Background: Phyllanthus urinaria, a traditional herbal medicine, has aroused widespread
concern at home and abroad. However, there are few studies on the effects of Phyllanthus urinaria on
CYP450. Therefore, this study aims to explore the main chemical compositions of Phyllanthus urinaria
and its effect on the activity of CYP450 enzyme in rats.
Methods: Acetonitrile and 0.1% Trifluoroacetic Acid (TFA) were used as mobile phase, along with the
application of gradient elution to simultaneously determine the main chemical constituents in Phyllanthus
urinaria by HPLC (r2>0.999). Sprague-Dawley (SD) rats, randomly divided into control group,
low-dose group and high-dose group, were treated with normal saline and different doses of Phyllanthus
urinaria extract solution, respectively. Additionally, the rats were given intragastric administration of
cocktail probe (specific substrates of CYP450 isoenzyme) at 15th day; the plasma was collected by tail
vein at various times. Furthermore, the UPLC-MS/MS method (r2>0.99) was used to detect the probe
concentration, along with the evaluation of the activity of CYP450 enzyme according to the pharmacokinetic
parameters of the probe.
Results: Gallic acid, 3, 4-dihydroxybenzoic acid, caffeic acid, corilagin and ellagic acid were found in
the Phyllanthus urinaria extract solution by HPLC. Compared with the control group, the metabolism
of bupropion, metoprolol, midazolam and tolbutamide slowed down significantly in the Phyllanthus
urinaria group, with no significant metabolic changes in phenacetin.
Conclusion: Phyllanthus urinaria could induce activity of CYP2D6, CYP2B1, CYP3A4 and CYP2C9,
without exerting a significant effect on CYP1A2.