Mechanisms, Dose and Target Tissues: 2010-2015

Results in NIHReporter

Director:  William G. Helferich, Ph.D.
Institution:  University of Illinois at Urbana-Champaign, Urbana, IL
Website: link disclaimer 
Partners: University of Mississippi, University, MS; Oregon State University, Corvallis, OR; National Center for Toxicological Research, Jefferson, AR

This center addressed safety, efficacy, and mechanism of action of botanical estrogens consumed by women. The projects looked at molecular mechanisms and cellular pathways of botanical estrogens and their actions on bone, uterus, mammary tissue, breast cancer metastasis, and cognition. Projects included: Molecular Mechanisms and Cellular Pathways of Botanical Estrogen Activity; Botanical Estrogen Actions in Bone, Uterus, Mammary, and Breast Cancer Metastasis; and Botanical Estrogens and Cognitive Function.

Highlighted Publications  

Boonmuen N, Gong P, Ali Z, Chittiboyina AG, Khan I, Doerge DR, Helferich WG, Carlson KE, Martin T, Piyachaturawat P, Katzenellenbogen JA, Katzenellenbogen BS. Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities. Steroids. 2016 Jan;105:42-9. doi: 10.1016/j.steroids.2015.11.006.external link disclaimer Epub 2015 Nov 26.  PubMed Central PMCID: PMC4714869.
The findings presented in the article classify the components of licorice root extracts as low potency, mixed estrogen receptor agonists and antagonists, having a character akin to that of selective estrogen receptor modulators or SERMs.

Kundu P, Korol DL, Bandara S, Monaikul S, Ondera CE, Helferich WG, Khan IA, Doerge DR, Schantz SL. Licorice root components mimic estrogens in an object location task but not an object recognition task. Horm Behav. 2018 Jul;103:97-106. doi: 10.1016/j.yhbeh.2018.06.002.external link disclaimer Epub 2018 Jul 1. PubMed Central PMCID: PMC6086590.
The goal of our botanical estrogens research is to find compounds that offer some of the beneficial effects of estrogen supplementation, without the harmful effects. This work suggests that isoliquiritigenin may not carry the cognitive risks associated with most other estrogenic compounds tested to date.

Madak-Erdogan Z, Gong P, Zhao YC, Xu L, Wrobel KU, Hartman JA, Wang M, Cam A, Iwaniec UT, Turner RT, Twaddle NC, Doerge DR, Khan IA, Katzenellenbogen JA, Katzenellenbogen BS, Helferich WG. Dietary licorice root supplementation reduces diet-induced weight gain, lipid deposition, and hepatic steatosis in ovariectomized mice without stimulating reproductive tissues and mammary gland. Mol Nutr Food Res. 2016 Feb;60(2):369-80. doi: 10.1002/mnfr.201500445external link disclaimer. Epub 2015 Nov 10. PubMed Central PMCID: PMC4738101.
In this article we showed that licorice root provided improvement of multiple metabolic parameters under conditions of low estrogen and high-fat diets without the potential negative effects of exogenous estrogen, as indicated by the lack of estrogenic response in female reproductive tissues.

Song H, Hughes JR, Turner RT, Iwaniec UT, Doerge DR, Helferich WG. (±)-Equol does not interact with genistein on estrogen-dependent breast tumor growth. Food Chem Toxicol. 2020 Feb;136:110979. doi: 10.1016/j.fct.2019.110979external link disclaimer. Epub 2019 Nov 28. PubMed Central PMCID: PMC7254865.
In this study we observed that equol has similar estrogenic effects as genistein in vitro, but dietary equol did not interact with genistein to alter breast cancer tumor growth in our preclinical model of estrogen-dependent breast cancer. 


 Prior CARBON Awards | NIH CARBON Program