Effects of Salvia miltiorrhiza extract on the liver CYP3A activity in humans and rats

Salvia miltiorrhiza (Danshen) is a famous Traditional Chinese medicine used widely in the treatment of cardiovascular and cerebrovascular diseases. This study explored the effects of Danshen capsules commonly used in clinical practice on the liver CYP3A activity in humans and rats. The effects of Danshen extract on liver CYP3A activity were determined by metabolism of model substrates in vitro in human and rat liver microsomes and in the rat in vivo. HPLC was used to determine model substrates and metabolites. Danshen extract (50-2000 μg/mL) competitively inhibited human and rat liver microsomal CYP3A activity with inhibition constant (K _i) values of 51 and 65 μg/mL, respectively. In the rat, 14-day Danshen extract treatment (100 mg/kg/day, i.p. or 200 mg/kg/day, p.o.) decreased midazolam clearance (11-14%), with a concomitant increase in area under the curve (AUC; 12-17%) and a decrease in the volume of distribution (11-15%). These studies demonstrated that Danshen extract affected the metabolism of CYP3A substrates through competitive inhibition in human and rat liver in vitro and had no enzyme inducing effects on rat CYP3A in vivo after chronic administration.