Effects of unprocessed vs. cooked-processed Gastrodia elata on cytochrome P450 enzymes in rats

Gastrodia elata Blume (GE) has been used as a traditional herb and is considered one of the most important medicinal plants in Oriental countries since centuries.

The purpose of this study was to find out the differences between the effects of unprocessed and cooked-processed GE (CGE) on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9 and CYP3A4) by using cocktail probe drugs in vivo.

A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), tolbutamide (5 mg/kg) and midazolam (10 mg/kg), was orally administration to rats treated with GE or CGE for 14 days orally. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0.

Both GE and CGE did not have significant influences on the pharmacokinetic parameters of phenacetin (P>0.05). In addition, CGE decreased the t1/2, Cmax, AUC(0-∞) of tolbutamide (P<0.05) and it increased CL significantly (P<0.01). Furthermore, the trend in CGE was similar but far more significant than GE on t1/2, Cmax, AUC(0-∞), and other parameters of midazolam (P<0.05).

In conclusion, GE and CGE had no effects on rat CYP1A2. GE did not affect CYP2C9 activity, but CGE induced the CYP2C9 activity. Moreover, CGE was more potent than GE for inhibitory effect on CYP3A4 activity. These results provide useful scientific data for the safe clinical application of either extract of GE or in combination with other drugs, which should lack the side effects induced by other herb-drug interactions.