Inhibitory potential of herbal medicines on human cytochrome P450-mediatedoxidation: Properties of Umbelliferous or Citrus crude drugs and their relative prescriptions

To investigate the possible drug interaction with herbal medicine, hot wate r decoctions or 40% ethanol infusions of several Umbelliferous or Citrus cr ude drugs and their prescriptions were examined in vitro for their abilitie s to inhibit human cytochrome P450 3A (CYP3A). Addition of each decoction o r infusion from Baizhi (Angelica dahurica and varieties), Qianghuo (Notopte rygium incisum or N.forbesii), Duhuo (Angelica biserrata), Fangfeng (Saposh nikovia divaricata), Danggui (Angelica sinensis), Zhishi or Zhiqiao (Citrus aurantium) resulted in various degrees of human CYP3A inhibition as determ ined by microsomal testosterone 6 beta -hydroxylation, The inhibitory poten cy was consistent with the abundance of the hydrophobic components for each sample. Experiments on the infusion of a Japanese Baizhi (BZ1) showed the major role of furanocoumarins on human CYP3A inhibition. Some of the crude drugs and a related prescription showed increased inhibition after the prei ncubation, suggesting the involvement of a mechanism-based inhibition. Some formulated prescriptions, however, showed intense inhibition with their hy drophobic fractions rather than with their hydrophobic fractions, suggestin g that components other than furanocoumarins in herbal prescriptions may al so cause CYP3A inhibition. These results indicate the necessity of intensiv e investigations on the possible drug interaction with traditional medicine s.