Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Mar 22:3:4.
doi: 10.1186/s40203-015-0008-z. eCollection 2015.

A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements

Chelsea N Powers  1 , William N Setzer  1
Affiliations

A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements

Chelsea N Powers et al. In Silico Pharmacol. .

Abstract

Purpose: The purpose of this study is to use a molecular docking approach to identify potential estrogen mimics or anti-estrogens in phytochemicals found in popular dietary herbal supplements.

Methods: In this study, 568 phytochemicals found in 17 of the most popular herbal supplements sold in the United States were built and docked with two isoforms of the estrogen receptor, ERα and ERβ (a total of 27 different protein crystal structures).

Results: The docking results revealed six strongly docking compounds in Echinacea, three from milk thistle (Silybum marianum), three from Gingko biloba, one from Sambucus nigra, none from maca (Lepidium meyenii), five from chaste tree (Vitex agnus-castus), two from fenugreek (Trigonella foenum-graecum), and two from Rhodiola rosea. Notably, of the most popular herbal supplements for women, there were numerous compounds that docked strongly with the estrogen receptor: Licorice (Glycyrrhiza glabra) had a total of 26 compounds strongly docking to the estrogen receptor, 15 with wild yam (Dioscorea villosa), 11 from black cohosh (Actaea racemosa), eight from muira puama (Ptychopetalum olacoides or P. uncinatum), eight from red clover (Trifolium pratense), three from damiana (Turnera aphrodisiaca or T. diffusa), and three from dong quai (Angelica sinensis). Of possible concern were the compounds from men's herbal supplements that exhibited strong docking to the estrogen receptor: Gingko biloba had three compounds, gotu kola (Centella asiatica) had two, muira puama (Ptychopetalum olacoides or P. uncinatum) had eight, and Tribulus terrestris had six compounds.

Conclusions: This molecular docking study has revealed that almost all popular herbal supplements contain phytochemical components that may bind to the human estrogen receptor and exhibit selective estrogen receptor modulation. As such, these herbal supplements may cause unwanted side effects related to estrogenic activity.

Keywords: Estrogen receptor; Herbal supplements; Molecular docking.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Relationship between herbal supplement purchases in the United States and the year.
Figure 2
Figure 2
Alkaloid ligands examined in this work.
Figure 3
Figure 3
Chalcone ligands examined in this work.
Figure 4
Figure 4
Coumarin ligands examined in this work.
Figure 5
Figure 5
Additional coumarin ligands examined in this work.
Figure 6
Figure 6
Diterpenoid ligands examined in this work.
Figure 7
Figure 7
Additional diterpenoid ligands examined in this work.
Figure 8
Figure 8
Additional diterpenoid ligands examined in this work.
Figure 9
Figure 9
Additional diterpenoid ligands examined in this work.
Figure 10
Figure 10
Flavonoid ligands examined in this work.
Figure 11
Figure 11
Additional flavonoid ligands examined in this work.
Figure 12
Figure 12
Additional flavonoid ligands examined in this work.
Figure 13
Figure 13
Additional flavonoid ligands examined in this work.
Figure 14
Figure 14
Additional flavonoid ligands examined in this work.
Figure 15
Figure 15
Additional flavonoid ligands examined in this work.
Figure 16
Figure 16
Additional flavonoid ligands examined in this work.
Figure 17
Figure 17
Additional flavonoid ligands examined in this work.
Figure 18
Figure 18
Isoflavonoid ligands examined in this work.
Figure 19
Figure 19
Additional isoflavonoid ligands examined in this work.
Figure 20
Figure 20
Additional isoflavonoid ligands examined in this work.
Figure 21
Figure 21
Lignan ligands examined in this work.
Figure 22
Figure 22
Phenanthrenoid ligands examined in this work.
Figure 23
Figure 23
Miscellaneous phenolic compounds examined in this work.
Figure 24
Figure 24
Additional miscellaneous phenolic compounds examined in this work.
Figure 25
Figure 25
Additional miscellaneous phenolic compounds examined in this work.
Figure 26
Figure 26
Sesquiterpenoid ligands examined in this work.
Figure 27
Figure 27
Steroid ligands examined in this work.
Figure 28
Figure 28
Additional steroid ligands examined in this work.
Figure 29
Figure 29
Additional steroid ligands examined in this work.
Figure 30
Figure 30
Additional steroid ligands examined in this work.
Figure 31
Figure 31
Additional steroid ligands examined in this work.
Figure 32
Figure 32
Additional steroid ligands examined in this work.
Figure 33
Figure 33
Additional steroid ligands examined in this work.
Figure 34
Figure 34
Additional steroid ligands examined in this work.
Figure 35
Figure 35
Stilbenoid ligands examined in this work.
Figure 36
Figure 36
Additional stilbenoid ligands examined in this work.
Figure 37
Figure 37
Triterpenoid ligands examined in this work.
Figure 38
Figure 38
Additional triterpenoid ligands examined in this work.
Figure 39
Figure 39
Additional triterpenoid ligands examined in this work.
Figure 40
Figure 40
Additional triterpenoid ligands examined in this work.
Figure 41
Figure 41
Additional triterpenoid ligands examined in this work.
Figure 42
Figure 42
Miscellaneous phytochemical ligands examined in this work.
Figure 43
Figure 43
Additional miscellaneous phytochemical ligands examined in this work.
Figure 44
Figure 44
Lowest-energy docked poses of alkaloids [ N-trans -feruloyltyramine (aqua), cis- clovamide (red), and trans- clovamide (blue) along with the co-crystallized ligand, genistein (green)] with ERα (PDB 1X7R). A: Docked poses showing the entire ribbon structure of the protein. B: Close-up of the docked poses.
Figure 45
Figure 45
Lowest-energy docked pose of cis- clovamide with ERα (PDB 1X7R) showing the principle amino acid contacts in the binding site. Hydrogen bonds are indicated by blue dashed lines.
Figure 46
Figure 46
Lowest-energy docked pose of N-trans- feruloyltyramine with ERβ (PDB 1X7B) showing the principle amino acid contacts in the binding site. Hydrogen bonds are indicated by blue dashed lines.
Figure 47
Figure 47
Lowest-energy docked pose of the prenylated chalcone kanzonol Y with ERβ (PDB 1X7J) showing the hydrophobic amino acid contacts with the isoprenyl groups of the ligand.
Figure 48
Figure 48
Lowest-energy docked poses of pregnane steroids [2,3-dihydroxypregn-16-en-20-one (magenta), 3,16-dihydroxypregn-5-en-20-one (dark green), 3,21-dihydroxypregna-5,16-dien-20-one (white), and pregnadienolone (bright green)] with ERβ (PDB 1U3R). A: Docked poses showing the entire ribbon structure of the protein. B: Close-up of the docked poses.
See this image and copyright information in PMC

References

    1. Abdel-Barry JA, Abdel-Hassan IA, Al-Hakiem MHH. Hypoglycaemic and antihyperglycaemic effects of Trigonella foenum-graecum leaf in normal and alloxan induced diabetic rats. J Ethnopharmacol. 1997;58:149–155. doi: 10.1016/S0378-8741(97)00101-3. - DOI - PubMed
    1. Al-Bareeq RJ, Ray AA, Nott L, Pautler SE, Razvi H. Dong quai (Angelica sinensis) in the treatment of hot flashes for men on androgen deprivation therapy: results of a randomized double-blind placebo controlled trial. Can Urol Assoc J. 2010;4:49–53. - PMC - PubMed
    1. Ali Z, Smillie TJ, Khan IA. Cholestane steroid glycosides from the rhizomes of Dioscorea villosa. Carbohydr Res. 2013;370:86–91. doi: 10.1016/j.carres.2012.12.022. - DOI - PMC - PubMed
    1. Au AM, Ko R, Boo FO, Hsu R, Perez G, Yang Z. Screening methods for drugs and heavy metals in Chinese patent medicines. Bull Environ Contam Toxicol. 2000;65:112–119. doi: 10.1007/s001280000102. - DOI - PubMed
    1. Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Comparison of hormonal activity (estrogen, androgen, and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. Mol Biol. 2003;84:259–268. - PubMed