Journal
JAPANESE JOURNAL OF PHARMACOLOGY
Volume 85, Issue 4, Pages 399-408Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jjp.85.399
Keywords
furanocoumarin; crude drug; traditional prescription; cytochrome P450 3A; inhibition
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To investigate the possible drug interaction with herbal medicine, hot water decoctions or 40% ethanol infusions of several Umbelliferous or Citrus crude drugs and their prescriptions were examined in vitro for their abilities to inhibit human cytochrome P450 3A (CYP3A). Addition of each decoction or infusion from Baizhi (Angelica dahurica and varieties), Qianghuo (Notopterygium incisum or N.forbesii), Duhuo (Angelica biserrata), Fangfeng (Saposhnikovia divaricata), Danggui (Angelica sinensis), Zhishi or Zhiqiao (Citrus aurantium) resulted in various degrees of human CYP3A inhibition as determined by microsomal testosterone 6 beta -hydroxylation, The inhibitory potency 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 preincubation, suggesting the involvement of a mechanism-based inhibition. Some formulated prescriptions, however, showed intense inhibition with their hydrophobic fractions rather than with their hydrophobic fractions, suggesting that components other than furanocoumarins in herbal prescriptions may also cause CYP3A inhibition. These results indicate the necessity of intensive investigations on the possible drug interaction with traditional medicines.
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