Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents

Abstract

The potential of licorice dietary supplements to interact with drug metabolism was evaluated by testing extracts of three botanically identified licorice species (Glycyrrhiza glabra L., Glycyrrhiza uralensis Fish. ex DC. and Glycyrrhiza inflata Batalin) and 14 isolated licorice compounds for inhibition of 9 cytochrome P450 enzymes using a UHPLC-MS/MS cocktail assay. G. glabra showed moderate inhibitory effects against CYP2B6, CYP2C8, CYP2C9, and CYP2C19, and weak inhibition against CYP3A4 (testosterone). In contrast, G. uralensis strongly inhibited CYP2B6 and moderately inhibited CYP2C8, CYP2C9 and CYP2C19, and G. inflata strongly inhibited CYP2C enzymes and moderately inhibited CYP1A2, CYP2B6, CYP2D6, and CYP3A4 (midazolam). The licorice compounds isoliquiritigenin, licoricidin, licochalcone A, 18β-glycyrrhetinic acid, and glycycoumarin inhibited one or more members of the CYP2C family of enzymes. Glycycoumarin and licochalcone A inhibited CYP1A2, but only glycycoumarin inhibited CYP2B6. Isoliquiritigenin, glabridin and licoricidin competitively inhibited CYP3A4, while licochalcone A (specific to G. inflata roots) was a mechanism-based inhibitor. The three licorice species commonly used in botanical dietary supplements have varying potential for drug-botanical interactions as inhibitors of cytochrome P450 isoforms. Each species of licorice displays a unique profile of constituents with potential for drug interactions.

Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies

“…55 It should be noted that some previous investigations have revealed that licorice constituents can affect the pharmacokinetic behaviour of some therapeutic drugs via inhibiting the hepatic drug metabolizing enzymes (cytochrome P450 enzymes and UDP-glucuronosyltransferases). [56][57][58] In this study, our results demonstrate that thrombin activity can be inhibited by the chalcones in licorice. Therefore, it is conceivable that both pharmacokinetic and pharmacodynamics interactions may occur when anticoagulant or antiplatelet drugs are used in combination with licorice-containing products.…”

Nutrigenomics-Associated Impacts of Nutrients on Genes and Enzymes With Special Consideration of Aromatase

“…Induction of aromatase and thus increase of breast cancer risk can be associated with ethanol. Liquorice (glycyrrhizin from glycyrrhiza glabra) reduces serum testosterone and induces ovulation by induction of aromatase (85)(86)(87)(88)(89)(90). Various flavonoids have been tested and the effect been quantified on cell lines only, but not in vivo (e.g., H295R adrenocortical carcinoma cells).…”

Factors Affecting Dexamethasone Suppression Test Results

“…Important examples of agents influencing CYP3A4 are displayed in (▶ table 4S). Curiously, diverse natural compounds, such as for instance grapefruit, pomegranate, ginkgo, echinacea, St. John's wort, or licorice, impair the cytochrome's function as well [49][50][51][52][53][54][55][56][57].…”