Identification of metabolites of epiberberine in rat liver microsomes and its inhibiting effects on CYP2D6 / 中国中药杂志

Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 μmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.

Effect of comparability of Coptis chinensis and Scutellaria baicalensis on five sub-enzymatic activities of liver microsomes in rats / 中国中药杂志

To study the mechanism of metabolic interaction between Coptis chinensis and Scutellaria baicalensis. Rats were given C. chinensis and S. baicalensis for 7 days to produce hepatic microsomal enzyme. Cocktail probe substrate and liver microsome in vitro temperature incubation method were adopted. Meanwhile, the metabolic elimination percentages of the five probe substrates were detected with HPLC, in order to evaluate the effect of each administration group on the enzymatic activity of rat liver microsome CYP450. Compared with the blank group, C. chinensis obviously inhibited CYP2D6 and CYP1A2, and S. baicalensis remarkably inhibited CYP1A2, CYP2E1 and CYP2C9. The compatibility of C. chinensis and S. baicalensis with the ratio of 1:1 not only inhibited CYP1A2, but also remarkably activated CYP2D6 and CYP3A4. However, their activation effect disappeared under the ratio of 2: 1, and turned into the inhibitory effect on CYP1A2 and CYP2C9. The results showed that C. chinensis and S. baicalensis had an inhibitory effect on CYP450, but their compatibility with certain ratio resulted in double effects of activation and inhibition, which was related to their compatibility ratio. It is speculated that the inhibitory and inducing effects of C. chinensis and S. baicalensis on metabolic enzymes are among causes for their attenuation and synergistic effects.