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Modulation of Estrogen Oxidative Metabolism by Botanicals (Hops and Licorice) Used for Women’s Health

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Title: Modulation of Estrogen Oxidative Metabolism by Botanicals (Hops and Licorice) Used for Women’s Health
Author(s): Wang, Shuai
Advisor(s): Bolton, Judy
Contributor(s): Thomas, Douglas; Moore, Terry; Dietz, Birgit; Bosland, Maarten; Thatcher, Gregory
Department / Program: Medicinal Chemistry and Pharmacognosy
Degree Granting Institution: University of Illinois at Chicago
Degree: PhD, Doctor of Philosophy
Genre: Doctoral
Subject(s): Estrogen oxidative metabolism Botanical dietary supplements
Abstract: Estrogen is the primary hormone in women that plays an important role in maintaining normal functions of various tissues and organs. However, elongated exposure to estrogen from the use of hormone therapy has been found to be a risk factor for breast cancer carcinogenesis. Consequently, botanical dietary supplements are more and more being used by women as a surrogate for hormone therapy. Neither safety, efficacy, nor standardization is required prior to the marketing of these botanical dietary supplements. In this study, botanical extract as well as botanical pure compounds were evaluated for their effects on estrogen chemical carcinogenesis. Estrogen chemical carcinogenesis involves 4-hydroxylation of estrogens by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. A LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as non-toxic and 4-MeOE1 as genotoxic biomarkers in the human mammary epithelial cell lines. P450 1A1 and 1B1 enzyme activity and expression was measured and upstream aryl hydrocarbon receptor activation tested to explore the mechanisms. Two commonly used botanical extract licorice and hops were shown to have beneficial activity in modulating estrogen oxidative metabolism to potentially lower the risk of breast cancer. Bioactive compounds licochalcone A and 6-prenylnaringenin from these botanical extracts were identified to contribute to the activity of the extracts. Results from this study can be used to help standardize botanical dietary supplements with better safety and reproducible biological outcomes.
Issue Date: 2017-02-02
Type: Thesis
Date Available in INDIGO: 2017-10-27
Date Deposited: May 2017

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