Evaluating the effect of Ganoderma lucidum polysaccharides on five cytochrome P450 isozymes with cocktail probe drugs in rats by LC–MS/MS

Abstract

Ganoderma lucidum polysaccharides (GLPs) are commonly used as health-promoting medicine and dietary supplement due to the positive effects in immune modulation, antitumor and antioxidant activities. However, whether GLPs executes other uncharacterized effects is largely unclear. The rats were pre-primed with GLPs and then administrated with canonical “cocktail probes” of cytochrome P450 (CYP450) isozymes including caffeine, tolbutamide, dextromethorphan, omeprazole, and midazolam. The plasma concentrations of probes at each indicated time point were simultaneously detected using the designed high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. The results suggested that GLPs could increase the accumulated levels of caffeine, tolbutamide and midazolam in plasma as compared to control group. Besides, GLPs reduced the concentration of dextromethorphan in blood at high dose, while elevated it at low dose. GLPs could inhibit the activities of CYP1A2, and CYP3A4, additionally; GLPs at low dose suppressed the activity of CYP2D6, which demonstrated that drugs co-administrated with GLPs might require strictly evaluating the dose relation.