br Material and methods br Results br

Material and methods


CYP1A2 is a metabolic enzyme for theophylline, tizanidine, and caffeine. In several cases, Bakumondo-to was co-administrated with theophylline for airway inflammation and chronic Cy3.5 hydrazide treatment. Saruwatari et Cy3.5 hydrazide al. (2004) reported that Bakumondo-to tended to inhibit the CYP1A2 activity after 7days in an in vivo human study. In our study, it was observed that Bakumondo-to significantly inhibited CYP1A2 activity, but its protein expression was not changed compared with that of the control. It suggested that the inhibition of CYP1A2 activities by Bakumondo-to is independent of protein expression. Taking our and Saruwatari’s study data into account, Bakumondo-to may change the affinity of CYP1A2. Chang reported that Ginseng root extract, one of the components of Bakumondo-to, inhibited CYP1A2 activity (Chang et al., 2002). However, the inhibitory components and mechanisms are still unknown and need to be clarified.
CYP2C is approximately 25% of P450 in human liver microsomes (Imaoka et al., 1996). It is reported that CYP2C is the key enzyme for the metabolism of zafirlukast, montelukast, omeprazole, and phenytoin (Dekhuijzen and Koopmans, 2002; Karonen et al., 2012). Zafirlukast or montelukast, a leukotriene receptor antagonist, is used for the treatment of asthma and allergic rhinitis. Bakumondo-to is co-administrated with zafirlukast or montelukast in several cases. Therefore, we also examined the effect of Bakumondo-to on CYP2C. The activities were increased by 158%, and the density of CYP2C bands were increased by 288% compared with that of the control groups. The data suggest that the increased activities depend on the induced protein expression. Only 4days of treatment caused CYP2C induction. If Bakumondo-to is administered for long periods in clinical situations caution should be taken to prevent drug-herbal interactions via CYP2C.