Metabolism and Bioactivity Studies of Licorice Species and the Active Compounds

Botanical products have a long history of use as dietary supplements to maintain or improve health. Considering the complexity of the herbal products, obtaining scientific evidence for their efficacy and safety is important for customers. Licorice root extract is used in botanical dietary supplements all around the world. In recent years, licorice products have become popular among women seeking relief from premenstrual syndrome and menopausal symptoms. However, the bioactive constituents vary considerably between different licorice species, which will affect the bioactivity of licorice commercial products. This dissertation focused on the discovery of bioactive compounds from licorice and the investigation of their human metabolism. Some of these compounds may have the potential to cause drug-botanical interaction such as drug metabolizing enzyme inhibition or induction. To expedite these studies, a new screening assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a triple quadrupole mass spectrometer was developed for detecting reactive metabolites and electrophilic compounds from licorice extracts. In addition, several licorice chalcones have been reported to function as chemoprevention agents while at the same time potentially causing drug-botanical interactions such as induction or inhibition of drug metabolizing enzymes. Specifically, licochalcone A (LicA), a licorice chalcone and potential chemoprevention agents from Glycyrrhizza inflata, was investigated with respect to its in vitro phase I and phase II metabolism. These in vitro data will facilitate the design of animal studies and clinical trials of LicA and licorice dietary supplements containing LicA.