. / Boonmuen, Nittaya; Gong, Ping; Ali, Zulfiqar; Chittiboyina, Amar G.; Khan, Ikhlas; Doerge, Daniel R.; Helferich, William G; Carlson, Kathryn E.; Martin, Teresa Anne; Piyachaturawat, Pawinee; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.

In: Steroids, Vol. 105, 01.01.2016, p. 42-49.

Research output: Contribution to journalArticle

Boonmuen, Nittaya ; Gong, Ping ; Ali, Zulfiqar ; Chittiboyina, Amar G. ; Khan, Ikhlas ; Doerge, Daniel R. ; Helferich, William G ; Carlson, Kathryn E. ; Martin, Teresa Anne ; Piyachaturawat, Pawinee ; Katzenellenbogen, John A. ; Katzenellenbogen, Benita S. / Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities. In: Steroids. 2016 ; Vol. 105. pp. 42-49.
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AU - Khan, Ikhlas

AU - Doerge, Daniel R.

AU - Helferich, William G

AU - Carlson, Kathryn E.

AU - Martin, Teresa Anne

AU - Piyachaturawat, Pawinee

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