Screening of Eleven Commonly Used Traditional Chinese Medicines for Inhibitory Effects on Human Cytochrome P450 Enzymes / 中草药·英文版

Objective Traditional Chinese medicines (TCMs) as natural therapeutic agents have been widely used and received great attention over the world. However, the information on them to cause herb-drug interactions mediated by cytochrome P450 (CYP) enzymes is limited. The present study aims to evaluate the inhibitory effects of 11 commonly used TCMs, including Nelumbinis Folium, Ginseng Radix et Rhizoma, Ziziphi Spinosae Semen, Chrysanthemi Flos, Lonicera Japonica Flos, Lycii Fructus, Cassiae Semen, Poria, Crataegi Fructus, Schisandrae Chinensis Fructus, and Polygonati Rhizoma, on the five human major CYP isoenzymes 2C19, 2D6, 3A4, 2E1, and 2C9. Methods An in vitro cocktail method was used. Results The aqueous extracts of all tested TCMs were found no significant inhibitory effect, with IC50 values higher than 100 μg/mL. While, the ethanolic extracts of some herbs showed more potent inhibition. These herbs include Nelumbinis Folium with IC50 values of 12.05 and 61.43 μg/mL on CYP2D6 and CYP2E1, Schisandrae Chinensis Fructus with IC50 values of 64.42 and 47.24 μg/mL on CYP2C19 and CYP3A4, and Chrysanthemi Flos with IC50 values of 45.25 μg/mL on CYP2C9, respectively. Conclusion Co-administration of these TCMs and their products with conventional medicines should be paid much attention to, and their potential inhibitory effects on CYP enzyme activities need to be further investigated.

Identification of Icaritin Metabolites in Rats by LC-MS/MS / 中草药·英文版

Objective: Icaritin is the main aglycone and also active intestinal metabolite of prenylflavonoids from the Chinese materia medica Epimedii Herba. Modern pharmacological studies have demonstrated that icaritin has a wide range of biological activities. However, its metabolites and biotransformation pathways have not yet been comprehensively investigated. The present study aims to identify icaritin metabolites in rats by using a sensitive and effective LC-MS/MS method. Methods: The plasma and urine samples of rats were collected before (blank) and after oral administration of icaritin, and subjected to liquid-liquid extraction with ethyl acetate. The full-scan LC-MS chromatograms of the plasma and urine samples were compared with those of blank samples to detect the possible metabolites, which were later detected by their product ion spectra. Results: A total of 23 metabolites were identified, and conjugated icaritins produced by glucuronidation, glycosylation, and sulfation were its major metabolites. Minor demethylation, hydrogenation, and oxidation metabolites were also found. Conclusion: Phase II metabolism is the main metabolic pathway of icaritin.

In vitro inhibition of quercetin and its glycosides on P450 enzyme activities / 中国药学杂志

OBJECTIVE: To evaluate inhibitory effect of the flavonoids, quercetin and its glycosides, on the activities of human liver microsomes isoforms CYP2C19, CYP2D6, CYP3A4 CYP2E1 and CYP2C9 in vitro for predicting prudential drug-drug interactions in clinical application. METHODS: Human liver microsomes and five probes were incubated with tested flavonoids at 37°C, in presence of NADPH. The concentrations of produced metabolites in the reaction solution were determined by liquid chromatography/tandem mass spectrometry method, and compared for evaluating the activity of isoenzymes. RESULTS: Quercetin inhibited CYP3A4 and CYP2C9 activities with IC50 values of 13.14 and 23.09 μmol·L-1, respectively. While, the quercetin glycosides, quercetin-3-O-glu-curonide, isoquercitrin, hyperoside and rutin were found no significant inhibition effects on the five tested enzymes, with IC50 values higher than 100 μmol·L-1. CONCLUSION: Quercetin shows moderate inhibition on CYP3A4 and CYP2C9, there is very little inhibition on the other tested flavonoids because sufficiently high levels are not clinically achieved more than 100 μmol·L-1. The quercetin glycoside compounds are less likely to cause potential drug-drug interactions.