Evidence for Chemopreventive and Resilience Activity of Licorice: <i>Glycyrrhiza Glabra</i> and G. <i>Inflata</i> Extracts Modulate Estrogen Metabolism in ACI Rats

Abstract

Women are increasingly using botanical dietary supplements (BDS) to reduce menopausal hot flashes. Although licorice (<i>Glycyrrhiza</i> sp.) is one of the frequently used ingredients in BDS, the exact plant species is often not identified. We previously showed that in breast epithelial cells (MCF-10A), <i>Glycyrrhiza glabra</i> (GG) and <i>G. inflata</i> (GI), and their compounds differentially modulated P450 1A1 and P450 1B1 gene expression, which are responsible for estrogen detoxification and genotoxicity, respectively. GG and isoliquiritigenin (LigC) increased <i>CYP1A1</i>, whereas GI and its marker compound, licochalcone A (LicA), decreased <i>CYP1A1</i> and <i>CYP1B1</i> The objective of this study was to determine the distribution of the bioactive licorice compounds, the metabolism of LicA, and whether GG, GI, and/or pure LicA modulate NAD(P)H quinone oxidoreductase (NQO1) in an ACI rat model. In addition, the effect of licorice extracts and compounds on biomarkers of estrogen chemoprevention (<i>CYP1A1</i>) as well as carcinogenesis (<i>CYP1B1</i>) was studied. LicA was extensively glucuronidated and formed GSH adducts; however, free LicA as well as LigC were bioavailable in target tissues after oral intake of licorice extracts. GG, GI, and LicA caused induction of NQO1 activity in the liver. In mammary tissue, GI increased <i>CYP1A1</i> and decreased <i>CYP1B1</i>, whereas GG only increased <i>CYP1A1</i> LigC may have contributed to the upregulation of <i>CYP1A1</i> after GG and GI administration. In contrast, LicA was responsible for GI-mediated downregulation of <i>CYP1B1</i> These studies highlight the polypharmacologic nature of botanicals and the importance of standardization of licorice BDS to specific <i>Glycyrrhiza</i> species and to multiple constituents.