Effects of Unprocessed Versus Vinegar-Processed Schisandra chinensison the Activity of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 andCYP2D6 Enzymes in Rats

Schisandra chinensis (SC) is a well-known traditional Chinese herbal medicine that has been used in clinical practices for thousands of years. However, the differences between the effects of unprocessed and vinegarprocessed Schisandra chinensis (VSC) on cytochrome P450 (CYP450) activities are poorly understood. To evaluate the differences between processed and unprocessed SC on the metabolism of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2D6 substrates in rats using a cocktail method based on a developed and validated high performance liquid chromatography-mass spectrometry (HPLC-MS) method. Six probe substrates (coumarin (CYP2A6), bupropion (CYP2B6), paclitaxel (CYP2C8), tolbutamide (CY2C9), omeprazole (CYP2C19) and metoprolol (CYP2D6)) were delivered simultaneously into rats treated with single or multiple doses of processed or crude SC extract. The plasma concentrations of the six probes were profiled by HPLC-MS, and their corresponding pharmacokinetic parameters were calculated. Treatment with single or multiple doses of either extract of SC or VSC induced CYP2A6, CYP2B6 and CYP2C9 enzyme activity and inhibited CYP2D6, CYP2C19 and CYP2C8 enzyme activity in rats. Furthermore, the inhibitory or induced effect of multiple doses of SC was more potent after vinegar processing than without vinegar processing. CYP2A6, 2B6 and 2C9 enzyme activity were induced significantly after treatment with multiple doses but not after a single dose. CYP2C19 enzyme activity were inhibited significantly after treatment with multiple doses but not after a single dose. These results provide useful scientific data for the safe clinical application of either extract of SC in combination with other drugs, which should lack the side effects induced by other herb-drug interactions.