Liu Wei Di Huang Wan, a well-known traditional Chinese medicine, induces CYP1A2 while suppressing CYP2A6 and N-acetyltransferase 2 activities in man

Ethnopharmacological relevanceLiu Wei Di Huang Wan (LDW), a well-known traditional Chinese medicine, is frequently combined with other prescription or non-prescription drugs in China.Aim of the studyThis study was designed to investigate the effects of LDW on the activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO) in healthy subjects, using caffeine as a probe drug.Materials and methodsTwelve unrelated healthy males were enrolled in a single-blind, randomized, placebo-controlled, two-phase crossover study. Placebo or LDW (12 pills, 0.2 g/pill, twice daily) was given to each participant for 14 continuous days with a wash-out period of 2 weeks. A dose of 100 mg caffeine was given afterwards to test the activities of drug-metabolizing enzymes of interest.ResultsCompared to placebo, LDW significantly induced the CYP1A2 activity, as determined by an increase in the ratio of (AFMU + 1U + 1X)/17U and the formation of 17X and 1X after taking caffeine. Interestingly, LDW significantly decreased the ratio of 17U/(17U + 17X + 1X + 1U + AFMU) and the formation of 17U (CYP2A6-mediated) (by 39.2%; 95%CI: 23.1–55.3%; P = 0.026), and decreased the ratio of AFMU/(AFMU + 1U + 1X) and the formation of AFMU (NAT2-catalized) (by 26.2%; 95%CI: 9.2–61.6%; P = 0.038), suggesting a marked inhibition of CYP2A6 and NAT2, respectively.ConclusionsLDW can induce CYP1A2 and suppress CYP2A6 and NAT2 activities, and affect caffeine metabolism in vivo.

Liu Wei Di Huang Wan (LDW) is one of the well-known traditional Chinese medicines, which is the main mixture of rehmannia, alisma, cornus, moutan, dioscorea and hoelen, our study demonstrate that LDW can induce CYP1A2 and suppress CYP2A6, NAT2 activities and affect the pathways of caffeine metabolism and metabolites in vivo.Figure optionsDownload as PowerPoint slide