UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.
Center for Natural Product Technologies, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.
Cancer Prev Res (Phila). 2018 Dec;11(12):819-830. doi: 10.1158/1940-6207.CAPR-18-0178. Epub 2018 Oct 4.
Women are increasingly using botanical dietary supplements (BDS) to reduce menopausal hot flashes. Although licorice ( 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), (GG) and (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 , whereas GI and its marker compound, licochalcone A (LicA), decreased and 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 () as well as carcinogenesis () 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 and decreased , whereas GG only increased LigC may have contributed to the upregulation of after GG and GI administration. In contrast, LicA was responsible for GI-mediated downregulation of These studies highlight the polypharmacologic nature of botanicals and the importance of standardization of licorice BDS to specific species and to multiple constituents.
女性越来越多地使用植物性膳食补充剂 (BDS) 来减轻更年期热潮红。虽然甘草 (sp.) 是 BDS 中常用的成分之一，但通常无法确定确切的植物种类。我们之前表明，在乳腺上皮细胞 (MCF-10A) 中，(GG) 和 (GI) 及其化合物差异调节 P450 1A1 和 P450 1B1 基因表达，分别负责雌激素解毒和遗传毒性。GG 和异甘草素 (LigC) 增加 ，而 GI 和其标记化合物，甘草查尔酮 A (LicA) 减少 和 。本研究的目的是确定生物活性甘草化合物的分布、LicA 的代谢以及 GG、GI 和/或纯 LicA 是否在 ACI 大鼠模型中调节 NAD(P)H 醌氧化还原酶 (NQO1)。此外，还研究了甘草提取物和化合物对雌激素化学预防 (BC) 以及致癌作用 () 的生物标志物的影响。LicA 广泛地葡萄糖醛酸化并形成 GSH 加合物；然而，在口服甘草提取物后，游离 LicA 以及 LigC 均可在靶组织中生物利用。GG、GI 和 LicA 导致肝脏中 NQO1 活性的诱导。在乳腺组织中，GI 增加 并减少 ，而 GG 仅增加 。LigC 可能有助于 GG 和 GI 给药后 的上调。相反，LicA 是 GI 介导的 下调的原因。这些研究强调了植物药的多药理学性质以及对甘草 BDS 进行标准化以针对特定 物种和多种成分的重要性。
